Mercury Amalgam Fillings, Chronic Mercury Poisoning, and Mercury Detoxification: Referenced Articles with Abstracts - Page 2

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Cellular Damage

Ag, Cu, Hg and Ni ions alter the metabolism of human monocytes during extended low-dose exposures. Wataha JC, Lockwood PE, Schedle A, Noda M, Bouillaguet S. J Oral Rehabil. 2002 Feb; 29(2):133-9. 11856391 PubMed. The differences between concentrations with minimal effects and those which were lethal (8 versus 12 micromol L(-1) for Ag, 1.0 versus 1.5 micromol L(-1) for Hg) were small. Finally, concentrations which caused total suppression of cellular activity were sometimes preceded by an increased activity (Hg, Ni). We concluded that metal ions alter monocyte metabolic activity during extended exposures in vitro, but that the concentrations required are often near long-term lethal levels. Clinically, these results imply that the levels of metals released from dental alloys may be significant to monocytic function.

Block of sodium channels by divalent mercury: role of specific cysteinyl residues in the P-loop region. Hisatome I, Kurata Y, Sasaki N, Morisaki T, Morisaki H, Tanaka Y, Urashima T, Yatsuhashi T, Tsuboi M, Kitamura F, Miake J, Takeda S, Taniguchi S, Ogino K, Igawa O, Yoshida A, Sato R, Makita N, Shigemasa C. Biophys J. 2000 Sep; 79(3):1336-45. 10968996 PubMed. In summary, Hg(2+) probably inhibits the muscle Na(+) channels at more than one cysteinyl residue in the Na(+) channel P-loop region. Hg(2+) exhibits a lower K(d) value (<1. 23 microM) for inhibition by forming a sulfur-Hg-sulfur bridge, as compared to reaction at a single cysteinyl residue with a higher K(d) value (>8.47 microM) by forming sulfur-Hg(+) covalently. The heart Na(+) channel isoform with more than two cysteinyl residues in the P-loop region exhibits an extremely high sensitivity (K(d) < 0. 43 microM) to Hg(+), accounting for heart-specific high sensitivity to the divalent mercury.

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Calcium channels as target sites of heavy metals. Busselberg D. Toxicol Lett. 1995 Dec ;82-83:255-61. 8597062 PubMed. Hg, Al and Zn had only minor effects on voltage-activated potassium and sodium channels, while MeHg reduced potassium channel currents (IC50 = 2.2 microM) and, at higher concentrations, sodium channel currents (IC50 = 12.3 microM). Al also reduced other receptor-activated channel currents. These results demonstrate that a variety of metal species produce different actions at the level of the cell membrane.

Comparison of the interaction of methyl mercury and mercuric chloride with murine macrophages. Christensen MM, Ellermann-Eriksen S, Rungby J, Mogensen SC. Arch Toxicol. 1993; 67(3):205-11. 7684221 PubMed. The toxicity of organic methyl mercury was studied on murine macrophages in cell culture and compared to that of inorganic mercuric chloride. Long-term treatment of macrophage cultures with methyl mercury resulted in decreased cell viability in a concentration-dependent fashion. Experiments showed that 20 microM methyl mercury was highly toxic, causing cell death within a few days, while cultures exposed to lower levels were less severely affected. Comparison of the toxicity of organic and inorganic mercury by cell viability showed no difference between equimolar concentrations of methyl mercury and mercuric chloride. Furthermore, protein synthesis (interferon-alpha/beta) was reduced in a concentration dependent manner and had the same reduced magnitude in cells treated with either methyl mercury or mercuric chloride. However, impairment of random migration and phagocytosis of macrophages appeared at lower concentrations in cells exposed to methyl mercury than in cells exposed to mercuric chloride. Electron microscopy of cells exposed to methyl mercury revealed mercury deposits in lysosomes and dispersed in the cytoplasm and nuclei. The present study shows that methyl mercury and mercuric chloride impair cell viability and protein production in cell cultures at equimolar concentrations, while methyl mercury inhibits macrophage functions such as migration and phagocytosis at lower concentrations than mercuric chloride.

Cytotoxicity of dental composite components and mercury compounds in lung cells. Reichl FX, Walther UI, Durner J, Kehe K, Hickel R, Kunzelmann KH, Spahl W, Hume WR, Benschop H, Forth W. Dent Mater. 2001 Mar; 17(2):95-101. 11163377 PubMed. SIGNIFICANCE: The toxic effect of HgCl2 and MeHgCl from the L2 cells was about 100-700-fold higher than of the dental composite components.

Effects of inorganic and organic mercury on intracellular calcium levels in rat T lymphocytes. Tan XX, Tang C, Castoldi AF, Manzo L, Costa LG. J Toxicol Environ Health. 1993 Feb; 38(2):159-70. 8433400 PubMed. The importance of cytosolic free calcium level ([Ca2+]i) in lymphocyte activation prompted us to investigate changes in [Ca2+]i in T cells caused by mercury compounds, which have been shown to have immunomodulatory and immunotoxic properties. These results suggest that MeHg and HgCl2 exert their effects of [Ca2+]i in different ways: MeHg-induced increases in [Ca2+]i are due to influx from outside the cells as well as to mobilization from intracellular stores, possibly the endoplasmic reticulum, and, to a minor extent, the mitochondria; on the other hand, HgCl2 causes only Ca2+ influx from the extracellular medium.

Effects of lead, mercury, and methyl mercury on gap junctions and [Ca2+]i in bone cells. Schirrmacher K, Wiemann M, Bingmann D, Busselberg D. Calcif Tissue Int. 1998 Aug; 63(2):134-9. 9685518 PubMed. Heavy metals such as lead (Pb), mercury (Hg), and methyl mercury (MeHg) impair cell functions. For bone it is known that Pb changes bone formation rates, which depend on intracellular free calcium concentration ([Ca2+]i). Since heavy metals compete with Ca2+ at multiple sites and increased [Ca2+]i reduces gap junctional coupling between bone cells, we analyzed the effects of extracellular (e) and intracellular (i) application of Pb, Hg, and MeHg on these channels. In conclusion, Pb(e), Pb(i) and Hg(e) do not affect gap junctional coupling per se. Since MeHg(e) and Hg(i) deplete calcium stores, the decrease of the electric coupling is attributable to increased [Ca2+]i, which affects gap junction channels.

Effects of occupational metallic mercury vapour exposure on suppressor-inducer (CD4+CD45RA+) T lymphocytes and CD57+CD16+ natural killer cells. Park SH, Araki S, Nakata A, Kim YH, Park JA, Tanigawa T, Yokoyama K, Sato H. Int Arch Occup Environ Health. 2000 Nov; 73(8):537-42. 11100948 PubMed. OBJECTIVES: To examine the effects of metallic mercury vapour on the cellular and humoral immune system. METHODS: We measured T lymphocyte and natural killer (NK) cell subpopulations, B lymphocytes, and serum immunoglobulins (i.e. IgG, IgA and IgM) together with total T (CD3 +) lymphocytes and total lymphocytes in blood samples from 20 male, fluorescent-lamp makers (mercury workers) and the same number of gender-, age- and smoking-matched controls. Urinary concentrations of inorganic mercury (UHg) in the 20 workers ranged from 1.8 to 163.5 (mean 44.8) microg/l. They had been exposed to mercury vapour for 4 to 62 (mean 31) months. RESULTS: Numbers of CD4+CD45RA+ (suppressor-inducer) T lymphocytes and total CD4+ T lymphocytes in the mercury workers were significantly smaller than those in the controls (paired-sample t-test, P < 0.01). The number of CD57+CD16+ NK cells was inversely correlated with UHg. CONCLUSION: It is suggested that numbers of CD4+CD45RA+ T lymphocytes and CD57+CD16+ NK cells are inversely affected by exposure to metallic mercury vapour in workers, with an average urinary inorganic mercury concentration of 45 microg/l being found.

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Enzymatic oxidation of mercury vapor by erythrocytes. Halbach S, Clarkson TW. Biochim Biophys Acta. 1978 Apr 12; 523(2):522-31. 656439 PubMed. The formation of glutathione radicals, the evolution of nascent oxygen or the peroxidatic reaction with catalase complex I are considered as possible mechanisms for the oxidation of mercury vapor by red blood cells. To select among these, the uptake of atomic mercury by erythrocytes from different species was studied and related to their various activities of catalase (hydrogenperoxide : hydrogen-peroxide oxidoreductase, EC 1.11.1.6) and glutathione peroxidase (glutathione : hydrogen-peroxide oxidoreductase, EC 1.11.1.9). A slow and continuous infusion of diluted H2O2 was used to maintain steady concentrations of complex I. 1% red cell supsensions were found most suitable showing high rates of Hg uptake and yielding still enough cells for subsequent determinations. The results indicate that the oxidation of mercury depends upon the H2O2-generation rate and upon the specific acticity of red-cell catalase. The oxidation occurred in a range of the catalase-H2O2 reaction where the evolution of oxygen could be excluded. Compounds reacting with complex I were shown to be effective inhibitors of the mercury uptake. GSH-peroxidase did not participate in the oxidation but rather, was found to inhibit it by competing with catalase for hydrogen peroxide. These findings support the view that elemental mercury is oxidized in erythrocytes by a peroxidatic reaction with complex I only.

Interaction of heavy metal toxicants with brain constitutive nitric oxide synthase. Mittal CK, Harrell WB, Mehta CS. Mol Cell Biochem. 1995 Aug-Sep; 149-150:263-5. 8569738 PubMed. This study was designed to evaluate the in vitro effects of transition heavy metal cations on activity of constitutive isoform of nitric oxide synthase (cNOS) in rat brain. NOS activity was determined in the cytosolic fractions of rat cerebral hemispheres by conversion of 3H-L-arginine to 3H-L-citrulline. Different concentrations of mercury (Hg2+), nickel (Ni2+), manganese (Mn2+), zinc (Zn2+), cadmium (Cd2+), lead (Pd2+) and calcium (Ca2+) were tested on NOS activity. While all the cations caused inhibition, there were differences in the apparent inhibition constants (Ki) among the cations. With the exception of calcium ion no other cation required preincubation with the enzyme preparation. These results indicate that while calcium ion modulate cNOS activity at regulatory site(s), inhibitory influence of toxic heavy metal cations may be exerted on the catalytic site(s) either by direct binding to it or by interfering with the electron transfer during catalysis.

Localized cellular inflammatory responses to subcutaneously implanted dental mercury. Nadarajah V, Neiders ME, Aguirre A, Cohen RE. J Toxicol Environ Health. 1996 Oct 11; 49(2):113-25. 8874531 PubMed. The results revealed acute inflammatory cell infiltration at 2 and 3 d, followed by chronic inflammation that persisted after 8 wk. The numbers of monocytes, resident macrophage subsets, and mononuclear cells expressing la antigen were significantly different from control tissues at 1-2 wk. The numbers of resident macrophages remained significantly higher even after 8 wk. These data showed that in situ mercury accumulation can lead to altered expression of MHC class II determinants with persistent chronic inflammation and shifts in mononuclear cell subpopulations.

Low concentrations of inorganic mercury inhibit Ras activation during T cell receptor-mediated signal transduction. Mattingly RR, Felczak A, Chen CC, McCabe MJ Jr, Rosenspire AJ. Toxicol Appl Pharmacol. 2001 Nov 1; 176(3):162-8. 11714248 PubMed. The inhibitory effect of mercury is selective, as activation of MAP kinase by phorbol diesters remain intact. Since the Ras/MAP kinase pathway is both highly conserved and central to signal transduction processes mediated by a myriad of diverse membrane receptor systems in a variety of cell types, these results suggest a mechanism for adverse health effects resulting from exposure to low levels of mercury. They also support a model for regulation of the Ras/MAP kinase pathway, whereby partial but unproductive activation of Ras can diminish signaling from cell surface receptors.

Mercuric chloride uncouples glutamate uptake from the countertransport of hydroxyl equivalents. Nagaraja TN, Brookes N. Am J Physiol. 1996 Nov; 271(5 Pt 1):C1487-93. 8944631 PubMed. There is evidence that glutamate transport is regulated by intracellular pH. Mercuric mercury may disrupt the regulation of glutamate transport at lower concentrations than those that block transport.

Mercuric compounds inhibit human monocyte function by inducing apoptosis: evidence for formation of reactive oxygen species, development of mitochondrial membrane permeability transition and loss of reductive reserve. InSug O, Datar S, Koch CJ, Shapiro IM, Shenker BJ. Toxicology. 1997 Dec 31; 124(3):211-24. 9482123 PubMed. The focus of this investigation was to examine the effects of low concentrations of organic mercuric compounds on human monocyte function and to relate these effects to apoptosis. We noted that treated cells generated ROS, as evidenced by oxidation of hydroethidine and the generation of the fluorescent product, ethidium. Finally, since ROS would also lower monocyte reductive reserve, we also measured GSH levels in mercury-treated cells. Chemical measurement of GSH indicated that there was thiol depletion. We suggest that the low thiol reserve predisposes cells to ROS damage and at the same time activates death-signaling pathways.

Mercury-induced apoptosis in human lymphocytes: caspase activation is linked to redox status. Shenker BJ, Pankoski L, Zekavat A, Shapiro IM. Antioxid Redox Signal. 2002 Jun; 4(3):379-89. 12215206 PubMed. There is growing evidence that heavy metals, in general, and mercurial compounds, in particular, are toxic to the human immune system. We have previously shown that methyl mercuric chloride (MeHgCl) is a potent human T-cell apoptogen; moreover, mitochondria appear to be a target organelle for the induction of cell death. The objective of this study was to determine the impact of MeHgCl on mitochondrial function in lymphocytes in terms of modulating reactive oxygen species (ROS) generation, thiol status, and caspase activation. We propose that the target organelle for MeHgCl is the mitochondrion and that induction of oxidative stress is critical to activation of death-signaling pathways. Additonally, mercury acts as a genotoxin significantly altering the expression of genes that affect cell survival and apoptosis.

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Mercury-induced apoptosis in human lymphoid cells: evidence that the apoptotic pathway is mercurial species dependent. Shenker BJ, Guo TL, Shapiro IM. Environ Res. 2000 Oct; 84(2):89-99. 11068922 PubMed. There is growing evidence that heavy metals, in general, and mercurial compounds, in particular, are toxic to the human immune system. In this regard, we have previously shown that both inorganic and organic mercurials are potent human T-cell apoptogens; moreover, mitochondria appear to be a target organelle for the induction of cell death. To ascertain whether both mercury species utilize the same molecular pathway to trigger the apoptotic cascade, cells were treated with MeHgCl or HgCl2 and mitochondrial activity was examined. We show that both mercury species affect mitochondrial activity by inducing the development of a membrane permeability transition. This state is characterized by a decline in both the transmembrane potential and the intracellular pH, as well as the generation of reactive oxygen species. We also determined that mercury exposure results in a decline in the T-cell GSH content. Since mitochondrial dysfunction and the development of a permeability transition may result in the release of cytochrome c, a factor that promotes apoptosis, we assessed the abilities of both species of mercury to induce the translocation of cytochrome c from mitochondria to the cytosol. We noted that MeHgCl caused a significant increase in cytosolic cytochrome c. Surprisingly, however, HgCl2 did not alter the level of cytosolic cytochrome c. We next determined whether the mercurials could alter the level of the anti-apoptotic protein Bcl-2. Our results demonstrate that HgCl2 induces a significant elevation in the Bcl-2 content of T-cells; in contrast, T-cells treated with MeHgCl did not exhibit altered levels of this anti-apoptotic protein. Regardless of whether cytochrome c is released from the mitochondria, both mercurial species were capable of activating the caspase cascade, as evident by cleavage of poly (ADP-ribose) polymerase. Thus, our study shows that, whereas each of the mercury species shares common features in the apoptotic process, profound differences exist in a number of key steps in the pathway.

Mercury vapor inhalation inhibits binding of GTP to tubulin in rat brain: similarity to a molecular lesion in Alzheimer diseased brain. Pendergrass JC, Haley BE, Vimy MJ, Winfield SA, Lorscheider FL. Neurotoxicology. 1997; 18(2):315-24. 9291481 PubMed. Hg2+ interacts with brain tubulin and disassembles microtubules that maintain neurite structure. Since the rate of tubulin polymerization is dependent upon binding of GTP to tubulin dimers, we conclude that chronic inhalation of low-level Hg0 can inhibit polymerization of brain tubulin essential for formation of microtubules.

Mercury vapor uptake and hydrogen peroxide detoxification in human and mouse red blood cells. S, Ballatori N, Clarkson TW. Toxicol Appl Pharmacol. 1988 Dec; 96(3):517-24. 3206529 PubMed. The uptake of Hg vapor (Hg0) by suspensions of human and BALB-c mouse erythrocytes was studied in a closed exposure system. The formation of catalase-compound-I and thereby the oxidation of Hg0 was initiated by microinfusion of hydrogen peroxide. The degradation of H2O2 by the glutathione (GSH)/GSH peroxidase system was reduced by t-butyl-hydroperoxide (t-BOOH) or by 1-chloro-2,4-dinitrobenzene (CDNB). In human red blood cells, CDNB and t-BOOH increased the rate of Hg vapor oxidation at the low and intermediate H2O2 supplementation rates. In mouse erythrocytes, Hg uptake was increased by CDNB over the entire H2O2 infusion range. In human cells, t-BOOH (0.1 mM) produced a remarkably high Hg uptake even without added H2O2. This Hg uptake in absence of exogenous H2O2 was inhibited by aminotriazole as was the activity of catalase. Hence, the Hg uptake was likely to have been induced by endogenous hydrogen peroxide. These findings support the view that the intact GSH/GSH peroxidase system can diminish the efficiency of compound-I-induced Hg vapor oxidation in erythrocytes.

Methyl mercury, mercuric chloride, and silver lactate decrease superoxide anion formation and chemotaxis in human polymorphonuclear leucocytes. Obel N, Hansen B, Christensen MM, Nielsen SL, Rungby J. Hum Exp Toxicol. 1993 Sep; 12(5):361-4. 7902111 PubMed. Cytotoxic effects of mercuric chloride, methyl mercury, and silver lactate on polymorphonuclear leucocytes have been examined by assaying superoxide anion formation capability and chemotaxis of metal-exposed cells. Both superoxide anion formation and chemotaxis were negatively affected by all three metal compounds. Both bacteriotoxic functions were affected in a dose-dependent fashion, the functional deficits were seen at doses not affecting cell viability. Dose-response curves were remarkably similar for all three compounds. The bacteriotoxic capacity of polymorphonuclear leucocytes may be hampered by mercury and silver.

Mitochondrial calcium release as induced by Hg2+. Chavez E, Holguin JA. J Biol Chem. 1988 Mar 15; 263(8):3582-7. 3346209 PubMed. In the electrophoretic analysis of Hg-labeled mitochondrial proteins it was found that 203Hg2+ bound mainly to proteins that have molecular masses of 20 and 30 kDa. It is proposed that Hg2+-induced Ca2+ release is due to modification of--SH groups of these latter proteins.

Modifications of Ca2+ signaling by inorganic mercury in PC12 cells. Rossi AD, Larsson O, Manzo L, Orrenius S, Vahter M, Berggren PO, Nicotera P. FASEB J. 1993 Dec; 7(15):1507-14. 8262335 PubMed. Exposure to the lower Hg2+ concentrations (0.3-0.5 microM) greatly potentiated NGF-induced PC12 cell differentiation. Conversely, treatment with 2 microM Hg2+ caused cell death. Our results show that inorganic mercury has selective and different effects on Ca2+ signaling in PC12 cells depending on the concentration, within a narrow range.

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Modulation of neuronal nicotinic acetylcholine receptors by mercury. Mirzoian A, Luetje CW. J Pharmacol Exp Ther. 2002 Aug; 302(2):560-7. 12130716 PubMed. Mercuric chloride exerted a biphasic modulatory effect on rat neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus laevis oocytes as heteromers of the alpha3 or alpha4 and beta2 or beta4 subunits. The degree of modulation was subunit-dependent, with beta4-containing receptors displaying greater potentiation and alpha4-containing receptors displaying greater inhibition. Thus, alpha4beta4 receptors displayed both robust potentiation and robust inhibition. During prolonged coapplication of HgCl(2), first potentiation then inhibition of the acetylcholine (ACh) response was observed. Upon coapplication of 1 microM HgCl(2), a 2-fold increase in ACh-induced current was achieved in 55 +/- 1 s. With continued HgCl(2) application, the ACh response was slowly inhibited until, after 5 min, less than 10% of the initial response remained. By measuring potentiation at its peak and inhibition 5 min after the start of HgCl(2) coapplication, we obtained EC(50) and IC(50) values of 262 +/- 75 and 430 +/- 72 nM, respectively. HgCl(2) potentiation was voltage-dependent, increasing at more positive holding potentials. Upon washout of mercury chloride, potentiation reversed with a t(1/2) of 4.6 min. Inhibition reversed more slowly, with less than half the initial response recovered after 15 min of wash. Although free cysteine residues are common targets for mercury, elimination of all free cysteines located in the extracellular domains of the alpha4 and beta4 subunits did not alter the effects of mercuric chloride. Potentiation and inhibition of neuronal nAChRs may occur through action at a transmembrane or cytoplasmic location after passive diffusion of mercuric chloride across the plasma membrane.

Oxidative mechanisms underlying methyl mercury neurotoxicity. Sarafian T, Verity MA. Int J Dev Neurosci. 1991; 9(2):147-53. 1905456 PubMed. Cerebellar granule cells from 5-12-day-old rats can be incubated in suspension at 37 degrees C for up to 3 hr with minimal decline in viability. Methyl mercury was found to produce time- and concentration-dependent cell killing with greater than 85% cell death after 3 hr exposure to a concentration of 20 microM. Previously characterized inhibition of protein and RNA synthesis as well as known methyl mercury-induced defects in cellular ATP production have been shown to be incapable of causing this degree of cell death. Here we report that methyl mercury induced a concentration-dependent increase in membrane lipoperoxidation and a rapid decline in reduced glutathione in this cerebellar neuronal preparation. Hydrogen peroxide at 5 mM was found to closely reproduce each of the cytotoxic effects manifested by methyl mercury suggesting that oxidizing conditions produced by methyl mercury may account for the observed cell death. Methyl mercury-induced lipoperoxidation was not the cause of cell death since malonaldehyde production could be blocked by alpha-tocopherol or EDTA without appreciable protecting against cell death. Significant protection from methyl mercury-induced cell death was observed, with EGTA, deferoxamine and KCN. We propose that oxidative events contribute to the toxic mechanism of action of methyl mercury in isolated cerebellar granule neurons.

Role of glutathione metabolism in the glutamate-induced programmed cell death of neuronal-like PC12 cells. Froissard P, Monrocq H, Duval D. Eur J Pharmacol. 1997 May 12; 326(1):93-9. 9178660 PubMed. Our results therefore confirm that oxidative stress and intracellular glutathione depletion are able to trigger programmed cell death in neuronal-like cells, although the exact nature of the death mechanisms remains largely unknown.

Specificity and reversibility of the inhibition by HgCl2 of glutamate transport in astrocyte cultures. Brookes N. J Neurochem. 1988 Apr; 50(4):1117-22. 2894409 PubMed. These results suggest that Hg2+ can impair glial glutamate transport reversibly at exposure levels that do not compromise some other vital cell functions.

Studies on Hg (II)-induced H2O2 formation and oxidative stress in vivo and in vitro in rat kidney mitochondria. Lund BO, Miller DM, Woods JS. Biochem Pharmacol. 1993 May 25; 45(10):2017-24. 8512585 PubMed. These findings support the view that Hg (II) causes depolarization of the mitochondrial inner membrane with consequent increased H2O2 formation. These events, coupled with Hg (II)-mediated GSH depletion and pyridine nucleotide oxidation, create an oxidant stress condition characterized by increased susceptibility of mitochondrial membranes to iron-dependent lipid peroxidation (TBARS formation). Since increased H2O2 formation, GSH depletion and lipid peroxidation were also observed in vivo following Hg (II) treatment, these events may underlie oxidative tissue damage caused by mercury compounds. Moreover, Hg (II)-induced alterations in mitochondrial Ca2+ homeostasis may exacerbate Hg (II)-induced oxidative stress in kidney cells.

The involvement of microtubular disruption in methylmercury-induced apoptosis in neuronal and nonneuronal cell lines. Miura K, Koide N, Himeno S, Nakagawa I, Imura. N. Toxicol Appl Pharmacol. 1999 Nov 1; 160(3):279-88. 10544062 PubMed. Methylmercury (MeHg) is known to interfere with cell cycle progression by disruption of microtubules. The relationship between the changes in cell cycle and the induction of apoptosis caused by MeHg was investigated in cultured mammalian cells. MeHg caused nuclear fragmentation and DNA ladder formation in rat pheochromocytoma (PC12) and mouse neuroblastoma cells exposed to MeHg. Flow cytometric analysis revealed that the occurrence of apoptosis was preceded by the accumulation of cells in G2/M after MeHg treatment. Exposure to colchicine, a well-characterized mitotic inhibitor, also caused G2/M-phase arrest followed by the appearance of apoptotic cells. These results suggest that G2/M-phase arrest through the disruption of microtubules is an important event in the development of apoptosis by MeHg. MeHg treatment led to G2/M-phase arrest followed by apoptosis in nonneuronal HeLa cells also. Bcl-2 was phosphorylated by MeHg treatment in HeLa cells but not in PC12 cells; however, p53 expression was not changed in either cell line. Thus, MeHg induces apoptosis via a p53-independent pathway in both cell lines, however, different pathways may be activated after the disruption of microtubules in PC12 and HeLa cells.

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Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Ercal N, Gurer-Orhan H, Aykin-Burns N. Curr Top Med Chem. 2001 Dec; 1(6):529-39. 11895129 PubMed. Recent studies indicate that transition metals act as catalysts in the oxidative reactions of biological macromolecules therefore the toxicities associated with these metals might be due to oxidative tissue damage. Redox-active metals, such as iron, copper and chromium, undergo redox cycling whereas redox-inactive metals, such as lead, cadmium, mercury and others deplete cells' major antioxidants, particularly thiol-containing antioxidants and enzymes. Either redox-active or redox-inactive metals may cause an increase in production of reactive oxygen species (ROS) such as hydroxyl radical (HO.), superoxide radical (O2.-) or hydrogen peroxide (H2O2). Enhanced generation of ROS can overwhelm cells' intrinsic antioxidant defenses, and result in a condition known as "oxidative stress". Cells under oxidative stress display various dysfunctions due to lesions caused by ROS to lipids, proteins and DNA. Consequently, it is suggested that metal-induced oxidative stress in cells can be partially responsible for the toxic effects of heavy metals.

Transition metals in control of gene expression. O'Halloran TV. Science. 1993 Aug 6; 261(5122):699. 8342038 PubMed. Metalloproteins play structural and catalytic roles in gene expression. The metalloregulatory proteins are a subclass that exerts metal-responsive control of genes involved in respiration, metabolism, and metal-specific homeostasis or stress-response systems, such as iron uptake and storage, copper efflux, and mercury detoxification. Two allosteric mechanisms for control of gene expression were first discovered in metalloregulatory systems: an iron-responsive translational control mechanism for ferritin production and a mercury-responsive DNA-distortion mechanism for transcriptional control of detoxification genes. These otherwise unrelated mechanisms give rise to a rapid physiological response when metal ion concentrations exceed a dangerous threshold. Molecular recognition in these allosteric metal ion receptors is achieved through atypical coordination geometries, cluster formation, or complexes with prosthetic groups, such as sulfide and heme. Thus, many of the inorganic assemblies that otherwise buttress the structure of biopolymers or catalyze substrate transformation in active sites of enzymes have also been adapted to serve sensor functions in the metalloregulatory proteins. Mechanistic studies of these metal-sensor protein interactions are providing new insights into fundamental aspects of inorganic chemistry, molecular biology, and cellular physiology.

Urinary excretion of mercury, copper and zinc in subjects exposed to mercury vapour. Sallsten G, Barregard L Biometals. 1997 Oct; 10(4):357-61. 9353886 PubMed. This study indicates that mercury exposure in humans, as in animals, causes increased urinary excretion of zinc. The mechanisms may be induced synthesis of metallothionein in the kidneys, displacement of Zn from preexisting metallothionein by Hg, or a decreased reabsorption of zinc in the kidneys owing to a slight tubular dysfunction.

Composite Fillings and Bis-GMA

Assessment of Exposure and Risks from Components and Degradation Products of Composite Resin Dental Materials. Richardson GM. Human Ecolog Risk Assess. 3(4):683-97. 1997. A probabilistic assessment was undertaken of adult exposures to two principal components of composite resins - silica, bisphenol-A glycidylmethacraylate (BIS-GMA) and two degradation products of BIS-GMA; formaldehyde and methacrylic acid. Assuming that the Canadiam adult population with fillings had only composite resin materials, results indicated that average exposures to formaldehyde and methacrylic acid were 10,000 times and 1,600,000 times lower, respectively, than relevant reference doses. Worst case exposures were also well below applicable reference levels. Risks posed by exposures to BIS-GMA and silca could not be assessed due to a lack of published ingestion reference doses for these substances. Gaps in the data base relating to the risks posed by composite resin dental materials were discussed, particlularly in reference to the recently reported estrogenic postential of other degradation products of BIS-GMA.

Bisphenol-A content of resin monomers and related degradation products. Schmalz G, Preiss A, Arenholt-Bindslev D. Clin Oral Investig. 1999 Sep; 3(3):114-9. 10803121 PubMed. Hence, we conclude that the results reported in the literature may be attributed to the Bis-DMA-content of the fissure sealant tested (Delton). No BPA-release is expected under physiologic conditions from fissure sealants based on Bis-GMA if pure base monomers are used.

Pharmacokinetics of bisphenol A released from a dental sealant. Fung EY, Ewoldsen NO, St Germain HA Jr, Marx DB, Miaw CL, Siew C, Chou HN, Gruninger SE, Meyer DM. J Am Dent Assoc. 2000 Jan;131(1):51-8. 10649872 PubMed. This study showed that BPA released orally from a dental sealant may not be absorbed or may be present in nondetectable amounts in systemic circulation. The concern about potential estrogenicity of sealant may be unfounded.

Time-related bisphenol-A content and estrogenic activity in saliva samples collected in relation to placement of fissure sealants. Arenholt-Bindslev D, Breinholt V, Preiss A, Schmalz G. Clin Oral Investig. 1999 Sep; 3(3):120-5. 10803122 PubMed. In conclusion, minute amounts of BPA, however considerably lower than previously reported, were detected in saliva samples collected immediately after but not 1 and 24 h(s) after placement of Delton LC fissure sealant. BPA was not detected after placement of Visio-Seal fissure sealant. 3

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Dentists and Dental Office

Behavioral effects of low-level exposure to elemental Hg among dentists. Echeverria D, Heyer NJ, Martin MD, Naleway CA, Woods JS, Bittner AC. Jr.Neurotoxicol Teratol, 17(2):161-8, 1995. 7760775 PubMed. However, the pooled sum of rank scores for combinations of tests within domains were significantly associated with urinary Hg, providing evidence of subtle preclinical changes in behavior associated with Hg exposure. Coproporphyrin, one of three urinary porphyrins altered by mercury exposure, was significantly associated with deficits in digit span and simple reaction time.

Behavioral effects of low-level exposure to HgO among dental professionals: a cross-study evaluation of psychomotor effects. Bittner AC Jr, Echeverria D, Woods JS, Aposhian HV, Naleway C, Martin MD, Mahurin RK, Heyer NJ, Cianciola M. Neurotoxicol Teratol. 1998 Jul-Aug; 20(4):429-39. 9697969 PubMed. Results indicated remarkable differences in the effects of relative level of Hg0 on psychomotor performance.

Blood mercury levels of dental students and dentists at a dental school. Tezel H, Ertas OS, Erakin C, Kayali A. Br Dent J. 2001 Oct 27;191(8):449-52. 11720018 PubMed. To determine the blood mercury levels in dental students and clinical teaching staff in a dental school using amalgam as a restorative material. There were statistically significant increases (p<0.001) in plasma mercury concentration between measurements in all groups at the end of the academic year. Red cell mercury levels were also consistently elevated. Although the highest levels of mercury were recorded in persons working with amalgam, increased levels were also found in subjects working in the teaching classrooms but not with amalgam (controls and first year students). Increased mercury levels appeared to be due to background exposure from spillage of mercury and amalgam residues on floors. Increased mercury hygiene and regular control of working atmosphere should be implemented to prevent mercury exposure in the dental pre-clinical laboratory.

Chronic neurobehavioural effects of elemental mercury in dentists. Ngim CH, Foo SC, Boey KW, Jeyaratnam J. Br J Ind Med. 1992 Nov; 49 (11):782-90. 1463679 PubMed. These results raise the question as to whether the current threshold limit value of 0.050 mg/m3 (TWA) provides adequate protection against adverse effects of mercury.

Comparison of hair, nails and urine for biological monitoring of low level inorganic mercury exposure in dental workers. Morton J, Mason HJ, Ritchie KA, White M. Biomarkers. 2004 Jan-Feb;9(1):47-55. 15204310 PubMed. Dentists and dental nurses remain a group of workers with potential exposure to inorganic mercury through their handling of mercury-containing amalgam, although changes in work practices have reduced the current, likely exposure to mercury. Therefore, dental workers remain an occupational cohort in whom the value of using different biological media to identify exposure to low level inorganic mercury can be investigated. Samples of head hair, pubic hair, fingernails, toenails and urine were analysed for mercury content from a cohort of UK dentists (n=167) and a socioeconomically similar reference population (n=68) in whom any mercury exposure was primarily through diet. The mercury content in all biological material was significantly higher in the dental workers than in the control population (p<0.0001).

Dental amalgam and mercury in dentistry. Spencer AJ. Aust Dent J. 2000 Dec;45(4):224-34. 11225523 PubMed. Mercury in dentistry has re-emerged as a contentious issue in public health, predominantly because so many people are inadvertently exposed to mercury in order to obtain the benefits of dental amalgam fillings, and the risks remain difficult to interpret. Evidence on the health effect of dental amalgams comes from studies of the association between their presence and signs or symptoms of adverse effects or health changes after removal of dental amalgam fillings. Policy will also reflect prudent and cautious approaches, encouraging minimization of exposure to mercury in potentially more sensitive population groups. Wider environmental concerns and decreasing tolerance of exposure to other mercury compounds (for example, methylmercury in seafoods) will ensure the use of mercury in dentistry remains an issue, necessitating dentists keep their patients informed of health risks and respect their choices.

Dentist's exposure to elemental mercury vapor during clinical work with amalgam. Pohl L, Bergman M. Acta Odontol Scand. 1995 Feb;53(1):44-8. 7740931 PubMed. Continuous measurements of mercury vapor in the breathing zone of the dentist were made under ordinary clinical conditions. Fifty old amalgam fillings were removed and replaced by new ones. The mercury vapor measurements were performed by means of atomic absorption spectrophotometry. On the basis of the type of suction device used, the measurements were divided into seven groups, each of which consisted of a series of measurements. During the cutting, filling, and polishing operations the mean mercury vapor levels in the breathing zone of the dentist were in the range of 1-2 micrograms Hg m-3 air when proper mercury hygiene measures were taken. This is far below the currently valid threshold limit value (30 micrograms Hg m-3 air) in Sweden. The saliva extractor and the dental mirror-evacuator did not influence the mercury vapor levels when used together with the high-volume evacuator. However, when only a saliva extractor was used, the cutting of amalgam fillings caused highly fluctuating mercury vapor levels, which were 2-15 times higher than the threshold limit value.

Disinfectants' effect on mercury release from amalgam. Roberts HW, Marek M, Kuehne JC, Ragain JC. J Am Dent Assoc. 2005 Jul;136(7):915-9. 16060472 PubMed. Mercury environmental discharge is under increased scrutiny by the U.S. Environmental Protection Agency (EPA). Dental amalgam should be processed properly to prevent an additional environmental burden. Chlorine disinfectant materials discharged the most mercury ions, followed by bromide, iodophor, peroxide/peracetic acid and phenolic disinfectants. Dentists are obligated to be good environmental stewards and should follow practices that reduce environmental mercury release. Dental personnel should be aware that oxidizing disinfectants mobilize mercury ions into solution, which will be added to the environment if they are processed improperly. If required by processing, dental personnel should consider the different oxidizing effects of commonly used disinfectants.

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Effect of occupational exposure to elemental mercury in the amalgam on thymulin hormone production among dental staff. Farahat SA, et al.Toxicology and Industrial Health, Vol. 25, No. 3, 159-167 (2009) DOI: 10.1177/0748233709105270. 19482909 PubMed. Results show that dentists and dental nurses have significant exposure to mercury vapor and point to the negative impact of mercury on thymus gland functions and confirm the implication that the nitric oxide pathway is a possible mechanism for this impact. Moreover, the study raises attention to the importance of hygiene measures in reduction of exposure to mercury vapor released from dental amalgam.

Effectiveness of wet and dry mercury vapour suppressant systems in a faculty of dentistry clinic. Sutow EJ, Hall GC, MacLean CA. J Oral Rehabil. 2004 Aug;31(8):822-6. 15265221 PubMed. The objective of this study was to determine the effectiveness of a liquid and a dry commercial mercury vapour suppressant system. The two products examined were Mercon vap liquid in a stock jar and the Mercon tainer dry jar system. It was concluded that the dry system is more effective and reliable than the liquid system. The reliability of the liquid system may be influenced by contact of amalgam scrap with the portion of the inner wall of the jar that is not covered by liquid. It is proposed that amalgam scrap contaminates the wall with mercury during its insertion.

Examination of urinary mercury levels in dentists in Turkey. Karahalil B, Rahravi H, Ertas N. Hum Exp Toxicol. 2005 Aug;24(8):383-8. 16138728 PubMed. Exposure to Hg can occur in occupational and environmental settings. The toxicity of Hg compounds in dentistry has been an issue of increasing concern. Dental personnel are occupationally exposed to Hg vapor in their working environment and this exposure constitutes a potential risk to people in the dental surgery, mainly from the inhalation of Hg vapor and fine particles of amalgam. Attention to important hygiene measures, such as the avoidance of spills of Hg, cleaning of floors after such spills, ventilation and the installation of ventilation, depending on technology, should be taken into consideration. Age and smoking habits did not influence the urinary Hg excretion. Our results showed that dentists had significant exposure to Hg vapor compared to control subjects and therefore might be subject to possible adverse effects due to Hg toxicity.

Health and neuropsychological functioning of dentists exposed to mercury. Ritchie KA, Gilmour WH, Macdonald EB, Burke FJ, McGowan DA, Dale IM, Hammersley R, Hamilton RM, Binnie V, Collington D. Occup Environ Med. 2002 May; 59(5):287-93. 11983843 PubMed. Dentists had, on average, urinary mercury concentrations over four times that of control subjects, but all but one dentist had urinary mercury below the Health and Safety Executive health guidance value. Dentists were significantly more likely than control subjects to have had disorders of the kidney and memory disturbance.

High mercury emissions from dental clinics despite amalgam separators. Hylander LD, Lindvall A, Gahnberg L. Sci Total Environ. 2006 Jun 1;362(1-3):74-84. Epub 2005 Jul 28. 16054673 PubMed. Mercury (Hg) as amalgam has been used as a dental filling material for more than 150 years. Thereby, dentists and their patients have been directly exposed to Hg, and the public and the environment indirectly exposed via Hg emissions from incinerators and Hg in waste water from households and dental clinics. Here we present actual Hg emissions via waste water from 12 dental clinics equipped with the same type of amalgam separator based on sedimentation. All waste water was collected for four consecutive working days, initially at ordinary operating conditions and a second time after a thorough revision and cleaning of the discharge system. The results indicate that mercury emissions from dental clinics can be reduced by an improved design of the discharge system, a sensible use of high pressure water cleaning, and regular maintenance, including replacement of amalgam separators and filters at certain intervals. The study also indicates that banning Hg in dentistry is the one long-term way to stop Hg emissions from dental amalgam.

Historical exposure to mercury among Norwegian dental personnel. Svendsen K, Syversen T, Melø I, Hilt B.

Scand J Work Environ Health. 2010 May;36(3):231-41. Epub 2009 Dec 1. 19953215 PubMed. The aims of this part of the study were to: (i) describe Norwegian dental personnel's exposure to mercury during the last 50 years, (ii) develop a model for scoring that reflects the cumulative exposure on an individual basis, and (iii) relate the calculated score to earlier measured levels of mercury in urine. The results revealed a widespread exposure to mercury in both the individual exposure score and the measured mercury values in urine. It seems evident that the exposure to mercury among dental personnel varies substantially; this is important to take into account when making exposure assessments for this group of workers.

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Mercury accumulation in tissues from dental staff and controls in relation to exposure. Nylander M, Friberg L,  Eggleston D, Bjorkman L. Swed Dent J. 1989; 13(6):235-43. 2603127 PubMed. The results revealed high mercury concentrations in pituitaries from the dental staff cases compared to controls.

Mercury exposure of different origins among dentists and dental nurses. Skare I, Bergstrom T, Engqvist A, Weiner JA. Scand J Work Environ Health. 1990 Oct; 16(5):340-7. 2255875 PubMed. Mercury exposure was studied among dental personnel with the use of urinary mercury excretion rates and questionaries. The study covered 314 dentists and dental nurses employed in public clinics and private practices in Stockholm. The obtained urinary mercury excretion rates were analyzed by stepwise regression for assigning them to different origins, such as environmental factors, number of amalgam surfaces, chewing of gum, kind of employment and profession, age, sex, amalgam handling time, and use of amalgam capsules. One the average the occupational contribution to the total urinary excretion rate was small and of the same order as the contribution from their own amalgam fillings (approximately 2 ug of mercury/24 h). There were, however, individuals showing excretion rates close to the levels at which effects on the central nervous system and the kidneys have been reported.

Mercury exposure of the population. IV. Mercury exposure of male dentists, female dentists and dental aides. Zander D, Ewers U, Freier I, Brockhaus A. Zentralbl Hyg Umweltmed. 1992 Dec; 193(4):318-28. 1290562 PubMed. Regarding total exposure to mercury in dental personnel, the contribution of mercury exposure from the occupational environment is of the same order of magnitude as their exposure from their own amalgam fillings. Dental nurses were found to be more exposed than dentists. This finding seems to be related predominantly to the larger number of amalgam fillings in dental nurses.

Mercury generation potential from dental waste amalgam. Drummond JL, Cailas MD, Croke K. J Dent. 2003 Sep;31(7):493-501. 12927461 PubMed. The main objective of this study was to quantify the total amount of amalgam used in dental offices in the state of Illinois and to estimate the fractions of amalgam waste material generated during dental procedures. Based on survey data from the ADA concerning the number of working days per year, the number of practicing dentists, a 50%, by weight, mercury content in amalgam, and the generation estimates from this project, it was estimated that the practicing dentists in the State of Illinois (6455) have the potential to generate 947 kg of non-contact mercury per year, which is recyclable, and 144 kg of contact mercury which has the potential to be discarded in the environment, or be partially recycled. If this approach is applied to the total population of practicing dentist in the United States (123,641), then 18,159 kg of recyclable, non-contact mercury may be generated per year, whereas 2763 kg of contact mercury may be discarded in the environment, or be partially recycled.

Mercury levels among dental personnel in Israel: a preliminary study. Steinberg D, Grauer F, Niv Y, Perlyte M, Kopolovic K. Isr J Med Sci. 1995 Jul; 31(7):428-32. 7607870 PubMed. Our results indicate that the urinary mercury levels of the tested dental professionals were significantly higher than those of the control group.

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Mercury levels in urine and head hair of dental personnel. Saengsirinavin C, Pringsulaka P. J Dent Assoc Thai. 1988 Jul-Aug;38(4):170-9. 3270646 PubMed. The objective was to investigate the mercury level in these dental personnel. The results showed that mercury levels in the urine and head hair of dental personnel were significantly higher than in the controls. The amounts of urine mercury from dental assistants, dentists and dental students were 81.0%, 38.2% and 43.5% higher than the threshold limit value respectively. The mean head hair mercury concentration of unexposed controls ranged from 0.3-12.2 micrograms/g (means = 2.8 +/- 0.36 micrograms/g). The mean head hair mercury levels found in dental assistants, dentists, dental students and dental technicians were 10.1 +/- 0.84, 7.5 +/- 1.2, 6.5 +/- 1.54 and 2.8 +/- 0.53 micrograms/g respectively.

Mercury vapour levels in dental practices and body mercury levels of dentist and controls. Ritchie KA, et al. Br Dent J. 2004 Nov 27; 197 (10):625-32; discussion 621. 15611750 PubMed. Dentists were found to have, on average, urinary mercury levels over 4 times that of control subjects although all but one dentist had urinary mercury below the Health and Safety Executive health guidance value of 20 mumol mmol(-1) creatinine. Urine was found to be a better biological marker for mercury exposure than hair or nails. On the basis of these findings, it is recommended that greater emphasis should be made relating to safe handling of amalgam in the training and continuing professional development of dentists, that further studies are carried out on levels of mercury exposure of dental team members during the course of their working day, and that periodic health surveillance, including urinary mercury monitoring, of dental personnel should be conducted to identify possible effects of practising dentistry.

I Personally Consider it Important for All Dentists to Read this Article

Need for informed consent for dentists who use mercury amalgam restorative material as well as technical considerations in removal of dental amalgam restorations. Edlich RF, et al. J Environ Pathol Toxicol Oncol. 2007;26(4):305-22. 18197828 PubMed. Amalgam restorative material generally contains 50% mercury (Hg) in a complex mixture of copper, tin, silver, and zinc. It has been well documented that this mixture continually emits mercury vapor, which is dramatically increased by chewing, eating, brushing, and drinking hot liquids. Mercury has been demonstrated to have damaging effects on the kidney, central nervous system, and cardiovascular system, and has been implicated in gingival tattoos. While mercury amalgams may result in detrimental exposure to the patient, they can also be a danger in dental practices. In Europe, the federal governments of Norway, Finland, Denmark, and Sweden have enacted legislation requiring that dental patients receive informed consent information about the dental restorative material that will be used. In the United States, a few state governments have enacted informed consent legislation for dental patients receiving dental restorations. These state legislations were enacted by Maine, California, Connecticut, and Vermont. It is a sad tragedy that mercury is causing such health damage to many people. The American Dental Association has said for the past 150 years that the mercury in amalgam is safe and does not leak; however, no clinical studies were ever done and the Food and Drug Administration approved amalgam under a grandfather clause. Subsequent studies have shown this claim of safety not to be true. Over ten years ago, the Federation of American Societies for Experimental Biology Journal published a comprehensive article calling mercury restorative material a major source of mercury exposure to the U.S. population. The authors of this paper recommend that federal and state legislation be passed throughout our country to ensure that consent forms are given to patients receiving silver-mercury amalgam restorative material.

Prospective study on the mercury uptake of dental students. Part 1: Increase in mercury excretion during simulated training. Pieper K, Visser H, Isemann M, Stalder K. Dtsch Zahnarztl Z. 1989 Sep; 44(9):714-6. 2637853 PubMed. It was the goal of this study performed in two subsequent technical courses of operative dentistry to find out if the first "professional" contact of dental students with amalgam resulted in a increased mercury excretion. At six different points in time urine analyses using (flame-free) cold vapor nuclear absorption spectroscopy were performed. At the first measurement, prior to working with amalgam, the median values were at 0.53 micrograms Hg/g creatinine (summer term 88) and 1.46 micrograms Hg/g creatinine (winter term 88/89). At the end of the course the median values have increased to 2.49 micrograms Hg/g creatinine (summer term 88) and 2.56 micrograms Hg/g creatinine (winter term 88/89). In the subsequent vacations the Hg values in the students' urine clearly decreased.

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Suicide among Swedish dentists. A ten-year follow-up study. Arnetz BB, Horte LG, Hedberg A, Malker H. Scand J Soc Med. 1987; 15(4):243-6. 3500511 PubMed. In the present study, we have followed a national cohort of dentists, academics, i.e. people with three or more years of post-high school education, and the general population for a period of ten years, and identified all cases of recognized suicide during the period 1961 to 1970. The aim of the study was to assess whether suicide rates are higher among dentists even after adjustment for socioeconomic factors. Results show an elevated standardized mortality ratio (SMR) for male dentists compared to other male academics. Female dentists did not exhibit any increased risk. It is suggested that enhanced interest should be given to the possible etiologic role of not only psychosocial factors but also to psychoorganic consequences of mercury exposure among dentists.

Symptoms of intoxication in dentists associated with exposure to low levels of mercury. Neghab M, Choobineh A, Hassan Zadeh J, Ghaderi E. Occupational health department, School of Health and Nutrition, Shiraz University of Medical Sciences, Shiraz, Iran. Ind Health. 2011;49(2):249-54. Epub 2010 Dec 16. 21173523 Pubmed.

The present study examined the effects of occupational exposure of a group of dentists to low levels of mercury. The study population consisted of 106 dentists and 94 general practitioners (referent group), from private and public clinics in Shiraz city. The data were analysed by χ(2) test, independent sample t-test and multivariate logistic regression analysis, where applicable. Both groups were similar as far as most demographic and socioeconomic variables, but age and number of personal amalgam fillings, were concerned. Median of atmospheric concentration of mercury was found to be 3.35 μg/m(3). Likewise, the urinary concentration of mercury in dentists was estimated to be 3.16 μg/g creatinine. This value was significantly higher than that of the referent group. Similarly, analysis of the data revealed that neuropsychological, muscular, respiratory, cardiovascular and dermal symptoms were more prevalent in dentists. Our findings indicate that occupational exposure of dentists to mercury, even at low levels, is associated with a significant increase in the prevalence of symptoms of intoxication.

 

The effect of occupational exposure to mercury vapour on the fertility of female dental assistants. Rowland AS, et al. Occup Environ Med. 1994 Jan;51(1):28-34. 8124459 PubMed. Exposure to mercury vapour or inorganic mercury compounds can impair fertility in laboratory animals. To study the effects of mercury vapour on fertility in women, eligibility questionnaires were sent to 7000 registered dental assistants in California. The final eligible sample of 418 women, who had become pregnant during the previous four years, were interviewed by telephone. Detailed information was collected on mercury handling practices and the number of menstrual cycles without contraception it had taken them to become pregnant. Dental assistants not working with amalgam served as unexposed controls. Women with high occupational exposure to mercury were less fertile than unexposed controls.

The Environmental Impact of Mercury-Containing Dental Amalgams. Chairman Dan Burton Subcommittee on Human Rights and Wellness Committee on Government Reform. House of Representatives, United States Congress. October 8, 2003. http://reform.house.gov/UploadedFiles/Opening.pdf. Collectively, Americans are walking around today with 800 metric tons of mercury in their mouths. And tens-of-millions of mercury-containing fillings continue to be put into American teeth every year. The Association of Metropolitan Sewerage Agencies (AMSA) estimates that on-average, dentists contribute 35 to 40-percent of the influent mercury received by publicly-owned sewerage treatment plants. In many municipalities, dentists are the single largest source of wastewater mercury. And as an element, mercury remains always mercury. Wastewater treatment plants cannot simply treat it; it must be completely removed from the wastewater stream.AMSA has estimated that it costs as much as $21 Million per pound to safely remove mercury once it becomes part of the wastewater stream. If the American Dental Association’s estimate is correct that approximately 6.5 tons of mercury enter public wastewater treatment facilities from dental offices every year, at $21 Million per pound, the cost to remove that amount of mercury would be approximately $273 Billion annually.

The Mercury Conundrum. Jeff Johnson. Chemical & Engineering. February 5, 2001. Volume 79, Number 6. CENEAR 79 6 pp. 21-24. ISSN 0009-2347. Dentists use approximately 44 tons of mercury per year, filling 100 million cavities per year.

The Poison in Your Teeth: Mercury Amalgam (Silver) Fillings . . . Hazardous to Your Health. Tom McGuire, DDS, 2008. The most informative book on amalagam fillings available today. Covers every aspect of this controversial issue and an important source for of information about this subject for the layperson and the dental profession. Contains 300 references. Published by the Dental Wellness Institute, ISBN 978-0-9815630-0-8. The book is available at www.mercurysafedentists.com or by calling 800-335-7755

Urinary porphyrin profiles as a biomarker of mercury exposure: studies on dentists with occupational exposure to mercury vapor. Woods JS, Martin MD, Naleway CA, Echeverria D.  J Toxicol Environ Health. 1993 Oct-Nov; 40(2-3):235-46. 8230299 PubMed. These findings suggest that urinary porphyrin profiles may serve as a useful biomarker of mercury exposure in clinical or epidemiologic studies of mercury-related human health risks.

Diseases and Symptoms

Neurological
Alzheimer’s

Alzheimer disease: mercury as pathogenetic factor and apolipoprotein E as a moderator. Mutter J, Naumann J, Sadaghiani C, Schneider R, Walach H. Neuro Endocrinol Lett. 2004 Oct;25(5):331-9. Institute for Environmental Medicine and Hospital Epidemiology, University Hospital Freiburg, Germany. jmutter@iuk3.ukl.uni-freiburg.de. 15580166 PubMed. The etiology of most cases of Alzheimer's disease (AD) is as yet unknown. Epidemiological studies suggest that environmental factors may be involved beside genetic risk factors. Some studies have shown higher mercury concentrations in brains of deceased and in blood of living patients with Alzheimer's disease. Experimental studies have found that even smallest amounts of mercury but no other metals in low concentrations were able to cause all nerve cell changes, which are typical for Alzheimer's disease. The most important genetic risk factor for sporadic Alzheimer's disease is the presence of the apolipoprotein Ee4 allele whereas the apolipoprotein Ee2 allele reduces the risk of developing Alzheimer's disease. Some investigators have suggested that apolipoprotein Ee4 has a reduced ability to bind metals like mercury and therefore explain the higher risk for Alzheimer's disease. Therapeutic approaches embrace pharmaceuticals which bind metals in the brain of patients with Alzheimer's disease. In sum, both the findings from epidemiological and demographical studies, the frequency of amalgam application in industrialized countries, clinical studies, experimental studies and the dental state of AD patients in comparison to controls suggest a decisive role for inorganic mercury in the etiology of AD.

Amalgams and Alzheimer’s disease (AD). Boyd Haley. (Long, but I felt this was important to include)

Friends: This is an E-mail that I sent to Barbara Snelgrove in reply to her response that their is no relationship between amalgams and AD.

Dear Barbara:

We do not know each other and I don't know what your occupation or background is. However, I was sent an e-mail where you stated that there was no connection between mercury and Alzheimer's disease. I agree that no connection has been made since studies in this area have for the most part been avoided. The only one I know of was so poorly done that it has no credibility in the scientific community. However, I believe that there is a connection between AD and mercury exposure as I will explain.

First, research from my laboratory, published in highly respected research journals demonstrates the following: Both beta-tubulin and creatine kinase are dramatically inhibited in AD brain. This is also supported by publications from other laboratories.

Adding low micromolar mercury to non-AD brain causes the rapid and specific inhibition of these two proteins mimicking the effects observed in AD brain. This inhibiton by mercury would be expected by any competent biochemist as the literature would support this happening.

We exposed rats to mercury vapor for 4 hours a day for 4 weeks at levels of mercury that would be expected in someone with extensive amalgam fillings. This exposure caused a major decrease in tubulin viability, similar as observed in AD brain.

Amalgams leak mercury, this is a fact that any chemistry department can confirm. We have made amalgam fillings outside of the mouth, placed these fillings in sterile water for 15 minutes to several hours. We then tested this water for toxicity to tubulin and creatine kinase. The result was that the solutions in which amalgams were soaked (even for 15 minutes) were extremely toxic. Results using these solutions were identical to those with addition of mercury solutions to the brain. This work is also supported by reports doing similar experiments at the University of Michigan Dental School where they described solutions in which amalgams were soaked as being "extremely cytotoxic"

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Additional support by others for mercury exacerbating or being a major contributor for AD is as follows:

The form of APO-E protein that is a major risk factor for AD is the one that has lost much, if not all, of its ability to bind mercury in the cerebrospinal fluid giving reduced protection against mercury (especially) and other oxidant heavy metals. The APO-E protein that affords the best protection against AD is the one that would bind and remove mercury the very best.

This year in the Journal of Neurochemistry a report came out that showed that the exposure of neuroblastoma cells in culture to nanomolar levels of mercury (much lower than is found in brain) lead to the subsequent "hyperphosphorylation of a protein called Tau" and to greatly increased secretion of "beta amyloid protein---the protein that makes up amyloid or 'senile' plaques". Senile plaques are the "diagnostic hallmark of AD" and projected by many as being causal of AD.

Dr. Lorscheider, my collaborator in mercury research, has submitted an article where a neuron in culture was exposed to 0.1 nanomolar mercury and filmed through a microscope. The result was that the axon broke open and the tubulin and tubulin associated proteins abnormally aggregated into a body that was "indistinguishable from a neurofibillary tangle" the second "diagnostic hallmark" of AD on pathology. If mercury causes neurons to produce the "diagnostic hallmark" then shouldn't mercury be consider causal or contributory to this disease?? Especially when most Americans of age 50 plus have had amalgams in their mouths for scores of years or greater!

Also, I am the Chair of a Department of Chemistry and it is exceeding easy to measure mercury escape from a dental amalgam and I can tell you that it is excessive if related to any measure of safe exposure levels. The risk assessment expert for Health Canada on doing an assessment on mercury exposure for Canadians told me that the amount of mercury exposure from industrial produced mercury was much less that that coming from dental amalgams.

We cannot do the experiments that would prove amalgams do or do not contribute to AD. There are just to many confounding factors associated with human behaviour. I believe in going to the bottom line--do amalgams leak toxic levels of mercury and I have proven that they do. Ask anyone in the "pro-amalgam field" to give you a research article that shows that amalgams do not leak toxic levels of mercury and they will provide you with opinion papers stating that amalgams are safe. These papers are different from research papers in that they do not present actual experimental protocols that can be tested.

Invariably, they will say only an "insignificant amount of mercury is released" or something to that effect. Ask them to put a scientific value on this insignificant amount (like how many micrograms/cm2 of mercury is released per day). This has been reported and it was 43.5 micrograms/cm2/day and remained constant for 2 years. No one has claimed this report was wrong and this is a very toxic level of mercury. Also, it was collected in a test tube with no additional heat, pressure or galvanism on the amalgam which would occur in the mouth and greatly increase the level of mercury released.

I strongly believe that having dental amalgams in one’s mouth for scores of years increases the risk for AD. Mercury would at the very least be an exacerbating toxic exposure. I believe this because I read the literature and do research in this area. Is there direct proof?--no there isn't. But there is also no proof that amalgams do not contribute and 'absence of proof is not proof of absence'.

However, the bottom line is that amalgams make both water and saliva toxic by increasing the mercury levels and this would place excess stress on those humans who are unfortunate enough to be genetically susceptible to AD or mercury toxicity. I hope you know that AD is not a directly inherited disease and that some form of 'toxic or infective insult' is needed to cause the onset of the disease.

Finally, I know that you can find numerous dentists and physicians that will say amalgams are not a risk factor for AD---see if you can find one that will debate me publicly after allowing me to present a short scientific talk on the subject. I feel like I have been in an 8 year argument with a town drunk on this issue.

Sincerely,
Boyd Haley
Professor and Chair, Department of Chemistry, University of Kentucky http://www.whale.to/d/haley.html   

Does inorganic mercury play a role in Alzheimer's disease? A systematic review and an integrated molecular mechanism. Mutter J, Curth A, Naumann J, Deth R, Walach HJ Alzheimers Dis. 2010;22(2):357-74. 20847438 PubMed. Mercury is one of the most toxic substances known to humans. It has been introduced into the human environment and has also been widely used in medicine. Since circumstantial evidence exists that the pathology of Alzheimer's disease (AD) might be in part caused or exacerbated by inorganic mercury, we conducted a systematic review using a comprehensive search strategy. Studies were screened according to a pre-defined protocol. Two reviewers extracted relevant data independent of each other. One thousand and forty one references were scrutinized, and 106 studies fulfilled the inclusion criteria. Most studies were case control or comparative cohort studies. Thirty-two studies, out of 40 testing memory in individuals exposed to inorganic mercury, found significant memory deficits. Some autopsy studies found increased mercury levels in brain tissues of AD patients. Measurements of mercury levels in blood, urine, hair, nails, and cerebrospinal fluid were inconsistent. In vitro models showed that inorganic mercury reproduces all pathological changes seen in AD, and in animal models inorganic mercury produced changes that are similar to those seen in AD. Its high affinity for selenium and selenoproteins suggests that inorganic mercury may promote neurodegenerative disorders via disruption of redox regulation. Inorganic mercury may play a role as a co-factor in the development of AD. It may also increase the pathological influence of other metals. Our mechanistic model describes potential causal pathways. As the single most effective public health primary preventive measure, industrial, and medical usage of mercury should be eliminated as soon as possible.

Imbalances of trace elements related to oxidative damage in Alzheimer's disease brain. Cornett CR, Markesbery WR, Ehmann WD. Neurotoxicology. 1998 Jun; 19(3):339-45. 9621340 PubMed. Four elements that have been implicated in free-radical-induced oxidative stress in Alzheimer's disease (AD) were measured by instrumental neutron activation analysis (INAA) in seven brain regions from 58 AD patients and 21 control subjects. A statistically significant elevation of iron and zinc was observed in multiple regions of AD brain, compared with controls. Mercury was elevated in AD in most regions studied, but the high variability of mercury levels in both AD and control subjects prevented the AD-control difference from reaching significance. Selenium, a protective agent against mercury toxicity, was significantly elevated only in AD amygdala. The elevation of iron and zinc in AD brain has the potential of augmenting neuron degeneration through free radical processes.

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Increased blood mercury levels in patients with Alzheimer's disease. Hock C, Drasch G, Golombowski S, Muller-Spahn F, Willershausen-Zonnchen B, Schwarz P, Hock U, Growdon JH, Nitsch RM. J Neural Transm. 1998; 105(1):59-68. 9588761 PubMed. These results demonstrate elevated blood levels of mercury in AD, and they suggest that this increase of mercury levels is associated with high CSF levels of A beta, whereas tau levels were unrelated. Possible explanations of increased blood mercury levels in AD include yet unidentified environmental sources or release from brain tissue with the advance in neuronal death.

Mercury and Alzheimer's disease. Mutter J, Naumann J, Schneider R, Walach H. Fortschr Neurol Psychiatr. 2007 Sep;75(9):528-38. Epub 2007 Jul 12. Institut für Umweltmedizin und Krankenhaushygiene, Universitätsklinik Freiburg (Franz Daschner), Breidacher Strasse 115b, 79106 Freiburg i. Brsg. joachim.mutter@uniklinik-freiburg.de. 17628833 PubMed. Higher mercury concentrations were found in brain regions and blood of some patients with Alzheimer's disease (AD). Low levels of inorganic mercury were able to cause AD- typical nerve cell deteriorations in vitro and in animal experiments. Other metals like zinc, aluminum, copper, cadmium, manganese, iron, and chrome are not able to elicit all of these deteriorations in low levels, yet they aggravate the toxic effects of mercury (Hg). Main human sources for mercury are fish consumption (Methyl-Hg) and dental amalgam (Hg vapour). Regular fish consumption reduces the risk of development of AD. Amalgam consists of approx. 50 % of elementary mercury which is constantly being vaporized and absorbed by the organism. Mercury levels in brain tissues are 2 - 10 fold higher in individuals with dental amalgam. Persons showing a genetically determined subgroup of transportation protein for fats (apolipoprotein E4) have an increased AD risk. Apoliprotein E (APO E) is found in high concentrations in the central nervous system. The increased AD risk through APO E4 might be caused by its reduced ability to bind heavy metals. Latest therapeutic approaches to the treatment of Alzheimer disease embrace pharmaceuticals which remove or bind metals from the brain. Preliminary success has been documented with chelation of synergistic toxic metals (Fe, Al, Zn, Cu) and therefore also Hg. The available data does not answer the question, whether mercury is a relevant risk factor in AD distinctively. In sum, the findings from epidemiological and demographical studies, the frequency of amalgam application in industrialized countries, clinical studies, experimental studies and the dental state of Alzheimer patients in comparison to controls suggest a decisive role for inorganic mercury in the etiology of Alzheimer's disease. Other factors currently discussed as causes (e. g. other metals, inflammations, dietetic factors, vitamin deficiency, oxidative distress, and metabolic impairments) may act as co-factors.

Mercury induces cell cytotoxicity and oxidative stress and increases beta-amyloid secretion and tau phosphorylation in SHSY5Y neuroblastoma cells. Olivieri G, Brack C, Muller-Spahn F, Stahelin HB, Herrmann M, Renard P, Brockhaus M, Hock C. J Neurochem. 2000 Jan; 74(1):231-6. 10617124 PubMed. Concentrations of heavy metals, including mercury, have been shown to be altered in the brain and body fluids of Alzheimer's disease (AD) patients. Tau phosphorylation was significantly increased in the presence of mercury (n = 9, p<0.001), whereas melatonin preincubation reduced the phosphorylation to control values. These results indicate that mercury may play a role in pathophysiological mechanisms of AD.

Mercury Linked to Alzheimer's Disease. Leong CW, Syed NI, Lorscheider  FL. University of Calgary Medical School. 26-Mar-2001. Research conducted at the University of Calgary Faculty of Medicine has demonstrated that trace amounts of mercury can cause the type of damage to nerves that is characteristic of the damage found in Alzheimer’s Disease. The level of mercury exposure is consistent with those levels found in humans with mercury/silver amalgam dental fillings. The exposure to mercury caused the formation of “neurofibrillar tangles,” which are one of the two diagnostic markers for Alzheimer’s Disease. The scientists found that other metals, including aluminum, did not cause the damage. Previous research has shown that mercury can cause the formation of the other Alzheimer’s Disease diagnostic marker, “amyloid plaques.” In 2000, researchers at the Neurobiology Laboratory, Psychiatric University Hospital in Basel, Switzerland using neuroblastoma cells exposed to mercury demonstrated an increase in production of amyloid protein that makes up the amyloid plaques as well as significantly increasing the phosphorylation of Tau protein.

Mercury Vapor Inhalation Inhibits Binding of GTP to Tubulin in Rat Brain: Similarity to a Molecular Lesion in Human Alzheimer Brain. Pendergrass JC, Haley BE, Vimy, MJ, Winfield SA, Lorscheider FL. NeuroToxicology 18 (2): 315-324, 1997. 9291481 PubMed. We conclude that chronic inhalation of low-level Hg0 can inhibit polymerization of brain tubulin essential for formation of microtubules.

Metals and trace elements in plasma and cerebrospinal fluid in normal aging and Alzheimer's disease. Basun H, Forssell LG, Wetterberg L, Winblad B. J Neural Transm Park Dis Dement Sect. 1991; 3(4):231-58. 1772577 PubMed. Cerebro-spinal fluid (CSF) and blood levels of aluminium, cadmium, calcium, copper, lead, magnesium, and mercury were studied in 24 subjects with dementia of the Alzheimer type (DAT) and in 28 healthy volunteers. Furthermore, arsenic, bromine, chrome, iron, manganese, nickel, rubidium, selenium, strontium, and zinc were measured only in blood. There were significant changes in the DAT group when compared to the controls. The plasma levels of aluminium, cadmium, mercury and selenium were increased and the contents of iron and manganese were lower in the DAT group as compared to control subjects. In CSF there were low levels of cadmium and calcium and increased content of copper in DAT cases. Iron and zinc levels in blood and calcium in both blood and CSF of DAT patients correlated with memory and cognitive functions. Iron, manganese and strontium levels of DAT sufferers in blood and aluminium in CSF were related with changes in behaviour.

Regional brain trace-element studies in Alzheimer's disease. Thompson CM, Markesbery WR, Ehmann WD, Mao YX, Vance DE. Neurotoxicology. 1988 Spring; 9(1):1-7. 3393299 PubMed. Alzheimer's disease (AD) brain trace-element imbalances in the amygdala, hippocampus and nucleus basalis of Meynert (nbM) are found in most cases to be consistent with those previously reported in samples derived principally from AD cerebral cortex (Ehmann et al., 1986). The elevation of mercury in AD nbM, as compared to age-matched controls, is the largest trace-element imbalance observed to date in AD brain. In addition to the general confirmation of imbalances for Cs, Hg, N, Na, P, and Rb noted previously in cerebral cortex samples, imbalances for Fe, K, Sc, and Zn were observed in two regions and one region also exhibited imbalances for both Co and Se. Persistent imbalances for the univalent cations Na, K, Rb and Cs support arguments for a membrane abnormality in AD. The data presented here also provide the first comprehensive simultaneous multi-element determinations in both control and AD nbM.

Results from the Boyd Haley Laboratory. Relating the Toxic Effects of Mercury to Exacerbation of the Medical Condition Classified as Alzheimer's Disease. Boyd Haley. Research regarding Alzheimer's disease (AD) in our laboratory has been directed towards detecting aberrancy in the nucleotide binding proteins of AD post-mortem brain versus age matched control brain samples. Basic to all of our findings is the following observation. Two very important brain nucleotide binding proteins, tubulin and creatine kinase (CK), show greatly diminished nucleotide binding ability and they are abnormally partitioned into the membrane fraction of brain tissue. What tubulin and CK have in common is that both have a very reactive sulfhydryl which, if modified, inhibits their biological activity. Mercury has a very high affinity for sulfhydryls and has been proven to be a potent inhibitor of both of these proteins biological activity. After our laboratory demonstrated that tubulin had diminished biological activity in AD brain, and only AD brain, we searched for possible toxicants that might mimic this biological problem. Our finding was simple and straight-forward. After testing numerous heavy metals we observed that only mercury-II cation (Hg2+) could mimic this effect in homogenates of normal brain at concentrations that might be expected to be found under toxic conditions (3,4). The observation was that Hg2+ at 1-5 micromolar levels could selectively and totally abolish the binding activity of tubulin without any noticeable effect on other proteins. http://home.iprimus.com.au/asomat/Frame/Main.htm   

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Deleterious effects of low micromolar mercury on important brain and cerebrospinal fluid proteins. Pendergrass J, Israel M, Haley B. American Association of Pharmaceutical Scientists, Annual Meeting,5-9 November 1995, Miami, Florida ASOMAT (home.iprimus.com)

Trace Element Imbalances in Isolated Subcellular Fractions of Alzheimer's Disease Brains. Wenstrup D, Ehmann WD, Markesbery WR. Brain Research, 533 125-131 Elsevier Science Publishers (1990). 2085723 PubMed. Overall our studies suggest that Hg could be an important toxic element in AD. Whether Hg deposition in AD is a primary or secondary event remains to be determined.

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis and mercury--preliminary report. Mano Y, Takayanagi T, Abe T, Takizawa Y. Rinsho Shinkeigaku. 1990 Nov; 30(11):1275-7. 2085936 PubMed. It is well known that the selenium decreases the toxicity of mercury in the human body. From these data mercury with low content of selenium might be one of the environmental factors which are thought to be involved in producing of ALS.

Effects of metals on the nervous system of humans and animals. Carpenter DO. Int J Occup Med Environ Health. 2001; 14(3):209-18. 11764847 PubMed. Several metals have toxic actions on nerve cells and neurobehavorial functioning. These toxic actions can be expressed either as developmental effects or as an increased risk of neurodegenerative diseases in old age. The major metals causing neurobehavioral effects after developmental exposure are lead and methylmercury. Lead exposure in young children results in a permanent loss of IQ of approximately 5 to 7 IQ points, and also results in a shortened attention span and expression of anti-social behaviors. There is a critical time period (<2 years of age) for development of these effects, after which the effects do not appear to be reversible even if blood lead levels are lowered with chelation. Methylmercury has also been found to have effects on cognition at low doses, and prenatal exposure at higher levels can disrupt brain development. Metals have also been implicated in neurodegenerative diseases, although it is unlikely that they are the sole cause for any of them. Elevated aluminum levels in blood, usually resulting from kidney dialysis at home with well water containing high aluminum, result in dementia that is similar to but probably different from that of Alzheimer's disease. However, there is some epidemiological evidence for elevated risk of Alzheimer's in areas where there is high concentration of aluminum in drinking water. Other metals, especially lead, mercury, manganese and copper, have been implicated in amvotrophic lateral sclerosis and Parkinson's disease.

Inorganic mercury is transported from muscular nerve terminals to spinal and brainstem motoneurons. Arvidson B. Muscle Nerve. 15(10):1089-1094, Oct 1992. 1383815 PubMed. The selective accumulation of mercury in spinal and brainstem motoneurons is most probably due to a leakage of metal-protein complexes from capillaries in muscle into myoneural junctions, followed by uptake into nerve terminals and retrograde axonal transport. The possible link between this process and the development of motor neuron degeneration in ALS is discussed.

Lou Gehrig’s Disease (ALS). The mercury Connection. Bioprobe. Volume 9 Issue 5 Sept. 1993. http://www.bcd.com.au/111NewSite/Documents/AmalgamNervEffs.htm 

Mercury intoxication simulating amyotrophic lateral sclerosis. Adams CR, Ziegler DK, Lin JT. JAMA. 1983 Aug 5; 250(5):642-3. 6864963 PubMed. Mercury toxicity must be considered not only in individuals with recent anterior horn-cell dysfunction but also with otherwise unexplained peripheral neuropathy, tremor, ataxia, and a gamut of psychiatric symptoms including confusion and depression.

Recovery from amyotrophic lateral sclerosis and from allergy after removal of dental amalgam fillings. Redhe O & Pleva J. Int J Risk & Safety in Med 4:229-236. 1994. Five months after the completion of DA removal (29 August 1984) the patient was called for a week-long investigation at the same University clinic where the diagnosis ALS had been made. She felt now extraordinarily healthy and her health status was also confirmed by the words in her record: "The neurologic status is completely without comment. Hence, the patient does not show any motor neuron disease of type ALS. She has been informed that she is in neurological respect fully healthy." ...At the time of writing (early 1993), 9 years have elapsed since removal of the DA fillings, and the patient continues to enjoy good health. http://www.bcd.com.au/ 

Trace element imbalances in amyotrophic lateral sclerosis. Khare SS, Ehmann WD, Kasarskis EJ, Markesbery WR. Neurotoxicology. 1990 Fall; 11(3):521-32. 2284056 PubMed. However the widespread changes observed in Hg and Se levels in ALS tissues deserve special attention. The significance of these alterations in trace element levels in relation to the pathogenesis of ALS is discussed.

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Arthritis

Mercury poisoning: an unusual cause of polyarthritis. Karatas GK, Tosun AK, Karacehennem E, Sepici V. Clin Rheumatol. 2002 Feb; 21(1):73-5. 11954892 PubMed. Mercury is a toxic metal that is widely used in everyday life. It has organic and inorganic forms that are both toxic. As acute mercury poisoning is uncommon, diagnosis is difficult if the exposure is not manifest. It has usually a slow onset and non-specific symptoms. In this paper we report a patient who developed polyarthritis after mercury exposure.

Autoimmunity and Heavy Metals. Bigazzi PE. Lupus. 1994; 3: 449-453. Autoimmunity and heavy metals. Lupus. 1994 Dec; 3(6):449-53. 7704000 PubMed. Similarly, there is solid evidence that mercury can induce autoimmune disease both in humans and experimental animals. The lessons to be derived from metal-induced autoimmunity relate to structure-activity relationship, pathogenesis, etiology and genetics. They probably apply to xenobiotic-induced autoimmune disease in general.

Candida

Candida albicans therapy. Is there ever an end to it? Dental mercury removal: an effective adjunct. Zamm AV. J. Orthomol. Med. 1, 1986, 261-266.

Chronic Fatigue Syndrome (CFS)

Mercury from dental amalgam and Chronic Fatigue Syndrome. Hamre HJ. The CFIDS Chronicle, Fall 1994, p44-47. http://www.toxicteeth.net/RemovalResults.cfm     

Mercury and nickel allergy: risk factors in fatigue and autoimmunity. Sterzl I, Prochazkova J, Hrda P, Bartova J, Matucha P, Stejskal VD. Neuroendocrinol Lett. 1999; 20(3-4):221-228. 11462117 PubMed. This study examined the presence of hypersensitivity to dental and environmental metals in patients with clinical disorders complicated with chronic fatigue syndrome. Three groups of patients were examined through medical history, dental examination, and by using a modified test of blast transformation for metals-MELISA(R). The three groups consisted of the following: 22 patients with autoimmune thyroiditis with or without polyglandular autoimmune activation; 28 fatigued patients free from endocrinopathy; and 22 fatigued professionals without evidence of autoimmunity. As controls, a population sample or 13 healthy subjects without any evidence of metal sensitivity was included. Healthy controls did not complain of marked fatigue and their laboratory tests did not show signs of autoimmunity and endocrinopathy. We have found that fatigue, regardless of the underlying disease, is primarily associated with hypersensitivity to inorganic mercury and nickel. The lymphocyte stimulation by other metals was similar in fatigued and control groups. To evaluate clinical relevance of positive in vitro findings, the replacement of amalgam with metal-free restorations was performed in some of the patients. At a six-month follow-up, patients reported considerably alleviated fatigue and disappearance of many symptoms previously encountered; in parallel, lymphocyte responses to metals decreased as well. We suggest that metal-driven inflammation may affect the hypothalamic-pituitary-adrenal axis (HPA axis) and indirectly trigger psychosomatic multisymptoms characterizing chronic fatigue syndrome, fibromyalgia, and other diseases of unknown etiology.

Mercury toxicity presenting as chronic fatigue, memory impairment and depression: diagnosis, treatment, susceptibility, and outcomes in a New Zealand general practice setting (1994-2006). Wojcik DP, et al. Wojcik DP. Neuro Endocrinol Lett. 2006 Aug;27(4):415-23. 16891999 In a group of 465 patients diagnosed as having chronic mercury toxicity (CMT), 32.3% had severe fatigue, 88.8% had memory loss, and 27.5% had depression. A significant correlation was found between CMT and the Apo-lipoprotein E4 genotype (p=0.001). An investigation into an additional 864 consecutively seen general practice patients, resulted in 30.3% having evidence consistent with CMT, and once again a significant correlation was found with the APO-E4 genotype (p=0.001). Removal of amalgam mercury fillings when combined with appropriate treatment resulted in a significant symptom reduction (p<0.001) to levels reported by healthy subjects.

Metal-specific lymphocytes: biomarkers of sensitivity in man. Stejskal VD, Danersund A, Lindvall A, Hudecek R, Nordman V, Yaqob A, Mayer W, Bieger W, Lindh U. Neuroendocrinol Lett. 1999; 20(5):289-298. 11460087 PubMed. The effect of dental metal removal was studied in 111 patients with metal hypersensitivity and symptoms resembling Chronic Fatigue Syndrome (CFS). A significant number of patients had metal-specific lymphocytes in the blood. Nickel was the most common sensitizer, followed by inorganic mercury, gold, phenylmercury, cadmium and palladium. Following dental metal removal, 83 patients (76%) reported long-term health improvement. Twenty-four patients (22%) reported unchanged health and two (2%) reported worsening of symptoms. Following dental metal replacement, the lymphocyte reactivity to metals decreased as well. We propose that an inflammatory process induced by metals may modulate the hypothalamic-pituitary-adrenal axis (HPA axis) and trigger multiple non-specific symptoms characterizing CFS and other chronic conditions like myalgic encephalitis (ME) and multiple chemical sensitivity (MCS).

Reactions to metals in patients with chronic fatigue and autoimmune endocrinopathy. Sterzl I, Hrda P, Prochazkova J, Bartova J, Matucha P. Vnitr Lek. 1999 Sep; 45(9):527-31. 10951876 PubMed. Fatigue regardless of the underlying disease is primarily associated with hypersensitivity to inorganic and organic mercury, nickel, and gold. The groups differed in their hypersensitivity to other metals. In the control group, hypersensitivity--mostly to cadmium and lead--was found in four of the examined individuals only. Statistical analysis of data obtained from professionals and controls revealed a higher incidence of positivity to organic and inorganic mercury and nickel in professionals.

Diabetes

Evidence of a relationship between childhood-onset type I diabetes and low groundwater concentration of zinc. Haglund B, Ryckenberg K, Selinus O, Dahlquist G. Diabetes Care. 1996 Aug; 19(8):873-5. 8842606 PubMed. Zinc deficiency has shown to increase the risk for diabetes in diabetes-prone experimental animals. Low concentrations of zinc have also been shown in serum of recent onset cases with IDDM. It is concluded that this study for the first time provides evidence that a low groundwater content of zinc, which may reflect long-term exposure through drinking water, is associated with later development of childhood onset diabetes.

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Neurologic features of chronic minamata disease (organic mercury poisoning) and incidence of complications with aging. Uchino M, Tanaka Y, Ando Y, Yonehara T, Hara A, Mishima I, Okajima T, Ando M. J Environ Sci Health B. 1995 Sep; 30(5):699-715. 8522732 PubMed. To elucidate the neurologic features of chronic Minamata disease, and the incidence of complications with aging, we studied 80 patients with documented Minamata disease (organic mercury poisoning) from 1986 to 1994 (mean age: 63 years). These results accurately reflect the recent epidemiological disease tendencies in Japan toward a decreased incidence of hypertension and an increased incidence of diabetes.

Fibromyalgia

Mercury exposure from dental amalgam fillings in the etiology of primary fibromyalgia: a pilot study. Kotter I, Durk H, Saal JG, Kroiher A, Schweinsberg F. J Rheumatol. 1995 Nov; 22(11):2194-5. 8596179 PubMed. Heavy metals are believed to play a role in fibromyalgia. Some symptoms of fibromyalgia mimic those of heavy metal poisoning, such as depression and anxiety, fatigue, and neuromuscular problems. This study suggests that exposure to mercury from dental amalgam fillings may be a factor in precipitating symptoms of fibromyalgia.    

Herpes

Effect of mercuric chloride on macrophage-mediated resistance mechanisms against infection with herpes simplex virus type 2. Ellermann-Eriksen S, Christensen MM, Mogensen SC. Toxicology. 1994 Nov 11; 93(2-3):269-87. 7526487 PubMed. Macrophages play an important role in the early, nonspecific resistance to infection with herpes simplex virus. Mercuric chloride (HgCl2) accumulates in macrophages and has in certain concentrations a marked influence on the functional capacity of these cells. However the production by macrophages of both cytokines during the HSV-2 infection, but especially interferon-alpha/beta, which is essential for the activation, was reduced at low concentrations of HgCl2. Collectively these data indicate that mercury, by interfering with the early macrophage-production of cytokines, disables the early control of virus replication, leading to an enhanced infection.

MS (Multiple Sclerosis)

A comparison of mental health of multiple sclerosis patients with silver/mercury dental fillings and those with fillings removed. Siblerud RL. Psychol Rep. 1992 Jun; 70(3 Pt 2):1139-51. 1496084 PubMed. On the SCL-90 Revised, subjects with amalgam fillings had significantly more symptoms of depression, hostility, psychotism, and were more obsessive-compulsive than the patients with such fillings removed. On a questionnaire containing 18 mental health symptoms multiple sclerosis subjects with amalgam fillings reported a history of 43% more symptoms than those without amalgam fillings over the past 12 months. These data suggested that the poorer mental health status exhibited by multiple sclerosis subjects with dental amalgam fillings may be associated with mercury toxicity from the amalgam.

Cerebrospinal fluid protein changes in multiple sclerosis after dental amalgam removal. Huggins HA, Levy TE. Altern Med Rev. 1998 Aug; 3(4):295-300. 9727079 PubMed. A relationship between multiple sclerosis (MS) and dental silver-mercury fillings has been suggested by some investigators, but never proven. This study documents objective biochemical changes following the removal of these fillings along with other dental materials, utilizing a new health care model of multidisciplinary planning and treatment. The dramatic changes in photolabeling of cerebrospinal fluid (CSF) proteins following these dental interventions suggest CSF photolabeling may serve as an objective biomarker for monitoring MS. The clear-cut character of these changes should also encourage more research to better define this possible association between dental mercury and MS.

Evidence that mercury from silver dental fillings may be an etiological factor in multiple sclerosis. Siblerud RL, Kienholz E. Sci Total Environ. 1994 Mar 15; 142 (3):191-205. 8191275 PubMed. A health questionnaire found that MS subjects with amalgams had significantly more (33.7%) exacerbations during the past 12 months compared to the MS volunteers with amalgam removal. The paper also examines epidemiological correlations between dental caries and MS; as well as how mercury could be causing the pathological and physiological changes found in multiple sclerosis.

Evidence that Mercury from Dental Amalgam May Cause Hearing Loss in Multiple Sclerosis Patients. Robert L. Siblerud; Eldon Kienholz  The Journal of Orthomolecular Medicine Vol. 12, 4th Quarter 1997   Seven female subjects diagnosed with multiple sclerosis were tested for hearing at threshhold frequencies of 250, 500, 1000, 4000 and 8000 Hz. The subjects then had their silver dental fillings (amalgams) removed. Between six and eight months after amalgam removal, testing for hearing was repeated. Six of the seven subjects showed improvement in hearing of the right ear and five of the seven showed improvement in the left ear. Four of the six frequencies tested in the right ear improved significantly and three of six improved significantly in the left ear. The total frequencies were averaged before amalgam removal and compared to after amalgam removal. Hearing improved an average of 8 dB (p=0.02). http://www.orthomolecular.org/library/jom/1997/articles/1997-v12n04-p240.shtml

 

Mercury in cerebrospinal fluid in multiple sclerosis. Ahlrot-Westerlund B. Swed J. Biol Med 1:6, Mar 1989. ASOMAT (home.iprimus.com)  

Multiple Sclerosis and mercury in cerebrospinal fluid. Ahlrot-Westerlund B. Second Nordic Symposium on Trace Elements in Human Health and Disease. Odense University, Denmark, August 17-21, 1987.

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Parkinson’s Disease

Direct evidence for glutathione as mediator of apoptosis in neuronal cells. Nicole A, Santiard-Baron D, Ceballos-Picot I. Biomed Pharmacother. 1998; 52(9):349-55. 9856280 PubMed. These results suggested that redox desequilibrium induced by GSH depletion may serve as a general trigger for apoptosis in neuronal cells, and are consistent with the hypothesis that GSH depletion contribute to neuronal death in Parkinson's disease.

Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson's disease and heavy metal exposure. Uversky VN, Li J, Fink AL. J Biol Chem. 2001 Nov 23; 276(47):44284-96. Epub 2001 Sep 11. 11553618 PubMed. The potential for ligand bridging by polyvalent metal ions is proposed to be an important factor in the metal-induced conformational changes of alpha-synuclein. The results indicate that low concentrations of some metals can directly induce alpha-synuclein fibril formation.

Occupational exposures to metals as risk factors for Parkinson's disease. Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Kortsha GX, Brown GG, Richardson RJ. Neurology. 1997 Mar; 48(3):650-8. 9065542 PubMed. In a population-based case-control study, we investigated the potential role of occupational exposure to iron, copper, manganese, mercury, zinc, and lead as risk factors for Parkinson's disease (PD).These findings suggest that chronic exposure to these metals is associated with PD, and that they may act alone or together over time to help produce the disease.

Occupational metal exposures and the risk of Parkinson's disease. Gorell JM, Rybicki BA, Cole Johnson C, Peterson EL. Neuroepidemiology. 1999; 18(6):303-8. 10545782 PubMed. Occupational exposure to specific metals (manganese, copper, lead, iron, mercury, zinc, aluminum and others) appears to be a risk factor for Parkinson's disease (PD) in some, but not all, case-control studies. These epidemiological studies are reviewed. Several methodological issues that may account for the lack of unanimity of findings are discussed, and suggestions for improved case-control methodology are offered. The study of the neurological disease outcome of workers who have had long-term, well-defined occupational exposure to one or more metals is also urged, with collaborative work including industrial hygienists, occupational toxicologists, neurologists, epidemiologists and biostatisticians. Such efforts, employing state-of-the-art case and control ascertainment and enrollment from suitable population bases, neurological diagnostic rigor and exposure assessment, will help to further define the potentially important roles played by metals in PD and other neurodegenerative disorders.

The enigma of parkinsonism in chronic borderline mercury intoxication, resolved by challenge with penicillamine. Finkelstein Y, Vardi J, Kesten MM, Hod I. Neurotoxicology. 1996 Spring; 17(1):291-5. 8784840 PubMed. A 47 year old female dentist suffered from hemiparkinsonism which had started eighteen months earlier and was manifested mainly by resting tremor and cogwheel rigidity. A baseline quantitative urinary mercury excretion was 46 micrograms/day. The patient was treated with chelating agent d-penicillamine for a week. Chelation therapy resulted in clinical improvement of parkinsonism and in dynamic changes in daily urinary mercury excretion with a prompt increase to 79 micrograms/day, a subsequent decline followed by increase in the mercury urinary excretion. After a week chelation therapy was stopped. During a follow-up period of five years, the neurological status remained unchanged after the initial penicillamine-induced improvement. This case may be evidence, therefore, of a rare clinical variant of elemental mercury intoxication associated with parkinsonism, in the absence of most classical neuropsychiatric signs of chronic mercurialism.

Systems

Adrenal

Alterations of heme, cytochrome P-450, and steroid metabolism by mercury in rat adrenal. Veltman JC, Maines MD. Arch Biochem Biophys. 1986 Aug 1; 248(2):467-78. 2943220 PubMed. The treatment of male rats with Hg2+ resulted in significant alterations in heme and hemoprotein metabolism in the adrenal gland which, in turn, were reflected in abnormal steroidogenic activities and steroid output. It is suggested that Hg2+ directly caused a defect in adrenal steroid biosynthesis by inhibiting the activity of 21 alpha-hydroxylase. The apparent physiological consequences of this effect included lowered plasma levels of corticosterone and elevated concentrations of progesterone and dehydroepiandrosterone. This abnormal plasma steroid profile is indicative of a 21 alpha-hydroxylase impairment.

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Heart

Effects of mercury on myosin ATPase in the ventricular myocardium of the rat. Moreira CM, Oliveira EM, Bonan CD, Sarkis JJ, Vassallo DV. Comp Biochem Physiol C Toxicol Pharmacol. 2003 Jul; 135C (3):269-75. 12927901 PubMed. Our results suggest that mercury reduces the activity of the myosin ATPase by an uncompetitive mechanism at a very low dose that does not depress force. DTT and glutathione are effective for protection against the actions of mercury suggesting that SH groups might be the sites of action of the metal on the myosin molecule.

Effects of mercury on the isolated heart muscle are prevented by DTT and cysteine. Vassallo DV, Moreira CM, Oliveira EM, Bertollo DM, Veloso TC. Toxicol Appl Pharmacol. 1999 Apr 15; 156(2):113-8. 10198276 PubMed. These findings suggest that several but not all toxic effects of Hg2+ on the mechanical activity of the heart muscle are prevented by protectors of SH groups such as DTT and cysteine.

Intake of mercury from fish, lipid peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in eastern Finnish men. Salonen JT, Seppanen K, Nyyssonen K, Korpela H, Kauhanen J, Kantola M, Tuomilehto J, Esterbauer H, Tatzber F, Salonen R. Circulation. 1995 Feb 1; 91(3):645-55. 7828289 PubMed. These data suggest that a high intake of mercury from nonfatty freshwater fish and the consequent accumulation of mercury in the body are associated with an excess risk of acute myocardial infarction (AMI) as well as death from coronary heart disease (CHD), cardiovascular disease (CVD), and any cause in Eastern Finnish men and this increased risk may be due to the promotion of lipid peroxidation by mercury.

Marked elevation of myocardial trace elements in idiopathic dilated cardiomyopathy compared with secondary cardiac dysfunction. Frustaci A, Magnavita N, Chimenti C, Caldarulo M, Sabbioni E, Pietra R, Cellini C, Possati GF, Maseri A. J Am Coll Cardiol. 1999 May; 33(6):1578-83. 10334427 PubMed. A large increase (>10,000 times for mercury and antimony) of TE concentration has been observed in myocardial but not in muscular samples in all pts with IDCM.   

Mercury effects on the contractile activity of the heart muscle. Oliveira EM, Vassallo DV, Sarkis JJ, Mill JG. Toxicol Appl Pharmacol. 1994 Sep; 128(1):86-91. 8079358 PubMed. These findings suggest that Hg2+ promotes dose-dependent toxic effects on heart muscle via actions on the sarcolemma, the sarcoplasmic reticulum, and contractile proteins.

I Personally Consider it Important for All Dentists to Read this Article

Role of mercury toxicity in hypertension, cardiovascular disease, and stroke. Houston MC. J Clin Hypertens (Greenwich) 2011 Aug;13(8):621-7. doi: 10.1111/j.1751-7176.2011.00489.x. Epub 2011 Jul 11. From the Department of Medicine, Vanderbilt University School of Medicine; Hypertension Institute and Vascular Biology;the Division of Human Nutrition, Saint Thomas Medical Group, Saint Thomas Hospital, Nashville, TN. © 2011 Wiley Periodicals, Inc. 21806773 Pubmed.

Mercury has a high affinity for sulfhydryl groups, inactivating numerous enzymatic reactions, amino acids, and sulfur-containing antioxidants (N-acetyl-L-cysteine, alpha-lipoic acid, L-glutathione), with subsequent decreased oxidant defense and increased oxidative stress. Mercury binds to metallothionein and substitute for zinc, copper, and other trace metals, reducing the effectiveness of metalloenzymes. Mercury induces mitochondrial dysfunction with reduction in adenosine triphosphate, depletion of glutathione, and increased lipid peroxidation. Increased oxidative stress and reduced oxidative defense are common. Selenium and fish containing omega-3 fatty acids antagonize mercury toxicity. The overall vascular effects of mercury include increased oxidative stress and inflammation, reduced oxidative defense, thrombosis, vascular smooth muscle dysfunction, endothelial dysfunction, dyslipidemia, and immune and mitochondrial dysfunction. The clinical consequences of mercury toxicity include hypertension, coronary heart disease, myocardial infarction, cardiac arrhythmias, reduced heart rate variability, increased carotid intima-media thickness and carotid artery obstruction, cerebrovascular accident, generalized atherosclerosis, and renal dysfunction, insufficiency, and proteinuria. Pathological, biochemical, and functional medicine correlations are significant and logical. Mercury diminishes the protective effect of fish and omega-3 fatty acids. Mercury inactivates catecholaminei-0-methyl transferase, which increases serum and urinary epinephrine, norepinephrine, and dopamine. This effect will increase blood pressure and may be a clinical clue to mercury-induced heavy metal toxicity. Mercury toxicity should be evaluated in any patient with hypertension, coronary heart disease, cerebral vascular disease, cerebrovascular accident, or other vascular disease. Specific testing for acute and chronic toxicity and total body burden using hair, toenail, urine, and serum should be performed.

The relationship between mercury from dental amalgam and the cardiovascular system. Siblerud RL. Sci Total Environ. 1990 Dec 1; 99(1-2):23-35. 2270468 PubMed. The findings presented here suggest that mercury poisoning from dental amalgam may play a role in the etiology of cardiovascular disorders. Comparisons between subjects with and without amalgam showed amalgam-bearing subjects had significantly higher blood pressure, lower heart rate, lower hemoglobin, and lower hematocrit. Hemoglobin, hematocrit, and red blood cells were significantly lower when correlated to increased levels of urine mercury. The amalgam subjects had a greater incidence of chest pains, tachycardia, anemia, fatigue, tiring easily, and being tired in the morning. The data suggest that inorganic mercury poisoning from dental amalgam does affect the cardiovascular system.

Hearing

Amalgam dental fillings and hearing loss Janet A. Rothwell; Paul J. Boyd;  Audiology Department, General Hospital, St. Helier, Jersey, Channel Islands  School of Psychological Sciences, University of Manchester, United Kingdom. Online Publication Date: 01 December 2008. Int J Audiol. 2010 Jan;49(1):69-70. 19085401 PubMed. In this study we investigated the effects of amalgam dental fillings on auditory thresholds. However, there was a significant positive linear correlation between amalgam filling data and auditory thresholds at 8, 11.2, 12.5, 14, and 16 kHz. The strongest association (r=0.587, n=39, p<.001, r(2)=0.345) was at 14 kHz, where each additional amalgam filling was associated with a 2.4 dB decline in hearing threshold (95% confidence interval [CI], 1.3-3.5 dB). The results suggest an association between more amalgam fillings and poorer thresholds at higher frequencies, which could contribute to presbyacusis in developed countries. However, the data from the current study provide an additional argument against the continued use of dental amalgam where suitable alternatives

exist.

Evidence that mercury from dental amalgam may cause hearing loss in multiple sclerosis patients. Siblerud RL, Kienholz E. Journal of Orthomolecular Medicine. 1997. Vol. 12. 240-44. The leaching of toxic mercury from amalgam fillings has been implicated in hearing loss. Mercury toxicity has also been linked to multiple sclerosis (MS). It is believed that the toxic effects of mercury cause damage to the blood brain barrier, demyelination (damage to the nerves' myelin sheaths) and slowing of the nerve conduction velocity. This experiment involved seven women aged 32-46 years who had been diagnosed with MS. The women underwent a standard hearing test in a sound booth and then had all their amalgam fillings replaced with composites. Six to eight months later they were again given the hearing test. Six of the seven patients had significantly improved hearing in the right ear and five of the seven showed improvement in the left ear. Overall, hearing improved an average of eight decibels. The conclusion is that amalgam fillings may be a significant factor in hearing loss experienced by MS patients and could be a factor in hearing loss in other people as well. http://www.orthomolecular.org/library/jom/1997/articles/1997-v12n04-p240.shtml

Neurotoxic effects of mercury on auditory cortex networks growing on microelectrode arrays: a preliminary analysis. Gopal KV. Neurotoxicol Teratol. 2003 Jan-Feb; 25(1):69-76. 12633738 PubMed. Mercury is known to cause sensorineural hearing loss and impaired speech perception. However, there is still a lack of a quantitative description of mercury toxicity on central auditory structures. This is a preliminary study using the novel technique of microelectrode array (MEA) recordings to evaluate acute and chronic neurotoxic effects of mercury on auditory cortex networks (ACNs) in vitro. Results of acute experiments indicated that <75 mM of HgCl(2) had an excitatory effect of variable magnitude on the spontaneous activity of ACNs; however, concentrations above 100 microM completely and irreversibly inhibited spike and burst activity. Chronic exposure of ACNs to 10 microM HgCl(2) completely blocked the spontaneous activity. Morphological analysis indicated that 10 microM HgCl(2) caused neuronal cell death in 3 days. It is concluded that HgCl(2) has a more toxic effect on auditory networks when exposed chronically, and the levels of mercury showing toxic effects on ACNs are within the dose range shown to cause neurologic symptoms in humans.

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Kidney

A significant dose-dependent relationship between mercury exposure from dental amalgams and kidney integrity biomarkers: A further assessment of the Casa Pia children’s dental amalgam trial. DA Geier, T Carmody, JK Kern, PG King, MR Geier. Hum Exp Toxicol. 2013 Apr;32(4):434-440. Epub 2012 Aug 14. 22893351 PubMed

Our study determined whether there was a significant dose-dependent correlation between increasing Hg exposure from dental amalgams and GST-a and GST-p as biomarkers of kidney integrity. Overall, the present study, using a different and more sensitive statistical model than the parent study, revealed a statistically significant dose-dependent

correlation between cumulative exposure to Hg from dental amalgams and urinary levels of GST-a, after covariate adjustment; where as, a nonsignificant relationship was observed with urinary levels of GST-p. Furthermore, it was observed that urinary GST-a levels increased by about 10% over the 8-year course of the study among individuals with an average exposure to amalgams among the study subjects from the amalgam group, in comparison with study subjects with no exposure to dental amalgams. The results of our study suggest that dental amalgams contribute to ongoing kidney damage at the level of the PTs in a dose-dependent fashion. 

Mercuric ion attenuates nuclear factor-kappaB activation and DNA binding in normal rat kidney epithelial cells: implications for mercury-induced nephrotoxicity. Dieguez-Acuna FJ, Ellis ME, Kushleika J, Woods JS. Toxicol Appl Pharmacol. 2001 Jun 15; 173(3):176-87. 11437639 PubMed. Mercuric ion (Hg(2+)), one of the strongest thiol-binding agents known, mediates the toxicity associated with elemental, inorganic, and organic mercurial compounds. Studies of cellular events associated with Hg(2+) toxicity have focused largely on disruption of cell membranes and impairment of mitochondrial functions. In contrast, few studies have sought to define the specific molecular mechanisms through which Hg(2+) might affect toxicity via alteration of thiol-dependent signal transduction pathways that regulate cell proliferation and survival. These findings demonstrate that Hg(2+), at low cellular concentrations, attenuates NF-kappaB activation at sites associated with IkappaBalpha phosphorylation and degradation, nuclear translocation of the p50p65 heterodimer, and association of p50-cys(62) with the DNA kappaB binding site. Attenuation of NF-kappaB activation by Hg(2+) through these mechanisms may underlie apoptotic or other cytotoxic responses that are known to be associated with low level Hg(2+) exposure in kidney epithelial cells.

Mercury concentrations in the human brain and kidneys in relation to exposure from dental amalgam fillings. Nylander M, Friberg L, Lind B. Swed Dent J. 1987; 11(5):179-87. 3481133 PubMed. It is concluded that the cause of the association between amalgam load and accumulation of mercury in tissues is the release of mercury vapour from amalgam fillings.

Mercury in dental restoration: is there a risk of nephrotoxicity? Mortada WL, Sobh MA, El-Defrawy MM, Farahat SE. J Nephrol. 2002 Mar-Apr; 15(2):171-6. 12018634 PubMed. Urinary excretion of NAG, gammaGT and albumin was significantly higher in persons with dental amalgam than those without. In the amalgam group, urinary excretion of NAG and albumin significantly correlated with the number of fillings. Albuminuria significantly correlated with blood and urine Hg. CONCLUSION: From the nephrotoxicity point of view, dental amalgam is an unsuitable filling material, as it may give rise to Hg toxicity. Hg levels in blood and urine are good markers of such toxicity. In these exposure conditions, renal damage is possible and may be assessed by urinary excretions of albumin, NAG, and gamma-GT.

Mercury induces regional and cell-specific stress protein expression in rat kidney. Goering PL, Fisher BR, Noren BT, Papaconstantinou A, Rojko JL, Marler RJ. Toxicol Sci. 2000 Feb; 53(2):447-57. 10696793 PubMed. These results demonstrate that expression of specific stress proteins in rat kidney exhibits regional heterogeneity in response to Hg(II) exposure, and a positive correlation exists between accumulation of some stress proteins and acute renal cell injury.

Understanding renal toxicity of heavy metals. Diamond GL, Zalups RK. Toxicol Pathol. 1998 Jan-Feb; 26(1):92-103. 9502391 PubMed. The mechanisms by which metals induce renal injury are, in general, poorly understood. Characteristic features of metal nephrotoxicity are lesions that tend to predominate in specific regions of the nephron within specific cell types. This suggests that certain regions of the nephron are selectively sensitive to specific metals. Regional variability in sensitivity could result from the localization of molecular targets in certain cell populations and/or the localization of transport and binding ligands that deliver metals to targets within the nephron. Significant progress has been made in identifying various extracellular, membrane, and intracellular ligands that are important in the expression of the nephrotoxicity of metals. As an example, mercuric chloride induces a nephropathy that, at the lowest effective doses, is restricted primarily to the S3 segment of the proximal tubule, with involvement of the S2 and S1 segments at higher doses. This specificity appears to be derived, at least in part, from the distribution of enzymes and transport proteins important for the uptake of mercury into proximal tubule cells: apical gamma-glutamyltranspeptidase and the basolateral organic anion transport system. Regional distributions of transport mechanisms for binding proteins appear to be important in the expression of nephrotoxicity of metals. These and other new research developments are reviewed.

Respiratory

Mercury--is it a respiratory tract allergen. Drouet M, Le Sellin J, Bonneau JC, Sabbah A. Allerg Immunol (Paris). 1990 Mar; 22(3):81, 84-8. 2187473 PubMed. Mercury is a well-known allergen in dermato-allergology, often manifesting as delayed type hypersensitivity contact eczema. Immediate hypersensitivity reactions (urticaria, anaphylactic shock) have also been described for this allergen, most frequently seen in patients with the delayed type contact eczema. To our knowledge this allergen has not been implicated in production of respiratory symptoms. We describe a patient who had aggravation of asthma by mercury contained in dental amalgam. When the dental amalgam was removed there was a great improvement in his asthma. This observation suggests that mercury in the form of dental amalgam may also be an allergen of the respiratory tract, which should not be surprising, bearing in mind the work that shows the existence of mercury vapours from dental amalgam.

Thyroid

Effects of low mercury vapour exposure on the thyroid function in chloralkali workers. Ellingsen DG, Efskind J, Haug E, Thomassen Y, Martinsen I, Gaarder PI. J Appl Toxicol. 2000 Nov-Dec; 20(6):483-9. 11180271 PubMed. The study could indicate a slight effect of low mercury vapour exposure on the function of the enzyme type I iodothyronine deiodinase, possibly modified by comparatively low urinary iodine concentrations.

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Vision

Reversible color vision loss in occupational exposure to metallic mercury. Cavalleri A, Gobba F. Environ Res. 1998 May; 77(2):173-7. 9600811 PubMed. The results add evidence that the color vision loss observed during the first part of the study was related to Hg exposure and, moreover, show that this effect is reversible. These data indicate that metallic Hg can induce a reversible impairment in color perception. This suggests that color vision testing should be included in studies on the early effects of Hg.

Color discrimination impairment in workers exposed to mercury vapor. Urban P, Gobba F, Nerudova J, Lukas E, Cabelkova Z, Cikrt M. Neurotoxicology. 2003 Aug; 24(4-5):711-6. 12900084 PubMed. CONCLUSION: In agreement with previous studies by Cavalleri et al. [Toxicol. Lett. 77 (1995) 351; Environ. Res. Sec. A 77 (1998) 173], the results of this study support the hypothesis that exposure to mercury vapor can induce sub-clinical color vision impairment. This effect was observed at an exposure level below the current biological limit for occupational exposure to mercury. This raises doubts on the actual protection afforded by this limit concerning the effect of mercury on color vision.

Colour vision loss in workers exposed to elemental mercury vapour. Cavalleri A, Belotti L, Gobba F, Luzzana G, Rosa P, Seghizzi P. Toxicol Lett. 1995 May; 77(1-3):351-6. 7618161 PubMed. In the workers whose HgU exceeded 50 micrograms/g creatinine, mean colour confusion index (CCI) was significantly increased compared to the matched referents. The results suggest that exposure to elemental Hg inducing HgU values exceeding 50 micrograms/g creatinine can induce a dose-related colour vision loss.

Visual evoked potentials and the time of motor reaction to visual stimuli in chronic metallic mercury poisoning. Langauer-Lewowicka H, Sikora A, Kazibutowska Z. Neurol Neurochir Pol. 1988 Nov-Dec; 22(6):495-9. 3268732 PubMed. In a group of 10 patients with diagnosed occupational chronic poisoning with metallic mercury a correlation was sought between the parameters of the visual evoked potentials and the results of the psychological test evaluating the rapidity of motor response to the visual stimuli. The analysis suggest a cerebral dysfunction of the visual neurons and reduced rate of visual information transformation to the motor effector at the level of the cortical association centre.

Environmental Release

Amalgam use and mercury emission in the Netherlands. Burger WG, van den Heuvel J, Kolsteeg E, Schuurs AH. Ned Tijdschr Tandheelkd. 1997 Mar; 104(3):95-8. 11924382 PubMed. An overview is presented of the emission of mercury to the environment by restoring teeth with amalgam, extraction, replacement of amalgam, and the final phase of teeth. Important input data were the trade figures of amalgam. The emission of mercury from amalgam fillings are characterized by diffuse spreading. Many small sources are together a substantial source of the leakage of mercury to the environment. Amalgam adhering to cotton-wool and in extracted teeth deliver a relevant contribution to the mercury load in municipal waste. The total mercury emission from dental amalgam to the environment in the Netherlands is at the estimate 500 kg a year, with a worst case maximum of 935 kg.

Mercury in the Environment. Electric Power Research Institute. EPRI Journal 1990 April, p5; and EPRI Technical Brief: Mercury in the Environment. 1993. Because of the extreme toxicity of mercury, only ½ gram is required to contaminate the ecosystem and fish of a 10 acre lake to the extent that a health warning would be issued by the government to not eat the fish.

Mercury in the environment: a volatile problem. Lutter, Randall. Environment. Nov, 2002. Mercury is present in the environment due to human activity as well as natural sources such as volcanoes and forest fires. The scope of mercury releases relevant to determining the causes of contamination in U.S. waters may be regional or even global rather than local, because mercury travels long distances in the air. Forty percent (32 metric tons (t)) of the mercury deposited from the air onto U.S. water and soil in 1995 came from the global mercury reservoir (the amount of mercury circulating worldwide at any one time); the other 60 percent came from anthropogenic sources in the United States. Both natural and anthropogenic emissions contribute to the global mercury reservoir, and although significant uncertainty exists as to the length of time that some forms of mercury persist in the atmosphere, an authoritative estimate of annual global input to the reservoir is about 4,900 t.  There is also substantial uncertainty about the share of worldwide emissions that originates from human activity. One study concluded that natural sources, industrial sources, and the "recycling" of anthropogenic mercury each account for about one-third of the mercury burden in the global atmosphere at a given moment. Recycling occurs when mercury in water volatilizes and contributes to the buildup of atmospheric mercury concentrations.  Mercury releases from ongoing human activity in the United States can be divided into four broad categories. These include "area sources" such as landfills, dental preparations, and laboratory use; combustion processes, including coal-fired power generation, medical waste incinerators, and municipal waste combustors; some manufacture of metals, alkali, and cement; and other various industrial processes, from pigment manufacture to geothermal power generation. EPA estimated that emissions from these source categories generated 2.76 t, 112.3 t, 12.67 t, and 1.16 t of environmental mercury per year, respectively, in 1994-95. Thus, combustion sources accounted for nearly 90 percent of total U.S. anthropogenic emissions. In recent years, EPA has regulated medical waste incinerators, municipal waste combustors, and hazardous waste combustors. When these regulations are fully implemented in the fall of 2002, EPA estimates annual mercury emissions of about 54 t lower than they would be without these regulations.  Mining in the past has raised mercury concentrations in some areas. Releases of quicksilver mercury in the hydraulic placer-gold mines of the Sierra Nevadas added 1,360 t to 3,630 t of mercury to the environment from the 1860s through the early 1900s. According to the U.S. Geological Survey (USGS), "High mercury levels in fish, amphibians, and invertebrates downstream of the hydraulic mines are a consequence of historic mercury use."

Mercury study report to congress. A report released on December 19, 1997 by the Environmental Protection Agency. http://www.epa.gov/oar/mercover.html   

Factors Affecting Release of Mercury from Amalgam Fillings

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Tooth Grinding

The effect of dental amalgam restorations on blood mercury levels. Abraham JE, Svare CW, Frank CW. J Dent Res. 1984 Jan; 63(1):71-3. 6582086 PubMed. Mercury levels in blood and in mouth air before and after chewing were measured in 47 persons with and 14 persons without dental amalgam restorations. Questionnaires relating to exogenous sources of mercury exposure were administered to both groups. Differences in the mouth air mercury levels before and after chewing were statistically significant in the group with amalgams, but not in the group without amalgams. Analysis of the data from the questionnaires indicated that little or no exogenous exposure to mercury occurred among the two groups. Blood mercury concentrations were positively correlated with the number and surface area of amalgam restorations and were significantly lower in the group without dental amalgams.

Impact of nocturnal bruxism on mercury uptake from dental amalgams. Isacsson G, Barregard L, Selden A, Bodin L. Eur J Oral Sci. 1997 Jun; 105 (3):251-7. 9249192 PubMed. This study indicates that mechanical wear on amalgams from nocturnal bruxism may increase the Hg uptake, but the magnitude of this effect seems to be less than from the use of chewing gum.

Hot Drinks

Factors influencing mercury evaporation rate from dental amalgam fillings. Bjorkman L, Lind B. Scand J Dent Res. 1992 Dec; 100(6):354-60. 1465570 PubMed. 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.

Acid conditions in Mouth

Dissolution of mercury from dental amalgam at different pH values. Marek M. J Dent Res. 1997 Jun; 76(6):1308-15. 9168865 PubMed. At all pH values, more mercury dissolved from the tin-free phase than from the tin-containing phase, and the rate of dissolution was lowest for the dental amalgams.

Fecal Metals

Diversion or prevention of biliary outflow from the liver diminishes the renal uptake of injected inorganic mercury. Zalups RK, Barfuss DW. Drug Metab Dispos. 1996 Apr; 24(4):480-6. 8801064 PubMed. There was an almost 3-fold increase in the content of mercury in the liver of the rats whose bile duct had been ligated.

Fecal Mercury. ISTERH Third International Conference and NTES Fourth Nordic Conference on Disease. Malmström C, Hansson M, Magnus N. Stockholm (Huddinge), May 25 - 29, 1992. Mercury (Hg) vapor release from amalgam fillings has been well documented. Urine and feces levels are positively related to oral amalgam surface. However, the major excretion route for Hg is via feces. Human experiments demonstrate that even one small amalgam filling, (0,12g ANA 70) in an 11 years old girl (37 kilo) with no previous amalgam fillings, increases HG levels in feces from 23 ppb ~3 µgHg/24h to 3200 ppb ~ 400 µgHg/24h on the third day. Inorganic mercury is mainly execreted in feces and urine and to some extent sweat. Minimal studies show that the distribution of the execretion between the different routes is dose dependent, Rothstein & Hayes, 1960 and 1964; Ceber 1962; Kristensen & Hansen 1980 i.e. at decreasing doses the importance of fecal route increases, 85% was found in feces. Cherian et al. 1978 exposed human volunteers to radioactively labelled Hg vapor, 79% of the excreted amount was in feces.

Skare & Engqvist, 1992, found fecal excretion of mercury from amalgam in the range 27-190 micrograms/day in persons having from 18-82 amalgam surfaces (crowns counted as 6 surfaces). Urine levels were "normal" with only one value over 8 micrograms/day.

There are only a few previous studies on fecal levels of mercury after amalgam placement. Borinski, 1931, measured a total excreation (feces + urine) of 10-100 micrograms/day in 50% and more than 100 in 50% of the children after amalgam therapy. The increased levels lased for some months and subsequently dropped considerably. The levels in feces were generally five (5) times higher than those in urine.

Frykholm, 1957, found somewhat increased urine mercury levels after amalgam placement in dogs and in humans but up to 87.000 micrograms/100g feces in dog and 1.900 micrograms/100 g in humans where a much smaller amount of amalgam was used. A second peak of mercury excreation occurred after removal of the fillings, irrespective of precautions (rubber dam) or extraction of teeth instead of drilling.

More recent experiments on sheep, Hahn et al, 1989, and monkeys, Hahn et al 1990, clearly shows the major part of amalgam derived mercury to pass via the gastrointestinal tract where some of it is absorbed in tissues. These animal experiments also demonstrated a considerable absorption directly into the jaw bone an Hg accumulation in various tissues.

Skare, 1992, estimated that half of the gastrointestinal mercury might be swallowed material from corrosion and abrasion and half absorbed and execreted into the gastrointestinal tract. More accurate information is difficult to obtain when amalgam is still present in the teeth.

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Mechanisms of metal transport across liver cell plasma membranes. Ballatori N. Drug Metab Rev. 1991; 23(1-2):83-132. 1868779 PubMed. The liver's pivotal role in the homeostasis of essential trace metals and detoxification of exogenous metals is attributed to its ability to efficiently extract metals from plasma, metabolize, store, and redistribute them in various forms either into bile or back into the bloodstream. Bidirectional transport across the sinusoidal plasma membrane allows the liver to control plasma concentrations and therefore availability to other tissues. In contrast, transport across the canalicular membrane is largely, but not exclusively, unidirectional and is a major excretory pathway. Although each metal has relatively distinct hepatic transport characteristics, some generalizations can be made. First, movement of metals from plasma to bile follows primarily a transcellular route. The roles of the paracellular pathway and of ductular secretion appear minimal. Second, intracellular binding proteins and in particular metallothionein play only indirect roles in transmembrane flux. The amounts of metallothionein normally secreted into plasma and bile are quite small and cannot account for total metal efflux. Third, metals traverse liver cell plasma membranes largely by facilitated diffusion, and by fluid-phase, adsorptive, and receptor-mediated endocytosis/exocytosis. There is currently no evidence for primary active transport. Because of the high rate of hepatocellular membrane turnover, metal transport via endocytic vesicles probably makes a larger contribution than previously recognized. Finally, there is significant overlap in substrate specificity on the putative membrane carriers for the essential trace metals. For example, zinc and copper share many transport characteristics and apparently compete for at least one common transport pathway. Similarly, canalicular transport of five of the metals discussed in this overview (Cu, Zn, Cd, Hg, and Pb) is linked to biliary GSH excretion. These metals may be transported as GSH complexes by the canalicular glutathione transport system(s). Unfortunately, none of the putative membrane carrier proteins have been studied at the subcellular or molecular level. Our knowledge of their biochemical properties is rudimentary and rests almost entirely on indirect evidence obtained in vivo or in intact cell systems. The challenge for the future is to isolate and characterize these putative metal carriers, and to determine how they are functionally regulated.

Mercury in saliva and feces after removal of amalgam fillings. Bjorkman L, Sandborgh-Englund G, Ekstrand J. Toxicol Appl Pharmacol. 1997 May; 144(1):156-62. 9169079 PubMed. The toxicological consequences of exposure to mercury (Hg) from dental amalgam fillings is a matter of debate in several countries. The purpose of this study was to obtain data on Hg concentrations in saliva and feces before and after removal of dental amalgam fillings. In addition Hg concentrations in urine, blood, and plasma were determined. Ten subjects had all amalgam fillings removed at one dental session. Before removal, the median Hg concentration in feces was more than 10 times higher than in samples from an amalgam free reference group consisting of 10 individuals (2.7 vs 0.23 mumol Hg/kg dry weight, p < 0.001). A considerable increase of the Hg concentration in feces 2 days after amalgam removal (median 280 mumol Hg/kg dry weight) was followed by a significant decrease. Sixty days after removal the median Hg concentration was still slightly higher than in samples from the reference group. In plasma, the median Hg concentration was 4 nmol/liter at baseline. Two days after removal the median Hg concentration in plasma was increased to 5 nmol/liter and declined subsequently to 1.3 nmol/liter by Day 60. In saliva, there was an exponential decline in the Hg concentration during the first 2 weeks after amalgam removal (t 1/2 = 1.8 days). It was concluded that amalgam fillings are a significant source of Hg in saliva and feces. Hg levels in all media decrease considerably after amalgam removal. The uptake of amalgam mercury in the GI tract in conjunction with removal of amalgam fillings seems to be low.

Speciation of mercury excreted in feces from individuals with amalgam fillings. Engqvist A, Colmsjo A, Skare I. Arch Environ Health. 1998 May-Jun; 53(3):205-13. 9814717 PubMed. Investigators established methods for the analysis of total mercury (Hg-total), oxidized mercury and mercury bound to sulfhydryl groups (Hg-S), mercury vapor (Hg0), and mercury from amalgam particles (APs) in fecal samples. Two individuals consumed mercury as a mercury-cysteine complex mercury vapor, and mercury from amalgam particles, and the cumulative excretion of mercury in feces was followed. Investigators found that 80% of the mercury from amalgam particles and mercury bound to sulfhydryl groups was excreted, but only 40% of the mercury vapor was excreted. Speciation of mercury excreted in feces from 6 individuals with a moderate loading of amalgam fillings showed that most of the mercury originating from the fillings consisted of oxidized mercury, which was probably bound to sulfhydryl-containing compounds. The proportion of amalgam particles in fecal samples from these individuals was low, and it did not exceed 26% of the total amount of mercury excreted.

The kinetics of intravenously administered methyl mercury in man. Smith JC, Allen PV, Turner MD, Most B, Fisher HL, Hall LL. Toxicol Appl Pharmacol. 1994 Oct; 128(2):251-6. 7940540 PubMed. The blood contained predominantly methyl mercury, while the excreta contained principally inorganic mercury. The behavior of both methyl mercury and inorganic mercury in the body was modeled with the simplest compartmental model which fit the data. This five-compartment model shows that inorganic mercury accumulates in the body and at longer times is the predominant form of mercury present.

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Fetus, Baby, and Child

A prospective study of prenatal mercury exposure from maternal dental amalgams and autism severity. Geier DA, Kern JK, Geier MR. Acta Neurobiol Exp (Wars). 2009;69(2):189-97. Dental amalgams containing 50% mercury (Hg) have been used in dentistry for the last 150 years, and Hg exposure during key developmental periods was associated with autism spectrum disorders (ASDs). This study examined increased Hg exposure from maternal dental amalgams during pregnancy among 100 qualifying participants born between 1990-1999 and diagnosed with DSM-IV autism (severe) or ASD (mild) Subjects with more than 6 amalgams were 3.2-fold significantly more likely to be diagnosed with autism (severe) in comparison to ASD (mild) than subjects with 5 or fewer amalgams. Dental amalgam policies should consider Hg exposure in women before and during the child-bearing age and the possibility of subsequent fetal exposure and adverse outcomes. 19593333 PubMed.

 

A Child with elemental mercury poisoning and unusual brain MRI findings. Abbaslou, P, et al. Clin Toxicol (Phila). 2006;44(1):85-8. 16496500 Mercury vapor poisoning is a serious and potentially fatal problem. Neurological manifestations involving the central nervous system are seen with chronic mercury intoxication. We present the case of a 10-year-old child who demonstrated acrodynia, seizures, and visual impairment following 20 days of exposure to elemental mercury at home. The initial blood mercury concentration was 27.7 microg/L (normal <2 microg/L) and the initial 24-hour urine mercury concentration was 34.4 microg/L (normal =10 microg/L). After 9 months of treatment with D-penicillamine, the patient's clinical condition, biochemical laboratory parameters, and mercury concentrations all returned to normal. The T2-weighted MRI images of the patient's brain initially showed multiple hyperintense lesions in cerebral white matter, left globus pallidus, and putamen, which also improved.

Behavioral consequences of in utero exposure to mercury vapor: alterations in lever-press durations and learning in squirrel monkeys. Newland MC, Warfvinge K, Berlin M. Toxicol Appl Pharmacol. 1996 Aug;139(2):374-86. 8806855 PubMed. Exposed monkeys were found to produce smaller or slower transitions than controls. The magnitude and stability of lever-press durations for controls and exposed monkeys were indistinguishable early in the experiment, but at the end the exposed monkeys had longer lever-press durations and the session-to-session variability was much greater. One monkey's exposure began during the third week of gestation (earlier than any of the others) and the behavior of this monkey was so erratic that some of the analyses could not be accomplished. Long-term effects of prenatal mercury vapor exposure included instability in lever-press durations and steady-state performance under concurrent schedules of reinforcement as well as aberrant transitions. The levels used were close to those reported in occupational settings under conditions of poor hygiene, but were at least 10- to 50-fold greater than those more commonly reported.

Behavioural effects of prenatal metallic mercury inhalation exposure in rats. Danielsson BR, Fredriksson A, Dahlgren L, Gardlund AT, Olsson L, Dencker L, Archer T. Neurotoxicol Teratol. 1993 Nov-Dec; 15(6):391-6. 8302240 PubMed. The effects of administration by inhalation of metallic mercury vapour (Hg0) to pregnant rats, approximately corresponding to doses of 0.2 mg Hg0/kg/day (high dose) or 0.07 mg Hg0/kg/day (low dose), on the developmental and behavioural repertoire of the offspring were studied. A simple test of learning, habituation to a novel environment (activity chambers), indicated a reduced ability to adapt. These data suggest that prenatal exposure to Hg0 vapour results in similar behaviour changes in the offspring as reported for methylmercury.

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Breast-feeding exposure of infants to cadmium, lead, and mercury: a public health viewpoint. Abadin HG, Hibbs BF, Pohl HR. Toxicol Ind Health. 1997 Jul-Aug;13(4):495-517. 9249931 PubMed. Women exposed environmentally or occupationally can have higher levels in their breast milk. Concentrations of about 5 micrograms/L (cadmium), 20 micrograms/L (lead), and 3.5 micrograms/L (mercury) appear to be adequate screening levels. Many factors affect both the distribution of cadmium, lead, and mercury in breast milk and the health consequences to an infant. It is not clear what additional impact low-level exposure via breast milk may have on an infant born with a body burden to one of these metals. There is sufficient evidence to make the case that contaminated breast milk is a source of potential risk to infants in certain populations. Prevention strategies that include behavior modification and proper nutrition should be communicated to women at risk. Identification and elimination of exposure pathways and a critical analysis of the benefits of breast feeding versus heavy metal exposure are needed on a site-specific or individual basis. Research is required to better understand the impact of low-level exposure to heavy metals via breast milk. Breastfeeding should be encouraged under most circumstances.

Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Grandjean P, Weihe P, White RF, Debes F, Araki S, Yokoyama K, Murata K, Sorensen N, Dahl R, Jorgensen PJ. Neurotoxicol Teratol. 1997 Nov-Dec; 19(6):417-28. 9392777 PubMed. However, mercury-related neuropsychological dysfunctions were most pronounced in the domains of language, attention, and memory, and to a lesser extent in visuospatial and motor functions. The effects on brain function associated with prenatal methylmercury exposure therefore appear widespread, and early dysfunction is detectable at exposure levels currently considered safe.

Comparison of mercury levels in maternal blood, fetal cord blood, and placental tissues. Kuhnert PM, Kuhnert BR, Erhard P. Am J Obstet Gynecol. 1981 Jan 15; 139(2):209-13. 7457537 PubMed. From our data it is clear that methyl mercury accumulates in cord erythrocytes: A total of 30% more methyl mercury was found in fetal erythrocytes than in maternal erythrocytes. Also correlation analysis of the methyl mercury levels in maternal and fetal erythrocytes showed a strong correlation (r = 0.87). In regard to inorganic mercury, the highest concentration was found in the placenta, suggesting a barrier role, but a significant correlation (r = 0.62) was also found between the maternal and fetal plasma levels of inorganic mercury. Moreover, the inorganic mercury concentration per gram of plasma was higher in fetal cord plasma than in maternal plasma.

Concentrations of heavy metals in maternal and umbilical cord blood. Ong CN, Chia SE, Foo SC, Ong HY, Tsakok M, Liouw P. Biometals. 1993 Spring; 6(1):61-6. 8471826 PubMed. These results suggest that, like essential metals, most heavy metals can move rather freely across the human placenta. The potential health effects of heavy metal transfer from mothers to young infants cannot be discounted.

Concentrations of mercury, cadmium and lead in brain and kidney of second trimester fetuses and infants. Lutz E, Lind B, Herin P, Krakau I, Bui TH, Vahter M. J Trace Elem Med Biol. 1996 Jun;10(2):61-7. 8829128 PubMed. The median concentration of Hg in the brain was 4 micrograms/ kg wet weight in both fetuses and infants (total range < or = 2-23 micrograms/kg). The concentrations of Hg in the kidneys were significantly higher than in brain, median of Hg 6 micrograms/kg (range < or = 5-34 micrograms/kg) in fetuses and 10 micrograms/kg (< or = 7-37) in infants.

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Disposition of inhaled mercury vapor in pregnant rats: maternal toxicity and effects on developmental outcome. Morgan DL, Chanda SM, Price HC, Fernando R, Liu J, Brambila E, O'Connor RW, Beliles RP, Barone S Jr. Toxicol Sci. 2002 Apr;66(2):261-73. 11896293 PubMed. Total Hg concentrations in maternal tissues increased with increasing number of exposure days and concentration. In general, approximately 70% of Hg was eliminated from maternal tissues during the week following the last exposure (GD 15 to PND 1). Elimination of Hg from maternal brain and kidney was slower than in other tissues, possibly due to higher levels of metallothionein. Total Hg concentrations in fetal tissues increased with increasing number of exposure days and concentration, demonstrating that a significant amount of Hg crossed the placenta. One week after the last exposure, significant amounts of Hg were still present in brain, liver, and kidney of PND 1 neonates. The total amount of Hg in neonatal brain (ng/brain) continued to increase after termination of inhalation exposure, suggesting a redistribution of Hg from the dam to neonatal brain. These data demonstrate that inhaled Hg0 vapor is distributed to all maternal and fetal tissues in a dose-dependent manner. Adverse effects of Hg on developmental outcome occurred only at a concentration that caused maternal toxicity.

Distribution and transfer pathways of antioxidant molecules inside the first trimester human gestational sac. Jauniaux E, Cindrova-Davies T, Johns J, Dunster C, Hempstock J, Kelly FJ, Burton GJ. J Clin Endocrinol Metab. 2004 Mar;89(3):1452-8. 15001647 PubMed. The first-trimester human placenta has limited antioxidant enzyme capacity. We investigated the distribution and transfer pathways of antioxidant molecules inside the first trimester gestational sac. The coelomic fluid of the exocoelomic cavity, which borders the inside of the first-trimester placenta, contained a very low level of reduced glutathione. Glutathione disulfide was undetectable in most coelomic samples, suggesting that the role of glutathione-related detoxification system is limited in fetal fluid compartments. The coelomic fluid contained similar concentrations of ascorbic and uric acid to maternal plasma. The levels of alpha- and gamma-tocopherol were lower in coelomic fluid, compared with maternal plasma. The presence of these molecules inside the early gestational sac suggests that they may play an essential role in the fetal tissues' antioxidant capacity at a time when the fetus is most vulnerable to oxidative stress. We also demonstrated by immunostaining the presence of alpha-tocopherol transfer protein in the cytoplasm of trophoblastic cells, glandular epithelium of the decidua, and mesothelial layer of the secondary yolk sac. This finding indicates that the uterine glands and the secondary yolk sac play key roles in supplying this essential vitamin to the developing fetus before the placental circulations are established.

Effect of inorganic mercury on in vitro placental nutrient transfer and oxygen consumption. Urbach J, Boadi W, Brandes JM, Kerner H, Yannai S. Reprod Toxicol. 1992; 6(1):69-75. 1562801 PubMed. The effect of mercury (HgCl2) on placental amino acid and glucose transfer as determined by the use of their nonmetabolizable radioactive analogues, aminoisobutyric acid (AIB) and 3-o-methyl glucose (3MG), respectively, was studied in an in vitro perfusion model of a term human placenta. Hg2+ was found to decrease the transfer and accumulation of AIB without affecting 3MG transfer. It was also found to decrease the placental oxygen consumption rate. Placental circulation and tissue morphology remained intact, as demonstrated by the antipyrine transfer rate, and by electron microscopy, respectively. The mechanism by which Hg2+ may interfere with placental amino acid transfer and accumulation is discussed. Although much higher concentrations than those found in the ordinary polluted environment were used, this is the first report showing that Hg2+ interferes with an essential human placental function in a system employing a whole human placental cotyledon. This finding may indicate the possible involvement of Hg2+ in impaired organogenesis in early pregnancy or deranged fetal growth during the last trimester.

Environmental factors associated with a spectrum of neurodevelopmental deficits. Mendola P, Selevan SG, Gutter S, Rice D. Ment Retard Dev Disabil Res Rev. 2002; 8(3):188-97. 12216063 PubMed. At high levels of prenatal exposure, methylmercury produces mental retardation, cerebral palsy and visual and auditory deficits in children of exposed mothers. Exposure to environmental agents with neurotoxic effects can result in a spectrum of adverse outcomes from severe mental retardation and disability to more subtle changes in function depending on the timing and dose of the chemical agent.

Evolution of our understanding of methylmercury as a health threat. Watanabe C, Satoh H. Environ Health Perspect. 1996 Apr; 104 Suppl 2:367-79. 9182044 PubMed. After repeated occurrences of MeHg poisoning, it gradually became clear that the fetus is much more susceptible to the toxicity of this compound than the adult. The results of these studies revealed that the effects encompass a wide range of behavioral categories without clear identification of the functional categories distinctively susceptible to MeHg.

 
Glutathione S-transferases and thiol concentrations in embryonic and early fetal tissues. Raijmakers MT, Steegers EA, Peters WH. Hum Reprod. 2001 Nov;16(11):2445-50. Department of Gastroenterology, University Hospital St Radboud, Nijmegen, The Netherlands. 11679536 PubMed. BACKGROUND: Glutathione S-transferases (GSTs) are important in intracellular binding and transport of numerous compounds, and play a central role in human detoxification processes. Human GSTs mainly consist of class Pi (GSTP), Mu (GSTM), Alpha (GSTA) and Theta (GSTT) enzymes, each subdivided into one or more isoenzymes. They catalyse the conjugation of glutathione (GSH) to toxic compounds, resulting in more water-soluble and less biologically active products that may be easily excreted. The reactive -SH group in GSH is provided by cysteine, an important amino acid in GSH synthesis. METHODS: GST expression, enzyme activity and concentrations of cysteine and GSH in cytosolic fractions of organs from an embryo and a fetus at 8 and 13 weeks gestational age respectively were investigated. RESULTS: GSTP1 was predominantly present in all tissues of both the embryo and fetus. GSTA (GSTA1 + GSTA2) concentrations were moderate as compared with GSTP1, whereas GSTM1 was present in only low amounts. GSTT1 was not detected in any tissue. GST activity was highest in organs exposed directly to amniotic fluid. In all embryonic and fetal organs, considerable amounts of GSH and cysteine were detected, with higher GSH concentrations in organs where lower cysteine concentrations were demonstrated. CONCLUSIONS: These results suggest that in embryonic and early fetal development cysteine, GSH and GSTs are present in high amounts, and that GSTP1 is the most important GST isoform at these developmental stages.

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Influence of prenatal mercury exposure upon scholastic and psychological test performance: benchmark analysis of a New Zealand cohort. Crump KS, Kjellstrom T, Shipp AM, Silvers A, Stewart A. Risk Anal. 1998 Dec; 18(6):701-13. 9972579 PubMed. The original analyses of five test scores found an association between high prenatal mercury exposure and decreased test performance, using category variables for mercury exposure. Our regression analyses, which utilized the actual hair mercury level, did not find significant associations between mercury and children's test scores. However, this finding was highly influenced by a single child whose mother's mercury hair level (86 mg/kg) was more than four times that of any other mother. When that child was omitted, results were more indicative of a mercury effect and scores on six tests were significantly associated with the mothers' hair mercury level. BMDs calculated from five tests ranged from 32 to 73 mg/kg hair mercury, and corresponding BMDLs (95% lower limits on BMDs) ranged from 17 to 24 mg/kg.

Intrauterine methylmercury intoxication. Consequence of the inherent brain lesions and cognitive dysfunction in maturity. Kakita A, Wakabayashi K, Su M, Yoneoka Y, Sakamoto M, Ikuta F, Takahashi H. Brain Res. 2000 Sep 22; 877(2):322-30. 10986347 PubMed. Morphometric analysis of the amygdala and hippocampus revealed significantly fewer neurons in both areas in the MeHg-exposed rats. Thus, chronic intrauterine exposure to low-dose MeHg induces a decrease in neuron population in the limbic system, and the offspring have impaired higher brain function.

In vitro effect of mercury on enzyme activities and its accumulation in the first-trimester human placenta. Boadi WY, Urbach J, Brandes JM, Yannai S. Environ Res. 1992 Feb; 57(1):96-106. 1740099 PubMed. The data suggest that contamination with low Hg levels from the environment during pregnancy may affect placental enzymatic activity. The accumulation of Hg during short incubation indicates a strong placental cell affinity for Hg, which could affect its other metabolic functions. The system used in sensitive, as it shows alteration in enzyme activity even with relatively low concentrations of the metal and the response is dose-related.

Longitudinal study of methylmercury and inorganic mercury in blood and urine of pregnant and lactating women, as well as in umbilical cord blood. Vahter M, Akesson A, Lind B, Bjors U, Schutz A, Berglund M. Environ Res. 2000 Oct ;84(2):186-94. 11068932 PubMed. We have investigated exposure to methylmercury (MeHg) and mercury vapor (Hg0) in pregnant women and their newborns in Stockholm. The women were followed for 15 months post delivery. MeHg, inorganic Hg (I-Hg), and total Hg (T-Hg) in maternal and cord blood were determined by automated alkaline solubilization/reduction and cold vapor atomic fluorescence spectrometry. T-Hg in urine was determined by inductively coupled plasma mass spectrometry. About 72% of the Hg in blood (n = 148) in early pregnancy was MeHg (median 0.94 microg/L, maximum 6.8 microg/L). Blood MeHg decreased during pregnancy, partly due to decreased intake of fish in accordance with recommendations to not eat certain predatory fish during pregnancy. Cord blood MeHg (median 1.4 microg/L, maximum 4.8 microg/L) was almost twice that in maternal blood in late pregnancy and was probably influenced by maternal MeHg exposure earlier and before pregnancy. Blood I-Hg (median 0.37 microg/L, maximum 4.2 microg/L) and urine T-Hg (median 1.6 microg/L, maximum 12 microg/L) in early pregnancy were highly correlated, and both were associated with the number of amalgam fillings. The concentrations decreased during lactation, probably due to excretion in milk. Cord blood I-Hg was correlated with that in maternal blood. The results show the importance of speciation of Hg in blood for evaluation of exposure and health risks.

Maternal amalgam dental fillings as the source of mercury exposure in developing fetus and newborn. Palkovicova, L et al.. J Expo Sci Environ Epidemiol. 2007 Sep 12; 17851449 Dental amalgam is a mercury-based filling containing approximately 50% of metallic mercury (Hg(0)). Human placenta does not represent a real barrier to the transport of Hg(0); hence, fetal exposure occurs as a result of maternal exposure to Hg, with possible subsequent neurodevelopmental disabilities in infants. This study represents a substudy of the international NIH-funded project "Early Childhood Development and polychlorinated biphenyls Exposure in Slovakia". The main aim of this analysis was to assess the relationship between maternal dental amalgam fillings and exposure of the developing fetus to Hg. The study subjects were mother-child pairs (N=99). Questionnaires were administered after delivery, and chemical analyses of Hg were performed in the samples of maternal and cord blood using atomic absorption spectrometry with amalgamation technique. The median values of Hg concentrations were 0.63 mug/l (range 0.14-2.9 mug/l) and 0.80 mug/l (range 0.15-2.54 mug/l) for maternal and cord blood, respectively. None of the cord blood Hg concentrations reached the level considered to be hazardous for neurodevelopmental effects in children exposed to Hg in utero (EPA reference dose for Hg of 5.8 mug/l in cord blood). A strong positive correlation between maternal and cord blood Hg levels was found (rho=0.79; P<0.001). Levels of Hg in the cord blood were significantly associated with the number of maternal amalgam fillings (rho=0.46, P<0.001) and with the number of years since the last filling (rho=-0.37, P<0.001); these associations remained significant after adjustment for maternal age and education. Dental amalgam fillings in girls and women of reproductive age should be used with caution, to avoid increased prenatal Hg exposure.

Maternal-fetal distribution of mercury (203Hg) released from dental amalgam fillings. Vimy MJ, Takahashi Y, Lorscheider FL. Am J Physiol. 1990 Apr; 258(4 Pt 2):R939-45. 2331037 PubMed. In humans, the continuous release of Hg vapor from dental amalgam tooth restorations is markedly increased for prolonged periods after chewing. The present study establishes a time-course distribution for amalgam Hg in body tissues of adult and fetal sheep. Under general anesthesia, five pregnant ewes had twelve occlusal amalgam fillings containing radioactive 203Hg placed in teeth at 112 days gestation. Blood, amniotic fluid, feces, and urine specimens were collected at 1- to 3-day intervals for 16 days. From days 16-140 after amalgam placement (16-41 days for fetal lambs), tissue specimens were analyzed for radioactivity, and total Hg concentrations were calculated. Results demonstrate that Hg from dental amalgam will appear in maternal and fetal blood and amniotic fluid within 2 days after placement of amalgam tooth restorations. Excretion of some of this Hg will also commence within 2 days. All tissues examined displayed Hg accumulation. Highest concentrations of Hg from amalgam in the adult occurred in kidney and liver, whereas in the fetus the highest amalgam Hg concentrations appeared in liver and pituitary gland. The placenta progressively concentrated Hg as gestation advanced to term, and milk concentration of amalgam Hg postpartum provides a potential source of Hg exposure to the newborn. It is concluded that accumulation of amalgam Hg progresses in maternal and fetal tissues to a steady state with advancing gestation and is maintained. Dental amalgam usage as a tooth restorative material in pregnant women and children should be reconsidered.

Maternal-fetal transfer of metallic mercury via the placenta and milk. Yang J, Jiang Z, Wang Y, Qureshi IA, Wu XD. Ann Clin Lab Sci. 1997 Mar-Apr; 27(2):135-41. 9098513 PubMed. Therefore, this study concluded that the metallic mercury can be transferred to the fetus via the placenta and secreted to a newborn via milk.

Mercury and selenium concentrations in maternal and neonatal scalp hair: relationship to amalgam-based dental treatment received during pregnancy. Razagui IB, Haswell SJ. Biol Trace Elem Res. 2001 Jul; 81(1):1-19. 11508328 PubMed. The data from this preliminary study suggest that amalgam-based dental treatment during pregnancy is associated with higher prenatal exposure to mercury, particularly in cases of amalgam removal and replacement. The ability of a peripheral biological tissue, such as hair, to elicit such marked differences in neonatal mercury concentrations provides supporting evidence of high fetal susceptibility to this form of mercury exposure. The data are discussed in relation to the differences between maternal and fetal mercury metabolisms and to mercury-selenium metabolic intereactions in response to mercury exposure.

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Mercury burden of human fetal and infant tissues. Drasch G, Schupp I, Hofl H, Reinke R, Roider G. Eur J Pediatr. 1994 Aug; 153(8):607-10. 7957411 PubMed. The total mercury concentrations in the liver (Hg-L), the kidney cortex (Hg-K) and the cerebral cortex (Hg-C) of 108 children aged 1 day-5 years, and the Hg-K and Hg-L of 46 fetuses were determined. As far as possible, the mothers were interviewed and their dental status was recorded. The results were compared to mercury concentrations in the tissues of adults from the same geographical area. The Hg-K (n = 38) and Hg-L (n = 40) of fetuses and Hg-K (n = 35) and Hg-C (n = 35) of older infants (11-50 weeks of life) correlated significantly with the number of dental amalgam fillings of the mother. The toxicological relevance of the unexpected high Hg-K of older infants from mothers with higher numbers of dental amalgam fillings is discussed. CONCLUSION: Future discussion on the pros and cons of dental amalgam should not be limited to adults or children with their own amalgam fillings, but also include fetal exposure. The unrestricted application of amalgam for dental restorations in women before and during the child-bearing age should be reconsidered.

Mercury distribution in cortical areas and fiber systems of the neonatal and maternal adult cerebrum after exposure of pregnant squirrel monkeys to mercury vapor. Warfvinge K, Hua J, Logdberg B. Environ Res. 1994 Nov;67(2):196-208. 7982394 PubMed. Mapping of the distribution of mercury in the neocortical layers of the maternal brains revealed that the pyramidal cells contained more visualized mercury than the other neurons. In addition, the mapping disclosed that the deeper the pyramidal cells were situated the more mercury they contained. In the offspring brains, no laminar distribution pattern was found. In the hippocampal formation, the pyramidal cells again contained more mercury than the other neurons. By contrast, the stratum granulosa of the dentate gyrus was always devoid of visualized mercury. The claustrum and the amygdaloid complex always contained mercury. In the fiber systems, the offspring brains contained more mercury than the adult brains. Mercury was found in both glial cells and neurons both in the cortical areas and in the fiber systems.

Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children. Dufault R, Schnoll R, Lukiw WJ, Leblanc B, Cornett C, Patrick L, Wallinga D, Gilbert SG, Crider R. Behav Brain Funct. 2009 Oct 27;5:44. 19860886 PubMed. Among dietary factors, learning and behavior are influenced not only by nutrients, but also by exposure to toxic food contaminants such as mercury that can disrupt metabolic processes and alter neuronal plasticity. Neurons lacking in plasticity are a factor in neurodevelopmental disorders such as autism and mental retardation. Essential nutrients help maintain normal neuronal plasticity. Nutritional deficiencies, including deficiencies in the long chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, the amino acid methionine, and the trace minerals zinc and selenium, have been shown to influence neuronal function and produce defects in neuronal plasticity, as well as impact behavior in children with attention deficit hyperactivity disorder. Nutritional deficiencies and mercury exposure have been shown to alter neuronal function and increase oxidative stress among children with autism. These dietary factors may be directly related to the development of behavior disorders and learning disabilities. Mercury, either individually or in concert with other factors, may be harmful if ingested in above average amounts or by sensitive individuals. High fructose corn syrup has been shown to contain trace amounts of mercury as a result of some manufacturing processes, and its consumption can also lead to zinc loss. Consumption of certain artificial food color additives has also been shown to lead to zinc deficiency. Dietary zinc is essential for maintaining the metabolic processes required for mercury elimination. Since high fructose corn syrup and artificial food color additives are common ingredients in many foodstuffs, their consumption should be considered in those individuals with nutritional deficits such as zinc deficiency or who are allergic or sensitive to the effects of mercury or unable to effectively metabolize and eliminate it from the body.

Mercury exposure and child development outcomes. Davidson PW, Myers GJ, Weiss B. Pediatrics. 2004 Apr;113(4 Suppl):1023-9. 15060195 PubMed. Mercury is ubiquitous in the global environment, ensuring universal exposure. Some forms of mercury are especially neurotoxic, including clinical signs at high doses. However, typical human exposures occur at low to moderate doses. Only limited data about neurotoxicity at low doses are available, and scientists differ in their interpretation. Dose-response data on neurodevelopment are particularly limited. Despite or perhaps because of the lack of sufficient or consistent scientific data, public concern about a link between mercury exposure and developmental disabilities has been rising. After reviewing the data, the US Environmental Protection Agency proposed a reference dose (an estimate of a daily dose that is likely to be without a risk of adverse effects over a lifetime) for methyl mercury that is substantially lower than previous guidelines from the World Health Organization, the US Agency for Toxic Substances and Disease Registry, and the US Food and Drug Administration. Some questions have been raised about the Environmental Protection Agency's guidelines, but the issue remains unresolved. Meanwhile, consumer groups have raised questions about the potential link between mercury exposure and autism spectrum disorders as well as other adverse neurodevelopmental outcomes. This hypothesis has prompted some parents to seek regulatory, legal, or medical remedies in the absence of firm evidence. This article reviews what is known about mercury neurotoxicity and neurodevelopmental risk. Our intent is to focus the debate about mercury on 1) additional research that should be sought and 2) defining the principal issues that public policy makers face.

Mercury in human colostrum and early breast milk. Its dependence on dental amalgam and other factors. Drasch G, Aigner S, Roider G, Staiger F, Lipowsky G. J Trace Elem Med Biol. 1998 Mar; 12(1):23-7. 9638609 PubMed. The Hg-M in the breast milk samples correlates positively with the number of maternal teeth with dental amalgam. The mean Hg-M of amalgam-free mothers was < 0.2 microgram/L, while milk from mothers with 1-4 amalgam fillings contained 0.57 microgram/L, with 5-7 fillings 0.50 microgram/L and with more than 7 fillings 2.11 micrograms/L.

Mercury in the Umbilical Cord: Implications for Risk Assessment for Minamata Disease. Dalgard C, Grandjean P, Jorgensen PJ, Weihe P. Environ Health Perspect. 1994 Jun; 102(6-7):548-50. 9679113 PubMed. These levels agree well with other evidence of susceptibility of the fetus to increased exposure to methylmercury.

Mercury levels in maternal and cord blood and attained weight through the 24months of life. Kim BM, Lee BE, Hong YC, Park H, Ha M, Kim YJ, Kim Y, Chang N, Kim BN, Oh SY, Yoo M, Ha EH. Sci Total Environ. 2011 Dec 1;410(411):26-33. Epub 2011 Oct 15. 22000783 PubMed. Birth weight is a strong determinant of attained weight at early ages. Until now, many studies have reported that low birth weight corresponds with high mercury levels. However, the relationship between mercury exposure and attained weight of infant has not been well studied. Therefore, the aim of the present study was to assess the degree of prenatal exposure to mercury by measuring the total mercury levels in maternal and cord blood, and examine the relationship between the mercury level during pregnancy and the attained weight of infant during the first 24months of life. The prospective cohort study of Mothers and Children's Environmental Health (MOCEH) was built up in 2006, and 921 mother-infant pairs were recruited. Information on the socio-demographic characteristics, health behavior and environmental exposure were collected from an interview with trained nurses. After delivery, infants and mothers were followed up at 6, 12 and 24months and the weights of the infants were measured. The mercury concentrations in the late maternal blood (β=-0.19. p=0.05) and cord blood (β=-0.36. p=0.01) were negatively associated with the infants' attained weight over the first 24months of age. The infants' attained weight in the small for their gestational age (SGA) group was lower than the normal birth weight group at the highest quartile of the mercury level. Therefore, efforts should be made to reduce the mercury level in the maternal blood at late pregnancy and cord blood. Further research on the possible harmful effects of prenatal mercury exposure on postnatal growth is recommended.

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Methyl mercury and inorganic mercury in Swedish pregnant women and in cord blood: influence of fish consumption. Bjornberg KA, Vahter M, Petersson-Grawe K, Glynn A, Cnattingius S, Darnerud PO, Atuma S, Aune M, Becker W, Berglund M. Environ Health Perspect. 2003 Apr; 111(4):637-41. 12676628 PubMed. Inorganic mercury (I-Hg) in cord blood (median 0.15 microg/L; range 0.03-0.53 microg/L) increased significantly with increasing number of maternal dental amalgam fillings.

Monitoring methylmercury during pregnancy: maternal hair predicts fetal brain exposure. Cernichiari E, Brewer R, Myers GJ, Marsh DO, Lapham LW, Cox C, Shamlaye CF, Berlin M, Davidson PW, Clarkson TW. Neurotoxicology. 1995 Winter; 16(4):705-10. 8714874 PubMed. Autopsy brains were obtained from infants dying from a variety of causes within a few days of birth in a population exposed to methylmercury in fish. Infant and maternal blood and hair samples were also obtained. The concentration of total mercury in 6 major brain regions were highly correlated with maternal hair levels. This correlation was confirmed by a sequence of comparisons of maternal hair to maternal blood to infant blood and finally to infant brain. The results lend support to the use of maternal hair in assessing fetal exposure to methylmercury in fish-eating populations.

Neurobehavioral effects of combined prenatal exposure to low-level mercury vapor and methylmercury. Yoshida M, Suzuki M, Satoh M, Yasutake A, Watanabe C. J Toxicol Sci. 2011 Jan;36(1):73-80. 21297343 PubMed. We evaluated the effects of prenatal exposure to low-level mercury (Hg(0)) or methylmercury (MeHg) as well as combined exposure (Hg(0) + MeHg exposure) on the neurobehavioral function of mice. ….However, prenatal exposure to 5 ppm of MeHg affected exploratory activity in the OPF test, and, in particular, male mice were highly sensitive to MeHg. The MeHg and Hg(0) + MeHg exposure groups showed similar neurobehavioral effects. Concerning the effects of prenatal mercury exposure under the conditions of this study, the effects of MeHg exposure may be more marked than those of Hg(0) exposure.

Organic and inorganic mercury in neonatal rat brain after prenatal exposure to methylmercury and mercury vapor. Ishitobi H, et al. Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA. Environ Health Perspect. 2010 Feb;118(2):248. 20123608 Pubmed. Many populations are exposed to multiple species of mercury (Hg), predominantly organic Hg as methylmercury (MeHg) from fish, and inorganic Hg as Hg vapor from dental amalgams. Most of our knowledge of the neurotoxicity of Hg is based on research devoted to studying only one form at a time, mostly MeHg. In this study we investigated the effects of prenatal exposure to MeHg and Hg vapor on Hg concentrations in the brain of neonatal rats. CONCLUSION: This interaction, heretofore not reported, suggests that coexposure to MeHg and Hg vapor at levels relevant to human exposure might elevate neurotoxic risks.

Placental to fetal transfer of mercury and fetotoxicity. Yoshida M. Tohoku J Exp Med. 2002 Feb; 196(2):79-88. 12498319 PubMed. Mercury vapor is known penetrate the placental barrier more easily than inorganic mercury. A relative amount of mercury accumulates in the fetus after exposure of pregnant animals to mercury vapor. Mercury concentration in fetal organs is much lower than that in maternal organs except the liver, and fetal liver shows significantly higher mercury concentrations than maternal liver. In fetal liver, a substantial portion of mercury is bound to metallothionein (MT), which plays an important role as a reservoir of mercury during the prenatal period. The mercury retained in fetal liver is redistributed to other organs, such as the brain and kidney, with diminishing MT levels during postnatal development. Consequently, an increase in mercury concentration in the brain and kidney of the neonate is observed. In studies on animal offspring in utero exposed to mercury vapor, behavioral changes, such as radial arm maze, morris maze and lever-press durations, are observed when the levels of mercury vapor exceed the threshold limit value (TLV).

Placental transfer of mercury in pregnant rats which received dental amalgam restorations. Takahashi Y, Tsuruta S, Arimoto M, Tanaka H, Yoshida M. Toxicology. 2003 Mar 14; 185(1-2):23-33. 12505442 PubMed. The results of the present study demonstrated that mercury vapor released from the amalgam fillings in pregnant rats was distributed to maternal and fetal organs in dose-dependent amounts of the amalgam fillings.

Prenatal coexposure to metallic mercury vapour and methylmercury produce interactive behavioural changes in adult rats. Fredriksson A, Dencker L, Archer T, Danielsson BR. Neurotoxicol Teratol. 1996 Mar-Apr; 18(2):129-34. 8709923 PubMed. Generally, the results indicate that prenatal exposure to Hg degrees causes alterations to both spontaneous and learned behaviours, suggesting some deficit in adaptive functions. Coexposure to MeHg, which by itself did not alter these functions at the dose given in this study, served to significantly aggravate the changes.

Relationship between the prenatal exposure to low-level of mercury and the size of a newborn's cerebellum. Cace IB, et al. J. Med Hypotheses. 2011 Apr;76(4):514-6. Epub 2010 Dec 30. 21195558 PubMed. Exposure to methylmercury at any stage of central nervous system development could induce alterations and result in severe congenital abnormalities. Total mercury level in maternal hair during pregnancy correlates well with blood levels of methylmercury and with total mercury levels in fetal brain. A prospective study has been conducted and a total of 137 childbearing women living at the coastal region with term, normal pregnancies were included and their newborns evaluated by ultrasonography. … However, comparison related to the length of cerebellum shows statistically significant smaller cerebellum in newborns whose mother had hair mercury levels higher than 1 μg/g (Mann-Whitney test: Z = 2329; p = 0.019). Our results lead to a conclusion that prenatal exposure to, what we consider to be, low-levels of methylmercury does influence fetal brain development detected as decreased size of newborn's cerebellum. From a clinical point of view, a question related to the influence of prenatal low-level methylmercury exposure on fetal neurodevelopment remains open. Our further objectives are to direct the research towards performing detailed neuropshychological tests on children at the age of 18 months. Such tests could indicate the presence of subtle neurological or neuropsychological deficits.

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Tagum study II: follow-up study at two years of age after prenatal exposure to mercury. Ramirez GB, Pagulayan O, Akagi H, Francisco Rivera A, Lee LV, Berroya A, Vince Cruz MC, Casintahan D. Pediatrics. 2003 Mar; 111(3):e289-95. 12612286 PubMed. Study suggests that prenatal Hg exposure is correlated with lower scores in neurodevelopmental screening, but more so in the linguistic pathway.

Technical report: Mercury in the environment: Implications for pediatricians. Goldman LR, Shannon MW. American Academy of Pediatrics: Committee on Environmental Health.  Pediatrics. 2001 Jul; 108(1):197-205. 11433078 PubMed. Mercury is a ubiquitous environmental toxin that causes a wide range of adverse health effects in humans. Three forms of mercury (elemental, inorganic, and organic) exist, and each has its own profile of toxicity. Exposure to mercury typically occurs by inhalation or ingestion. Readily absorbed after its inhalation, mercury can be an indoor air pollutant, for example, after spills of elemental mercury in the home; however, industry emissions with resulting ambient air pollution remain the most important source of inhaled mercury. Because fresh-water and ocean fish may contain large amounts of mercury, children and pregnant women can have significant exposure if they consume excessive amounts of fish. The developing fetus and young children are thought to be disproportionately affected by mercury exposure, because many aspects of development, particularly brain maturation, can be disturbed by the presence of mercury. Minimizing mercury exposure is, therefore, essential to optimal child health. This review provides pediatricians with current information on mercury, including environmental sources, toxicity, and treatment and prevention of mercury exposure.

The effect of mercury vapour on cholinergic neurons in the fetal brain: studies on the expression of nerve growth factor and its low- and high-affinity receptors. Soderstrom S, Fredriksson A, Dencker L, Ebendal T. Brain Res Dev Brain Res. 1995 Mar 16;85(1):96-108. 7781173 PubMed. These findings suggest that low levels of prenatal mercury vapour exposure can alter the levels of the NGF and its receptors, indicating neuronal damage and disturbed trophic regulations during development.

The Effect on Pregnancy Outcome and Fetal Brain Development of Prenatal Exposure to Mercury Vapour. Warfinge, K; Berlin, M; Logdberg, B. Neurotoxicology, 15(4), 1994. Fourteen pregnant female squirrel monkeys were exposed to mercury vapour (Hg0) 5 days/week from 57 weeks of gestation until delivery in an exposure chamber. Hg0 exposure varied from 1 mg/m3 for 22 hr/d (1 monkey), 7 hr/d or 4 hr/d to 0.5 mg/m3 for 7 hr/d or 4 hr/d. Hg concentration in maternal blood ranged 0.05-0.09 mcg/g. There was a dose related increase in abortion rate and perinatal mortality in the exposed monkeys compared to unexposed controls. The morphology of perinatally sacrificed or succumbed offspring brains showed signs of migration disturbances such as increased cell density in the cerebral subcortical white matter, abnormal cell collections near the cerebral lateral ventricles. Autometallographically, Hg was preferentially localized in the heterotopic cells and in the verticular aspects of the pseudostratified neuroepithelium. Hg concentration in the brain of exposed offspring ranged 0.01-0.70 mcg/g. Autometallography of the maternal brains revealed that the pyramidal neurons of neocortical layer V contained more visualized Hg than the other neurons. In the offspring brains, Hg was visualized throughout the whole neocortex and no laminar distribution pattern was found. In the fiber systems, the offspring brains contained more Hg than the adult brains. In the cerebellum, the Purkinje cells, the Bergmann glial cells, the astrocytes of the medullary layer and the deep cerebellar nuclei were the main targets, for Hg accumulation in both maternal and offspring brains.

The mercury concentration in breast milk resulting from amalgam fillings and dietary habits. Drexler H, Schaller KH. Environ Res. 1998 May;77(2):124-9. 9600805 PubMed. The concentration of mercury in the breast milk collected immediately after birth showed a significant association with the number of amalgam fillings as well as with the frequency of meals. Urine mercury concentrations correlated with the number of amalgam fillings and amalgam surfaces.

Total and inorganic mercury in breast milk in relation to fish consumption and amalgam in lactating women. Oskarsson A, Schultz A, Skerfving S, Hallen IP, Ohlin B, Lagerkvist BJ. Arch Environ Health. 1996 May-Jun;51(3):234-41. 8687245 PubMed. The concentrations of total mercury and organic mercury (calculated by subtraction of inorganic mercury from total mercury) in blood (r = .59, p = .0006, and r = .56, p = .001; respectively) and total mercury in hair (r = .52, p = .006) were correlated with the estimated recent exposure to methylmercury via intake of fish. A significant correlation was found between levels of total mercury in blood and in milk (r = .66, p = .0001), with milk levels being an average of 27% of the blood levels. There was an association between inorganic mercury in blood and milk (r = .96, p < .0001); the average level of inorganic mercury in milk was 55% of the level of inorganic mercury in blood. The results indicated that there was an efficient transfer of inorganic mercury from blood to milk and that, in this population, mercury from amalgam fillings was the main source of mercury in milk. Exposure of the infant to mercury from breast milk was calculated to range up to 0.3 microg/kg x d, of which approximately one-half was inorganic mercury. This exposure, however, corresponds to approximately one-half the tolerable daily intake for adults recommended by the World Health Organization. We concluded that efforts should be made to decrease mercury burden in fertile women.

The toxicological estimation of the heavy metal content (Cd, Hg, Pb) in food for infants and small children. Schumann K. Z Ernahrungswiss. 1990 Mar; 29(1):54-73. 2185600 PubMed. Hg++ and methyl-Hg can cause Hg encephalopathia, and frequently cause mental retardation in adults. Correspondingly, Hg++ accumulation in the brains of suckling rats is approx. 10 times higher than in grown animals. Milk increases the bioavailability of Hg++. In suckling rats Hg is bound to a greater extent to ligands in the erythrocytes. Methyl-Hg concentrations in breast milk reach 5% of those in maternal plasma and that is a severe hazard for breastfed children of exposed mothers.

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Toxic threats to neurologic development of children. Schettler T. Environ Health Perspect. 2001 Dec;109 Suppl 6:813-6. 11744499 PubMed. Learning disabilities, attention deficit hyperactivity disorder, developmental delays, and emotional and behavioral problems are among childhood disabilities of increasing concern. Interacting genetic, environmental, and social factors are important determinants of childhood brain development and function. For many reasons, however, studying neurodevelopmental vulnerabilities in children is challenging. Moreover, inadequate incidence and trend data interfere with full understanding of the magnitude of the problem. Despite these difficulties, extensive laboratory and clinical studies of several neurodevelopmental toxicants, including lead, mercury, polychlorinated biphenyls, alcohol, and nicotine, demonstrate the unique vulnerability of the developing brain to environmental agents at exposure levels that have no lasting effect in adults. Historically, understanding the effects of these toxicants on the developing brain has emerged slowly while generations of children are exposed to unsafe levels. Unfortunately, with few exceptions, neurodevelopmental toxicity data are missing for most industrial chemicals in widespread use, even when populationwide exposures are documented. The personal, family, and communitywide costs of developmental disabilities are profound. In addition to the need for more research, a preventive public health response requires mitigation of exposures to potential neurodevelopmental toxicants when available evidence establishes the plausibility of harm, despite residual toxicologic uncertainties.

Fish and Food

Evaluation of the dose of mercury in exposed and control subjects. Apostoli P, Colombi A, Buratti M, Elia G, Flore C, Carta P, Ibba A, Cortesi I, Mangili A, Alessio, L. Med Lav. 2002 May-Jun; 93(3):159-75. 12197266 PubMed. The results of the present research confirmed that the U-Hg excretion in non-occupationally exposed subjects is influenced by amalgam dental fillings. Furthermore, in our study Hg urinary excretion was significantly related with fish consumption. This fact can be explained, according to several recent experimental human and animal trials, considering that methylmercury contained in fish is partially converted, through breakage of the carbon-Hg bond, into Hg inorganic forms, which accumulate in the kidney and have a urinary excretion pathway.

Low level methylmercury exposure affects neuropsychological function in adults. Yokoo EM, Valente JG, Grattan L, Schmidt SL, Platt I, Silbergeld EK. Environ Health. 2003 Jun 4; 2(1):8. Epub 2003 Jun 04. 12844364 PubMed. This study suggests that adults exposed to MeHg may be at risk for deficits in neurocognitive function. The functions disrupted in adults, namely attention, fine-motor function and verbal memory, are similar to some of those previously reported in children with prenatal exposures.

Neurotoxicity of organomercurial compounds. Sanfeliu C, Sebastia J, Cristofol R, Rodriguez-Farre E. Neurotox Res. 2003; 5(4):283-305. 12835120 PubMed. Mercury is a ubiquitous contaminant, and a range of chemical species is generated by human activity and natural environmental change. Elemental mercury and its inorganic and organic compounds have different toxic properties, but all them are considered hazardous in human exposure. In an equimolecular exposure basis, organomercurials with a short aliphatic chain are the most harmful compounds and they may cause irreversible damage to the nervous system. Methylmercury (CH(3)Hg(+)) is the most studied following the neurotoxic outbreaks identified as Minamata disease and the Iraq poisoning. The first description of the CNS pathology dates from 1954. Since then, the clinical neurology, the neuropathology and the mechanisms of neurotoxicity of organomercurials have been widely studied. The high thiol reactivity of CH(3)Hg(+), as well as all mercury compounds, has been suggested to be the basis of their harmful biological effects. However, there is clear selectivity of CH(3)Hg(+) for specific cell types and brain structures, which is not yet fully understood. The main mechanisms involved are inhibition of protein synthesis, microtubule disruption, increase of intracellular Ca(2+) with disturbance of neurotransmitter function, oxidative stress and triggering of excitotoxicity mechanisms. The effects are more damaging during CNS development, leading to alterations of the structure and functionality of the nervous system. The major source of CH(3)Hg(+) exposure is the consumption of fish and, therefore, its intake is practically unavoidable. The present concern is on the study of the effects of low level exposure to CH(3)Hg(+) on human neurodevelopment, with a view to establishing a safe daily intake. Recommendations are 0.4 micro g/kg body weight/day by the WHO and US FDA and, recently, 0.1 micro g/kg body weight/day by the US EPA. Unfortunately, these levels are easily attained with few meals of fish per week, depending on the source of the fish and its position in the food chain.

Sub-clinical neurobehavioral abnormalities associated with low level of mercury exposure through fish consumption. Carta P, Flore C, Alinovi R, Ibba A, Tocco MG, Aru G, Carta R, Girei E, Mutti A, Lucchini R, Randaccio FS. Neurotoxicology. 2003 Aug; 24(4-5):617-23. 12900074 PubMed. In order to assess early neurotoxic effects associated with relatively low levels of mercury absorbed through fish eating, two groups of 22 adult male subjects, habitual consumers of tuna fish, and 22 controls were examined using a cross-sectional field study. The assessment included neurobehavioral tests of vigilance and psychomotor function, hand tremor measurements and serum prolactin assessment. Mercury in urine (U-Hg) and serum prolactin (sPRL) were measured in all exposed subjects and controls, whereas measurements of the organic component of mercury in blood (O-Hg) were available for only 10 exposed and six controls. U-Hg was significant higher among exposed subjects (median 6.5 microg/g of creatinine, range 1.8-21.5) than controls (median 1.5 microg/g of creatinine, range 0.5-5.3). The median values of O-Hg were 41.5 microg/l among the tuna fish eaters and 2.6 microg/l in the control group. Both U-Hg and O-Hg were significantly correlated with the quantity of fish consumed per week. Significant differences in sPRL were found between exposed (12.6 ng/ml) and controls (9.1 ng/ml). Individual sPRL were significantly correlated with both U-Hg and O-Hg levels. The neurobehavioral performance of subjects who consumed tuna fish regularly was significantly worse on color word reaction time, digit symbol reaction time and finger tapping speed (FT). After considering the education level and other covariates, the multiple stepwise regression analysis indicated that O-Hg concentration was most significantly associated with individual performance on these tests, accounting for about 65% of the variance in test scores.

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Free Radicals

Accumulation of mercury and its effect on antioxidant enzymes in brain, liver, and kidneys of mice. Hussain S, Atkinson A, Thompson SJ, Khan AT. J Environ Sci Health B. 1999 Jul;34(4):645-60. 10390852 PubMed. Mercury is known to generate reactive oxygen species (ROS) in vivo and in vitro, therefore, it is likely that enzyme activities increased to scavenge ROS levels produced as a result of mercury accumulation. Glutathione content increased in liver and kidneys of mercury treated mice compare to control. The results showed that the highest oral dose of mercury significantly increased antioxidant enzymes in kidneys and liver. The increased antioxidant enzymes enhance the antioxidant potential of the organs to reduce oxidative stress.

Activated human T lymphocytes exhibit reduced susceptibility to methylmercury chloride-induced apoptosis. Close AH, Guo TL, Shenker BJ. Toxicol Sci. 1999 May;49(1):68-77. 10367343 PubMed. Mercurials have been shown to cause apoptosis in human T cells. The objective of this study was to evaluate and compare the relative susceptibility of resting versus activated T cells to methyl mercury chloride (MeHgCl)-induced cell death. Apoptosis was assessed by Hoechst 33258 and 7-AAD staining and annexin V binding. Our results show that activation of T cells by PHA, PMA, and ionomycin, or IL-2, reduces mercury-induced apoptosis by approximately 50%. We have previously shown that the underlying basis for these toxic effects involves perturbation of mitochondrial function leading to oxidative stress and the release of cytochrome c to the cytosol. Therefore, the ability of MeHgCl to alter the mitochondrial transmembrane potential (delta psi m) and to induce the generation of reactive oxygen species (ROS) was evaluated in activated T-cells. Both resting and activated cells treated with MeHgCl exhibited a decrease in delta psi m when compared to respective control cells. ROS production was elevated in resting cells following treatment with mercury; in contrast, fewer activated T cells exhibit increased levels of ROS in the presence of MeHgCl. Similarly, MeHgCl treatment resulted in the release of cytochrome c to the cytoplasm in non-activated T cells but failed to do so in the activated population. These results lead us to examine intracellular levels of bcl-2, a protein that has been shown to regulate apoptosis, presumably via its ability to associate with the mitochondrial membrane. Bcl-2 levels were found, in resting cells, to be low in the presence or absence of mercury. In comparison, activated T cells expressed elevated levels of bcl-2. The relationship between mercury-induced apoptosis in human T cells, mitochondrial dysfunction, and intracellular levels of bcl-2 are discussed.

Cytotoxicity of inorganic mercury in murine T and B lymphoma cell lines: involvement of reactive oxygen species, Ca(2+) homeostasis, and cytokine gene expression. Kim SH, Sharma RP. Toxicol In Vitro. 2003 Aug; 17(4):385-95. 12849721 PubMed. Mercury is a highly toxic heavy metal; exposure to mercury in humans and animals causes damage in several organs or systems including the immune system. To characterize the toxicity of mercury in the immune cells, the cytotoxic effects of inorganic mercury were studied in two distinct lymphoma lines, the murine T lymphoma (EL4) and B lymphoma (A20) cells. Mercury concentration-dependently decreased cell viability, membrane integrity, and proliferation in both EL4 and A20 cells. Mercury increased the reactive oxygen species (ROS) production in both EL4 and A20 cells, and pretreatment with antioxidants reversed mercury-induced ROS generation.

Mercuric compounds inhibit human monocyte function by inducing apoptosis: evidence for formation of reactive oxygen species, development of mitochondrial membrane permeability transition and loss of reductive reserve. InSug O, Datar S, Koch CJ, Shapiro IM, Shenker BJ. Toxicology. 1997 Dec 31; 124(3):211-24. 9482123 PubMed. We noted that treated cells generated ROS, as evidenced by oxidation of hydroethidine and the generation of the fluorescent product, ethidium. Finally, since ROS would also lower monocyte reductive reserve, we also measured GSH levels in mercury-treated cells. Chemical measurement of GSH indicated that there was thiol depletion. We suggest that the low thiol reserve predisposes cells to ROS damage and at the same time activates death-signaling pathways.

Mechanism of HgCl2 cytotoxicity in cultured mammalian cells. Cantoni O, Christie NT, Swann A, Drath DB, Costa M. Mol Pharmacol. 1984 Sep; 26(2):360-8. 6090887 PubMed. HgCl2 treatment of cells also caused a rapid leakage of superoxide radicals that were detected in their media by measurement of the reduction of exogenously added cytochrome c. There was a linear relationship between the production of radicals and the induction of DNA strand breaks, and there were also excellent temporal correlations in these parameters.

Mercuric chloride induces a stress response in cultured astrocytes characterized by mitochondrial uptake of iron. Brawer JR, McCarthy GF, Gornitsky M, Frankel D, Mehindate K, Schipper HM. Neurotoxicology. 1998 Dec; 19(6):767-76. 9863766 PubMed. Mercury exerts a variety of toxic effects on both neurons and glia. Mercury induces aberrations in microtubules, ion channels and mitochondria presumably by binding to sulfhydryl groups. Indirect evidence further suggests that mercury targeted to mitochondria may induce iron-catalyzed oxygen radical production. We have previously shown that the mitochondria of astrocytes subjected to oxidative stress accumulate redox active transition metals that may catalyze the formation of cytotoxic oxygen free radicals. In the present study we have investigated the effect of mercuric chloride on astrocytes in monolayer culture in order to determine whether mercury accumulates in astrocytic mitochondria and whether mercury exposure triggers a stress response-associated uptake of iron. Our results indicate that mercuric chloride exposure initiates the constellation of changes in mitochondrial structure that typifies the response of these cells to oxidative stress. Energy dispersive Xray microspectroscopy demonstrates that these altered mitochondria concentrate both mercury and iron. Concurrent with these changes, mercuric chloride treatment activates transcription of the heme oxygenase-1 (HO-1) gene in a dose dependent manner, further indicating an oxidative stress response. Thus, mercury-induced stress may transform innocuous astrocytes into potentially lethal sources of cytotoxic oxygen free radicals.

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Mercury-induced H2O2 production and lipid peroxidation in vitro in rat kidney mitochondria. Lund BO, Miller DM, Woods JS. Biochem Pharmacol. 1991 Dec 11; 42 Suppl:S181-7. 1768276 PubMed. These results suggest that Hg(II) at low concentrations depletes mitochondrial GSH and enhances H2O2 formation in kidney mitochondria under conditions of impaired respiratory chain electron transport. The increased H2O2 formation by Hg(II) may lead to oxidative tissue damage, such as lipid peroxidation, observed in mercury-induced nephrotoxicity.

Mercury inhibits nitric oxide production but activates proinflammatory cytokine expression in murine macrophage: differential modulation of NF-kappaB and p38 MAPK signaling pathways. Kim SH, Johnson VJ, Sharma RP.  Nitric Oxide. 2002 Aug; 7(1):67-74. 12175822 PubMed. Mercury is well known to adversely affect the immune system; however, little is known regarding its molecular mechanisms. Macrophages are major producers of nitric oxide (NO) and this signaling molecule is important in the regulation of immune responses. The present study was designed to determine the impact of mercury on NO and cytokine production and to investigate the signaling pathways involved. The murine macrophage cell line J774A.1 was used to study the effects of low-dose inorganic mercury on the production of NO and proinflammatory cytokines. Cells were treated with mercury in the presence or absence of lipopolysaccharide (LPS). Mercury (5-20 microM) dose-dependently decreased the production of NO in LPS-stimulated cells. Concomitant decreases in the expression of inducible nitric oxide synthase (iNOS) mRNA and protein were detected. Treatment of J774A.1 cells with mercury alone did not affect the production of NO nor the expression of iNOS mRNA or protein. Interestingly, mercury alone stimulated the expression of tumor necrosis factor alpha (TNFalpha), and increased LPS-induced TNFalpha and interleukin-6 mRNA expression. Mercury inhibited LPS-induced nuclear translocation of nuclear factor kappaB (NF-kappaB) but had no effect alone. In contrast, mercury activated p38 mitogen-activated protein kinase (p38 MAPK) and additively increased LPS-induced p38 MAPK phosphorylation. These results indicate that mercury suppresses NO synthesis by inhibition of the NF-kappaB pathway and modulates cytokine expression by p38 MAPK activation in J774A.1 macrophage cells.

Microencapsulated iNOS-expressing cells cause tumor suppression in mice. Xu W, Liu L, Charles IG. FASEB J. 2002 Feb;16(2):213-5. Epub 2001 Dec 28. 11772948 PubMed. Macrophages can kill tumor cells by releasing high levels of nitric oxide (NO) and related reactive nitrogen species such as nitroxyl and peroxynitrite, after up-regulation of expression of the inducible nitric oxide synthase gene (iNOS). In this paper we describe two novel human cell lines that are capable of expressing high levels of iNOS under the control of analogues of either the insect hormone ecdysone or tetracycline. We have entrapped these iNOS-expressing cells within a semipermeable alginate-poly-L-lysine membrane as a means of delivery to tumor sites in a nude mouse model. These encapsulated cells can be induced to generate sustainable high concentrations NO and reactive nitrogen species at tumor sites after treatment either with ponasterone A or muristerone A or with doxycycline. Delivery of these iNOS-expressing cells to tumors formed from human ovarian cancer SKOV-3 cells results in 100% killing, whereas treatment of tumors formed from human colon cancer DLD-1 cells results in 54% killing. We show that in these iNOS-expressing cells, tumor killing is associated with concomitant up-regulation of the Fas/FasL proteins.

Mutagenicity of mercury chloride and mechanisms of cellular defence: the role of metal-binding proteins. Schurz F, Sabater-Vilar M, Fink-Gremmels J. Mutagenesis. 2000 Nov; 15(6):525-30. 11077005 PubMed. Hg(2+) increased the intracellular amount of reactive oxygen species. This induction of oxidative stress was observed, although the intracellular glutathione (GSH) and metallothionein (MT) concentrations were increased significantly. Mercury-induced MT expression was even more pronounced after GSH depletion. Correspondingly, radical formation was more evident in the presence of the GSH-depleting agent L-buthioneine-[S:,R:]-sulfoximine. These findings suggest that the observed mutations might be a consequence of oxidative processes, rather than due to a direct interaction of mercury with nuclear DNA. The results also indicate that the auto-induction of MT by Hg(2+) fails to prevent these mutational events.

Oxidative mechanisms in the toxicity of metal ions. Stohs SJ, Bagchi D. Free Radic Biol Med. 1995 Feb; 18(2):321-36. 7744317 PubMed. Cadmium, mercury, and nickel, as well as lead, deplete glutathione and protein-bound sulfhydryl groups, resulting in the production of reactive oxygen species as superoxide ion, hydrogen peroxide, and hydroxyl radical. As a consequence, enhanced lipid peroxidation. DNA damage, and altered calcium and sulfhydryl homeostasis occur. Fenton-like reactions may be commonly associated with most membranous fractions including mitochondria, microsomes, and peroxisomes. Phagocytic cells may be another important source of reactive oxygen species in response to metal ions. Furthermore, various studies have suggested that the ability to generate reactive oxygen species by redox cycling quinones and related compounds may require metal ions. Recent studies have suggested that metal ions may enhance the production of tumor necrosis factor alpha (TNF alpha) and activate protein kinase C, as well as induce the production of stress proteins. Thus, some mechanisms associated with the toxicities of metal ions are very similar to the effects produced by many organic xenobiotics. Specific differences in the toxicities of metal ions may be related to differences in solubilities, absorbability, transport, chemical reactivity, and the complexes that are formed within the body. This review summarizes current studies that have been conducted with transition metal ions as well as lead, regarding the production of reactive oxygen species and oxidative tissue damage.

Stimulating effects of mercuric- and silver ions on the superoxide anion production in human polymorphonuclear leukocytes. Jansson G, Harms-Ringdahl M. Free Radic Res Commun. 1993; 18(2):87-98. 8386687 PubMed. In a survey of a number of heavy metal ions for effects on the oxidative metabolism (respiratory burst) of human polymorphonuclear leukocytes (neutrophils) we have found that mercury (II) and silver ions in micromolar concentration significantly increase the production of superoxide anions in cells.

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Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Ercal N, Gurer-Orhan H, Aykin-Burns N. Curr Top Med Chem. 2001 Dec; 1(6):529-39. 11895129 PubMed. Toxic metals (lead, cadmium, mercury and arsenic) are widely found in our environment. Humans are exposed to these metals from numerous sources, including contaminated air, water, soil and food. Recent studies indicate that transition metals act as catalysts in the oxidative reactions of biological macromolecules therefore the toxicities associated with these metals might be due to oxidative tissue damage. Redox-active metals, such as iron, copper and chromium, undergo redox cycling whereas redox-inactive metals, such as lead, cadmium, mercury and others deplete cells' major antioxidants, particularly thiol-containing antioxidants and enzymes. Either redox-active or redox-inactive metals may cause an increase in production of reactive oxygen species (ROS) such as hydroxyl radical (HO.), superoxide radical (O2.-) or hydrogen peroxide (H2O2). Enhanced generation of ROS can overwhelm cells' intrinsic antioxidant defenses, and result in a condition known as "oxidative stress". Cells under oxidative stress display various dysfunctions due to lesions caused by ROS to lipids, proteins and DNA. Consequently, it is suggested that metal-induced oxidative stress in cells can be partially responsible for the toxic effects of heavy metals. Several studies are underway to determine the effect of antioxidant supplementation following heavy metal exposure. Data suggest that antioxidants may play an important role in abating some hazards of heavy metals.

Galvanic and Corrosion Effects

Acceleration of corrosion of dental amalgam by abrasion. Marek M. J Dent Res. 1984 Jul; 63(7):1010-3. 6588084 PubMed. Dental amalgam shows passive behavior, but the protective film can be destroyed by abrasion. In this study, specimens of both low- and high-copper amalgam were abraded, and the effect on the corrosion behavior was examined. The electrochemical measurements showed that the corrosion rate was substantially increased, and that re-passivation was relatively slow.

Amalgam. III. Mercury release from amalgam restorations. Schuurs AH, Davidson CL. Ned Tijdschr Tandheelkd. 1993 Feb;100(2):45-8. 11822121 PubMed. With regard to the dissolution in saliva, corrosion of the restorations appears to be of importance. The modern amalgams have a lower corrosion rate than older ones but emit probably more mercury vapour.

Corrosion products from dental alloys and effects of mercuric and cupric ions on a neuroeffector system. Moberg LE. Swed Dent J Suppl. 1985;29:1-51. 3866332 PubMed.  In an aggressive solution the corrosion products could increase when amalgams, Co-Cr, and Ni-Cr alloys are in contact with gold alloys, a high-Cu amalgam is in contact with a conventional amalgam, a type III gold alloy is in contact with gold alloys for metallo-ceramic purposes. The high-Cu amalgams released more corrosion products into the saline solution than a conventional one. Greater quantities of corrosion products were released from amalgams at pH 4 than at pH 6. Hg2+ and Cu2+ both had diverse and dose-dependent effects on the guinea-pig ileum. In low concentrations, 10nM, both ions exerted effects, probably on the muscle cell membrane.

Cyclic voltammetry of dental amalgams. Horasawa N, Nakajima H, Ferracane JL, Takahashi S, Okabe T. Dent Mater. 1996 May; 12(3):154-60. 9002857 PubMed. OBJECTIVES: This study used cyclic voltammetry to examine the effect of the composition of dental amalgams on their electrochemical behavior, including reactions occurring outside of oral conditions. METHODS: Amalgams (residual mercury 47.5%) were prepared using two low-copper (3 wt% Cu) powders and five high-copper powders (40-80 wt% Ag, 12-30 wt% Cu) with and without zinc (1.5 wt%). Cyclic voltammograms were obtained at 37 degrees C in 1.0% NaCl scanning at 2 mV/s in the potential range from -1.5 V to +0.8 V vs. Ag/AgCl. RESULTS: During the anodic scans, AgCl and Hg2Cl2 films were formed on all amalgams except the one with only 40 wt% Ag. In all high-copper amalgams, a prominent Cu (oxidation) peak was found at -0.1 V, indicating the release of copper during corrosion. Zinc affected the oxidation process for both low- and high-copper amalgams. When zinc was absent, a peak for Sn2+ oxidation appeared at -0.4 V. When zinc was present, a Sn4+ oxidation peak was revealed at -0.6 V. In some amalgams, there was evidence of the selective corrosion (pitting corrosion) of tin and copper. In the lowest silver-content amalgam, no protective films were formed, which is indicative of its poor corrosion resistance. As expected, in all the low-copper amalgams, an extreme increase in current density was recorded immediately at 0 V, due to the release of tin from gamma 2. SIGNIFICANCE: Cyclic voltammetry is useful for the rapid examination (less than an hour) of the electrochemical behavior of amalgams, specifically to obtain information on the formation of compounds and the sequences of electrochemical reactions.

Initial corrosion of amalgams in vitro. Brune D, Evje DM. Scand J Dent Res. 1984 Apr; 92(2):165-71. 6585923 PubMed. The amounts of copper, mercury, silver or zinc released from two brands of freshly prepared, lathe cut amalgams and from one brand of dispersed phase type amalgam into artificial saliva have been measured. Samples were immersed in the solution a few minutes after the end of trituration and exposed statically for periods of up to about 4 days. The initial mercury release from such specimens could exceed the long term mercury release from old amalgams by more than two orders of magnitude. The measurements indicate that during the first day after insertion of two amalgam fillings, each with an assumed surface area of 1 cm2 and under presumably static conditions, mercury at the level of more than twice the mercury food and drink intake could be released in the oral cavity.

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In vitro study on the corrosion behavior of two amalgams in direct contact to different cast metal alloys. Willershausen-Zonnchen B, Gross E, Dermann K, Sonnabend E. Dtsch Zahnarztl Z. 1991 Apr; 46(4):290-2. 1815935 PubMed. The direct contact between amalgam and cast metal may enhance electrochemical reactions. In a study to determine the amount of mercury released in these reactions, six cast metal alloys with increasing precious metal contents were placed in immediate contact (contact area 10 mm2) to two non-gamma 2-amalgams (Amalcap, Valiant) and incubated with artificial saliva at 37 degrees C for up to 8 weeks; then the salivary mercury concentrations were measured. After the end of the incubation period the case metal surfaces were analyzed by ESCA for metal appositions. The results showed that direct contact between amalgam and cast metal after storage in artificial saliva for 8 weeks resulted in a minor release of mercury (22.7 +/- 10.63 ng/ml Hg).

Long-term corrosion studies in vitro of amalgams in contact. Moberg LE. Oden A. Acta Odontol Scand. 1985 Aug; 43(4):205-13. 3864339 PubMed. Three types of amalgams, one conventional and two with a high copper content, were stored in phosphate-buffered 0.9% NaCl solution, at pH 6, for 35 weeks. Every 7 weeks the solutions were changed and analyzed with regard to Cu, Zn, Sn, Hg, and Ag. In one of the amalgam combinations, the conventional amalgam and one of the copper-rich amalgams in an area ratio of 2:1, contact between the amalgams clearly increased the amounts of Cu, Hg, and Ag released the first 14 weeks compared with when immersed in separate solutions. With the reversed area relation, Cu, Hg, and Ag decreased when they were in contact. The conventional amalgam in contact with the other copper-rich amalgam, in an area ratio of 2:1, reduced the amount of Cu but increased the Zn released. Polishing initially decreased the amounts of Cu and Zn released compared with the unpolished amalgams.

Mercury release from amalgam specimens. Fritz U, Zellmann M. Dtsch Zahnarztl Z. 1991 Aug; 46(8):553-4. 1817929 PubMed. Over 7 days specimens of 5 gamma 2-free Amalgams were stored in KSCN-containing and KSCN-free lactic acid-salt solution. After 1, 4 and 7 days samples of the solution were analyzed for their mercury contents using inductively coupled plasma atom emission spectroscopy. In KSCN-containing solution the release of mercury was 45.4 micrograms, in KSCN-free solution it was 70.7 micrograms/50 mm2. KSCN, a part of natural saliva, has the effect of inhibiting corrosion.

Release of corrosion products from amalgam in phosphate containing solutions. Moberg LE, Johansson C. Scand J Dent Res. 1991 Oct; 99(5):431-9. 1754844 PubMed. The effect of phosphate concentration on corrosion was compared for two types of amalgam: a conventional alloy (ANA 68) and a high-Cu admixed alloy (Dispersalloy). The test specimens were stored for 4 months in electrolytes containing 85 mM NaCl and 85 mM NaCl with 2.5, 10, or 100 mM phosphate buffer respectively. The solutions were renewed each month and analyzed for Cu, Zn, Sn, Hg, and Ag in an atomic absorption spectrophotometer. The surfaces and cross-sections of the specimens were studied in a scanning electron microscope (SEM) with an energy dispersive detector (EDAX). The corrosion products, mainly Sn-compounds, at the surface of the amalgams were less in the solutions containing high concentrations of phosphate. In cross-section subsurface corrosion of the high-Cu amalgam was observed especially in specimens immersed in the NaCl solution without phosphate. The conventional amalgam showed surface corrosion only. The decrease in release of elements with time from the conventional amalgam in all the experimental solutions might indicate passivation. For the high-Cu amalgam the release of elements increased with time, except for Cu and Sn in the solution with 100 mM phosphate, indicating that phosphate inhibits corrosion of the Cu-Sn-phases. Release of corrosion products from the high-Cu amalgam was more dependent on the presence of phosphate than the conventional amalgam.

Unusual in vivo extensive corrosion of a low-silver amalgam restoration involving galvanic coupling: a case report. Toumelin-Chemla F, Lasfargues JJ. Quintessence Int. 2003 Apr; 34(4):287-94. 12731616 PubMed. The authors observed, in a few exceptional circumstances of defective restorations, a release of liquid metal droplets in the surrounding tissue. These particles were identified as elemental mercury.

General Health

Chronic illness in association with dental amalgam: Report of two cases. Godfrey ME. J Adv Med. 1990. 3:247-255. Two case studies, involving multiple symptomatology, are presented. A casual relationship with dental amalgam is proposed, with remission of symptoms and signs following removal of the source.  

Environmental medicine, part three: long-term effects of chronic low-dose mercury exposure. Crinnion WJ. Altern Med Rev. 2000 Jun; 5(3):209-23. 10869102 PubMed. Once introduced to the body through food or vapor, mercury is rapidly absorbed and accumulates in several tissues, leading to increased oxidative damage, mitochondrial dysfunction, and cell death. Mercury primarily affects neurological tissue, resulting in numerous neurological symptoms, and also affects the kidneys and the immune system. It causes increased production of free radicals and decreases the availability of antioxidants. It also has devastating effects on the glutathione content of the body, giving rise to the possibility of increased retention of other environmental toxins.

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Human exposure to elemental mercury in a contaminated residential building. Orloff KG, Ulirsch G, Wilder L, Block A, Fagliano J, Pasqualo J. Arch Environ Health. 1997 May-Jun; 52(3):169-72. 9169625 PubMed. Environmental and biomonitoring data indicated that the residents were being exposed to mercury levels that were cause for health concern.

Potential health hazard of use of mercury in dentistry: critical review of the literature. Enwonwu CO. Environ Res. 1987 Feb;42(1):257-74. 3542524 PubMed. This report examines recent publications on the health hazards associated with the use of mercury in dentistry with emphasis on the release of mercury vapor from silver-amalgam restorations.

Removal of dental amalgam and other metal alloys supported by antioxidant therapy alleviates symptoms and improves quality of life in patients with amalgam-associated ill health. Lindh U, Hudecek R, Danersund A, Eriksson S, Lindvall A. Neuroendocrinol Lett. 2002 Oct-Dec; 23(5-6):459-82. 12500173 PubMed. The purpose of this study was to evaluate treatment of patients suffering from chronic ill health with a multitude of symptoms associated with metal exposure from dental amalgam and other metal alloys. The hypothesis that metal exposure from dental amalgam can cause ill health in a susceptible part of the exposed population was supported. Treatment according to the Uppsala model proved to be adequate for more than 70% of the patients.

The dental amalgam issue. A review. Hanson M, Pleva J. Experientia. 1991 Jan 15; 47(1):9-22. 1999251 PubMed. Aspects of materials science, corrosion, mercury exposure, toxicology, neurology and immunology are included. New data on mercury exposure from corroded amalgam fillings in vivo are presented. The exposure can reach levels considerably over known threshold limit values. Also, measurements of mercury absorption from intraoral air are presented. The vital importance of avoiding a galvanic amalgam-gold coupling is emphasized. The symptomatology of a disabled patient, who recovered after amalgam removal, has been included. It is concluded that discussion of the dental amalgam issue has suffered from the lack of an interdisciplinary approach. It would be wise to learn from the lesson of acrodynia, and consider amalgam mercury among other possible factors in neurological and immunological diseases of unclear etiology.

Genetic/ Mutations

Genotoxicity of mercury compounds. De Flora S, Bennicelli C, Bagnasco M. Mutat Res. 1994 Feb; 317(1):57-79. 7507573 PubMed. Mercury compounds failed to induce point mutations in bacteria but often exerted clastogenic effects in eukaryotes, especially by binding SH groups and acting as spindle inhibitors, thereby causing c-mitosis and consequently aneuploidy and/or polyploidy. Inorganic mercury compounds were also found to induce the generation of reactive oxygen species and glutathione depletion in cultured mammalian cells. Although different mercury compounds tended to produce qualitatively comparable genetic effects, which suggests the involvement of a common toxic entity, methylmercury derivatives and other ionizable organomercury compounds were more active in short-term tests than either non-ionizable mercury compounds (e.g., dimethylmercury) or inorganic mercury salts (e.g., mercuric chloride). The results of cytogenetic monitoring in peripheral blood lymphocytes of individuals exposed to elemental mercury or mercury compounds from accidental, occupational or alimentary sources were either negative or borderline or uncertain as to the actual role played by mercury in some positive findings. Both genotoxic and non-genotoxic mechanisms may contribute to the renal carcinogenicity of mercury, which so far has been convincingly demonstrated only in male rodents treated with methylmercury chloride.

Lead and mercury mutagenesis: role of H2O2, superoxide dismutase, and xanthine oxidase. Ariza ME, Bijur GN, Williams MV. Environ Mol Mutagen. 1998; 31(4):352-61. 9654245 PubMed. It has been suggested that reactive oxygen intermediates (ROIs) may have a role in the genotoxic effects of lead (Pb2+) and mercury (Hg2+), but there have not been any definitive studies demonstrating a causal relationship between the induction of ROIs by these metals and mutagenesis. We previously demonstrated, using the transgenic Chinese hamster ovary cell line AS52, that low concentrations (0.1-1 microM) of Pb2+ and Hg2+ are mutagenic. In the present study, using a novel histochemical computer-enhanced image analysis technique, we demonstrate that Pb2+ and Hg2+ induce the formation of H2O2 in AS52 cells by at least two distinct mechanisms. One is characterized by the rapid induction of H2O2 following treatment of cells with concentrations of Pb2+ or Hg2+ below 0.8 and 1 microM, respectively, while the second occurs in AS52 cells treated with concentrations of Pb2+ or Hg2+ greater than 0.8 and 1 microM, respectively. Pb2+ and Hg2+ (0.1-1 microM) had no effect on the activities of partially purified catalase, glutathione peroxidase, or glutathione reductase, important enzymes involved with antioxidant defense, but these metals stimulated the activities of copper-zinc superoxide dismutase (CuZn-SOD) and xanthine oxidase (XO). Allopurinol (50 microM), a specific inhibitor of xanthine oxidase, inhibited the induction of H2O2 by Pb2+ (0.8-1 microM) and Hg2+ (1 microM) and also inhibited Pb2+- and Hg2+-induced mutagenesis. These results demonstrate that Pb2+ and Hg2+ disrupt the redox status of AS52 cells by enhancing the activities of CuZn-SOD and XO. Furthermore, the results of these studies also demonstrate that there is a causal relationship between the induction of H2O2 by these metals and mutagenesis.

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Lead and mercury mutagenesis: type of mutation dependent upon metal concentration. Ariza ME, Williams MV. J Biochem Mol Toxicol. 1999; 13(2):107-12. 9890195 PubMed. Lead and mercury are toxic metals that are widely distributed in the atmosphere, soil, and groundwater. It is estimated that 2-4 x 10(4) tons of these metals are released annually into the environment by natural and industrial processes. Therefore, human exposure to low relatively nontoxic concentrations of these metals is unavoidable. However, the possible health effects of such exposure remain controversial. We have previously reported that low, subthreshold concentrations (0.1-1 microM) of these metals are mutagenic in the transgenic Chinese hamster ovary cell line AS52. The purpose of the present study is to determine the types of mutations induced in the gpt gene in AS52 cells. Using multiplex polymerase chain reaction and southern blot analyses, we characterized the 138 lead-induced, 192 mercury-induced, 29 reactive oxygen radical-induced, and 20 spontaneously arising mutants for point and deletion mutations in the gpt gene. Similar levels of point mutations were observed in the lead- and mercury-induced populations (47.8 and 53.6, respectively), which was significantly less than that occurring in the spontaneously arising and reactive oxygen intermediate-induced mutants. However, further examination of the data revealed that at concentrations of the metals of equal to or less than 0.4 microM, the majority of the mutations in the gpt gene were point mutations, while at higher concentrations, deletions (partial and complete) were the predominant type of mutation. These results are consistent with the hypothesis that lead and mercury induce mutations in eukaryotic cells by at least two distinct mechanisms.

Mutagenicity of mercury chloride and mechanisms of cellular defence: the role of metal-binding proteins. Schurz F, Sabater-Vilar M, Fink-Gremmels J. Mutagenesis. 2000 Nov; 15(6):525-30. 11077005 PubMed. 11077005 PubMed. Hg(2+) increased the intracellular amount of reactive oxygen species. This induction of oxidative stress was observed, although the intracellular glutathione (GSH) and metallothionein (MT) concentrations were increased significantly. Mercury-induced MT expression was even more pronounced after GSH depletion. Correspondingly, radical formation was more evident in the presence of the GSH-depleting agent L-buthioneine-[S:,R:]-sulfoximine. These findings suggest that the observed mutations might be a consequence of oxidative processes, rather than due to a direct interaction of mercury with nuclear DNA. The results also indicate that the auto-induction of MT by Hg(2+) fails to prevent these mutational events.

Mutagenic effect of mercury (II) in eukaryotic cells. Ariza ME, Holliday J, Williams MV. In Vivo.1994 Jul-Aug; 8(4):559-63. 7893984 PubMed. Acute exposure of KB and Chinese hamster ovary cells (AS52) to low concentrations of mercury (II) results in a dose dependent binding of mercury to DNA. This binding of mercury (II) to the DNA occurs at concentrations of mercury that have little if any effect on glutatione levels or on superoxide dismutase activity. Mutational studies with AS52 cells demonstrated that concentrations (0.1 to 0.4 microM) of mercury (II) which were not cytotoxic caused an increase (1.7 to 3.1) in the frequency of mutations in the gpt gene when compared to non-treated controls. These results suggest that there may be risks associated with exposure to non-cytotoxic levels of mercury (II).

Mutagenesis of AS52 cells by low concentrations of lead (II) and mercury (II). Ariza ME, Williams MV. Environ Mol Mutagen. 1996; 27(1):30-3. 8625945 PubMed. Little is known at the molecular level concerning the genotoxic effects following the acute exposure of eukaryotic cells to low concentrations of lead (II) or mercury (II). There have been conflicting reports concerning the mutagenic potential of these heavy metals, and there have not been any studies performed to determine the molecular mechanism(s) by which these metals are mutagenic. The Chinese hamster ovary cell line, AS52, contains a stably integrated single functional copy of the Escherichia coli xanthine-guanine phosphoribosyltransferase (gpt) gene. Mutations in the gpt gene confer resistance to 6-thioguanine (TG). There was little effect on viability, as measured by relative cloning efficiency, of AS52 cells exposed to lead (II) or mercury (II) up to concentrations of 0.5 microM and 0.3 microM, respectively. However, higher concentrations of the metals caused a significant increase in cell death. There was also a dose-dependent increase in the isolation of mutants resistant to TG in treated cells when compared to non-treated controls. Concentrations of the metals as low as 0.1 microM caused a significant increase in the number of mutants resistant to TG when compared to the number of spontaneous mutants obtained in nontreated controls. While the molecular mechanism(s) by which lead and mercury (II) are genotoxic is unknown, the results of this study demonstrate that low concentrations of lead (II) and mercury (II) are mutagenic in eukaryotic cells.

Oxidative damage to nucleic acids in motor neurons containing mercury. Pamphlett R, Slater M, Thomas S. J Neurol Sci., 159(2):121-6, Aug 1998. 9741394 PubMed. Mercury within the motor neuron perikaryon therefore leads to increased avidin binding, an indicator of oxidative damage to DNA. The findings support the hypothesis that an environmental toxin such as mercury can enter and damage motor neurons.

Uptake, cellular distribution and DNA damage produced by mercuric chloride in a human fetal hepatic cell line. Bucio L, Garcia C, Souza V, Hernandez E, Gonzalez C, Betancourt M, Gutierrez-Ruiz MC. Mutat Res. 1999 Jan 25; 423(1-2):65-72. 10029678 PubMed. Our results showed that Hg induced DNA single-strand breaks or alkali labile sites using the single-cell gel electrophoresis assay (Comet assay). The percentage of damaged nucleus and the average length of DNA migration increased as metal concentration and time exposure increased. Lipid peroxidation, determined as malondialdehyde production in the presence of thiobarbituric acid, followed the same tendency, increased as HgCl2 concentration and time of exposure increased.

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Unusual amino acid usage in the variable regions of mercury-binding antibodies. Westhoff CM, Lopez O, Goebel P, Carlson L, Carlson RR, Wagner FW, Schuster SM, Wylie DE. Proteins. 1999 Nov 15; 37(3):429-40. 10591102 PubMed. Monoclonal antibodies (mAb) specific for mercuric ions were isolated from BALB/c mice injected with a mercury-containing, hapten-carrier complex. The antibodies reacted by enzyme-linked immunosorbent assay with bovine serum albumin-glutathione-mercuric chloride (BSA-GSH-HgCl) but not with BSA-GSH without mercury. Nucleotide sequences from polymerase chain reaction products encoding six of the antibody heavy-chain variable regions and seven light-chain variable regions revealed that all the antibodies contained an unpaired cysteine residue in one hypervariable region, which is unusual for murine antibodies. Mutagenesis of the cysteine to either tyrosine or serine in one of the Hg-binding antibodies, mAb 4A10, eliminated mercury binding. However, of two influenza-specific antibodies that contain cysteine residues at the same position as mAb 4A10, one reacted with mercury, although not so strongly as 4A10, whereas the other did not react at all. These results suggested that, in addition to an unpaired cysteine, there are other structural features, not yet identified, that are important for creating an appropriate environment for mercury binding. The antibodies described here could be useful for investigating mechanisms of metal-protein interactions and for characterizing antibody responses to structurally simple haptens.

Chewing and Grinding

Dental amalgam and mercury. Aronsson AM, Lind B, Nylander M, Nordberg M. Biol Met. 1989; 2(1):25-30. 2485649 PubMed. Maximum concentrations of mercury vapour in intraoral air for the 27 women who had chewed chewing gum for 5 min varied between 2-60 micrograms Hg/m3 (median value 19 micrograms Hg/m3). This corresponds to 0.07-2.20 ng Hg/s and a median value of 0.70 ng Hg/s.

Influence of chewing gum consumption and dental contact of amalgam fillings to different metal restorations on urine mercury content. Gebel T, Dunkelberg H. Zentralbl Hyg Umweltmed. 1996 Nov; 199(1):69-75. 9409909 PubMed. It could be shown that the consumption of chewing gum resulted in a significantly higher mean urinary mercury content in probands with amalgam fillings in comparison to people with similar amalgam status (gum chewers: 1.36 Hg/24 h vs. non-chewers 0.70 microgram Hg/24 h). Thus, gum chewing has to be considered as important parameter of influence on the urinary mercury levels of people with amalgam fillings.

Intra-oral air mercury released from dental amalgam. Vimy MJ, Lorscheider FL. J Dent Res. 1985 Aug; 64(8):1069-71. 3860538 PubMed. Subjects with dental amalgams had unstimulated Hg vapor concentrations that were nine times greater than basal levels in control subjects with no amalgams. Chewing stimulation in subjects with amalgams increased their Hg concentration six-fold over unstimulated Hg levels, or a 54-fold increase over levels observed in control subjects.

Long-term use of nicotine chewing gum and mercury exposure from dental amalgam fillings. Sallsten G, Thoren J, Barregard L, Schutz A, Skarping G. J Dent Res. 1996 Jan;75(1):594-8. 8655765 PubMed. In both groups, significant correlations were found between P-Hg or U-Hg on the one hand and the number of amalgam surfaces on the other. In the chewers, no correlations were found between P-Hg or U-Hg and chewing time per day or cotinine in urine. Cotinine in urine increased with the number of pieces of chewing gum used. The impact of excessive chewing on mercury levels was considerable.

People with high mercury uptake from their own dental amalgam filling. Barregard L, Sallsten G, Jarvholm B. Occup Environ Med. 1995 Feb; 52(2):124-8. 7757165 PubMed. Three cases excreted 23-60 micrograms of Hg/day (25-54 micrograms/g creatinine), indicating daily uptake of Hg as high as 100 micrograms. Blood Hg was 12-23 micrograms/l, which is five to 10 times the average in the general population. No other sources of exposure were found, and removal of the amalgam fillings resulted in normal Hg concentrations. Chewing gum and bruxism were the probable reasons for the increased Hg uptake.

Hair Analysis

The present mercury contents of scalp hair and clinical symptoms in inhabitants of the Minamata area. Harada M, Nakanishi J, Konuma S, Ohno K, Kimura T, Yamaguchi H, Tsuruta K, Kizaki T, Ookawara T, Ohno H. Environ Res. 1998 May; 77(2):160-4.  9600809 PubMed. The ratio of methyl mercury to total mercury was 79-94% on the average for each group examined, suggesting indirect contamination (perhaps through the food chain). Despite their low mercury level in scalp hair, however, the subjects showed various neurological symptoms, particularly, sensory disturbance (such as the glove and stocking type), at a very high rate.  

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Hearing Loss

Amalgam dental fillings and hearing loss.

Janet A. Rothwell; Paul J. Boyd;  Audiology Department, General Hospital, St. Helier, Jersey, Channel Islands  School of Psychological Sciences, University of Manchester, United Kingdom. Online Publication Date: 01 December 2008. Int J Audiol. 2010 Jan;49(1):69-70. 19085401 PubMed. In this study we investigated the effects of amalgam dental fillings on auditory thresholds. However, there was a significant positive linear correlation between amalgam filling data and auditory thresholds at 8, 11.2, 12.5, 14, and 16 kHz. The strongest association (r=0.587, n=39, p<.001, r(2)=0.345) was at 14 kHz, where each additional amalgam filling was associated with a 2.4 dB decline in hearing threshold (95% confidence interval [CI], 1.3-3.5 dB). The results suggest an association between more amalgam fillings and poorer thresholds at higher frequencies, which could contribute to presbyacusis in developed countries. However, the data from the
current study provide an additional argument against the continued use of dental amalgam where suitable alternatives
exist.

Immune System, Autoimmune, and Allergy

Adverse immunological effects and autoimmunity induced by dental amalgam and alloy in mice. Hultman P, Johansson U, Turley SJ, Lindh U, Enestrom S, Pollard KM. FASEB J. 1994 Nov; 8(14):1183-90. 7958626 PubMed. We hypothesize that under appropriate conditions of genetic susceptibility and adequate body burden, heavy metal exposure from dental amalgam may contribute to immunological aberrations, which could lead to overt autoimmunity.

Allergic disease, immunoglobulins, exposure to mercury and dental amalgam in Swedish adolescents. Herrstrom P, Hogstedt B, Holthuis N, Schutz A, Rastam L. Int Arch Occup Environ Health. 1997; 69(5):339-42. 9192218 PubMed. High-dose exposure to inorganic mercury in man can influence the immune system and in rare cases cause immune-related disease. Some experimental animals also react with autoimmunity after low doses of inorganic mercury.

An epidemiological study of factors relating to mercury sensitization. Sato K, Kusaka Y, Yanagihara M, Ueda K, Mori T, Miyakoshi S. Arerugi. 1995 Feb; 44(2):86-92. 7726753 PubMed. Mercury sensitized students had significantly more frequently experienced eczema caused by cosmetics, shampoos, soaps and haircreams (by the chi-square test, p < 0.005). They also had significantly more teeth treated with metals compared to the controls (one-tailed t-test, p < 0.05). And their urinary mercury concentrations were significantly higher than those of the controls (one-tailed t-test, p < 0.05). These findings suggest that mercury sensitization is associated with exposure to mercury in the living environment.

Autoimmunity and Heavy Metals. Bigazzi PE. Autoimmunity and heavy metals. Lupus. 1994 Dec; 3(6):449-53. 7704000 PubMed. Similarly, there is solid evidence that mercury can induce autoimmune disease both in humans and experimental animals. The lessons to be derived from metal-induced autoimmunity relate to structure-activity relationship, pathogenesis, etiology and genetics. They probably apply to xenobiotic-induced autoimmune disease in general.

Autoreactive T cells in mercury-induced autoimmune disease: in vitro demonstration. Pelletier L, Pasquier R, Hirsch F, Sapin C, Druet P. J Immunol. 1986 Oct 15; 137(8):2548-54. 2944958 PubMed. These experiments demonstrate that HgCl2 induces autoreactive T cells and suggest that these cells may be responsible for the autoimmune disease.

Dental amalgam as one of the risk factors in autoimmune diseases. Bartova J, Prochazkova J, Kratka Z, Benetkova K, Venclikova Z, Sterzl I. Neuroendocrinol Lett. 2003 Feb-Apr; 24(1-2):65-7. 12743535 PubMed. Experimental and clinical data published recently show that dental amalgam can give rise to undesirable immunological responses in susceptible individuals. In genetically susceptible strains of experimental animals, mercury and silver can induce autoimmune responses. Increased production of SSB/La autoantibodies in the media following stimulation of peripheral blood lymphocytes with HgCl2 was found in all cases. Using the Student's paired test, the results were significant on the p=0.05 significance level. CONCLUSION: Results imply that, in some patients with thyroiditis, mercury from dental amalgam can stimulate the production of antinuclear antibodies. Dental amalgam may be a risk factor in some patients with autoimmune disease.

Does amalgam affect the immune system? A controversial issue. Enestrom S, Hultman. P. Int Arch Allergy Immunol. 1995 Mar; 106(3):180-203. 7888781 PubMed. Dental amalgam fillings are the most important source of mercury exposure in the general population. Local, and in some instances, systemic hypersensitivity reactions to dental amalgam metals, especially mercury, occur at a low frequency among amalgam bearers. Experimental and clinical data strongly indicate that these and other subclinical systemic adverse immunological reactions to dental amalgam metals in humans will be linked to certain MHC genotypes, and affect only a small number of the exposed individuals. These individuals will be very difficult to detect in a mixed population of susceptible and resistant individuals, including persons with alleged symptoms due to dental amalgam fillings, where many of the individuals are likely to suffer from conditions with no proven immunological background such as multiple chemical sensitivity syndrome.

Does mercury from amalgam restorations constitute a health hazard? Weiner JA, Nylander M, Berglund F. Sci Total Environ. 1990 Dec 1;99(1-2):1-22. 2270464 PubMed. Animal studies suggest the possibility of immune system reactions to mercury, i.e. development of autoimmunity, that are not primarily dose-dependent, but rather depend on genetic susceptibility. From a toxicological point of view, amalgam is an unsuitable material for dental restorations.

Dose-response studies in murine mercury-induced autoimmunity and immune-complex disease. Hultman P, Enestrom S. Toxicol Appl Pharmacol. 1992 Apr; 113(2):199-208. 1532866 PubMed. The renal and splenic mercury concentration was significantly increased in all groups of mercuric chloride-exposed mice and correlated with the dose. We conclude that 10 weeks peroral treatment with mercuric chloride in drinking water is able to elicit autoimmunity and IC disease in genetically homogeneous, mercury-sensitive mice at a body burden similar to that reported in some occupationally exposed humans.

Effect of dental amalgam and nickel alloys on T-lymphocytes: preliminary report. Eggleston DW. J Prosthet Dent. 1984 May; 51(5):617-23. 6610046 PubMed. Preliminary data suggest that dental amalgam and dental nickel alloys can adversely affect the quantity of T-lymphocytes.

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Effects of mercury on human polymorphonuclear leukocyte function in vitro. Contrino J, Marucha P, Ribaudo R, Ference R, Bigazzi PE, Kreutzer DL. Am J Pathol. 1988 Jul; 132(1):110-8. 3394794 PubMed. These studies clearly demonstrate the ability of extremely low levels of HgCl2 not only to suppress various polymorphonuclear leukocytes (PMN) functions involved in host defense, but also to stimulate oxygen metabolism. In vivo, these HgCl2 effects would not only compromise host defense but also promote tissue injury via the local production of oxygen metabolites.

Effects of occupational exposure to mercury vapors on T-cell and NK-cell populations. Moszczynski P, Rutowski J, Slowinski S, Bem S, Jakus-Stoga D. Arch Med Res. 1996 Winter; 27(4):503-7. 8987185 PubMed. Presented changes in human T-lymphocytes population associated with occupational exposure to mercury vapors have been proposed to explain the origin of more frequent autoimmunity induced by mercury.  

Effects of Removing Amalgam Fillings from Patients with Diseases Affecting the Immune System. Lindqvist B, Mörnstad H. Medical Science Research. May 1996; 24(5):355-356. Fifty-three patients with complaints which they attributed to their amalgam fillings, and with pathological tests indicating abnormality of the immune system, were followed for 1-3 years after the removal of all, part of, or none of their amalgam fillings. Within the group of 34 individuals who had all their amalgam fillings replaced, there was a significant number of decreased antibody titres, but only two had normalised their laboratory tests after 1-3 years. A significant improvement in subjective symptoms occurred in 20 (59%) of cases. In the group of patients who still had amalgam fillings, there were no statistically significant changes in the antibody titres. It thus seems that mercury released from amalgam fillings may initiate or support an ongoing immune disease. However. this study group was rather heterogeneous, and had received various pharmacological treatments. Further studies, are, therefore, needed to confirm, or refute, the results.

Enhancement of ovalbumin-induced antibody production and mucosal mast cell response by mercury. Watzl B, Abrahamse SL, Treptow-van Lishaut S, Neudecker C, Hansch GM, Rechkemmer G, Pool-Zobel BL. Food Chem Toxicol. 1999 Jun; 37(6):627-37. 10478831 PubMed. In conclusion, these studies indicate that the food contaminant Hg can stimulate the immune response to ovalbumin (OVA) in immunized rats. One possible mechanism could be the toxicity of Hg to the intestinal epithelial and the lymph node cells. Whether humans with allergies respond to high oral doses of Hg in a similar way needs to be investigated in further studies.

Exposure to methylmercury results in serum autoantibodies to neurotypic and gliotypic proteins. el-Fawal HA, Gong Z, Little AR, Evans HL. Neurotoxicology. 1996 Summer; 17(2):531-9. 8856747 PubMed. Environmental exposure to methylmercury (MeHg) continues to pose a threat to humans, making early detection of neurotoxic effects a pressing concern. This study suggests that assay of autoantibodies against nervous system proteins may provide a means of assessing the early neurotoxic effects of environmental MeHg exposure.

Immune system alteration in the rat after indirect exposure to methyl mercury chloride or methyl mercury sulfide. Wild LG, Ortega HG, Lopez M, Salvaggio JE. Environ Res. 1997; 74(1):34-42. 9339212 PubMed. Indirect exposure of rats (during gestation and nursing) to different forms of methyl mercury reveals that chloride forms have prolonged predominantly enhancing effects on lymphoproliferative response of splenocytes, followed by significant depression of NK cell activity.

Immune thrombocytopenia and elemental mercury poisoning. Fuortes LJ, Weismann DN, Graeff ML, Bale JF Jr, Tannous R, Peters C. J Toxicol Clin Toxicol. 1995; 33(5):449-55. 7650769 PubMed. Three cases of severe mercury toxicity occurring within a family are reported. Two cases of thrombocytopenia occurred in this family and represent the second such report in the literature of an association between elemental mercury toxicity and thrombocytopenia. Three of the children presented with a combination of dermatologic and neurologic manifestations reminiscent of acrodynia or pink disease.

Immunoglobulin E and autoantibodies in mercury-exposed workers. Dantas DC, Queiroz ML. Immunopharmacol Immunotoxicol. 1997 Aug; 19(3):383-92. 9248865 PubMed. These results suggest that the humoral immune response is an indicator of cellular changes in workers chronically exposed to mercury, even in those with urinary mercury concentrations within levels considered safe in the occupational area.

Immunoglobulin levels in workers exposed to inorganic mercury. Queiroz ML, Perlingeiro RC, Dantas DC, Bizzacchi JM, De Capitani EM. Pharmacol Toxicol. 1994 Feb; 74(2):72-5. 8190705 PubMed. Increased IgG, IgA and IgM levels were found in the mercury-exposed individuals and in 16, a second evaluation was performed six months later. During the intervening six months, the level of hygiene was improved throughout the plant, and urinary mercury concentrations were determined monthly in each worker. Despite a significant reduction in mercury urinary concentrations, serum immunoglobulin levels did not return to the normal range. These results indicate that "safe" levels of mercury exposure may lead to humoral immunological stimulation.

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Immunological and Brain MRI Changes in Patients with Suspected Metal Intoxication. Tibbling L, Thuomas K, Lenkei R, Stejskal VD. International Journal of Occupational Medicine and Toxicology. Vol. 4. No. 2. 1995. Thirty-four patients with central nervous system (CNS) and systemic symptoms suggestive of intoxication from dental amalgam were examined with magnetic resonance imaging (MRI) of the brain (n=32) and with a Memory Lymphocyte Immuno Stimulation Assay (MELISA®) (n=17). Lymphocyte phenotype was analyzed with flow cytometry (FC) in 22 of the patients. One hundred twenty age-matched patients without CNS symptoms served as controls for the MRI study, seventy-seven healthy subjects with dental amalgam fillings served as controls for the MELISA® test, and seventy-five clinically healthy subjects were controls for the lymphocyte phenotype determination. Pathological MRI findings were present in 81% of the patients, most of them with signs of degeneration in the basal ganglia, but none in the controls. The lymphocyte phenotype determination was pathological in 58%. The MELISA® showed pathological findings in 88%, of which 60% showed an immune reaction to mercuric chloride, 62% of the patients had some kind of atopic disease, and 35% suffered from levothyroxine-treated hypothyreosis. A high rate of immunopathologies and objective signs of immunological reactions in the majority of the patients with MRI changes in the brain suggests that immunological mechanisms may play an important role in the development of the lesions.

Immunologic effects of exposure to low levels of inorganic mercury. Soleo L, Colosio C, Alinovi R, Guarneri D, Russo A, Lovreglio P, Vimercati L, Birindelli S, Cortesi I, Flore C, Carta P, Colombi A, Parrinello G, Ambrosi L. Med Lav. 2002 May-Jun; 93(3):225-32. 12197272 PubMed. The decrease in IL-8 serum levels observed in exposed workers might suggest an immunosuppressive effect of occupational exposure to very low doses of inorganic mercury. This result suggests the need to revise of current HgU BEI after further definition of its prognostic significance.

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. I. Suppression of T-cell activation. Shenker BJ, Rooney C, Vitale L, Shapiro IM. Immunopharmacol Immunotoxicol. 1992; 14(3):539-53. 1517533 PubMed. The results of this investigation clearly show that mercury-containing compounds are immunomodulatory; moreover, the decrease in T-cell function following exposure to mercury indicates that this metal is immunotoxic at very low exposure levels.

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. II. Alterations in cell viability. Shenker BJ, Berthold P, Decker S, Mayro J, Rooney C, Vitale L, Shapiro IM. Immunopharmacol Immunotoxicol. 1992; 14(3):555-77. 1517534 PubMed. Electron microscopic analysis of cells treated with mercury revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation and condensation of nucleoplasm. In concert with these nuclear changes, there was destruction of cytoplasmic organelles with loss of membrane integrity. Studies of phospholipid synthesis by mercury treated cells confirmed that there were alterations in membrane structure. Thus, there was a decrease in total phosphatide synthesis by treated cells. Moreover, monocyte phospholipid synthesis appeared to be more sensitive to the presence of mercury then lymphocytes. Finally, both forms of mercury caused a rapid and sustained elevation in the intracellular levels of Ca++. These morphological and biochemical changes are consistent with the notion that mercury initiates cytotoxic changes associated with programmed cell death.

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. III. Alterations in B-cell function and viability. Shenker BJ, Berthold P, Rooney C, Vitale L, DeBolt K, Shapiro IM. Immunopharmacol Immunotoxicol. 1993 Jan; 15(1):87-112. 8450183 PubMed. When exposed to high levels of HgCl2 (0.5-10 micrograms/ml) and MeHgCl (0.05-1 micrograms/ml), there was minimal reduction in B-cell viability at 1-4 hr, however, after exposure to mercury for 24 hr, cell death was apparent. MeHgCl was approximately 5-10 times more potent than HgCl2. Electron microscopic analysis revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation and condensation of nucleoplasm. Both forms of mercury caused a rapid and sustained elevation in the intracellular levels of Ca++. The results of this investigation clearly show that mercury-containing compounds are immunomodulatory; moreover, the decrease in B-cell function indicates that this metal is immunotoxic at very low exposure levels. Furthermore, the cytotoxic events are consistent with the notion that mercury initiates changes associated with programmed cell death.

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. IV. Alterations in cellular glutathione content. Shenker BJ, Mayro JS, Rooney C, Vitale L, Shapiro IM. Immunopharmacol Immunotoxicol. 1993 Mar-Jun; 15(2-3):273-90. 8349953 PubMed. The major goal of this investigation was to determine if the sensitivity of lymphocytes and monocytes to mercury (Hg++) was related to intracellular glutathione (GSH) levels and the thiol redox status [GSH/glutathione disulfide (GSSG)]. Results of the study clearly show that susceptibility to the immunotoxic effects of HgCl2 is, in part, dependent upon GSH levels and further that mercury inhibits GSH generation by lymphocytes and monocytes.

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Immunotoxicology of cadmium and mercury on B-lymphocytes--I. Effects on lymphocyte function. Daum JR, Shepherd DM, Noelle RJ. Int J Immunopharmacol. 1993 Apr; 15(3):383-94. 7685007 PubMed. In summary, both CdCl2 and HgCl2 exert early, inhibitory effects on B-cell activation. This is manifested by the inhibition of RNA, DNA and antibody synthesis. However, selective effects on the production of specific Ig isotypes by these metals may influence the ability of B-cells to mount effective immune responses to pathogens.

Induction of apoptosis in human T-cells by methyl mercury: temporal relationship between mitochondrial dysfunction and loss of reductive reserve. Shenker BJ, Guo TL, Shapiro IM. Toxicol Appl Pharmacol. 1999 May 15; 157(1):23-35. 10329504 PubMed. Finally, we established a temporal relationship between the decline in Deltapsim, generation of ROS, and depletion of thiol reserves. The earliest detectable event was at the level of the mitochondrion; in the presence of MeHgCl there was a profound reduction in mitochondrial Deltapsim and a decline in GSH levels within 1 h. Subsequently, a further decrease in thiol reserves was linked to the generation of ROS. We propose that the target organelle for MeHgCl is the mitochondrion and that induction of oxidative stress leads to activation of death-signaling pathways.

In vivo self-reactivity of mononuclear cells to T cells and macrophages exposed to HgCl2. Pelletier L, Pasquier R, Hirsch F, Sapin C, and Druet P. Eur J Immunol. 1985 May; 15(5):460-5. 3873339 PubMed. This data suggest that modified cells could trigger autologous lymphocyte subsets and be responsible for autoimmunity induced by HgCl2.

Low-level methylmercury exposure causes human T-cells to undergo apoptosis: evidence of mitochondrial dysfunction. Shenker BJ, Guo TL, Shapiro IM. Environ Res. 1998 May; 77(2):149-59. 9600808 PubMed. The results of the study indicate that a key event in the induction of T-cell apoptosis by mercuric compounds is depletion in the thiol reserve which predisposes cells to ROS damage and at the same time activates death signaling pathways.

Low and nontoxic levels of ionic mercury interfere with the regulation of cell growth in the WEHI-231 B-cell lymphoma. McCabe MJ Jr, Santini RP, Rosenspire AJ. Scand J Immunol. 1999 Sep; 50(3):233-41. 10447931 PubMed. These data suggest that low levels of mercury, which are not toxic, may still contribute to immune dysfunction by interfering with antigen-receptor-mediated and protein-kinase-dependent signal transduction in lymphocytes.

Measurement of the respiratory burst and chemotaxis in polymorphonuclear leukocytes from mercury-exposed workers. Perlingeiro RC, Queiroz ML. Hum Exp Toxicol. 1995 Mar; 14(3):281-6. 7779459 PubMed. During the intervening 6 months, the level of hygiene was improved throughout the plant and urinary mercury concentrations were determined monthly in each worker. Despite a significant reduction in urinary mercury concentrations, neutrophil migration did not return to within the normal range. These results suggest that 'safe' level mercury exposure may lead to impairment of neutrophil function.

Mercuric chloride induces apoptosis in human T lymphocytes: evidence of mitochondrial dysfunction. Guo TL, Miller MA, Shapiro IM, Shenker BJ. Toxicol Appl Pharmacol. 1998 Dec; 153(2):250-7. 9878595 PubMed. In conclusion, HgCl2 exposure results in oxidative stress and activation of death signaling pathways leading to apoptosis. Collectively, our studies indicate that individual mercurial species are capable of inducing T-cell death by activating specific apoptotic cascades.

Mercury and nickel allergy: risk factors in fatigue and autoimmunity. Sterzl I, Prochazkova J, Hrda P, Bartova J, Matucha P, Stejskal VD.  Neuroendocrinol Lett. 1999; 20(3-4):221-228. 11462117 PubMed. We have found that fatigue, regardless of the underlying disease, is primarily associated with hypersensitivity to inorganic mercury and nickel. We suggest that metal-driven inflammation may affect the hypothalamic-pituitary-adrenal axis (HPA axis) and indirectly trigger psychosomatic multisymptoms characterizing chronic fatigue syndrome, fibromyalgia, and other diseases of unknown etiology.  

Mercury-induced apoptosis in human lymphoid cells: evidence that the apoptotic pathway is mercurial species dependent. Shenker BJ, Guo TL, Shapiro IM. Environ Res. 2000 Oct; 84(2):89-99. 11068922 PubMed. Our results demonstrate that HgCl2 induces a significant elevation in the Bcl-2 content of T-cells; in contrast, T-cells treated with MeHgCl did not exhibit altered levels of this anti-apoptotic protein. Regardless of whether cytochrome c is released from the mitochondria, both mercurial species were capable of activating the caspase cascade, as evident by cleavage of poly (ADP-ribose) polymerase. Thus, our study shows that, whereas each of the mercury species shares common features in the apoptotic process, profound differences exist in a number of key steps in the pathway.

Mercury-induced autoimmunity in Brown Norway rats: kinetics of changes in RT6+ T lymphocytes correlated with IgG isotypes of circulating autoantibodies to laminin. Kosuda LL, Whalen B, Greiner DL, Bigazzi PE.  1.Toxicology. 1998 Feb 6; 125(2-3):215-31. 9570334 PubMed. The inverse correlation between levels of RT6.2+ T lymphocytes and autoantibodies to laminin 1 suggests that mercury may induce autoimmune responses in BN rats by its effects on these immunoregulatory cells.

Mercury inhibition of neutrophil activity: evidence of aberrant cellular signalling and incoherent cellular metabolism. Worth RG, Esper RM, Warra NS, Kindzelskii AL, Rosenspire AL, Todd RF 3rd, Petty HR. Scand J Immunol. 2001 Jan; 53(1):49-55. 11169206 PubMed. We examined the effects of HgCl(2) on cell surface distribution of membrane proteins. After exposure to environmentally relevant concentrations of HgCl(2) we found that CR3, but not other membrane proteins (e.g. uPAR, Fc gamma RIIA and the formyl peptide receptor), became clustered on cell surfaces. We suggest that HgCl2 disrupts integrin signalling/functional pathways in neutrophils.

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Mercury sensitization induced by environmental exposure. Mori T, Hirai T, Tomiyama T, Iida K, Miyakoshi S, Sato K, Kusaka Y, Yanagihara M, Ueda K. Nippon Eiseigaku Zasshi. 1998 Jan; 52(4):661-6. 9528265 PubMed. These results suggest that mercury sensitization is associated with increased hair mercury concentrations but not with urinary mercury concentrations. In this study it is confirmed that dental amalgam for treating teeth may be an important factor relating to mercury sensitization.

Mercury-specific lymphocytes: an indication of mercury allergy in man. Stejskal VD, Forsbeck M, Cederbrant KE, Asteman O. J Clin Immunol. 1996 Jan; 16(1):31-40. 8926283 PubMed. The results show that patients with oral lichen planus (OLP) have significantly higher lymphocyte reactivity to inorganic mercury, a corrosion product of amalgam, compared to control groups. Removal of amalgam fillings resulted in the disappearance of oral mucosal changes, thus indicating a causal relationship. Positive responses to phenylmercury (phenyl-Hg), a bactericidal agent in root fillings and in pharmaceutical preparations, were also noted in the oral lichen group but not in the control groups. Thus, low-grade chronic exposure to mercury may induce a state of systemic sensitization as verified by Hg-specific lymphocyte reactivity in vitro.

Metals and kidney autoimmunity. Bigazzi PE. Environ Health Perspect. 1999 Oct; 107 Suppl 5:753-65. 10502542 PubMed. However, mercury induces antinuclear antibodies, sclerodermalike disease, lichen planus, or membranous nephropathy in some individuals.

Monocyte-macrophage system and polymorphonuclear leukocytes in workers exposed to low levels of metallic mercury. Vimercati L, Santarelli L, Pesola G, Drago I, Lasorsa G, Valentino M, Vacca A, Soleo L. Sci Total Environ. 2001 Apr 10; 270(1-3):157-63. 11327389 PubMed. The results of our study suggest that the exposure to very low levels of metallic mercury led to subtle impairment of circulating monocyte and NK cells (as percentages) according to the increase in U-Hg levels, as well as of the PMNL chemotactic function in this particular group of workers, even though they remain clinically asymptomatic. Therefore, we suggest that impairment of these parameters provide a sensitive indicator of metallic mercury and other chemical contaminants present in the environment.

Murine mercury-induced autoimmunity: a model of chemically related autoimmunity in humans. Bagenstose LM, Salgame P, Monestier M. Immunol Res. 1999; 20(1):67-78. 10467984 PubMed. Human exposure to certain compounds or therapeutic drugs can result in the development of an autoimmune syndrome. Mercury (Hg) induced autoimmunity is one of the few animal models in which administration of a chemical induces a specific loss of tolerance to self-antigens. After receiving subtoxic doses of Hg or other heavy metals, susceptible mouse strains rapidly develop highly specific antibodies to nucleolar antigens. In addition, these animals display a general activation of the immune system, especially pronounced for the Th2 subset and a transient glomerulonephritis with immunoglobulin deposits. Like many human autoimmune diseases, this syndrome is associated with the expression of susceptible major histocompatibility complex (MHC) class II genes. In this article, we review the essential features of this model, and we discuss the putative mechanisms by which Hg creates such a severe immune dysfunction.

Oral exposure to inorganic mercury alters T lymphocyte phenotypes and cytokine expression in BALB/c mice. Kim SH, Johnson VJ, Sharma RP.  Arch Toxicol. 2003 Aug 20. 12928768 PubMed. Mercury altered the expression of inflammatory cytokines (tumor necrosis factor alpha, interferon gamma, and interleukin-12), c-myc, and major histocompatibility complex II, in various organs. Results indicated that a decrease in T lymphocyte populations in immune organs and altered cytokine gene expression may contribute to the immunotoxic effects of inorganic mercury.

Pretreatment of lymphocytes with mercury in vitro induces a response in T cells from genetically determined low-responders and a shift of the interleukin profile. Hu H, Abedi-Valugerdi M, Moller G. Immunology. 1997 Feb; 90(2):198-204. 9135547 PubMed. Mercury can induce autoimmune disease in susceptible mouse strains. We found that in vitro mercuric chloride induced a high proliferative response in spleen lymphocytes from mercury-susceptible SJL mice, but a low response in resistant mice. The continuous presence of mercury induced interleukin-2 (IL-2) and interferon-gamma, but not IL-4 production in spleen cells from both high- and low-responder mice. In contrast, by pretreating the cells with mercury and then washing, spleen cells from both high and low-responder mice produced IL-4. Our results suggest that spleen cells from both mercury-susceptible and -resistant mice have the potential to respond to mercury in vitro and produce both Th1- and Th2-type cytokines. But the mercury-induced cytokine profile can shift depending on the conditions for activation.

The beneficial effect of amalgam replacement on health in patients with autoimmunity. Prochazkova J, Sterzl I, Kucerova H, Bartova J, Stejskal VD. Neuro Endocrinol Lett. 2004 Jun;25(3):211-8. 15349088 PubMed. BACKGROUND: Patients with certain autoimmune and allergic diseases, such as systemic lupus, multiple sclerosis, autoimmune thyroiditis or atopic eczema, often show increased lymphocyte stimulation by low doses of inorganic mercury in vitro. The patients often report clinical metal hypersensitivity, especially to nickel. OBJECTIVE AND METHODS: In this study we examined the health impact of amalgam replacement in mercury-allergic patients with autoimmunity. The suitability of MELISA, an optimized lymphocyte stimulation test, for the selection of susceptible patients and monitoring of sensitization was also examined. Amalgam fillings were replaced with composites and ceramic materials. Follow-up health status and lymphocyte reactivity were assessed and evaluated half a year or later following amalgam removal. RESULTS: Results of lymphocyte reactivity measured with MELISA indicate that in vitro reactivity after the replacement of dental amalgam decreased significantly to inorganic mercury, silver, organic mercury and lead. Out of 35 patients, 25 patients (71%) showed improvement of health. The remaining patients exhibited either unchanged health (6 patients, 17%) or worsening of symptoms (4 patients, 11%). The highest rate of improvement was observed in patients with multiple sclerosis, the lowest rate was noted in patients with eczema. The initial mercury-specific lymphocyte reactivity was significantly higher in the responder group, than in the non-responders, whose health was not improved by amalgam removal. All patients with health improvement after amalgam replacement showed reduced proliferation to inorganic mercury in follow-up MELISA. In vitro responses to phenylmercury and nickel did not differ between the groups. CONCLUSIONS: Mercury-containing amalgam may be an important risk factor for patients with autoimmune diseases. MELISA is a valuable tool for selection of patients for amalgam replacement and also for monitoring of metal allergies.

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The possibilities of allergic reactions from silver amalgam restorations. Djerassi E, Berova N. Int Dent J. 1969 Dec;19(4):481-8. 5262217 PubMed. Studies of those with amalgam fillings finds that between 2% - 35% test hypersensitive to mercury.

Toxicology and immunotoxicology of mercury: a comparative review in fish and humans. Sweet LI, Zelikoff JT. J Toxicol Environ Health B Crit Rev. 2001 Apr-Jun; 4(2):161-205. 11341073 PubMed. Analysis of the reviewed studies supports the following conclusions in both lower and higher vertebrates: a threshold for mercury-induced immunotoxicological effects is likely; multiple exposure scenarios involving high and/or chronic exposures leading to increased body burdens are linked to increased risk of immunomodulation; and highly exposed and/or susceptible subpopulations are at greater risk of toxicological impact.

Infertility and Birth Defects

Autometallographic detection of mercury in testicular tissue of an infertile man exposed to mercury vapor. Keck C, Bergmann M, Ernst E, Muller C, Kliesch S, Nieschlag E. Reprod Toxicol. 1993 Sep-Oct; 7(5):469-75. 8274823 PubMed. A 25-year-old male patient presented with unexplained infertility. Semen analysis showed azoospermia or severe oligoasthenoteratospermia with elevated serum FSH. The history revealed that he had been employed in a chemical factory for 5 years working with chloralkali-electrophoresis. Mercury concentrations in hair, blood, and urine samples were considerably above levels of unexposed controls. Bilateral testicular biopsies revealed marked interstitial lymphatic infiltration. About 33% of the tubules analyzed showed a Sertoli-cell-only (SCO) syndrome and tubular atrophy. Fewer than 4% of tubules showed qualitatively intact spermatogenesis. Autometallographic (AMG) analysis of the biopsy material yielded silver-enhanced mercury grains, primarily in the interstitial Leydig cells. Sections from a control patient not exposed to mercury were devoid of mercury grains.

Blood mercury levels in US children and women of childbearing age, 1999-2000. Schober SE, Sinks TH, Jones RL, Bolger PM, McDowell M, Osterloh J, Garrett ES, Canady RA, Dillon CF, Sun Y, Joseph CB, Mahaffey KR. JAMA. 2003 Apr 2;289(13):1667-74. 12672735 PubMed. CONTEXT: Humans are exposed to methylmercury, a well-established neurotoxin, through fish consumption. The fetus is most sensitive to the adverse effects of exposure. The extent of exposure to methylmercury in US women of reproductive age is not known. OBJECTIVE: To describe the distribution of blood mercury levels in US children and women of childbearing age and the association with sociodemographic characteristics and fish consumption. DESIGN AND SETTING: The 1999-2000 data from the National Health and Nutrition Examination Survey, a cross-sectional survey of the noninstitutionalized US population. PARTICIPANTS: In 1999-2000, 1250 children aged 1 to 5 years and 2314 women aged 16 to 49 years were selected to participate in the survey. Household interviews, physical examinations, and blood mercury levels assessments were performed on 705 children (56% response rate) and 1709 women (74% response rate). MAIN OUTCOME MEASURE: Blood concentration of total mercury. RESULTS: Blood mercury levels were approximately 3-fold higher in women compared with children. The geometric mean concentration of total blood mercury was 0.34 micro g/L (95% confidence interval [CI], 0.30-0.39 microg/L) in children and 1.02 microg/L (95% CI, 0.85-1.20 microg/L) in women. Geometric mean mercury levels were almost 4-fold higher among women who ate 3 or more servings of fish in the past 30 days compared with women who ate no fish in that period (1.94 microg/L vs 0.51 microg/L; P<.001). CONCLUSI
ONS: Measures of mercury exposure in women of childbearing age and young children generally fall below levels of concern. However, approximately 8% of women had concentrations higher than the US Environmental Protection Agency's recommended reference dose (5.8 microg/L), below which exposures are considered to be without adverse effects. Women who are pregnant or who intend to become pregnant should follow federal and state advisories on consumption of fish.

Effect of heavy metals on immune reactions in patients with infertility. Podzimek S, Prochazkova J, Pribylova L, Bartova J, Ulcova-Gallova Z, Mrklas L, Stejskal VD. Cas Lek Cesk. 2003; 142(5):285-8. 12920793 PubMed. In patients with metal intolerance diagnosed by the Melisa test, metal ions released from the dental materials can represent a factor, that does not cause infertility but is able to influence it negatively.

Effect of organic and inorganic mercury on human sperm motility. Ernst E, Lauritsen JG. Pharmacol Toxicol. 1991 Jun;68(6):440-4. 1653954 PubMed. The effects of mercuric chloride and methyl mercuric chloride on the motility of human spermatozoa in vitro were investigated. Organic as well as inorganic mercury compounds decreased the percentage of motile spermatozoa. After 15 min. incubation with 40 microM mercuric chloride a significant decrease in sperm motility was observed. Less than 5% of spermatozoa were motile after 30 min. of exposure to 20 microM methyl mercuric chloride. These effects could not be attenuated by addition of 5 microM sodium selenite. The ultrastructural localization of mercury was demonstrated by autometallography. Silver-enhanced mercury deposits could be demonstrated only in spermatozoa exposed to inorganic mercury. In these cells mercury grains were most abundant in membranes of midpiece and tail.

Effects of metallic mercury on the perimenstrual symptoms and menstrual outcomes of exposed workers. Yang JM, Chen QY, Jiang XZ. Am J Ind Med. 2002 Nov; 42(5):403-9. 12382253 PubMed. The prevalence of abdominal pain in the exposed group was significantly higher than that in the control group (odds ratio (OR) = 1.47, 95% CI is 1.03-2.11). The prevalence of dysmenorrhea in the exposed group was significantly higher than that in the control group (OR = 1.66, 95% CI is 1.07-2.59). CONCLUSIONS: An increased prevalence of abnormal menstruation was found in mercury-exposed workers in China. Dysmenorrhea may be a useful biomarker for assessing female exposure to mercury occupationally. These observations suggest that further studies and preventive measures are warranted.

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Environmental pollutants and fertility disorders. Heavy metals and minerals. Gerhard I. Geburtshilfe Frauenheilkd. 1992 Jul; 52(7):383-96. 1499949 PubMed. So far, the influence of lead, cadmium and mercury on human fertility has hardly been considered. First experiences by the authors with the chelating agent 2,3 dimercaptopropane-1-sulfonate (DMPS), which mobilizes heavy metals deposited in the body, seem to favour an association between the body load of heavy metals and complications during the menstrual cycle and during pregnancy. By means of an extensive survey of references, the importance of heavy metals for reproduction is demonstrated. In addition, the deficiency of particular minerals and their interaction with heavy metals are considered. Indications are given for diagnosis and therapy of the exposure to heavy metals. The practical procedure is demonstrated by means of three case studies.

Evaluation of changes in methylmercury accumulation in the developing rat brain and its effects: a study with consecutive and moderate dose exposure throughout gestation and lactation periods. Sakamoto M, Kakita A, Wakabayashi K, Takahashi H, Nakano A, Akagi H. Brain Res. 2002 Sep 13;949(1-2):51-9. 12213299 PubMed. Methylmercury (MeHg) can be transferred to the fetus through the placenta and to newborn offspring through breast milk. The higher mercury (Hg) accumulation and susceptibility to toxicity in the fetus than in the mother during the gestation period is well known. However, the contribution of MeHg exposure through breast milk to the brain Hg concentration in offspring is not clear. The purposes of this study were to evaluate the changes in Hg concentration in the brain of offspring and its effects on the developing rat brain, based on consecutive and moderate doses of MeHg throughout gestation and lactation. Adult female rats were given a diet containing 5 ppm Hg (as MeHg) for 8 weeks. The administration level was thought not to cause adverse effects in adult rats. The rats were then mated and subsequently given the same diet throughout gestation and after parturition. The newborn offspring were placed with the mothers until postnatal day 30. The offspring were exposed to MeHg throughout their intrauterine life through the placenta, and during the postnatal developing phase via contaminated milk. Furthermore, they were given the same diet containing MeHg for 2 months following weaning. On the day of parturition, the concentration of Hg in the brains of newborns was 1.4 times higher than that in the mothers. During the suckling period the concentration in the brain of the offspring rapidly declined to 1/5 of that at birth, suggesting that MeHg transport by milk was limited while the brain and body volumes increased rapidly. The concentration increased gradually again after the offspring started the contaminated diet. In behavioral tests performed at 5 and 6 weeks of age, MeHg-exposed rats showed a significant deficit in motor coordination in the rotarod test and a learning disability in the passive avoidance response test, compared with controls. Histopathologically, focal cerebellar dysplasia, including the heterotopic location of Purkinje cells and granule cells, was observed. These abnormalities may be induced by the effect of highly accumulated MeHg in the brain during the gestation period. Thus, although offspring are subjected to consecutive and moderate dose MeHg exposure throughout both the gestation and suckling periods, the risk is especially high during gestation but may decrease during lactation.

Impact of heavy metals on hormonal and immunological factors in women with repeated miscarriages. Gerhard I, Waibel S, Daniel V, Runnebaum B. Hum Reprod Update. 1998 May-Jun; 4(3):301-9. 9741713 PubMed. We conclude that heavy metals seem to have a negative impact on ovarian as well as on pituitary function. The heavy metal-induced immunological changes may interfere with the physiological adaptation of the immune system to the state of pregnancy with the result of a miscarriage. The observed heavy metal-induced hormonal and immunological changes may be important factors in the pathogenesis of repeated miscarriages.

Infertility and Birth Defects: Is Mercury from Dental Fillings a Hidden Cause? Ziff S, Ziff M. Bio-Probe, Inc. ISBN: 0-941011-03-8.1987. Book.

Heavy metals and fertility. Gerhard I, Monga B, Waldbrenner A, Runnebaum B. J Toxicol Environ Health A. 1998 Aug 21; 54(8):593-611. 9726782 PubMed. Heavy metals have been identified as factors affecting human fertility. Diagnosis and reduction of an increased heavy metal body load improved the spontaneous conception chances of infertile women. Adequate treatment provides successful alternatives to conventional hormonal therapy.

Hong Kong male subfertility links to mercury in human hair and fish. Dickman MD, Leung CK, Leong MK. Sci Total Environ. 1998 Jun 18; 214:165-74. 9646524 PubMed. Mercury in the hair of 117 subfertile Hong Kong males (4.5 ppm, P < 0.05) was significantly higher than mercury levels found in hair collected from 42 fertile Hong Kong males (3.9 ppm). Subfertile males had approx. 40% more mercury in their hair than fertile males of similar age. Although there were only 35 female subjects, they had significantly lower levels of hair mercury than males in similar age groups. Overall, males had mercury levels that were 60% higher than females. Hair samples collected from 16 vegetarians living in Hong Kong (vegans that had consumed no fish, shellfish or meat for at least the last 5 years) had very low levels of mercury. Their mean hair mercury concentration was only 0.38 ppm. 


Occupational exposure to inorganic mercury vapour and reproductive outcomes. Elghany NA, Stopford W, Bunn WB, Fleming LE. Occup Med (Lond). 1997 Aug;47(6):333-6. 9327634 PubMed. The effect of exposure to inorganic mercury on the pregnant woman and her foetus has received little attention. Transport of elemental inorganic mercury into foetal tissues has been reported, and prior studies indicate a higher incidence of adverse pregnancy outcome. The effects of occupational exposure to inorganic mercury on pregnancy were investigated among 46 exposed women workers: controls were 19 women working in non-production areas of the same factory. There were 104 recorded total pregnancies during the period 1948-77. The study revealed a higher frequency of adverse reproductive outcomes, especially congenital anomalies, among the women exposed to inorganic mercury levels at or substantially lower than 0.6 mg/m3; no significant differences in the stillbirth or miscarriage rates were noted between the two groups of women. The overall foetal death rate in this study was similar to New York state (USA) and national levels for the same period.

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Paternal exposure to mercury and spontaneous abortions. Cordier S, Deplan F, Mandereau L, Hemon D. Br J Ind Med. 1991 Jun; 48(6):375-81. 2064975 PubMed. The potential reproductive toxicity of mercury vapour was investigated by comparing the rate of spontaneous abortions among the wives of 152 workers occupationally exposed to mercury vapour with the rate among the wives of 374 controls in the same plant. The results indicate an increase in the rate of spontaneous abortions with an increasing concentration of mercury in the fathers' urine before pregnancy. At concentrations above 50 micrograms/l the risk of spontaneous abortion doubles (odds ratio (OR) = 2.26; 95% confidence interval (95% CI) = 0.99-5.23). Special care was taken to avoid bias in reporting abortions and known risk factors of spontaneous abortions do not seem to explain the results. Several biological mechanisms might account for them including, in particular, direct action of mercury on the paternal reproductive system and indirect toxicity to the mother or embryo through transport of mercury from the father. These indications could be of practical importance and should therefore be further documented.

The effect of occupational exposure to mercury vapour on the fertility of female dental assistants. Rowland AS, Baird DD, Weinberg CR, Shore DL, Shy CM, Wilcox AJ. Occup Environ Med. 1994 Jan; 51(1):28-34. 8124459 PubMed. Women with high occupational exposure to mercury were less fertile than unexposed controls. The fecundability (probability of conception each menstrual cycle) of women who prepared 30 or more amalgams per week and who had five or more poor mercury hygiene factors was only 63% of that for unexposed women (95% CI 42%-96%) after controlling for covariates. Women with low exposure were more fertile, however, than unexposed controls.

Reproductive effects of occupational exposure to mercury on female workers in China: a meta-analysis. Zhonghua Liu Xing Bing Xue Za Zhi. 2007 Dec;28(12):1215-8. 18476585 Pubmed. CONCLUSION: Occupational exposure to mercury could cause dysfunction of the menstrual period, menstrual cycle, menstrual blood volume, as well as dysmenorrhea for female workers being exposed to mercury and inducing adverse reproductive outcomes, including pregnancy-induced hypertension, stillbirth, low birth weight and birth defects of their offspring.

Environmental pollutants and fertility disorders. Heavy metals and minerals. Gerhard I, Runnebaum B. Geburtshilfe Frauenheilkd. 1992 Jul; 52(7):383-96. 1499949 PubMed. So far, the influence of lead, cadmium and mercury on human fertility has hardly been considered. First experiences by the authors with the chelating agent 2,3 dimercaptopropane-1-sulfonate (DMPS), which mobilizes heavy metals deposited in the body, seem to favour an association between the body load of heavy metals and complications during the menstrual cycle and during pregnancy. By means of an extensive survey of references, the importance of heavy metals for reproduction is demonstrated. In addition, the deficiency of particular minerals and their interaction with heavy metals are considered. Indications are given for diagnosis and therapy of the exposure to heavy metals. The practical procedure is demonstrated by means of three case studies.

Infusions

Hall G. V-Tox. Int Symposium "Status Quo and Perspectives of Amalgam and Other Dental Materials." European Academy. Ostzenhausen/Germany. April 29 - May 1, 1994. Sodium ascorbate is administered in lactated Ringer's solution at a pH of 7.0 and an osmolality of over 1200 mOsmol/l dosage of 0.7-0.75 g/kg depending upon the type and severity of the condition presented by the patient. Sodium ascorbate is utilised in the body in oxidation/reduction reactions. It has two hydrogen atoms that can donate electrons. The position of hydrogen in the electrochemical table means that it can donate its electrons to mercury, silver, copper, platinum and palladium. These are the most frequently used metals in restorative dentistry. Once these metals are reduced, the previously prepared detoxification system of the body eliminate the metals via the bile into the faeces. The metals do not appear in the urine. Removal of amalgam fillings without the infusion and vitamin and mineral protection, but with IAOMT protocols in place never gave levels above 300 ug. Removal of amalgam fillings without the infusion and vitamin and mineral protection, but with IAOMT protocols in place never gave levels above 300 ug. Patients reported improvement of mental and psychosocial conditions such as anxiety and depression. Fatigue levels were reduced. Conditions reported improved using this regime include multiple sclerosis, chronic iritis, allergic conditions like eczema and peridontitis (gum disease). Advantages are: little risk to the patient, no possible allergic reaction to drugs used, very effective at symptom relief and very quick postoperative healing after surgery. Disadvantages: Preparation time and need for high level patient cooperation."

Some examples: mercury only stated here (ug/kg stool);

Patient

Age

before

after

no of amalgam fillings

Pat 1

39

<10.0

155,000

11

Pat 2

34

55.0

46,900

13

Pat 3

47

124.5

35,700

12 (all under crowns)

Pat 4

30

329.0

29,400

13

Pat 5

41

46.0

25,900

5

Pat 6

54

16.5

3,550

2 (small buccals)

Pat 7

20

<10.0

13

0 (never had any fillings)

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Intestinal

Bacterial mercury resistance from atoms to ecosystems. Barkay T, Miller SM, Summers AO. FEMS Microbiol Rev. 2003 Jun; 27(2-3):355-84. 12829275 PubMed. Bacterial resistance to inorganic and organic mercury compounds (HgR) is one of the most widely observed phenotypes in eubacteria.

Bacterial oxidation of mercury metal vapor, Hg(0). Smith T, Pitts K, McGarvey JA, Summers AO. Appl Environ Microbiol. 1998 Apr; 64(4):1328-32. 9546169 PubMed. These observations establish for the first time that bacteria can contribute, as do mammals and plants, to the oxidative phase of the global Hg cycle.

Intestinal handling of mercury in the rat: implications of intestinal secretion of inorganic mercury following biliary ligation or cannulation. Zalups RK. J Toxicol Environ Health A. 1998 Apr 24; 53(8):615-36. 9572160 PubMed. The findings from the present study show that when bile flow is obstructed or diverted, clear evidence for secretory movement of mercury into the lumen of the gastrointestinal (GI) tract can be demonstrated. These findings also indicate that the secretory movement of mercury into the lumen of the GI tract is a mechanism that contributes significantly to the pool of mercury that is excreted in the feces.

Legal and Political

Bill would ban mercury fillings in some dental patients. Kerry Fehr-Snyder. The Arizona Republic Mar. 24, 2003.  A bipartisan group of Arizona legislators is pushing a bill that would prohibit dentists from putting mercury fillings in the teeth of children, pregnant women and nursing mothers. The bill, which is waiting for a vote in the House, also requires dentists to inform patients of the advantages and disadvantages of mercury amalgams, which some researchers believe give off toxic vapors that cause neurological damage and other health problems. http://www.toxicteeth.net/natCamp_stateGovt_azrepublic.cfm 

Legal issues. There are signs that cooperation between other state boards and the ADA is starting to crumble. In Oregon the ACLU won a lawsuit that forced the dental board to rescind its rule that discussion of amalgam replacement constituted "fraud" because it violated dentists' First Amendment rights. They do not have an interest in science; their interest is economics." The ADA held patent on two amalgam products until 1994 and 1995 respectively. Lawsuits filed in other states, such as California and Maryland, challenge the ADA on scientific and economic grounds. The suits allege that the ADA engaged in "deceptive" business practices by referring to the fillings as "silver" rather than "mercury." Furthermore, in some cases, the suits claim, exposure from mercury coming partly from amalgams contributed to cases of childhood autism. The ADA claims the suits are without basis. www.princeofwalesonline.com/mercury.htm  

The science and politics of dental amalgam. Gelband H. Int J Technol Assess Health Care. 1998 Winter; 14(1):123-34. 9509800 PubMed. Sweden is phasing out amalgam entirely, possibly by the end of 1997. Germany has produced guidelines for limiting its use, other countries have signaled their intention to reduce it, and others--the United States and Canada--have studied the matter but taken no action. Policy differences within Europe have made dental amalgam a test case for the European Community's new medical device regulations. Relatively little epidemiologic research has been initiated to try to answer the question of dental amalgam's possible health effects. An international effort to define and carry out a research agenda to guide public policy is called for.

UN Committee Recommends Stricter Mercury Limits. New York, June 30, 2003 Environment News Service (ENS). A joint United Nations and World Health Organization (WHO) food safety committee called last week for a tougher standard for levels of mercury in food. The committee said the revised standard, which is nearly twice as strict as the existing world health exposure standard, is merited because of growing evidence of health risks from mercury to pregnant women and children. The experts reevaluated previous JECFA risk assessments for methylmercury and recommended that the Provisional Tolerable Weekly Intake be cut to 1.6 micrograms per kilograms of bodyweight - nearly half the original standard of 3.3 micrograms per kilogram. Scientists have shown that methylmercury can cause brain and nerve damage and studies indicate children and women of childbearing age are at a disproportionate risk. The experts reevaluated previous JECFA risk assessments for methylmercury and recommended that the Provisional Tolerable Weekly Intake be cut to 1.6 micrograms per kilograms of bodyweight - nearly half the original standard of 3.3 micrograms per kilogram. The U.S. Food and Drug Administration (FDA) weekly standard is 2.8 micrograms per kilogram.

Consumers for Dental Choice, Inc. The San Francisco Commission on the Environment. On July 9, the Commission mandated that all dentists must install amalgam separators by the end of 2003.

On July 11, the Dental Board of CA voted 7 to 1 to direct all dentists to give patients a dental materials fact sheet that will advise dental patients that mercury fillings "can harm the developing brain of a child or fetus," and that such fillings "cause exposure to mercury, a chemical known to the State of California to cause birth defects and other reproductive harm." The rationale, according to comments by Board member Dr.Hundley during the consideration: "We have established and we have conceded that there may be some harm in mercury.......We have chosen to accept the fact that there may be harm and we are placing that information out to the public." "We had scientific evidence that tend to show us there was no harm in silver fillings. On the flip side of that, we have scientific evidence that there was harm. We have chosen to accept the fact that there may be harm and we are placing that information out to the public. Now we are fulfilling our obligation under Proposition 65 to state to the patients and have them accept that there may be some harm in mercury fillings.”

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The new fact sheet was proposed by Dr. Chet Yokoyama, the board’s mercury-free dentist, who chaired a committee appointed by board president Dr. Alan Kaye. It implements a 1992 law under which the Board has been constantly criticized for ignoring, one requiring a statement of the “risks and efficacies” of dental fillings. An amendment in 2001 required the fact sheet to go to patients. Upon signing the law, Governor Davis said the “mercury risk fact sheet” would advise patients of the risks of mercury in some dental fillings in advance of their placement. http://www.toxicteeth.net/natCamp_stateGovt_sanFran.cfm   

Dentists Settle in Mercury Cleanup Case. American. Dental Association News. Aug. 15, 1988. Fifty-eight New England dentists who owned two dental supply companies and a company brokering dental amalgam were sued for improperly disposing of amalgam at two different waste sites. They lost and were fined and the two sites had to be cleaned up, involving the removal of over 1200 tons of contaminated soil.

David Kennedy, D.D.S., et al. v. American Dental Association, Civil Action No. 1-90 Civ. 1692 (N.D. Ohio 1990). On September 20, 1990, a class action suit was filed in federal court. Forty anti-amalgam dentists have charged the ADA with fraud for continuing to claim that amalgam fillings are safe.

California requires dentists to disclose dangers of mercury and other dental materials. Wholistic Research Company. January 2003.  For the first time anywhere, dentists will be required to post a warning about the dangers of mercury in their dental fillings. A California Superior court judge finalized the language for the warning to be posted in dentists' offices here today. The warning will read as follows: Notice to Patients, Proposition 65: Warning on dental amalgams, used in many dental fillings, causes exposure to mercury, a chemical known to the state of California to cause birth defects or other reproductive harm. Root canal treatments and restorations including fillings, crowns andbridges, use chemicals known to the state of California to cause cancer. The U.S. Food and Drug Administration has studied the situation and approved for use all dental restorative materials. Consult your dentist to determine which materials are appropriate for your treatment. The exact language of the warning was argued and then finalized before Superior Court Judge James A. Robertson II between the California Dental Association, the largest constituent organization of the American Dental Association and Attorney Shawn Khorrami (Cor-ahm-mee). The agreement requires its member dentists to warn patients about the toxic dangers of mercury dental fillings and root canals. The agreement also allows non-CDA dentists to opt in to the agreement and post the warning. This California consent judgment follows on the heels of recent lawsuits filed in Georgia, Texas, Ohio and Los Angeles, California charging that mercury fillings placed in a woman's mouth contributed to the autism of her child, as well as lawsuits in Maryland, California, and New York charging the American Dental Association with misrepresenting amalgam dental fillings as "silver." The lawsuits basically allege that such fillings actually contain approximately 50% mercury by weight. They cause continuous, daily exposure to mercury and, thereby pose substantial health risks to certain users. Mercury, a highly toxic substance, is the most widely used substance in dental fillings today. http://www.wholisticresearch.com/info/artshow.php3?artid=390  Web

Bans on Amalgam. Countries banning or restricting amalgam use.Germany and Austria have restricted the use of amalgams in children, women of childbearing age and patients with kidney problems. In addition, the German company Degussa, one of the world's leading manufacturers of dental fillings, has dropped its amalgam line entirely, and the Austrian government has set a goal of banning all amalgams by the year 2000. Austria won't be the first, either. Sweden is now the first country in the world to ban silver-mercury amalgam fillings outright. Amalagam fillings are banned in Sweden and Health Canada has proposed a limit of one (two surfaces) amalgam fillings in a child and four (eight surfaces) in an adult. Asorted sources

Report CÉTS 97-3 Re: The Safety of Dental Amalgam: A state of the art review. Montreal: CÉTS, 1997. 90 p. (ISBN 2-550-31684-3) Dental amalgam is available and used in virtually every country of the world today. This will change, however, in 1997, as Sweden becomes the first country to eliminate entirely the use of amalgam. Sweden’s phaseout is predicated on a goal of reducing environmental mercury contamination, and not on directly protecting the health of individuals. There has been, for at least adecade, however, a movement in Sweden to eliminate dental amalgam for health reasons. Germany has issued recommendations to restrict the use of amalgam in young children, pregnant women, and others with particular health problems. Other countries in Europe are considering following Sweden’s or Germany’s lead, using either environmental or health rationales for reducing or eliminating dental amalgam, but they are still in the minority. Most countries have no such restrictions and none on the horizon. The European Commission has undertaken a review of the safety of dental amalgam because of these policy differences. Health Canada’s recommendations to reduce the use of amalgam in the primary teeth of children, in pregnant women, and in individuals with kidney disease are consistent with the uncertain evidence regarding possible effects of dental amalgam. If there are effects, these populations are likely to be particularly vulnerable, so, from a public health standpoint, they are logical recommendations. http://www.aetmis.gouv.qc.ca/fr/publications/scientifiques/medecine_dentaire/1997_03_res_en.pdf  Web

Comments on the article "the toxicology of mercury and its chemical compounds" by Clarkson and Magos (2006). Crit Rev Toxicol. 2007;37(6):537-49; Mutter J, et al. University Hospital, Institute for Environmental Medicine and Hospital Epidemiology, Freiburg, Germany. joachim.mutter@uniklinik-freiburg.de. 17661216 Clarkson and Magos (2006) provide their perspectives on the toxicology of mercury vapor and dental amalgam. As scientists who are involved in preparing a German federal guideline regarding dental amalgam, we welcome additional scientific data on this issue. However, Clarkson and Magos do not present all the relevant studies in their review. The additional data provided here show that: (a) Dental amalgam is the main source of human total mercury body burden, because individuals with amalgam have 2-12 times more mercury in their body tissues compared to individuals without amalgam; (b) there is not necessarily a correlation between mercury levels in blood, urine, or hair and in body tissues, and none of the parameters correlate with severity of symptoms; (c) the half-life of mercury deposits in brain and bone tissues could last from several years to decades, and thus mercury accumulates over time of exposure; (d) mercury, in particular mercury vapor, is known to be the most toxic nonradioactive element, and is toxic even in very low doses, and (e) some studies which conclude that amalgam fillings are safe for human beings have important methodogical flaws. Therefore, they have no value for assessing the safety of amalgam.

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Methylation

Biosynthesis of methylmercury compounds by the intestinal flora of the rat. Rowland I, Davies M, Grasso P. Arch Environ Health. 1977 Jan-Feb; 32(1):24-8. 836083 PubMed. Pure cultures of bacteria, isolated from the intestinal tract of the rat, could methylate mercuric chloride. It was estimated that the total amount of methylmercury synthesized from ingested inorganic mercury in man in approximately 400 ng/day.

Dental amalgam fillings and the amount of organic mercury in human saliva. Leistevuo J, Leistevuo T, Helenius H, Pyy L, Osterblad M, Huovinen P, Tenovuo J. Caries Res. 2001 May-Jun; 35(3):163-6. 11385194 PubMed. The amount of organic and inorganic mercury in paraffin-stimulated saliva was significantly higher (p<0.001) in subjects with dental amalgam fillings (n = 88) compared to the nonamalgam study groups (n = 43 and n = 56): log(e) (organic mercury) was linearly related to log(e) (inorganic mercury, r(2) = 0.52). Spearman correlation coefficients of inorganic and organic mercury concentrations with the number of amalgam-filled tooth surfaces were 0.46 and 0.27, respectively. Our results are compatible with the hypothesis that amalgam fillings may be a continuous source of organic mercury, which is more toxic than inorganic mercury, and almost completely absorbed by the human intestine.  

Methylation of mercury from dental amalgam and mercuric chloride by oral streptococci in vitro. Heintze U, Edwardsson S, Derand T, Birkhed D. Scand J Dent Res. 1983 Apr; 91(2):150-2. 6222462 PubMed. The capacity of the oral bacteria Streptococcus mitior, S. mutans and S. sanguis to methylate mercury was investigated in vitro. Mercuric chloride and pulverized dental amalgam in distilled water, respectively, were used as sources of mercury. Methylmercury was found in the bacterial cells of all three tested strains. The results indicate that organic mercury compounds may be formed in the oral cavity.

The methylation of mercuric chloride by human intestinal bacteria. Rowland IR, Grasso P, Davies MJ. Experientia. 1975 SEP 15; 31(9):1064-5. 1100426 PubMed. Most strains of staphylococci, streptococci, yeasts and E. coli isolated from human faeces, could synthesize methylmercury compounds. In contrast, few strains of obligate anaerobes could do so. Up to 6 ng methylmercury/ml were formed in 44 h from 2 mug mercuric chloride.

Transformations of inorganic mercury by Candida albicans and Saccharomyces cerevisiae. Yannai S, Berdicevsky I, Duek L. Appl Environ Microbiol. 1991 Jan; 57(1):245-7. 2036011 PubMed. Saccharomyces cerevisiae and Candida albicans were incubated with 0.25, 0.5, or 0.75 micrograms of Hg (as HgCl2) per ml of Nelson's medium in the presence of trace amounts of oxygen at 28 degrees C for 12 days. Two control media were used, one without added Hg and one without yeast inoculum. Yeast cell growth was estimated after 1, 2, 3, and 8 days of incubation. The contents of organomercury in the system and of elemental mercury released from the media and collected in traps were determined at the end of the experiments. The results were as follows. (i) C. albicans was the more mercury-resistant species, but both yeast species failed to grow in the media containing 0.75 micrograms of Hg per ml. (ii) The amounts of organomercury produced by the two species were proportional to the amount of HgCl2 added to the medium. In all cases C. albicans produced considerably larger amounts of methylmercury than S. cerevisiae. (iii) The amounts of elemental Hg produced were inversely proportional to the HgCl2 level added in the case of S. cerevisiae but were all similar in the case of C. albicans. (iv) Neither organomercury nor elemental Hg was produced in any of the control media.

Mutations

Genotoxic effects of mercury on in vitro cultures of human cells. Bahia Mde O, De Amorim MI, Burbano RR, Vincent S, Dubeau H. An Acad Bras Cienc. 1999;71(3 Pt 1):437-43. 10530333 PubMed. Mercury is a highly deleterious environmental pollutant, with recognized mutagenic and teratogenic effects. Given this, we evaluated the changes induced in vitro by two mercury compounds (mercury chloride--MC--and methyl mercuric chloride--MMC) on the genetic) material of a human lymphoblastoid cell line (TK6) on the basis of both the frequency of mutations at the hprt locus, and the number of chromosomic anomalies. The frequencies of HPRT- mutants in the TK6 cell line following exposure to the mercury compounds are inconclusive with regard to a mutagenic effect. However, both mercury compounds exhibit a clear cytotoxic effect, which increases with dosage. There was also no statistically significant increase in the frequency of chromosomic bleakage or gaps, nor in the number of cells with chromosomic alterations in the lymphoblastoid line. Nevertheless, MMC did provoke a marked reduction in the frequency of mitosis, both on its own and in combination with MC.

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Oral Health

Amalgam associated mercury accumulations in normal oral mucosa, oral mucosal lesions of lichen planus and contact lesions associated with amalgam. Bolewska J, Holmstrup P, Moller-Madsen B, Kenrad B, Danscher G. J Oral Pathol Med. 1990 Jan; 19(1):39-42. 2313605 PubMed. The histochemical technique showed that three biopsies in Group IV (occlusal fillings only) and two in Group V (opposing buccal fillings) contained traces of mercury in the juxtaepithelial connective tissue. The silver enhanced mercury was found in macrophages. The two controls (Group VI) without amalgam fillings were devoid of precipitates.

An amalgam tattoo causing local and systemic disease? Weaver T, Auclair PL, Taybos GM. Oral Surg Oral Med Oral Pathol. 1987 Jan; 63(1):137-40. 3543795 PubMed. Amalgam tattoos are common oral lesions. The case presented here involved a 33-year-old woman who had had an amalgam tattoo for 2 years and complained of localized soreness and occasional swelling as well as systemic symptoms of weight loss, fatigue, sinusitis, and headaches. After excisional biopsy of the lesion, the patient's complaints ceased dramatically. It is suggested that alterations in healing due to the presence of amalgam particles led to systemic as well as local disease.

Mercury in saliva and feces after removal of amalgam fillings. Bjorkman L, Sandborgh-Englund G, Ekstrand J. Toxicol Appl Pharmacol. 1997 May; 144(1):156-62. 9169079 PubMed. It was concluded that amalgam fillings are a significant source of Hg in saliva and feces. Hg levels in all media decrease considerably after amalgam removal. The uptake of amalgam mercury in the GI tract in conjunction with removal of amalgam fillings seems to be low.

Oral lesions and symptoms related to metals used in dental restorations: a clinical, allergological, and histologic study. Koch P, Bahmer FA. J Am Acad Dermatol. 1999 Sep; 41(3 Pt 1):422-30. 10459117 PubMed. Our results suggest that sensitization to mercury is an important cause of OLL, whether all lesions or only a part of them are adjacent to amalgam fillings.

Oral lichen planus lesions in contact with amalgam fillings: a clinical, histologic, and immunohistochemical study. Ostman PO, Anneroth G, Skoglund A. Scand J Dent Res. 1994 Jun; 102(3):172-9. 8085124 PubMed. In 17 (33%) patients, an allergic reaction to mercury was found, and candidiasis was diagnosed in 13 (25%) patients. The true nature of OLP-like lesions in contact with amalgam fillings still remains to be explained. For that matter, we do not know whether OLP is one disease or a number of similar immunologic or other responses to various interacting stimuli. One such stimulus might be mercury from corroding amalgam fillings.  

Oral mucosal lesions related to silver amalgam restorations. Bolewska J, Hansen HJ, Holmstrup P, Pindborg JJ, Stangerup M. Oral Surg Oral Med Oral Pathol. 1990 Jul; 70(1):55-8. 2371051 PubMed. On the basis of these findings, contact allergy to mercury is suggested as a possible etiologic factor of the mucosal changes in group 1, and the designation contact lesion is proposed for such lesions.

The histopathology of oral mucosal lesions associated with amalgam or porcelain-fused-to-metal restorations. Larsson A, Warfvinge G. Oral Dis. 1995 Sep; 1(3):152-8. 8705821 PubMed. Amalgam-associated lichenoid lesions present a wide spectrum of histopathologic patterns, corresponding to similar patterns in dermatopathology but with no evidence of association with specific disease. PFM-associated lesions tend to display similar lichenoid features, suggestive of common pathogenetic mechanisms. Hg accumulations may play a role to maintain the chronicity of such lichenoid lesions.

The relationship between mercury from dental amalgam and oral cavity health. Siblerud RL. Ann Dent. 1990 Winter; 49(2):6-10. 2132561 PubMed. The findings presented here suggest that mercury from dental amalgam may play a role in the etiology of oral cavity health. Comparisons between subjects with and without amalgam showed significant differences of diseases of the mouth. Subjects who had amalgams removed reported that symptoms of diminished oral health were improved or eliminated after removal. The data suggest that inorganic mercuryfrom dental amalgam does affect the oral cavity.

Three cases of linear lichen planus caused by dental metal compounds. Sasaki G, Yokozeki H, Katayama I, Nishioka K.  J Dermatol. 1996 Dec; 23(12):890-2. 9037921 PubMed. Three cases of linear lichen planus on the lower extremities unaccompanied by mucous lesions are described. Dental metal compounds were thought to be the precipitating factor in all cases. These results suggest that metal compound specific T cells might be responsible for the development of linear lichen planus.

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Periodontal

Maternal periodontitis and prematurity. Part I: Obstetric outcome of prematurity and growth restriction. Offenbacher S, Lieff S, Boggess KA,Murtha AP, Madianos PN, Champagne CM, McKaig RG, Jared HL, Mauriello SM, Auten RL Jr, Herbert WN, Beck JD. Ann Periodontol. 2001 Dec; 6(1):164-74. 11887460 PubMed. In summary, the present study, although preliminary in nature, provides evidence that maternal periodontal disease and incident progression are significant contributors to obstetric risk for preterm delivery, low birth weight and low weight for gestational age. These studies underscore the need for further consideration of periodontal disease as a potentially new and modifiable risk for preterm birth and growth restriction.

Nutrition: impact on oral and systemic health. Enwonwu CO, Sanders C. Compend Contin Educ Dent. 2001 Jul; 22(3 Spec No):12-8. 11913248 PubMed. Malnutrition (particularly protein-energy malnutrition, which invariably involves concurrent deficiencies of the antioxidant micronutrients) promotes salivary gland hypofunction, impaired immunity, and an early shift in the oral microbial ecology toward a preponderance of anaerobic organisms. The immune suppression, which includes impaired cytokine function as well as diminished acute-phase response to infections, impactsnegatively on the natural history of inflammatory periodontal diseases. The pathogenesis of oral cancer is influenced by deficiencies of antioxidant nutrients, and there is evidence for diminished DNA methylation, disruption of DNA integrity, and increased DNA damage in folate deficiency.

Periodontal disease and cardiovascular disease: epidemiology and possible mechanisms. Genco R, Offenbacher S, Beck J. J Am Dent Assoc. 2002 Jun; 133 Suppl:14S-22S. 12085720 PubMed. The accumulation of epidemiologic, in vitro, clinical and animal evidence suggests that periodontal infection may be a contributing risk factor for heart disease. However, legitimate concerns have arisen about the nature of this relationship. These are early investigations. Since even a moderate risk contributed by periodontal disease to heart disease could contribute to significant morbidity and mortality, it is imperative that further studies be conducted to evaluate this relationship. One particularly important study to be carried out is the investigation of a possible clinically meaningful reduction in heart disease resulting from the prevention or treatment of periodontal disease.

Relationship between periodontal disease and C-reactive protein among adults in the Atherosclerosis Risk in Communities study. Slade GD, Ghezzi EM, Heiss G, Beck JD, Riche E, Offenbacher S. Arch Intern Med. 2003 May 26; 163(10):1172-9. 12767953 PubMed. Extensive periodontal disease and body mass index (BMI) are jointly associated with increased C-reactive protein (CRP) levels in otherwise healthy, middle-aged adults, suggesting the need for medical and dental diagnoses when evaluating sources of acute-phase response in some patients.

Periodontal disease is associated with lower antioxidant capacity in whole saliva and evidence of increased protein oxidation. Sculley DV, Langley-Evans SC. Clin Sci (Lond). 2003 Aug; 105(2):167-72. 12650638 PubMed. Poor periodontal health was associated with increased concentrations of protein carbonyls in saliva. Women had significantly lower total antioxidant status than men, regardless of periodontal health. Periodontal disease is associated with reduced salivary antioxidant status and increased oxidative damage within the oral cavity.

Regulatory Agencies

OSHA, NIOSH, ACGIH. Lists exposure limits for mercury types as of July 28, 2003.

Exposure Limits

 

 

Mercury, Alkyl Compounds

Mercury, Aryl Compounds

Mercury, Inorganic Compounds

OSHA

 

 

 

     8-Hour TWA

0.01 mg/m3

-

-

     Ceiling

0.04 mg/m3

0.1 mg/m3

0.1 mg/m3

NIOSH

 

 

 

     8-Hour TWA

0.01 mg/m3, Skin

0.05 mg/m3, Skin

0.05 mg/m3, Skin

     ST/Ceiling

0.03 mg/m3, (ST) Skin

0.1 mg/m3, (Ceiling) Skin

0.1 mg/m3, (Ceiling) Skin

     IDLH

2 mg/m3

10 mg/m3

10 mg/m3

ACGIH

 

 

 

     8-Hour TWA

0.01 mg/m3, Skin

0.1 mg/m3, Skin

0.025 mg/m3, Skin

     Short Term

0.03 mg/m3, Skin

-

-

 

Revised: 28 July 2003

 http://www.osha.gov/SLTC/mercury/exosure_limits.html  Web

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Relationship to Amalgam Fillings

Amalgam studies: disregarding basic principles of mercury toxicity. Mutter J, Naumann J, Sadaghiani C, Walach H, Drasch G. Int J Hyg Environ Health. 2004 Sep;207(4):391-7. 15471104 PubMed. Dental amalgam, which has been used for over 150 years in dental practice, consists of about 50% metallic mercury. Studies on animal and humans show that mercury is continuously released from dental amalgam and absorbed by several body tissues. It is widely accepted that the main source of mercury vapor is dental amalgam and it contributes substantially to mercury load in human body tissues. There is still a controversy about the consequences of this additional mercury exposure from amalgam to human health. Many studies were performed to evaluate possible adverse effects. In this comment, these studies were analyzed with regard to their methodical quality by considering the newest findings on mercury toxicity and metabolism. In sum, a number of studies are methodically flawed drawing inaccurate conclusions as to the safety of dental amalgam.

Conference on Trace Elements in Health and Disease. Stockholm May 25, 1992. Malmström C, Hanson M, Nylander M. Brain levels of mercury are directly proportional to the number of surfaces of amalgam fillings in the mouth.

Factors affecting internal mercury burdens among eastern German children. Trepka MJ, Heinrich J, Krause C, Schulz C, Wjst M, Popescu M, Wichmann HE. Arch Environ Health. 1997 Mar-Apr; 52(2):134-8. 9124874 PubMed. The most significant factor that affected urinary mercury levels was the number of dental amalgam fillings; 27% of the variance in the regression model was explained by the presence of these fillings.

Mercury in biological fluids after amalgam removal. Sandborgh-Englund G, Elinder CG, Langworth S, Schutz A, Ekstrand J. J Dent Res. 1998 Apr; 77(4):615-24.  9539465 PubMed. It is concluded that the process of removing amalgam fillings can have a considerable impact on Hg levels in biological fluids. After removal, there was a considerable decline in the Hg levels of blood, plasma, and urine, which slowly approached those of subjects without any history of amalgam fillings.

Mercury concentrations in the human brain and kidneys in relation to exposure from dental amalgam fillings. Nylander M, Friberg L, Lind B. Swed Dent J. 1987; 11(5):179-87. 3481133 PubMed. It is concluded that the cause of the association between amalgam load and accumulation of mercury in tissues is the release of mercury vapour from amalgam fillings.

Is dental amalgam safe for humans? The opinion of the scientific committee of the European Commission. Mutter J. J Occup Med Toxicol. 2011 Jan 13;6(1):2. 21232090 PubMed. It was claimed by the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR)) in a report to the EU-Commission that "....no risks of adverse systemic effects exist and the current use of dental amalgam does not pose a risk of systemic disease..." [1, available from: http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_016.pdf]. SCENIHR disregarded the toxicology of mercury and did not include most important scientific studies in their review. But the real scientific data show that: (a) Dental amalgam is by far the main source of human total mercury body burden. This is proven by autopsy studies which found 2-12 times more mercury in body tissues of individuals with dental amalgam. Autopsy studies are the most valuable and most important studies for examining the amalgam-caused mercury body burden. (b) These autopsy studies have shown consistently that many individuals with amalgam have toxic levels of mercury in their brains or kidneys. (c) There is no correlation between mercury levels in blood or urine, and the levels in body tissues or the severity of clinical symptoms. SCENIHR only relied on levels in urine or blood. (d) The half-life of mercury in the brain can last from several years to decades, thus mercury accumulates over time of amalgam exposure in body tissues to toxic levels. However, SCENIHR state that the half-life of mercury in the body is only "20-90 days". (e) Mercury vapor is about ten times more toxic than lead on human neurons and with synergistic toxicity to other metals. (f) Most studies cited by SCENIHR which conclude that amalgam fillings are safe have severe methodical flaws.

 

Release and Absorption

A model for recording mercury release from an amalgam surface. Brune D. Biomaterials. 1985 Sep; 6(5):357-9. 4052550 PubMed. The release rate of mercury from a conventional, a dispersed phase or a spherical high copper content amalgam under static conditions in stimulated or artificial saliva has been measured and found to decrease approximately exponentially with time. A higher initial release rate was observed for mercury in stimulated saliva than in artificial saliva during the in vitro experiments. In a pilot study corrosion current was recorded from an amalgam specimen immersed in saliva, and was found to decrease approximately exponentially with time. After brushing the surface of the amalgam during two subsequent periods, in a manner similar to toothbrushing, an increase in corrosion current was measured indicating the removal of loosely bound corrosion products. A model describing the periodical mercury release from an amalgam surface has been proposed.

An estimation of the uptake of mercury from amalgam fillings based on urinary excretion of mercury in Swedish subjects. Weiner JA, Nylander M. Sci Total Environ. 1995 Jun 30; 168(3):255-65. 7644912 PubMed. Mercury is released from amalgam fillings in several forms, i.e. as elemental vapour, ions and in fine particles. Despite many investigations there is still considerable uncertainty concerning the uptake of such mercury. Most available estimates have calculated the pulmonary uptake of mercury vapour based on measurements of concentrations intra-orally or in expired breath. Presented estimates vary by an order of magnitude from approximately 1 to 20 micrograms/day. The possibility of estimating this uptake based on levels of mercury in a biological index medium has received comparatively little attention. The purpose of the present work is to estimate the uptake of mercury from amalgam fillings based on urinary concentrations of mercury. It is estimated that the average uptake of mercury from amalgam fillings in Swedish subjects is within the interval 4-19 micrograms/day. This interval was arrived at after a detailed evaluation of the uncertainties in the data used and in the different assumptions. Not withstanding the considerable range of this estimate it indicates a higher uptake than several other estimates, some of which have had a large impact on the scientific debate concerning this issue.

Compositions of surface layers formed on amalgams in air, water, and saline. Hanawa T, Gnade BE, Ferracane JL, Okabe T, Watari F. Dent Mater J. 1993 Dec; 12(2):118-26. 8004906 PubMed. The surface layers formed on both a zinc-free and a zinc-containing dental amalgam after polishing and aging in air, water, or saline, were characterized using x-ray photoelectron spectroscopy (XPS) to determine the compositions of the surface layers which might govern the release of mercury from amalgam. The XPS data revealed that the formation of the surface layer on the zinc-containing amalgam was affected by the environment in which the amalgam was polished and aged, whereas that on the zinc-free amalgam was not affected. In addition, among the elements contained in amalgam, zinc was the most reactive with the environment, and was preferentially dissolved from amalgam into water or saline. Mercury atoms existed in the metallic state in the surface layer.

Dental amalgam and mercury. Jokstad A, Thomassen Y, Bye E, Clench-Aas J, Aaseth J.  Pharmacol Toxicol. 1992 Apr; 70(4):308-13. 1608917 PubMed. A differentiation of the mercury absorption due to exposure from dental amalgams and from the dietary intake, necessitates measurements of both organic and inorganic mercury in the plasma, and in the erythrocytes. The results suggest that individuals with many amalgam restorations, i.e., more than 36 restored surfaces, absorb 10-12 micrograms Hg/day.

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Documented clinical side-effects to dental amalgam. Ziff MF. Adv Dent Res. 1992 Sep; 6:131-4. 1292453 PubMed. 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).

Estimation of mercury body burden from dental amalgam: computer stimulation of a metabolic compartmental model. Vimy MJ, Luft AJ, Lorscheider FL. J Dent Res. 1986 Dec; 65(12):1415-9. 3465771 PubMed. The model predicted that continuous exposure to elemental Hg vapor, at 30 micrograms/day for 10 years, would result in a total Hg body burden of 5.9 mg, of which 4.8 mg could be contained in R4. Assuming that the Hg in R4 displayed uniform distribution throughout the body, then the brain concentration was estimated to be 68 ng/g wet weight. In contrast, if Hg in R4 reflected long-term preferential accumulation in brain and other neural tissue, then concentrations as high as 4.0 micrograms/g could be attained.

Factors influencing mercury evaporation rate from dental amalgam fillings. Bjorkman L, Lind B. Scand J Dent Res. 1992 Dec; 100(6):354-60. 1465570 PubMed. 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.

Human exposure to mercury and silver released from dental amalgam restorations. Skare I, Engqvist A. Arch Environ Health. 1994 Sep-Oct;49(5):384-94. 7944571 PubMed. In 35 healthy individuals, the number of amalgam surfaces was related to the emission rate of mercury into the oral cavity and to the excretion rate of mercury by urine. Oral emission ranged up to 125 micrograms Hg/24 h, and urinary excretions ranged from 0.4 to 19 micrograms Hg/24 h. In 10 cases, urinary and fecal excretions of mercury and silver were also measured. Fecal excretions ranged from 1 to 190 micrograms Hg/24 h and from 4 to 97 micrograms Ag/24 h. Except for urinary silver excretion, a high interplay between the variables was exhibited. The worst-case individual showed a fecal mercury excretion amounting to 100 times the mean intake of total Hg from a normal Swedish diet. With regard to a Swedish middle-age individual, the systemic uptake of mercury from amalgam was, on average, predicted to be 12 micrograms Hg/24 h.

Long-term mercury excretion in urine after removal of amalgam fillings. Begerow J, Zander D, Freier I, Dunemann L. Int Arch Occup Environ Health. 1994; 66(3):209-12. 7814102 PubMed. These results show that the release of mercury from dental amalgam contributes predominantly to the mercury exposure of non-occupationally exposed persons. The exposure from amalgam fillings thus exceeds the exposure from food, air and beverages. Within 12 months after removal of all amalgam fillings the participants showed substantially lower urinary mercury levels which were comparable to those found in subjects who have never had dental amalgam fillings.

Long-term dissolution of mercury from a non-mercury-releasing amalgam. Chew CL, Soh G, Lee AS, Yeoh TS. Clin Prev Dent. 1991 May-Jun;13(3):5-7. 1860296 PubMed. The hazards of mercury from dental amalgams have long been recognized. This study examined the mercury release from a "non-mercury-releasing" dental amalgam, Composil, over a 104-week period. Four cylindrical specimens were incubated in 10 ml of purified water at 37 degrees C. The incubate was changed at the end of each 24-hour period and assayed for its mercury content at biweekly intervals. Mercury estimation was carried out using cold-vapor, atomic absorption spectrophotometry over a 104-week period. Results showed that the overall mean release of mercury was 43.5 +/- 3.2 micrograms/cm2/24 hr, and the amount of mercury released remained fairly constant during the duration of the experiment. This study showed that Composil releases mercury in quantities that far exceed those detected in other amalgam systems.

Mercury. Pollution Prevention and Abatement Handbook. WORLD BANK GROUP. Effective July 1998. http://lnweb18.worldbank.org/ESSD/essdext.nsf/51DocByUnid/5D84EC1DFC34422785256BA5006C010C/$FILE/ HandbookMercury.pdf. About 80% of inhaled vapor is retained and absorbed in the bloodstream.

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Mercury toxicity and dental amalgam. Wolff M, Osborne JW, Hanson AL. Neurotoxicology. 1983 Fall; 4(3):201-4. 6361623 PubMed. There is adequate evidence that dental amalgam restorations, during and after placement, results in the release of Hg into the patient's body. Whether the Hg released from amalgam is due to placement procedures, surface abrasion, or later corrosion breakdown, there is evidence that a low level Hg release continues for years. It is generally agreed that if amalgam was introduced today as a restorative material, they would never pass F.D.A. approval. With new and more accurate techniques of measuring Hg levels, especially in tissue and blood, additional studies are necessary to relate blood-Hg levels with dental amalgam restorations. Studies must relate existing restorations as well as the placement of new restorations to body-Hg levels. It is possible that we have accepted a potentially dangerous material as being safe.

Patterns of mercury release from amalgam fillings into the oral cavity. Motorkina AV, Barer GM, Volozhin AI. Stomatologiia (Mosk). 1997;76(4):9-11. 9381508 PubMed. Seventy-five subjects aged 20 to 57 with 1 to 15 fillings of silver amalgam were examined. The level of mercury vapors in the oral cavity was assessed using an AGP-01 device and the method developed by the authors. Emission of mercury vapors in the oral cavity increased with the number of fillings. The concentration of mercury in the oral cavity depends largely on the number of silver amalgam fillings and less so on these fillings' length of service.

Quantitation of total mercury vapor released during dental procedures. Engle JH, Ferracane JL, Wichmann J, Okabe T. Dent Mater 1992 May; 8(3):176-180. 1521706 PubMed. An in vitro method is described in which measurements were made of the total amount of mercury vapor released from three types of amalgam during routine dental procedures. It was found that the greatest amount of mercury was released during dry polishing of one amalgam (44 micrograms). Removal of amalgam from a Class I cavity under water spray and high volume evacuation also generated large amounts of mercury as expected (15-20 micrograms). However, under the more clinically relevant conditions of extending evacuation for one minute to remove residual amalgam and mercury after cutting, this value was reduced by approximately 90%. The total amount of mercury generated during placement (6-8 micrograms), wet polishing (2-4 micrograms) and trituration (1-2 micrograms) were also measured. The study showed that dental procedures associated with amalgam do potentially expose the patient and operator to mercury vapor.

Release of mercury vapor from dental amalgam. Berglund A. Swed Dent J Suppl. 1992; 85:1-52. 1475757 PubMed. Mercury can be released from dental amalgam by evaporation and electrochemical corrosion as well as from amalgam particles which have been swallowed. A major route for mercury uptake from amalgam restorations is through inhalation of mercury vapor. The only relevant measurable quantity when determining the mercury vapor released from amalgam restorations is the amount released per time unit, i.e. the amount of mercury vapor collected during intra-oral sampling is proportional to the sampling time. The diffusion of mercury atoms inside an amalgam restoration results in the formation of a concentration gradient in the surface of the amalgam. This mercury diffusion is the rate-determining step for mercury vapor release in the long run. In the short run the mercury concentration gradient prevalent on the amalgam surface on the measuring occasion is the apparent rate-determining step. The in vitro results revealed obvious differences regarding the release rate of mercury vapor from dissimilar amalgam types.

Side-effects: mercury contribution to body burden from dental amalgam. Reinhardt JW. Adv Dent Res. 1992 Sep; 6:110-3. 1292449 PubMed. 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.

Significance of hydrogen ion concentration on the dissolution of mercury from dental amalgam. Soh G, Chew CL, Lee AS, Yeoh TS. Quintessence Int. 1991 Mar; 22(3):225-8. 2068263 PubMed. The potential risks of mercury dissolution from dental amalgam have long been recognized. This study examined the effect of hydrogen ion concentration on the release of mercury from two dental amalgams: an admixed high-copper amalgam and a new tin- and copper-free amalgam. Specimens of each type of amalgam were incubated citric acid buffer of pH 2.5 or pH 7.0. Results showed that, for both types of amalgam, specimens incubated at pH 2.5 released statistically significantly greater (P less than .0001) quantities of mercury than did specimens incubated at pH 7.0. Release of mercury from the tin- and copper-free amalgam was also statistically significantly greater (P less than .0001) than that of the higher-copper amalgam at both pH levels.

Silver amalgam: An unstable material. Malmström C, Nylander M. Danish Dental Journal. Tidsskr. f. Tandlaeger. October 1989. Swedish paper translated by Mats Hansson Ph.D., in Bio-Probe Newsletter, Vol 9(1):5-6, Jan.1993. Figure 3 of the study depicts the results of measuring mercury vapor emission from the amalgam fillings under various conditions.

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Fig 3

Figure 3

Unstimulated measurements were performed even in areas where there were no amalgam fillings and immediately before any type of stimulation (the researchers found that blowing air on the amalgam filling increased mercury release).

Stimulated values were

1.    chewing food, no tooth brushing before measuring.

2.    after chewing gum.

3.    tooth brushing for 15-30 seconds with the paste preferred by the patient, and then rinsing the mouth with 20 centigrade water.

4.    prophylactic polishing with rubber and polishing paste (Depurdent) and rinsing as in 3.

5.    wet polishing with rubber disk, grinding paper or fine burr under water spray for 20 - 30 seconds.
dry polishing with rubber disk, grinding paper or fine burr - no water spray - for 20 - 30 seconds. 

Silver concentrations in human tissues. Their dependence on dental amalgam and other factors. Drasch G, Gath HJ, Heissler E, Schupp I, Roider G. J Trace Elem Med Biol. 1995 Jul; 9(2):82-7. 8825980 PubMed. These results show that amalgam fillings release Ag as well. Considering the different toxicokinetics of Ag and Hg it can be concluded that Ag is a reliable marker for the fact that the elevated concentrations of inorg. Hg found in tissues of individuals with amalgam fillings derive mainly from these fillings and not from other theoretically possible sources.

The distribution of mercury in various tissues of guinea-pigs after application of dental amalgam fillings (a pilot study). Fredin B. Sci Total Environ. 1987 Oct; 66:263-8.  3685953 PubMed. Mercury accumulation in brain, kidney, liver and heart following insertion of amalgam in the teeth of guinea-pigs has been studied. During the accelerated wear of the amalgam in these gnawing animals, a significant mercury accumulation in the above tissues was demonstrated. Finely diffused and abraded amalgam must not be ignored as a source of absorbable mercury.

The level of mercury in human dental plaque and interaction in vitro between biofilms of Streptococcus mutans and dental amalgam. Lyttle HA, Bowden GH. J Dent Res. 1993 Sep; 72(9):1320-4. 8360382 PubMed. Mercury levels (micrograms/mg dry weight) in dental plaque from amalgam and enamel surfaces in human subjects with amalgam restorations were (range, mean, SD) 0.5-1.31, 0.72, 0.34 and 0.01-0.54, 0.2, 0.19, respectively. The levels of mercury in plaque from amalgam surfaces were significantly higher than those from plaque on enamel (p < 0.001). No mercury was detected in plaque from subjects without amalgam restorations. The mean level of mercury in a 24-hour collection of plaque was 2 micrograms (median, 1.8 micrograms), an amount close to those calculated by other workers (1.2-1.7 micrograms) for the amount of mercury liberated in the mouth from amalgam restorations in 24 h. Freshly prepared amalgam liberated relatively large amounts of mercury into culture broth in the first 24 h of exposure; subsequently, the levels declined except in the presence of Streptococcus mutans. In vitro, biofilms of Streptococcus mutans facilitated the release of mercury from freshly prepared amalgam, in what appeared to be a cyclical fashion. Amalgam aged for two years did not release mercury, even when supporting the growth of an S. mutans biofilm. The resistance of aged amalgam was attributed to the presence of a passive tarnish layer. The mercury released by the biofilm had an effect on the composition of the biofilm. The biofilms on fresh amalgam had significantly lower levels of carbohydrate (p < 0.001-p < 0.01) and protein (p < 0.001-p < 0.02) than did biofilms on aged amalgam and on control stainless steel wires.

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Urinary mercury after administration of 2, 3-dimercaptopropane-1-sulfonic acid: correlation with dental amalgam score. Aposhian HV, Bruce DC, Alter W, Dart RC, Hurlbut KM, Aposhian MM. FASEB J. 1992 Apr; 6(7):2472-6. 1563599 PubMed. Administration of 300 mg DMPS by mouth increased the mean urinary mercury excretion of the amalgam group from 0.70 to 17.2 micrograms and that of the nonamalgam group from 0.27 to 5.1 micrograms over a 9-h period. Two-thirds of the mercury excreted in the urine of those with dental amalgams appears to be derived originally from the mercury vapor released from their amalgams.

Excretion

A case of high mercury exposure from dental amalgam. Langworth S, Stromberg R. Eur J Oral Sci. 1996 Jun; 104(3):320-1. 8831068 PubMed. This report describes a patient who suffered from several complaints, which by herself were attributed to her amalgam fillings. Analysis of mercury in plasma and urine showed unexpectedly high concentrations, 63 and 223 nmol/l, respectively. Following removal of the amalgam fillings, the urinary excretion of mercury became gradually normalized, and her symptoms declined.

A compartmental model for the kinetics of mercury vapor in humans. Jonsson F, Sandborgh-Englund G, Johanson G. Toxicol Appl Pharmacol. 1999 Mar 1; 155(2):161-8. 10053170 PubMed. Further simulations indicated that the excretion of Hg via urine would not reach a plateau until several months postexposure for most subjects.  

Daily dose calculations from measurements of intra-oral mercury vapor. Olsson S, Bergman M. J Dent Res. 1992 Feb; 71(2):414-23. 1556301 PubMed. The mean swallowed amount of mercury from intra-oral mercury vapor was calculated as being in the order of 10 micrograms Hg/day (range, 2.4-17 micrograms Hg/day), resulting in an estimated absorption of about 1 microgram Hg/day from the gastro-intestinal tract.

Human exposure to mercury and silver released from dental amalgam restorations. Skare I, Engqvist A. Arch Environ Health. 1994 Sep-Oct; 49(5):384-94. 7944571 PubMed. In 35 healthy individuals, the number of amalgam surfaces was related to the emission rate of mercury into the oral cavity and to the excretion rate of mercury by urine. Oral emission ranged up to 125 micrograms Hg/24 h, and urinary excretions ranged from 0.4 to 19 micrograms Hg/24 h. In 10 cases, urinary and fecal excretions of mercury and silver were also measured. Fecal excretions ranged from 1 to 190 micrograms Hg/24 h and from 4 to 97 micrograms Ag/24 h. Except for urinary silver excretion, a high interplay between the variables was exhibited. The worst-case individual showed a fecal mercury excretion amounting to 100 times the mean intake of total Hg from a normal Swedish diet. With regard to a Swedish middle-age individual, the systemic uptake of mercury from amalgam was, on average, predicted to be 12 micrograms Hg/24 h.

Influence of amalgam fillings on Hg levels and total antioxidant activity in plasma of healthy donors. Pizzichini M, Fonzi M, Giannerini F, Mencarelli M, Gasparoni A, Rocchi G, Kaitsas V, Fonzi L. Sci Total Environ. 2003 Jan 1; 301(1-3):43-50. 12493183 PubMed. In order to evaluate the influence of specific factors on mercury (P-Hg) levels and antioxidant power (P-FRAP) in human plasma, 26 healthy donors were examined by a dentist, their plasma analyzed for Hg by atomic absorption spectrometry and for total antioxidant activity by FRAP method. Hg plasma concentration was found to be correlated with the number of amalgam fillings, suggesting that Hg released from fillings is a source of Hg in non-occupational exposed subjects. P-FRAP correlated negatively with P-Hg suggesting a pro-oxidant role of the Hg released from amalgam fillings.

Influence of liquid films on mercury vapor loss from dental amalgam. Mahler DB, Adey JD, Simms LE, Marek M. Dent Mater. 2002 Jul; 18(5):407-12. 12175580 PubMed. Hg emission from abraded surfaces under liquid films was one to two orders of magnitude less than Hg emission from abraded surfaces exposed to air. SIGNIFICANCE: In vitro measurement of Hg vapor emission from abraded surfaces exposed to air should not be used to estimate directly the Hg vapor release from dental amalgam restorations in vivo.

Interactions between dental amalgams and the oral environment. M. Marek. Adv Dent Res. 1992 Sep; 6:100-9. 1292448 PubMed. Phenomena and conditions that affect the amalgam/environment interaction include the chemistry and biochemistry of the environment, formation of biofilms on the amalgam surfaces, existence of localized corrosion cells, galvanic contacts with other metallic restorations, abrasion during mastication, and synergistic effects of the different forces. Corrosion processes result in a degradation of the functional amalgam properties, while tarnishing reactions cause discoloration. Corrosion degradation of amalgam fillings is due mainly to localized corrosion cells in pores and crevices. Corrosion on occlusal surfaces is accelerated by abrasion during mastication, which removes the protective surface films.

Intra-oral air mercury released from dental amalgam. Vimy MJ, Lorscheider FL. J Dent Res. 1985 Aug; 64(8):1069-71. 3860538 PubMed. Chewing stimulation in subjects with amalgams increased their Hg concentration six-fold over unstimulated Hg levels, or a 54-fold increase over levels observed in control subjects. Concentrations of Hg measured in intra-oral air larger than those reported in expired air were attributed to the rate and direction of air passage across amalgam surfaces. There were significant correlations between Hg vapor released into intra-oral air after chewing stimulation and the numbers and types of amalgam restorations. It is concluded that intraoral air is a reliable physiological indicator of Hg released from dental amalgam that may reflect a major source of chronic Hg exposure.

Mercury concentration in the mouth mucosa of patients with amalgam fillings. Willershausen-Zonnchen B, Zimmermann M, Defregger A, Schramel P, Hamm G. Dtsch Med Wochenschr. 1992 Nov 13; 117(46):1743-7. 1425293 PubMed. Thirteen patients without metallic fillings of any kind had mercury concentrations of 118.4 +/- 83.7 ng/g tissue, and in 17 patients with precious metal fillings but no amalgam the mean mercury concentrations were 144 +/- 290 ng/g tissue. Seventeen patients with 1-3 amalgam fillings had an average of 1975 +/- 4300 ng/g tissue and in 26 patients with 3-6 amalgam fillings the average concentration was 1158 +/- 2500 ng/g tissue. In 17 patients with more than six amalgam fillings the mean mercury concentration was 2302 +/- 5600 ng/g tissue.

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Mercury concentrations in the urine of children with and without amalgam fillings. Schulte A, Stoll R, Wittich M, Pieper K, Stachniss V.  Schweiz Monatsschr Zahnmed. 1994; 104(11):1336-40. 7984991 PubMed. The creatinine adjusted values were 0.19 microgram/g and 0.64 microgram/g, respectively. This difference was significant. Also, a significant correlation was found between the number of amalgam points (each amalgam surface had been given 1 to 3 points depending on its extent) and the urinary mercury concentration.

Mercury in saliva and feces after removal of amalgam fillings. Bjorkman L, Sandborgh-Englund G, Ekstrand J. Toxicol Appl Pharmacol. 1997 May; 144(1):156-62.  9169079 PubMed. It was concluded that amalgam fillings are a significant source of Hg in saliva and feces. Hg levels in all media decrease considerably after amalgam removal. The uptake of amalgam mercury in the GI tract in conjunction with removal of amalgam fillings seems to be low.

Mercury release from amalgam into saliva. An in-vitro study. Lussi A. Schweiz Monatsschr Zahnmed. 1993; 103(6):722-6. 8322057 PubMed. The aim of the study was to investigate mercury release into salivary fluid and to test whether this release is associated with flow rate, buffer capacity or pH of salivary fluid. Salivary fluid was collected from 18 persons (11 with amalgam fillings, 7 without) and the surface area of the fillings was assessed. Mercury loss in unstimulated saliva was 11.6 ng/min for persons with amalgam and 2.1 ng/min for those without. Multiple regression analysis revealed no association between flow rate, buffer capacity or pH of unstimulated salivary fluid and mercury release.

Model of mercury vapor transport from amalgam restorations in the oral cavity. Olsson S, Berglund A, Pohl L, Bergman M. J Dent Res. 1989 Mar; 68(3):504-8. 2921395 PubMed. Mercury appears to be transported as atoms both in the aqueous phase of saliva and in the gas phase. The majority of the mercury atoms reaching the gas phase appears to originate directly from the surface of the amalgam restorations, passing through the saliva layer, while only a minority originates from mercury dissolved in the aqueous phase. The amount of mercury released per unit of time to the gas phase was shown to be independent of the air flow rate during respiration and pumping. Furthermore, the released mercury atoms are distributed partly to the gas phase, from which they are respired to the lungs and the environment, and partly to the saliva and the gastro-intestinal tract, by swallowing.

Serial measurements of intra-oral air mercury: estimation of daily dose from dental amalgam. Vimy MJ, Lorscheider FL. J Dent Res. 1985 Aug; 64(8):1072-5. 3860539 PubMed. Serial measurements of Hg concentration in intra-oral air were made during and after chewing stimulation in 35 subjects with occlusal amalgam restorations. Hg concentrations remained elevated during 30 min of continuous chewing and declined slowly over 90 min after cessation of chewing. By curve-fitting and integration analysis of data during these time periods (including corrections for respiratory volume, retention rate of inspired Hg, oral-to-nasal breathing ratios, and consumption of three meals and three snacks per day), we calculated that all subjects received an average daily Hg dose of approximately 20 micrograms. Subjects with 12 or more occlusal amalgam surfaces were estimated to receive a daily Hg dose of 29 micrograms, whereas in subjects with four or fewer occlusal amalgam surfaces, the dose was 8 micrograms. These Hg dosages from dental amalgam were as much as 18-fold the allowable daily limits established by some countries for Hg exposure from all sources in the environment. The results demonstrate that the amount of elemental Hg released from dental amalgam exceeds or comprises a major percentage of internationally accepted threshold limit values for environmental Hg exposure. It is concluded that dental amalgam Hg makes a major contribution to total daily dose.

Speciation of mercury excreted in feces from individuals with amalgam fillings. Engqvist A, Colmsjo A, Skare I. Arch Environ Health. 1998 May-Jun; 53(3):205-13. 9814717 PubMed. Investigators established methods for the analysis of total mercury (Hg-total), oxidized mercury and mercury bound to sulfhydryl groups (Hg-S), mercury vapor (Hg0), and mercury from amalgam particles (APs) in fecal samples. Two individuals consumed mercury as a mercury-cysteine complex mercury vapor, and mercury from amalgam particles, and the cumulative excretion of mercury in feces was followed. Investigators found that 80% of the mercury from amalgam particles and mercury bound to sulfhydryl groups was excreted, but only 40% of the mercury vapor was excreted. Speciation of mercury excreted in feces from 6 individuals with a moderate loading of amalgam fillings showed that most of the mercury originating from the fillings consisted of oxidized mercury, which was probably bound to sulfhydryl-containing compounds. The proportion of amalgam particles in fecal samples from these individuals was low, and it did not exceed 26% of the total amount of mercury excreted.

The Exposure to mercury in the population. I. Mercury concentrations in the urine of normal subjects. Zander D, Ewers U, Freier I, Jermann E, Westerweller S, Brockhaus A. Zentralbl Hyg Umweltmed. 1990 Oct; 190(4):315-24. 2080963 PubMed. The levels of mercury were determined in 24 h urine samples collected from 703 subjects (age 1-79 years) living in the Eastern part of the Ruhr area (West-Germany). The mean HgU level was 0.75 micrograms/l (range less than 0.1-19.3 micrograms/l) and the mean HgU level standardized for creatinine was 0.64 micrograms/g creatinine (range: less than 0.1-27.4 micrograms/g creatinine). The mean mercury excretion per 24 h was 0.48 micrograms in subjects less than 18 years and 0.99 micrograms in subjects greater than 18 years. Females were found to have, on average, higher HgU levels and also a higher excretion of mercury per 24 h than males. Subjects greater than 18 years had significantly higher HgU levels than subjects less than 18 years of age. The effect of age was found to be substantially more pronounced in females than in males. Smoking did not affect the urinary mercury excretion.

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The Exposure to mercury in the population. II. Mercury release from amalgam fillings. Zander D, Ewers U, Freier I, Westerweller S, Jermann E, Brockhaus A. Zentralbl Hyg Umweltmed. 1990 Oct; 190(4):325-34. 2080964 PubMed. Urinary levels of mercury (HgU) were measured in 93 males and females aged 18-63 years. Subjects with amalgam fillings (n = 72) had, on average, significantly higher levels of mercury in urine (mean = 0.57 microgram Hg/l and 0.79 microgram Hg/g creatinine, respectively) than subjects without amalgam fillings (n = 21; mean = 0.18 micrograms Hg/l and 0.24 microgram Hg/g creatinine, respectively). Urinary mercury excretion was significantly correlated with the number of amalgam surfaces (log HgU (microgram/l) vs. number of amalgam fillings: r = 0.435, P less than 0.001; log HgU (microgram/g creatinine) vs. number of amalgam fillings: r = 0.575, p less than 0.001). The results indicate that internal mercury exposure from amalgam fillings is, on average, higher than internal exposure to mercury from food and other sources.

The mercury exposure of the population. III. Mercury mobilisation by DMPS (Dimaval) in subjects with and without amalgam fillings. Zander D, Ewers U, Freier I, Brockhaus A. Zentralbl Hyg Umweltmed. 1992 Feb;192(5):447-54. 1554403 PubMed. The urinary excretion of mercury (per 24 h) was determined in 29 subjects before and after application of DMPS (2.3-dimercapto-1-propane sulfonic acid, 300 mg per os). A 6-7 fold increase of mercury excretion was noted after application of DMPS. Subjects with amalgam fillings excreted significantly more mercury before as well as after application of DMPS than subjects without amalgam fillings. Urinary mercury excretion was significantly correlated with the number of amalgam fillings. About 50% of the variance of urinary mercury can be explained by the number of amalgam fillings. The results show that the release of mercury from amalgam fillings represents the main source of mercury exposure in subjects with amalgam fillings.

10 years of observation by public health offices in Baden-Wurttemberg--assessment of human biomonitoring for mercury due to dental amalgam fillings and other sources. Gabrio T, Benedikt G, Broser S, Felder-Kennel A, Fichtner G, Horras-Hun G, Jovanovic S, Kirsch H, Kouros B, Link B, Maisner V, Piechotowski I, Rzonca E, Schick KH, Schrimpf M, Schroder S, Schwenk M, Spoker-Maas K, Weidner U, Wuthe J, Zollner I. Gesundheitswesen. 2003 May; 65(5):327-35. 12772075 PubMed. The decrease in the body burden of mercury as a result of the declining usage of dental amalgam fillings, has been verified. In 1992/93, of all the children who had been surveyed, the 95 percentile for the body burden of mercury was 3.1 microg/l and in 2000/01 1.35 microg/l. The results support the opinion that mercury in urine is appropriate for estimating the mercury uptake from dental amalgam fillings. It can be assumed that these results reflect the situation in the entire Federal Republic of Germany.

The absorption, blood levels, and excretion of mercury after a single dose of mercury vapor in humans. Sandborgh-Englund G, Elinder CG, Johanson G, Lind B, Skare I, Ekstrand J. Toxicol Appl Pharmacol. 1998 May; 150(1):146-53. 9630463 PubMed. Nine healthy volunteers without amalgam fillings were exposed to 400 micrograms/m3 mercury vapor (Hg0) for 15 min, corresponding to 5.5 nmol Hg0/kg body wt (median range: 4.4-7.2). Frequent sampling of blood, urine, and exhaled air was performed for 30 days after exposure. The median retention of Hg0 was 69% of the inhaled dose. During the first 3 days after exposure 7.5-12% of the absorbed dose was lost by exhalation, with the median half time of Hg0 in expired breath being 2.0 days. In blood and plasma, a rapid absorption phase of Hg was seen, followed by a biexponential decline of the curves in both media. A substantial interindividual variation was observed in the area under the concentration-time curves of Hg in blood and plasma. In plasma the median half time of the second phase was 10 days. About 1.0% of the absorbed Hg was excreted via urine during the first 3 days after exposure, whereas the estimated amount excreted during 30 days ranged from 8 to 40%. In order to evaluate the chronic exposure to mercury from dental amalgam in the general population, the daily Hg dose from the fillings were estimated based on the plasma Hg levels found in subjects with amalgam fillings and on the plasma Hg clearance obtained in the present study. The daily Hg dose was estimated to 5-9 micrograms/day in subjects with an ordinary number of amalgam fillings.

Urinary excretion of mercury, copper and zinc in subjects exposed to mercury vapour. Sallsten G, Barregard L. Biometals. 1997 Oct; 10(4):357-61. 9353886 PubMed. This study indicates that mercury exposure in humans, as in animals, causes increased urinary excretion of zinc. The mechanisms may be induced synthesis of metallothionein in the kidneys, displacement of Zn from preexisting metallothionein by Hg, or a decreased reabsorption of zinc in the kidneys owing to a slight tubular dysfunction.

Urinary mercury clearance of dental personnel after a longterm intermission in occupational exposure. Skare I, Engqvist A. Swed Dent J. 1990; 14(6):255-9. 2096473 PubMed. The objective of this study was to get an estimate of the overall halftime for clearance of urinary mercury after cessation of a mercury vapor exposure. Ten dentists and dental nurses were selected and their urinary mercury excretion rates prior and after a summer vacation were measured. Estimates of their basic mercury excretions, originating from the environmental background and their own amalgam restorations, were individually subtracted to get the contributions deriving from occupational work. If assuming a first order of kinetics for the clearance of urinary mercury a median value of 41 days was achieved for the halftime searched, a value somewhat lower than those previously published. An explanation might be that the tailing effect of the decay curve here was eliminated by the taking of the background excretions into account.

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Removal Protocol

New Directions Dentistry. Dr. Tom McGuire and Dr. Paul Rubin, produced the DVD Course; How to Make Your Practice Mercury-Safe: Minimizing Occupational Exposure to Mercury in the Dental Office. The DVD is the key to accessing the information you need to make certain you are as mercury safe as possible. It is the only DVD of its kind available to dentists and sets the standard for learning how to protect yourself, your staff, your patients and the environment from unnecessary and excessive occupational exposure to mercury.

The DVD will be beneficial to your practice on many levels. Along with making certain you are doing everything you can to be as mercury-safe as possible, it is also a great tool to educate and motivate your staff. This in turn will result in them being more supportive and more active in promoting your practice within the community. It will also allow you to promote your practice as environmentally green for mercury and provides you with a significant “Marketing Edge”.

Of course protecting the patient is essential but, as you’ll see from the DVD, the long-term exposure to mercury for you and your staff, is far greater than a patient’s. Thus, it is essential that you make certain you are doing everything you can to protect everyone in your practice, and the environment, from needless exposure to mercury.

Utilizing the DVD course means there are no travel costs or related expenses of participating in a live seminar. For more information about this DVD Course go to www.newdirectionsdentistry.com or call: 800-335-7755.

IAOMT Standards of Care. Preferred Procedure. Reducing Mercury Vapor Exposure for the Patient During Amalgam Removal. September 1992. http://www.holisticmed.com/dental/amalgam/iaomt.txt 

Mercury levels in plasma and urine after removal of all amalgam restorations: the effect of using rubber dams. Berglund A, Molin M. Dent Mater. 1997 Sep; 13(5):297-304. 9823089 PubMed. The study showed that dental amalgam had a statistically significant impact on the mercury levels found in plasma and urine in the patients tested, and that the use of a rubber dam during removal of all amalgam restorations significantly reduced the peak of mercury in plasma following removal.  

Particulate inhalation during the removal of amalgam restorations. Nimmo A, Werley MS, Martin JS, Tansy MF. J Prosthet Dent. 1990 Feb; 63(2):228-33. 2406428 PubMed. An aerosol that contains amalgam particles is created when a high-speed hand-piece is used to remove an existing amalgam restoration. Those particles smaller than 10 microns are considered to be fully respirable. This means that a significant percentage of the particles have the potential to travel to the terminal alveoli, where they may become lodged. Long-term exposure to fully respirable particles may compromise a person's respiratory function. Amalgam restorations were placed in the typodont teeth of a mannequin designed to simulate the head and the respiratory tract of a patient. The amalgam restorations were removed under three experimental conditions: dry cut (control), wet cut (water spray) with high-velocity evacuation, and wet cut with high-velocity evacuation and a rubber dam. Particulate exposure was evaluated in the simulated respiratory tracts of the patient and the dentist that were equipped with ambient particle sizing samplers. Use of water spray and high-velocity evacuation significantly reduced patient exposure to particles. The use of a rubber dam, together with water spray and high-velocity evacuation, was responsible for a further significant reduction of exposure to particles when compared with water spray and high-velocity evacuation alone. The dentist, however, was exposed to moderate levels of fully respirable particles for all conditions tested. It is therefore recommended that all dental personnel wear face masks while removing existing amalgam restorations.  

Steady-state transfer and depletion kinetics of mercury from amalgam fillings. Halbach S, Welzl G, Kremers L, Willruth H, Mehl A, Wack FX, Hickel R, Greim H. Sci Total Environ. 2000 Oct 2; 259(1-3):13-21. 11032131 PubMed. Within 9 days after removal of the fillings, a transient increase in Hg levels was observed in plasma only; in the group without a rubber dam, concentrations increased significantly above pre-removal values at days 1 and 3, whereas they decreased significantly below pre-removal values at day 30 in the rubber-dam group and at day 100 in both groups. Excretion rates decreased significantly at day 100 in the protected group. Peak plasma-Hg was 0.6 ng/ml on average at day 1 and decreased with halftimes of 3 and 43 days in subjects protected by a rubber dam. The results indicated that concentrations of total mercury in plasma responded rapidly to changes in the amalgam status and reflected the actual absorption most reliably. Notably, plasma-Hg levels were sensitive enough to detect a transient attenuation of the additional exposure after using a rubber dam during the removal of only a few fillings.

Systemic transfer of mercury from amalgam fillings before and after cessation of emission. Halbach S, Kremers L, Willruth H, Mehl A, Welzl G, Wack FX, Hickel R, Greim H. Environ Res. 1998 May; 77(2):115-23. 9600804 PubMed. Within 9 days after removal of the fillings, a transient increase was observed in plasma Hg levels only. This was reduced in those volunteers to whom a rubber dam had been applied during removal. Peak plasma Hg was 0.6 ng/ml on average and decreased with halftimes between 5 and 13 days. A significant decrease in Hg excretion was noted not before 100 days after removal. Being relatively insensitive to dietary mercury, the determination of total mercury in plasma and of its urinary excretion rate appears, under practical aspects, most suitable for the investigation of Hg uptake from amalgam.

The release of mercury from dental amalgam and potential neurotoxicological effects. Sweeney M, Creanor SL, Smith RA, Foye RH. J Dent. 2002 Jul-Aug; 30(5-6):243-50. 12450715 PubMed. The mercury released into air from dry abraded amalgam was shown to be above the recommended industrial limit. Coating the abraded amalgam discs with saliva reduced the mercury by 66-72% with the levels recorded being significantly lower (p<0.001). The level of total mercury within the saliva was found to be highly variable. Little change was noted in the neuronal cultures treated with 1 microM mercuric chloride. However, the cultures exposed to high level (10 microM) mercuric chloride showed cells that became rounded and clumped together indicating pathological change.CONCLUSIONS: Amalgam placement appears to present minimal mercury exposure risk. To reduce the amount of mercury released into air, however, amalgam should be polished in a moist atmosphere with high volume aspiration. The neurotoxic effect of mercury appears to be related to concentration, as only in the cultures treated with 10 microM mercuric chloride showed striking qualitative and quantitative cellular changes.

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Resistance to Antibiotics

Antibiotic resistance in oral/respiratory bacteria. Roberts MC. Crit Rev Oral Biol Med. 1998; 9(4):522-40. 9825225 PubMed. Mechanisms of resistance for macrolides, lincosamides, streptogramins, trimethoprim, sulfonamides, aminoglycosides, and chloramphenicol are also discussed, along with the possible role that mercury resistance may play in the bacterial ecology.

Detection of heavy metal ion resistance genes in gram-positive and gram-negative bacteria isolated from a lead-contaminated site. Trajanovska S, Britz ML, Bhave M. Biodegradation. 1997; 8(2):113-24. 9342884 PubMed. Resistance to a range of heavy metal ions was determined for lead-resistant and other bacteria which had been isolated from a battery-manufacturing site contaminated with high concentration of lead. Several Gram-positive (belonging to the genera Arthrobacter and Corynebacterium) and Gram-negative (Alcaligenes species) isolates were resistant to lead, mercury, cadmium, cobalt, zinc and copper, although the levels of resistance to the different metal ions were specific for each isolate. Polymerase chain reaction, DNA-DNA hybridization and DNA sequencing were used to explore the nature of genetic systems responsible for the metal resistance in eight of the isolates. Specific DNA sequences could be amplified from the genomic DNA of all the isolates using primers for sections of the mer (mercury resistance determinant on the transposon Tn501) and pco (copper resistance determinant on the plasmid pRJ1004) genetic systems. Positive hybridizations with mer and pco probes indicated that the amplified segments were highly homologous to these genes. Some of the PCR products were cloned and partially sequenced, and the regions sequenced were highly homologous to the appropriate regions of the mer and pco determinants. These results demonstrate the wide distribution of mercury and copper resistance genes in both Gram-positive and Gram-negative isolates obtained from this lead-contaminated soil. In contrast, the czc (cobalt, zinc and cadmium resistance) and chr (chromate resistance) genes could not be amplified from DNAs of some isolates, indicating the limited contribution, if any, of these genetic systems to the metal ion resistance of these isolates.

Heavy metals, chlorine and antibiotic resistance in Escherichia coli isolates from ambulatory patients. Aguiar JM, Guzman E, Martinez JL. J Chemother. 1990 Aug; 2(4):238-40. 2230906 PubMed. The susceptibility of Escherichia coli strains isolated from ambulatory patients to heavy metals, chlorine and antibiotics was evaluated. It seemed that heavy metal resistance was associated with antibiotic resistance. On the other hand, chlorine resistant strains seemed to be more sensitive to antibiotics. Clinical and ecological implications of these results are discussed.

Mercury in saliva and the risk of exceeding limits for sewage in relation to exposure to amalgam fillings. Leistevuo J, Leistevuo T, Helenius H, Pyy L, Huovinen P, Tenovuo J. Arch Environ Health. 2002 Jul-Aug; 57(4):366-70. 12530606 PubMed. The concentration of total mercury in stimulated saliva was studied in humans with dental amalgam fillings and in 2 nonamalgam groups. The probability of exceeding the limits of mercury permitted in wastewater increased proportionally as the number of amalgam-filled surfaces increased. The mercury limit for sewage is 0.05 mg/l (= 250 nmol/l) effluent, according to the Council of European Communities directive 84/156/EEC. In neither of the nonamalgam groups was this limit exceeded, but 20.5% in the amalgam group exceeded the limit (p < .001). The risk of exceeding the limit increased 2-fold for every 10 additional amalgam-filled surfaces (odds ratio = 2.0; 95% confidence interval = 1.3, 3.3). These results demonstrate that humans, especially in populated areas, can be a significant source of mercury pollutants. As a consequence of mercury release, bacteria may acquire mercury resistance, as well as resistance to other antimicrobial agents, thus resulting in failure of antibiotic treatment.

Mercury released from dental "silver" fillings provokes an increase in mercury- and antibiotic-resistant bacteria in oral and intestinal floras of primates. Summers AO, Wireman J, Vimy MJ, Lorscheider FL, Marshall B, Levy SB, Bennett S, Billard L. Antimicrob Agents Chemother. 1993 Apr; 37(4):825-34. 8280208 PubMed. Our findings indicate that mercury released from amalgam fillings can cause an enrichment of mercury resistance plasmids in the normal bacterial floras of primates. Many of these plasmids also carry antibiotic resistance, implicating the exposure to mercury from dental amalgams in an increased incidence of multiple antibiotic resistance plasmids in the normal floras of nonmedicated subjects.

Mercury resistance among clinical isolates of Escherichia coli. Poiata A, Badicut I, Indres M, Biro M, Buiuc D. Roum Arch Microbiol Immunol. 2000 Jan-Jun; 59(1-2):71-9. 11845478 PubMed. Among the tested E. coli strains, mercury resistance rose to 29.2%. Mercury resistance in E. coli is significantly linked to multiresistance to antimicrobial agents. Between 91.5-23.6 of mercury chloride resistant isolates were also resistant to the tested antibiotics. The increased use of non antibiotic antimicrobial agents is a possible selection factor for antibiotic-resistant strains in clinical and domestic environments.

Polymorphonuclear phagocytosis and killing in workers exposed to inorganic mercury. Perlingeiro RC, Queiroz ML. Int J Immunopharmacol. 1994 Dec; 16(12):1011-7. 7705962 PubMed. The ability of neutrophils to phagocytose and kill Candida species as well as the splenic phagocytic function were investigated in workers from a mercury-producing plant. In the neutrophil phagocytosis study, two species of Candida were used since in individuals with myeloperoxidase deficiency neutrophils are unable to kill Candida albicans, while Candida pseudotropicalis can be effectively lysed. Phagocytosis of both antigens and splenic phagocytic function were normal in all the workers studied. However, following ingestion of the organisms there was considerable reduction in the ability of neutrophils from exposed workers to kill both species of Candida, and this was not explained by a mild impairment of phagocytosis. After improvement in the hygiene conditions in the factory, a new evaluation was performed, 6 months later, in the same workers and urinary mercury concentrations were determined monthly in each worker. Despite a significant reduction in urinary mercury concentrations, a greater impairment in the ability of neutrophils to kill C. albicans was observed. The killing of C. pseudotropicalis presented no further impairment when compared to the previous evaluation. These results suggest that impairment of the lytic activity of neutrophils from workers with urinary mercury concentrations within the safe level for exposed population is due, at least in part, to some interference with myeloperoxidase activity. In addition, the mercury-NADPH complex, once formed, could limit the utilization of reduced pyridine nucleotides by NADPH-dependent enzymes such as NADPH oxidase, thereby inhibiting the PMN respiratory burst.

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Resistance of the normal human microflora to mercury and antimicrobials after exposure to mercury from dental amalgam fillings. Edlund C, Bjorkman L, Ekstrand J, Sandborgh-Englund G & Nord CE. Clin Infect Dis. 1996 Jun; 22(6):944-50. 8783691 PubMed. Mercury levels in saliva and feces correlated significantly with the number of amalgam surfaces. A significant correlation between the prevalence of mercury resistance and multiple antimicrobial resistance in intestinal bacterial strains was observed.

Role of mercury (Hg) in resistant infections & effective treatment of Chlamydia trachomatis and Herpes family viral infections (and potential treatment for cancer) by removing localized Hg deposits with Chinese parsley and delivering effective antibiotics using various drug uptake enhancement methods. Omura Y, Beckman SL. Acupunct Electrother Res. 1995 Aug-Dec; 20(3-4):195-229. 8686573 PubMed. The authors found that antibiotics used to treat various infections often were ineffective in the presence of abnormal localized deposits of heavy metals like Hg and Pb, which were often observed to co-exist with Chlamydia trachomatis, Herpes Simplex Types I & II, Cytomegalovirus(CMV), and other micro-organisms. Our earlier research revealed that despite rigorous treatment with antibiotics together with various drug uptake enhancement techniques, subjects who had been treated for Chlamydia trachomatis infections, seemingly successfully with disappearance of their symptoms, were often experiencing recurrences within several months after completion of their treatment despite taking precautions against reinfection. Therefore we hypothesized that the infectious micro-organisms mentioned above, somehow utilize the Hg or Pb to protect themselves from what would otherwise be effective antibiotics, and/or that heavy metal deposits in some way make antibiotics ineffective. Since the micro-organisms retreat to areas in which Insulin-like Growth Factors I & II normally exist, they may be utilizing them for their own growth and multiplication.

The dental amalgam mercury controversy--inorganic mercury and the CNS; genetic linkage of mercury and antibiotic resistances in intestinal bacteria. Lorscheider FL, Vimy MJ, Summers AO, Zwiers H. Toxicology. 1995 Mar 31; 97(1-3):19-22. 7716785 PubMed. Mercury (Hg) vapor exposure from dental amalgam has been demonstrated to exceed the sum of all other exposure sources. Therefore the effects of inorganic Hg exposure upon cell function in the brain and in the intestinal bacteria have recently been examined. In rats we demonstrate that ADP-ribosylation of tubulin and actin brain proteins is markedly inhibited, and that ionic Hg can thus alter a neurochemical reaction involved with maintaining neuron membrane structure. In monkeys we show that Hg, specifically from amalgam, will enrich the intestinal flora with Hg-resistant bacterial species which in turn also become resistant to antibiotics.

The resistance and adaptation of selected oral bacteria to mercury and its impact on their growth. Lyttle HA, Bowden GH. J Dent Res. 1993 Sep; 72(9):1325-30. 7689600 PubMed. Enrichment cultures of samples of human dental plaque showed that streptococci were the most resistant organisms that could be cultured on the medium and that these strains could adapt to relatively high mercury concentrations. S. oralis and S. mitis biovar 1 were the most resistant organisms isolated from enriched cultures, growing in broth media with 65 micrograms/mL mercury. Mercury was bound to cell walls and cell cytoplasm of streptococci grown in the presence of mercury.

Saliva

Dental amalgam fillings and the amount of organic mercury in human saliva. Leistevuo J, et al. Caries Res. 2001 May-Jun;35 (3): 163-6. PubMed 11385194. Our results are compatible with the hypothesis that amalgam fillings may be a continuous source of organic mercury, which is more toxic than inorganic mercury, and almost completely absorbed by the human intestine.

 

Statistics

Are you aware that toxic metal pollution is the most frequent reason for the onset of chronic degenerative diseases and loss of life among North Americans? Townsend Letter for Doctors and Patients. Walker, Morton. June, 2003. Metallic poisons are everywhere on the continent, ranging from highly populated cities to the most isolated of rural communities. In the United States, metal toxins arise out of industrial, commercial and home pesticide usage with over 1.2 billion pounds spread around each year. That's an annual exposure of five pounds of cockroach and/or rat poison per United States resident. Toxins from metals are present in smog with each year recording 34.8 million tons floating in the air. Stored as "silver" dental fillings in American teeth is 557 tons of mercury, the most dangerous mineral known to science -- more poisonous than uranium. Each person averages eight amalgam dental fillings which daily leak 120 micrograms of mercury into one's body. And conventional dentists have done infants no favor since during pregnancy most of a new mother's dental mercury is abso rbed by the fetus.

Medical/dental scientists at the University of Calgary warned in 1990 that nearly all babies are now born with heavy metals in their bodies. Infants receive metal pollutants in utero from mothers who not only have dental amalgams, they might also drink metal-contaminated ground water, eat mercury-laden fish, spray with herbicides, apply metal-containing household solvents, inhale jet fuel or automobile exhaust loaded with lead, or take in metallic poisons from myriad other sources.

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Stimulation

Exposure to mercury vapor during setting, removing, and polishing amalgam restorations. Haikel Y, Gasser P, Salek P, Voegel JC. J Biomed Mater Res. 1990 Nov; 24(11):1551-8. 2279986 PubMed. The level of mercury vapors in the oral cavity was determined by analyzing 242 samples of intra-oral air before and after removing, setting, and polishing dental amalgam. The analysis was effected using atomic absorption spectrometry in cold vapors with the detection limit of 6 micrograms/m3. A score of 1 to 3 was assigned to each restoration to adjust the differences of the amalgam sizes. The present study showed that the vapor was released during any procedure: removing, setting, and polishing amalgam. The mean levels were between 85 and 326 micrograms/m3. However, before the restorative procedures, no mercury vapors had been detected in the oral cavity. This investigation has also demonstrated a significant direct correlation between Hg vapor concentrations in intra-oral air and the sizes of amalgam restorations during each procedure: removing, setting, and polishing. The statistic analysis showed no significant difference of mercury vapors in the oral cavity between the use or nonuse of water coolant during the amalgam polishing.

Silver Amalgam - An Unstable Material. Malmström C, et al. Tidsskr. f. Tandlaeger (Danish Dental Journal). October 1989. Bio-Probe Newsletter January 1993. p.5. (http://home.swipnet.se/misac/research1.html) This study was designed to measure "local" concentrations of mercury vapor directly over the amalgam dental fillings. A single - beam atomic absorption spectrometer developed at the Centre for Dental Technology and Biomaterials in Huddinge, Sweden was the instruments used for all measurements. The measurements were made with the air intake of the instrument 0,5 - 1 mm over the occlusal surface and maximum values were registered. Four measurements were made, one in each quadrant for unstimulated teeth.

Supplements/Nutrition/Exercise

Antioxidants in nutrition and their importance in the anti-/oxidative balance in the immune system. Biesalski HK, Frank J. Immun Infekt. 1995 Oct; 23(5):166-73. 8530128 PubMed. Free radicals and reactive oxygen species can damage cells and tissues of biological organisms. Due to the fact that these compounds are generated continuously in living cells defense mechanisms must exist. This so-called antioxidative system ensures that the formation of free radicals during different physiological processes does not result in cellular damage. Free radicals (oxidants) are produced form the immune system. The purpose of this immune cell products is to destroy invading organisms and damaged tissue. Oxidants enhance IL-1, IL-8 and TNF production in response to inflammatory stimuli. Sophisticated antioxidant defense systems like enzymes or vitamins protect directly and indirectly the host against the damaging influence of oxidants. While endogenous systems can hardly be influenced, exogenous antioxidants, delivered by the diet, can be upregulated in the body. By this way the pro-/antioxidative capacity can be balanced or even unbalanced.

Effects of dietary alpha-tocopherol and beta-carotene on lipid peroxidation induced by methyl mercuric chloride in mice. Andersen HR, Andersen O. Pharmacol Toxicol. 1993 Oct; 73(4):192-201. 8295846 PubMed. High dietary alpha-tocopherol protected against CH3HgCl induced hepatic lipid peroxidation, whereas the alpha-tocopherol deficient diet further enhanced CH3HgCl induced hepatic lipid peroxidation. Similar, though statistically non-significant effects occurred in the kidneys, alpha-Tocopherol did not protect against CH3HgCl induced lipid peroxidation in the brain. Excess dietary beta-carotene further enhanced CH3HgCl induced lipid peroxidation in liver, kidney and brain. CH3HgCl significantly decreased the activity of total glutathione peroxidase (T-GSH-Px) and Se-dependent glutathione peroxidase (Se-GSH-Px) in the kidneys in all dietary groups. High dietary alpha-tocopherol enhanced the activity of Se-GSH-Px in liver and kidney compared to the activity in mice fed the normal level of alpha-tocopherol. This occurred in mice exposed to CH3-HgCl as well as in unexposed mice, and the difference between CH3HgCl exposed and unexposed mice was not diminished. High dietary alpha-tocopherol increased the activity of both Se-GSH-Px and T-GSH-Px in the brain of CH3HgCl-exposed mice. The dietary level of beta-carotene did not affect the activity of the two enzymes in the organs investigated.

Fluctuation of trace elements during methylmercury toxication and chelation therapy. Bapu C, Purohit RC, Sood PP. Hum Exp Toxicol. 1994 Dec; 13(12):815-23. 7718300 PubMed. The aim of the present investigation was to check the fluctuation in essential elements, such as Na, K, Mg, Mn, Cu, Zn, Cr and Ni in the brain, spinal cord, liver and kidney of mice during methylmercury chloride (MMC) toxication and therapy with monothiols (N-acetyl-DL-homocysteine thiolactone and glutathione) and vitamins (vitamin B complex and E). Mercury deposition and its elimination during chelation therapy were also screened for comparative purposes. The animals were dosed for 7 days with MMC 1 mg/kg/d and some were then kept without treatment for a further. 7 days. Other MMC-treated animals were immediately given one of the above antidotes for 7 days. All the animals were sacrificed on the 15th day. There was a decrease in all elements during MMC toxication with few exceptions, for example, copper was increased in the liver as was sodium in the kidney. Treatment with the thiols and vitamins restored the levels of these elements in certain tissues towards normal, but their concentrations remained abnormal in most instances. The fluctuations in the concentration of these elements were attributed to their association with various macromolecules.

Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA, Joshi SS, Pruess HG. Toxicology. 2000 Aug 7; 148(2-3):187-97. 10962138 PubMed. These results demonstrate that GSPE provides excellent protection against oxidative stress and free radical-mediated tissue injury.

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Mercury exposure evaluations and their correlation with urine mercury excretion: 4. Elimination of mercury by sweating. Lovejoy HB, Bell ZG, Vizena TR. J Occup Med. 1973 15:590-591. The elimination of mercury via sweat has been shown to constitute a significant route for the removal of mercury from the body (blood stream).

Nutrition and metal toxicity. Goyer RA. Am J Clin Nutr. 1995 Mar; 61(3 Suppl):646S-650S. 7879732 PubMed. Lead, cadmium, and mercury are toxic metals that are not essential for nutrition. However, the toxic effects of these metals may be mediated or enhanced by interactions or deficiencies of nutritionally essential metals. Lead competes with calcium, inhibiting the release of neurotransmitters, and interferes with the regulation of cell metabolism by binding to second-messenger calcium receptors, blocking calcium transport by calcium channels and calcium-sodium ATP pumps, and by competing for calcium-binding protein sites and uptake by mitochondria. Dietary deficiencies of calcium, iron, and zinc enhance the effects of lead on cognitive and behavioral development. Iron deficiency increases the gastrointestinal absorption of cadmium, and cadmium competes with zinc for binding sites on metallothionein, which is important in the storage and transport of zinc during development. Selenium protects from mercury and methyl mercury toxicity by preventing damage from free radicals or by forming inactive selenium mercury complexes.

Protective effect of vitamin E against mercuric chloride reproductive toxicity in male mice. Rao MV, Sharma PS. Reprod Toxicol. 2001 Nov-Dec; 15(6):705-12. 11738524 PubMed. Mercuric chloride produced a reduction in epididymal sperm count, sperm motility, and sperm viability, and there were no sperm-positive smears in this group. Biochemical tests from the male reproductive organs were also altered by mercuric chloride treatment. Coadministration of vitamin E with mercuric chloride prevented the changes in sperm and biochemical parameters and was associated with control rates of sperm positive smears after cohabitation. Animals given vitamin E with mercuric chloride also had lower concentrations of mercury in the testis, epididimyis, and vas deferens. Permitting animals to recover for 45 days after mercuric chloride treatment resulted in partial recovery of sperm and biochemical parameters. Vitamin E cotreatment has a protective role against mercury-induced male reproductive toxicity.

Restoration of methylmercury inhibited adenosine triphosphatases during vitamin and monothiol therapy. Bapu C, Rao PA, Sood PP. J Environ Pathol Toxicol Oncol. 1998; 17(1):75-80. 9490323 PubMed. The aim of our investigation was to examine the efficacy of monothiols and vitamins in the restoration of ion-dependent ATPases in mice intoxicated with methylmercury chloride (MMC). A daily dose of glutathione (GSH), N-acetyl-DL-homocysteine thiolactone (NAHT), vitamin B complex, or vitamin E, either alone or in combination, resulted in significant recovery of N+, K+, Mg++ ATPases. A significant recovery was noted in some therapeutic groups. As the therapeutic agents used in this study are natural physiological components present in all the animals, they are unlikely to be injurious if applied in appropriate doses. Hence, they can be safely recommended for methylmercury detoxication.

Role of ascorbic acid on mercuric chloride-induced genotoxicity in human blood cultures. Rao MV, Chinoy NJ, Suthar MB, Rajvanshi MI. Toxicol In Vitro. 2001 Dec; 15(6):649-54. 11698165 PubMed. The data indicate the mutagenic activity of MC and the protective role of vitamin C on mercury-induced genotoxicity in human blood cultures is probably due to its strong antioxidant and nucleophilic nature.

Selenium: a quest for better understanding. Badmaev V, Majeed M, Passwater RA. Altern Ther Health Med. 1996 Jul; 2(4):59-62, 65-7. 8795924 PubMed. Selenium is an essential trace element in nutrition for the prevention of disease in humans. Epidemiological studies indicate an association between low nutritional selenium status and increased risks of cardiomyopathy, cardiovascular disease, and carcinogenesis in various sites of the body. The role of selenium supplementation in the prevention and treatment of AIDS-related pathology has been considered. Selenoproteins discovered in mammalian cells may account for the essentiality of selenium in the body's antioxidant defense; thyroid hormone function; immune system function, particularly the cellular immunity; formation of sperm; and functioning of the prostate gland. The seleno-organic compounds, primarily L-(+)-selenomethionine, generally are recognized as safe and effective forms of selenium supplementation. The nutritionally recommended dose of elemental selenium is estimated at 50 to 200 micrograms [corrected] per day. There is, however, increased discussion of a pharmacological dose of selenium, significantly higher than the nutritional dose of the microelement, to treat active conditions. One way of increasing the tissue levels of selenium is to combine its ingestible form with a nutrient bioavailability enhancing compound.

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The biological activity of undenatured dietary whey proteins: role of glutathione. Bounous G, Gold P. Clin Invest Med. 1991 Aug; 14(4):296-309. 1782728 PubMed. This study compared the effects of different sources of whey protein concentrate (20 g/100 g diet) and of casein on the spleen, liver, and heart glutathione content of C3H/HeJ mice, and on the immune response of their spleen cells to sheep red blood cells. Body weight curves were similar in all dietary groups. Our data indicate that the humoral immune response is highest in mice fed a dietary whey protein concentrate exhibiting the highest solubility (undenatured conformation) and a greater relative concentration of the thermolabile bovine serum albumin and immunoglobulins. In addition, the mice fed this type of whey protein concentrate exhibit higher levels of tissue glutathione. The presence in the serum albumin fraction of glutamylcysteine groups (rare in food protein) and the specific intramolecular bond as related to the undenatured conformation of the molecule are considered to be key factors in the glutathione-promoting activity of the protein mixture.

Toxic and essential metal interactions. Goyer RA. Annu Rev Nutr. 1997; 17:37-50. 9240918 PubMed. Cadmium, lead, mercury, and aluminum are toxic metals that may interact metabolically with nutritionally essential metals. Iron deficiency increases absorption of cadmium, lead, and aluminum. Lead interacts with calcium in the nervous system to impair cognitive development. Cadmium and aluminum interact with calcium in the skeletal system to produce osteodystrophies. Lead replaces zinc on heme enzymes and cadmium replaces zinc on metallothionein. Selenium protects from mercury and methylmercury toxicity. Aluminum interacts with calcium in bone and kidneys, resulting in aluminum osteodystrophy. Calcium deficiency along with low dietary magnesium may contribute to aluminum-induced degenerative nervous disease.

Zinc and immune function. Ripa S, Ripa R. Minerva Med. 1995 Jul-Aug; 86(7-8):315-8. 7478075 PubMed. Zinc and immune function relationship has been extensively studied. Both in experimentally induced mineral deficit and in genetically determined deficit observable in acrodermatitis enteropathica and in enteropathy of Danish A-46 cattle, a B and T dependent antibody response decrease, a T dependent cytolytic response decrease and a natural killer cytotoxic activity decrease are present noteviously. Serious reduction of the immune function is present, in proportion to the value of low zinc plasmatic level, in elderly patients, in malnourished and seriously zinc deficient children, in patients subjected to total parenteral supply, in HIV infections and especially in evident AIDS: in this condition the plasmatic zinc level can be considered, together with the CD4+ lymphocytes amount and the B2-microglobulin value, a disease progression marker. Zinc immunostimulating action mechanisms are complex, although thymic hormone (of which zinc is essential cofactor) stimulation seems to be most important. Zinc supplementation, also parenterally, can be useful in immunodeficiency (in the elderly, in the post-surgical patients, in genetically determined or alimentary induced deficit, in AIDS.

Zinc and metallothioneins on cellular immune effectiveness during liver regeneration in young and old mice. Mocchegiani E, Verbanac D, Santarelli L, Tibaldi A, Muzzioli M, Radosevic-Stasic B, Milin C. Life Sci. 1997; 61(12):1125-45. 9315504 PubMed. Zinc is relevant for good immune functioning. Restoration of zinc into both the thymus and thymocytes subsets in the late period of liver regeneration is observed in young pHx mice. These findings have suggested a link between the thymus and the liver influencing T-cell functions and involving zinc.

Symptoms

ABC on mercury-poisoning from dental amalgam fillings. Handbook for victims of mercury-poisoning from dental amalgam. Swedish Association of Dental Mercury Patients. Nov 1993. Mats Hanson, Ph.D. Booklet. The primary symptoms of mercury-poisoning are vague psychic ones. Short-time memory deteriorates. You will find it difficult to concentrate on tasks which require attention and thinking. It is easier to execute tasks that are well known rather than to learn something new. You avoid social contacts which demand that you get out of your introvert behavior. You loose your temper easily and switch between different moods for no particular reason. Little by little, a more physical kind of exhaustion is added to the condition. More and more effort is required to initiate activities and sometimes break things due to inability to co-ordinate your movements with your visual impressions (ataxia). Occasional headaches, minor involuntary muscle spasms or ticks within groups of muscles can also appear. Hands and feet become easily cold, attacks of dizziness or vertigo can occur, and periodically you may find it difficult to focus your eyes and to see clearly. Joint and muscle pains, stiffness, lumbago and similar symptoms often appear at an early stage. They can be caused or increased by low availability of the trace element selenium. Nervous heart, sometimes accompanied by a week pulse, sometimes by a hard pulse, creates a feeling of anxiety. You don't sleep well, you wake up stiff and never feel thoroughly rested. As a whole you need more sleep than before, and you are constantly tired. Some individuals develop pronounced intestinal and stomach disturbances. Bloating is common and diarrhea can alternate with constipation. From 50 to 200 micrograms mercury from amalgam daily passes the gastrointestinal tract. There is usually irritation where mercury first interacts with tissues. The upper respiratory tract easily becomes chronically inflamed and symptoms in mouth appear. The gums bleed when you brush your teeth, red and white irritations (lichen, leukoplakia) araise, blisters and sensitivity to certain nutritives develop, ypur teeth ache, the whole jaw can become more or less inflamed, and some persons develop sinusitis. Metal taste in your mouth is a direct sign of metal-poisoning (mercury, copper). The more poisoned you are, the more serious and chronic your problems become. The pituitary gland will be affected which often leads to frequent urination. When the thyroid gland is affected secondary effects on metabolism can appear. Both glands accumulate mercury. neurological symptoms such as numbness, hypersensitivity and paralysis exacerbate. It is often hard to determine if the cause is in the nervous or circulatory systems.

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Adverse health effects related to mercury exposure from dental amalgam fillings: toxicological or psychological causes? Bailer J, Rist F, Rudolf A, Staehle HJ, Eickholz P, Triebig G, Bader M, Pfeifer U. Psychol Med. 2001 Feb; 31(2):255-63. 11232913 PubMed. The two groups did not differ with respect to the number of amalgam fillings, amalgam surfaces or mercury levels assessed in blood, urine or saliva. However, amalgam sensitive subjects had significantly higher symptom scores both in a screening instrument for medically unexplained somatic symptoms (SOMS) and in the SCL-90-R Somatization scale. Additionally, more subjects from this group (50% versus 4.7%) had severe somatization syndromes. With respect to psychological risk factors, amalgam sensitive subjects had a self-concept of being weak and unable to tolerate stress, more cognitions of environmental threat, and increased habitual anxiety. These psychological factors were significantly correlated with the number and intensity of the reported somatic symptoms.

A multicenter survey of amalgam fillings and subjective complaints in non-selected patients in the dental practice. Melchart D, Wuhr E, Weidenhammer W, Kremers L. Eur J Oral Sci. 1998 Jun; 106(3):770-7. 9672099 PubMed. A higher number of symptoms as well as a higher intensity of symptoms were found in patients before amalgam removal compared to the remaining patients.

Changes in the nervous system due to occupational metallic mercury poisoning. Langauer-Lewowicka H, Zajac-Nedza M. Neurol Neurochir Pol. 1997 Sep-Oct; 31(5):905-13. 9513954 PubMed. The clinical picture of the poisoning consisted mainly of neurasthenic, cerebellar (30 persons), psychoorganic symptoms (20 persons) and behavioural changes (irritability, aggressive states). Headaches, sleep and recent memory disturbances, progressive behavioral changes, dizziness, were the most frequent complaints. The authors stressed the irreversibility of central nervous disorders despite cessession of the exposure to Hg.

Mercury: major issues in environmental health. Clarkson TW. Environ Health Perspect. 1993 Apr; 100:31-8. 8354179 PubMed. It crosses without hindrance the blood-brain and placental barriers to reach its principal target tissue, the brain. It is eliminated chiefly in the feces after conversion to inorganic mercury. The biological half-time of methylmercury in human tissues is about 50 days, but there is wide individual variation. Adult poisoning is characterized by focal damage to discrete anatomical areas of the brain such as the visual cortex and granule layer of the cerebellum. A latent period of weeks or months may ensue before the appearance of signs and symptoms of poisoning. The latter manifest themselves as paresthesia, ataxia, constriction of the visual fields, and hearing loss. The prenatal period is the most sensitive stage of the life cycle to methylmercury. Prenatally poisoned infants exhibit a range of effects from severe cerebral palsy to subtle developmental delays. Methylmercury is believed to inhibit those processes in the brain specially involved in development and growth such as neuronal cell division and migration.

Mercury vapour in the oral cavity in relation to the number of amalgam surfaces and the classic symptoms. Lichtenberg H. Journal of Orthomolecular Medicine Vol 11:2. 87-94 1996. This study shows that individuals with dental amalgam fillings who exhibit symptoms typical of chronic mercury poisoning, all have mercury vapour concentrations in their oral cavity far higher than acceptable levels and on average, higher than the maximum permitted levels for the industrial environment. Results indicate that those patients with only amalgam filling, high concentrations of mercury vapour in the oral cavity, and who have also many amalgam surfaces, exhibit on average more symptoms than those with lower concentrations of mercury vapour and few amalgam surfaces. This study shows that the mercury vapour concentration in individuals with symptoms of chronic mercury poisoning is on average, 54.6 microgram mercury per cubic metre air and consequently above the maximum permitted limit for the working environment of 50 microgram per cubic metre air 5 days a week 8 hours a day - and far, far above the set maximum permitted level of 0.014 microgram mercury vapour per cubic metre air per kilogram body weight, comparable to one microgram for a person of 70 kilogram. http://www.lichtenberg.dk/mercury_vapour_in_the_oral_cavit.htm   

Physical and mental problems attributed to dental amalgam fillings: a descriptive study of 99 self-referred patients compared with 272 controls. Malt UF, Nerdrum P, Oppedal B, Gundersen R, Holte M, Lone J. Psychosom Med. 1997 Jan-Feb; 59(1):32-41. 9021864 PubMed. The dental amalgam sample reported significantly more physical symptoms from all body regions. Self-reports suggested that 62% suffered from a chronic anxiety disorder (generalized anxiety disorder or panic). Forty-seven percent suffered from a major depression compared with 14% in the two clinical-comparison samples and none in the dental control sample. Symptoms suggesting somatization disorder were found in 29% of the dental amalgam sample compared with only one subject in the 272 comparison subjects. One third of the dental amalgam patients reported symptoms of chronic fatigue syndrome compared with none in the dental control sample and only 2 and 6%, respectively, in the two clinical comparison samples. The dental amalgam group reported higher mean neuroticism and lower lie scores than the comparison groups. CONCLUSION: Self-referred patients with health complaints attributed to dental amalgam are a heterogeneous group of patients who suffer multiple symptoms and frequently have mental disorders. There is a striking similarity with the multiple chemical sensitivity syndrome.

Relationship between mercury from dental amalgam and health. Siblerud RL. Toxic Substances Journal. 10:425-444 1990b. The findings presented here suggest that mercury poisoning from dental amalgam may play a role in the etiology of many health disorders. A comparison of 125 health symptoms was made between a group of subjects with amalgams and a control group without amalgams. The 47 amalgam subjects reported a total of 45 % (P=0.0001) more health symptoms per subject compared to an age- and sex-matched control group of 48 nonamalgam subjects. Symptoms that were exhibited significantly more by the amalgam group were less happiness, less peace of mind, poorer reading ability, foul breath, tremors, colds and respiratory infections, heart or chest pains, heartburn, menstrual difficulties, sudden anger, depression, irritability, tiring easily, tired in morning, hay fever, trouble with night vision, and a metallic taste in mouth. Most of these symptoms can be explained by mercury toxicity. The data suggest that inorganic mercury poisoning from dental amalgam does affect health.

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Results of dental amalgam removal and mercury detoxification using DMPS and neural therapy. Kidd RF. Altern Ther Health Med. 2000 Jul; 6(4):49-55. 10895513 PubMed. Sixty consecutive patients who had undergone replacement of dental amalgam fillings and a protocol of nutritional support and heavy metal detoxification using dimercapto-propanyl-sulfate and neural therapy were surveyed. A questionnaire was mailed to the patients and 42 responded, resulting in a response rate of 70%. The reasons for undergoing treatment were many, ranging from a patient's desire to avoid potential health problems in the future to treatment of serious current disease. Although medical diagnoses were made when possible before treatment, this survey studied only the patients' estimations of their most distressing symptoms and their evaluations of response to treatment. The most common complaints were problems with memory and/or concentration; muscle and/or joint pain; anxiety and insomnia; stomach, bowel, and bladder complaints; depression; food or chemical sensitivities; numbness or tingling; and eye symptoms, in descending order of frequency. The most distressing symptoms were headache and backache, fatigue, and memory and concentration problems. Headache and backache responded best to treatment, but all symptoms showed considerable improvement on average. Of the respondents, 78% reported that they were either satisfied or very satisfied with the results of treatment, and 9.5% reported that they were disappointed.

Side-effects: mercury contribution to body burden from dental amalgam. Reinhardt JW. Adv Dent Res. 1992 Sep; 6:110-3. 1292449 PubMed. 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.

Symptoms Improvement after Amalgam Removal

Amalgam. XII. Amalgam removed and patient cured. Eijkman MA, de Jongh A. Ned Tijdschr Tandheelkd. 1994 Feb; 101(2):50-3. 11830991 PubMed. It is concluded that, when the removal of dental amalgams in patients with a hypersensitivity to mercury is put aside, possible explanations for these questionable cures are not connected with the removal of amalgam but may involve the functioning of the immune system, the relation between environment and the opinions of patients and the influence of psychological factors on illness and health.

Amalgam Mercury Syndrome. DAMS Study. DAMS website has over 1000 medical study references documenting widespread chronic health effects from mercury exposure/amalgam, and over 60,000 clinical cases of recovery or significant improvement after amalgam replacement. Documentation of Mechanisms by which mercury/amalgam causes over 40 chronic health conditions. http://home.earthlink.net/~berniew1/damspr6.html.

Changes in Health Complaints After Removal of Amalgam Fillings. T T Sjursen, G B Lygre, K Dalen, V Helland, T Lægreid,* J Svahn, B F Lundekvam, and L Björkman. J Oral Rehabil. 2011 Nov; 38(11): 835–848. PMCID: PMC3229679. The aim of the present study was to investigate whether removal of all amalgam fillings was associated with long-term changes in health complaints in a group of patients who attributed subjective health complaints to amalgam fillings. There was a reference group and a treatment group. Participants in the treatment group had all amalgam fillings replaced with other restorative materials. Comparisons between the groups showed that reductions in intra-oral and general health complaints in the treatment group were significantly different from the changes in the reference group. In the treatment group, intra-oral and general health complaints were significantly reduced 3 years after completed replacement of amalgam fillings. Reductions in subjective health complaints after replacement of amalgam fillings have also been found in previous studies (24, 25). The reference group received no intervention, and no improvement in health complaints was found. This is in agreement with data from patients with health complaints attributed to dental restorations, mainly dental amalgam, who did not change the restorations to other materials (8).

Consolidated symptoms of 1,569 patients. Ziff S. Bio-Probe Newsletter. 9:2. March 1993. 7-8. Health system analysis of 1569 patients who eliminated mercury containing dental fillings. Compilation of 6 different studies evaluating the health effects of replacing mercury amalgam fillings. The patient base was drawn from Sweden, Denmark, Canada, and the United States (807) and (762) adverse reacton reports submitted to the FDA by individuals.

Coors Amalgam Study: Effects of placement and Removal of Amalgam fillings. Adolph Coors Foundation. 1995. http://www.toxicteeth.net/RemovalResults.cfm  

Dental Amalgam and Health Experience: Exploring Health Outcomes and Issues for People Medically Diagnosed with Mercury Poisoning. Jones L. The Bulletin of the New Zealand Psychological Society. 97, 29-33. 1999. Reports a qualitative investigation with people who have considered removing their dental amalgam fillings following a medical diagnosis of mercury poisoning. Seven focus groups involved 35 participants selected by random, criteria sampling from the computer records of one medical practice. The participants’ experiences represented four scenarios of presenting illnesses and patterns of linking mercury and health. Of the 32 who had begun amalgam removal, 29 reported enduring health gains. Many had been told their conditions were psychosomatic and had symptoms that included cognitive deficits and mood swings. Participants explored issues related to medical practice such as the focus on symptoms not etiology; how they had monitored health changes; the stigma of a psychosomatic label; and how detoxification was essential but problematic. A placebo effect and reduced galvanism as explanations for recovery are considered. The amalgam poisoning experience was costly financially and socially, so participants wished health professionals were more mercury conscious.

Dental mercury: A factor that aggravates and induces xenobiotic intolerance. Zamm AV. Journal of Orthomolecular Medicine. Vo. 6 No.2, Second Quarter 1991, pp.67-77. People with multiple sensitivities show symptom improvement.

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Elimination of symptoms by removal of dental amalgam from mercury poisoned patients, as compared with a control group of average patients. Lichtenberg HJ. Journal of Orthomolecular Medicine. 1993; 8: pp.145-148. This findings presented here suggest a correlation between many health complaints and mercury amalgam fillings. Removal of amalgam fillings result in significant improvement of these symptoms. These same symptoms which are improved or eliminated in amalgam-removal patients are present but undiagnosed in general polulation. Summery. Replacement of amalgam and sometimes removal of gold crowns, bridges and metallic porcelain crowns and replacement with one of the patient`s biocompatible plast materials has significant positive effect on symptoms and complaints of most patients. On average, 88% of the symptoms specified in this investigation either disappear or improve as indicated by responses taken at least one year after amalgam removal. All 120 patients continue to come for check-ups in the clinic and will continue to fill out questionnaires every few years. This research shows that 9 out of 10 health problems improved or disappeared completely after one year. http://www.lichtenberg.dk/experience_after_amalgam_removal.htm 

Health observations before and after amalgam removal. Engel P. Dr. Med.dent. Lyss_Strasse 24, 2560 Nidau, Switzerland. Fifty-two women and 23 men (i.e. approx. 4% of the patients treated by me in the last 4 years), mostly over 30 years old, complained of chronic symptoms such as migraine (36x), headache (32x), gastro-intestinal disturbances (27x), neck tension (25x), paraesthesia (19x), dizziness (18x), allergies (13x), vision disturbances (13x), back pain (12x), mental disorder (12x), joint pain (10x) and shoulder/arm pain (10x). After removing the amalgam, 68% of the patients believed their health had become "much better", 12% "better", 9% "somewhat better", 7% had experienced "no improvement" whatsoever, and 1% "worsening". www.amalgam-info.ch/engel-e.pdf  www.melisa.org/articles/engel-e.pdf 

Improvement of Nerve and Immunological Damages after Amalgam Removal. Daunderer M. Almost all patients were happy with their progress results during the detoxification program, although the most severe nerve damages improved only very gradually. Severe cases of poisonings require repetition of the DMPS-test every 6 to 12 weeks. About half of our patients needed half a year; while 40% of the cases had to be treat over one year. Since zinc is also strongly excreted and additionally promotes the elimination of mercury, it should always be determined in spontaneous urine.Amer. J. Of Probiotic Dentistry and Medicine, Jan 1991. http://www.rmdentalcentre.com/article.cfm?artid=4&catid=1 

Mercury toxicity presenting as chronic fatigue, memory impairment and depression: diagnosis, treatment, susceptibility, and outcomes in a New Zealand general practice setting (1994-2006). Wojcik DP, et al. Wojcik DP. Neuro Endocrinol Lett. 2006 Aug;27(4):415-23. 16891999 Pubmed In a group of 465 patients diagnosed as having chronic mercury toxicity (CMT), 32.3% had severe fatigue, 88.8% had memory loss, and 27.5% had depression. A significant correlation was found between CMT and the Apo-lipoprotein E4 genotype (p=0.001). An investigation into an additional 864 consecutively seen general practice patients, resulted in 30.3% having evidence consistent with CMT, and once again a significant correlation was found with the APO-E4 genotype (p=0.001). Removal of amalgam mercury fillings when combined with appropriate treatment resulted in a significant symptom reduction (p<0.001) to levels reported by healthy subjects.

Oral lichenoid reactions associated with amalgam: improvement after amalgam removal. Dunsche A, Kastel I, Terheyden H, Springer IN, Christophers E, Brasch J. Br J Dermatol. 2003 Jan; 148(1):70-6. 12534597 PubMed. Of all patients with OLR associated with dental amalgam fillings, 97.1% benefited from amalgam removal regardless of patch test results with amalgam or INM. We suggest that the removal of amalgam fillings can be recommended in all patients with symptomatic OLR associated with amalgam fillings if no cutaneous LP is present.

Removal of dental amalgam and other metal alloys supported by antioxidant therapy alleviates symptoms and improves quality of life in patients with amalgam-associated ill health. Lindh U, Hudecek R, Danersund A, Eriksson S, Lindvall A. Neuroendocrinol Lett. 2002 Oct-Dec; 23(5-6):459-82. 12500173 PubMed. OBJECTIVES: The purpose of this study was to evaluate treatment of patients suffering from chronic ill health with a multitude of symptoms associated with metal exposure from dental amalgam and other metal alloys. SETTING AND DESIGN: We included 796 patients in a retrospective study using a questionnaire about symptom changes, changes in quality of life as a consequence of treatment and assessment of care taking. METHODS: Treatment of the patients by removal of offending dental metals and concomitant antioxidant therapy was implemented according to the Uppsala model based on a close co-operation between physicians and dentists. RESULTS: More than 70% of the responders, remaining after exclusion of those who had not begun or completed removal, reported substantial recovery and increased quality of life. Comparison with similar studies showed accordance of the main results. Plasma concentrations of mercury before and after treatment supported the metal exposure to be causative for the ill health.

Results of dental amalgam removal and mercury detoxification using DMPS and neural therapy. Kidd RF. Altern Ther Health Med. 2000 Jul; 6(4):49-55. 10895513 PubMed. Sixty consecutive patients who had undergone replacement of dental amalgam fillings and a protocol of nutritional support and heavy metal detoxification using dimercapto-propanyl-sulfate and neural therapy were surveyed. A questionnaire was mailed to the patients and 42 responded, resulting in a response rate of 70%. The reasons for undergoing treatment were many, ranging from a patient's desire to avoid potential health problems in the future to treatment of serious current disease. Although medical diagnoses were made when possible before treatment, this survey studied only the patients' estimations of their most distressing symptoms and their evaluations of response to treatment. The most common complaints were problems with memory and/or concentration; muscle and/or joint pain; anxiety and insomnia; stomach, bowel, and bladder complaints; depression; food or chemical sensitivities; numbness or tingling; and eye symptoms, in descending order of frequency. The most distressing symptoms were headache and backache, fatigue, and memory and concentration problems. Headache and backache responded best to treatment, but all symptoms showed considerable improvement on average. Of the respondents, 78% reported that they were either satisfied or very satisfied with the results of treatment, and 9.5% reported that they were disappointed.

Symptoms and differential diagnosis of patients fearing mercury toxicity from amalgam fillings. Stenman S, Grans L. Scand J Work Environ Health. 1997; 23 Suppl 3:59-63. 9456068 PubMed. Among the patients there were 26 who had had their amalgam fillings removed and who, at the time of the follow-up, were subjectively cured.

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Symptoms before and after proper amalagam removal in relation to serum-globulin reaction to metals. Lichtenberg HJ. Orthomolec Med 1996:11:195-204. After amalgam removal, 79 participants had no amalgam or metals remaining. 39 had no visible amalgam, having elected to retain one or more gold or porcelain crowns, under which amalgam may be present. One to four years after removal, all patients responded to the same survey as previously noted, inquiring whether the 38 symptoms and complaints had improved, disappeared, or remained unchanged. The results of this survey indicate that for the average participant, out of 17 symptoms, 8.2 were reduced, 5.1 were eliminated, and 3.7 were unchanged. In other words, 48% of symptoms were reduced, 31% were eliminated, and 21% were unchanged. In total, 79% of the symptoms and complaints were reduced or eliminated after amalgam removal. http://www.lichtenberg.dk/symptoms_before_and_after_proper.htm 

The Marburg amalgam detoxification study. Bernhard A. Weber, Regina Schneider. Marburg Institute for Naturopathi Medicine. Investigations on more than 1200 patients have shown a chronic mercury poisoning from amalgam fillings. About 50% of those patients removed their amalgam fillings after the investigation. One-hundred patients finished the detoxification therapy and were questioned for improvement of their symptoms and were investigated again. According to the intensity of the detoxification, 80% of the patients showed a good even excellent improvement of symptoms. http://www.karlloren.com/ultrasound/p23.htm.  

The relationship between mercury from dental amalgam and mental health. Am J Psychother. Siblerud RL.1989 Oct; 43(4):575-87. 2618948 PubMed. Subjects who had amalgams removed reported that symptoms of mental illness lessened or disappeared after removal. The data suggest that inorganic mercury poisoning from dental amalgam does affect the mind and emotions.

Testing

Biological monitoring of mercury vapour exposure by scalp hair analysis in comparison to blood and urine. Wilhelm M, Muller F, Idel H. Toxicol Lett. 1996 Nov; 88(1-3):221-6. 8920740 PubMed. It is concluded that hair may be used as an indicator of internal uptake of mercury provided that it was not externally exposed to mercury vapour. In cases of occupational exposure to mercury vapour, hair is an useful tool for monitoring external exposure.

Brain autoantibodies to evaluate toxicity of mercury and other toxic chemicals in autism and PDD, multiple sclerosis, Alzheimer's disease, and Parkinson's disease. The Great Plains Laboratory. The Great Plains Laboratory is pleased to announce the availability of two new tests myelin basic protein antibodies and glial fibrillary acid protein antibody to evaluate autoantibodies to brain proteins that may be clinically useful for the treatment of autism and PDD, multiple sclerosis, and other neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (Lou Gehrig's disease).One of the major difficulties is that testing for mercury may not be able to detect mercury exposure that has occurred more than one year ago. In such cases, a biological marker for the harmful effects of mercury toxicity is very desirable. Elevated autoantibodies to brain proteins are frequently found in autism. Singh reported that patients with autism had significantly higher values for autoantibodies to myelin than controls. Organic mercury found in vaccines as the preservative thimerosal and in fish is especially potent in inducing brain autoantibodies. Mercury has the ability to react with the sulfhydryl groups of a wide range of proteins, altering their structure so significantly that the immune system no longer recognizes them as "self" and mounts an attack against these proteins.One of the major difficulties is that testing for mercury may not be able to detect mercury exposure that has occurred more than one year ago. In such cases, a biological marker for the harmful effects of mercury toxicity is very desirable. Elevated autoantibodies to brain proteins are frequently found in autism. Singh reported that patients with autism had significantly higher values for autoantibodies to myelin than controls. Organic mercury found in vaccines as the preservative thimerosal and in fish is especially potent in inducing brain autoantibodies. Mercury has the ability to react with the sulfhydryl groups of a wide range of proteins, altering their structure so significantly that the immune system no longer recognizes them as "self" and mounts an attack against these proteins. http://www.greatplainslaboratory.com/

Epidemiologic assessment of measures used to indicate low-level exposure to mercury vapor (Hg). Cianciola ME, Echeverria D, Martin MD, Aposian HV, Woods JS. J Toxicol Environ Health. 1997 Sep; 52(1):19-33. 9269320 PubMed. We conclude from this study that first morning void urine samples may be used to derive reasonably valid estimates of Hg concentrations found in the total amount of urine collected over a 24-h period. Thus, due to its comparability, ease of collection, and lower cost, the first morning urine void may be used in place of a sample collected over a full 24 h to facilitate Hg exposure assessments in epidemiologic studies that use urinary Hg levels as a measure of low-level Hg exposure.

Monitoring mercury exposure. Suggestions for testing blood and urine and medical monitoring. Mercury can be monitored in the body two ways, biologically and medically. Monitoring mercury is necessary if someone is exposed mercury, or think they might be exposed. http://pasture.ecn.purdue.edu/~mercury/src/monitor.htm

Significance of biological indicators of mercury exposure. Apostoli P, Mangili A, Alessio L. Med Lav. 2003 Mar-Apr; 94(2):231-41. 12852206 PubMed. It was confirmed that mercury in blood (B-Hg) is a good indicator of recent exposure, while urinary mercury (U-Hg) indicates current exposure when mercury reaches the renal steady state. B-Hg values are greatly influenced by fish consumption, while the variables influencing U-Hg values are amalgam fillings, commercial gamma-globulin preparations, vaccines, topical remedies, environmental pollution and hobbies, occupational exposure and, partly, fish consumption.  

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Testing Feces Metals. Doctor’s Data, Inc. Analysis of elements in feces provides a comprehensive evaluation of environmental exposure, accumulation and endogenous detoxification of potentially toxic metals. For several toxic elements such as mercury, cadmium, lead, antimony and uranium, biliary excretion of metals into feces is the primary natural route of elimination from the body. Studies performed at DDI demonstrate that the fecal mercury content and number of amalgam surfaces are highly correlated, as is the case for post-DMPS urine mercury levels and amalgam surface area. Results are reported as mg/kg dry weight of feces to eliminate the influence of variability in water content of fecal specimens. The reference values that appear in this report have been derived from both published data and in-house studies at DDI. Due to exposure to mercury in the oral cavity, people with dental amalgams typically have a considerably higher level of mercury in the feces than individuals without dental amalgams; therefore, two reference ranges have been established for mercury. To provide guidance in interpretation of results, patient values are plotted graphically with respect to percentile distribution of the population base. Since this test reflects both biliary excretion (metals to which the patient is exposed may not be absorbed) and exposure, it may not correlate with overt clinical effects. Further testing can assist in determining whether the metals are from endogenous (biliary excretion) or exogenous (oral exposure) sources.  www.doctorsdata.com 

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Testing for Toxic Metal- and Chemical-Induced Porphyrinuria. Carl P. Verdon, Ph.D., Terry A. Pollock, M.S. and J. Alexander Bralley, Ph.D., C.C.N. Metametrix Publications, 1998. Toxic metals induce porphyria and cell injury in that: 1) metals perturb cellular organelle function and promote an increase in reactive prooxidants, 2) metals complex with GSH thereby compromising antioxidant and thiol status, 3) metals impair enzymes and other proteins via SH-complexation, 4) the result of metal-induced oxidant stress is cell injury and the oxidation of porphyinogens to porphyrins that are excreted in the urine (porphyrinuria).

Trace element analysis in hair: factors determining accuracy, precision, and reliability. Bass DA, Hickock D, Quig D, Urek K. Altern Med Rev. 2001 Oct; 6(5):472-81. 11703167 PubMed. Trace element analysis in biological samples has improved significantly over the last 40 years. Improvements in instrumentation such as inductively coupled plasma-mass spectrometry and microwave digestion have resulted in improved precision, accuracy, reliability, and detection limits. The analysis of human scalp hair has benefited significantly from these improvements. A recent article in the Journal of the American Medical Association found significant inter-laboratory variation amongst several laboratories performing trace metal hair testing. It concluded that standardization was necessary to improve inter-laboratory comparability, and an accompanying commentary described the characteristics of a laboratory that should be used in performing hair analysis. The objective of this study is to demonstrate that good laboratory practices will generate precise, accurate, and reliable results. A method for establishing reference ranges and specific data on an analytical method will also be presented. The use of prescribed clinical quality control, including method validation, proficiency testing, split sampling, and good laboratory practices clearly demonstrates that measuring trace elements in hair can be analytically valid.

Teeth

Pulpal uptake of mercury from lined amalgam restorations in guinea pigs. Akyuz S, Caglar E. Eur J Oral Sci. 2002 Dec; 110(6):460-3. 12507220 PubMed. The aim of the present study was to examine pulp in amalgam-restored teeth of guinea pigs with respect to the presence of mercury, and to evaluate whether lining of cavities with resin modified glass ionomer cements had any effect on the penetration of mercury. Class V cavities were prepared in 63 incisor teeth of 21 guinea pigs. Three amalgam restorations were placed per animal, one without base liner and two with different resin-modified glass ionomer cements (GC Lining LC and Ionoseal). Following observation periods of 1, 7 or 30 d, teeth were extracted and the mercury concentration in the pulp tissue was evaluated using atomic absorption spectrophotometry. It was found that resin-modified glass ionomer cements significantly diminished the transport of mercury into the pulp between day 7 and day 30 after amalgam insertion.

Toxicity

Correlation of dental amalgam with mercury in brain tissue. Eggleston DW, Nylander M J Prosthet Dent. 1987 Dec; 58(6):704-7. 3480359 PubMed. Data from this project demonstrate a positive correlation between the number of occlusal surfaces of dental amalgam and mercury levels in the brain (p less than .0025 in white matter). This is indirect evidence suggesting that mercury from dental amalgam fillings may contribute to the body burden of mercury in the brain. The toxic levels of mercury in human tissues have not been sufficiently investigated and the amount of mercury in human brain tissue from dental amalgam may or may not be clinically significant. Nevertheless, dental amalgam exposure should be considered in monitoring sources of mercury accumulation in human brain tissue.

Demonstration of mercury in the human brain and other organs 17 years after metallic mercury exposure. Opitz H, Schweinsberg F, Grossmann T, Wendt-Gallitelli MF, Meyermann R. Clin Neuropathol. 1996 May-Jun; 15(3):139-44. 8793247 PubMed. A male subject became exposed to metallic mercury vapor at work in 1973. He excreted 1,850 mg Hg/l urine initially. Controls of urine mercury excretion after D-penicillamine administration led to the assumption of a total body clearance of mercury latest since 1976. Subsequently he developed an organic psychosyndrome without detectable signs of classical mercurialism. He never returned to work again and died of lung cancer in 1990. In different organs (brain, kidney, and lung) which were sampled at autopsy elevated levels of mercury were documented by atomic absorption analysis. Histological examination of the tissue by the Danscher and Schroder method, which is specific for mercury, showed a highly positive staining in the majority of nerve cells and cells of other organs.

Dental amalgam: a review of the literature. Eggleston DW. Compendium. 1989 Sep; 10(9):500-5. 2700133 PubMed. Since the 1800s, dental amalgam has been the most commonly used dental restorative material. Each year, dentistry in the United States uses over 100 tons of mercury, continuing a controversy regarding mercury's safety for patients and dental personnel.

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Dental mercury--a public health hazard. Pleva J. Rev Environ Health. 1994 Jan-Mar; 10(1):1-27. 8029522 PubMed. The aim of this review is to point out the health hazards of the uncontrolled global use of implanted mercury-leaking dental amalgam fillings. In spite of the pandemic use of amalgam, most dentists and doctors are still ignorant about the levels of mercury exposure and its health implications. This review discusses the following chronically neglected aspects in clinical practice: The use of materials science in calculating the mercury exposure levels, which may exceed the TLVs by an order of magnitude; Microbial dissolution and methylation of mercury from amalgam by oral and intestinal bacteria; Diagnostic problems and effects of chronic mercury exposure with emphasis on intestinal, cardiovascular, mental and neurologic symptoms and disorders; Diagnostic value of faeces--instead of urine examination--as the main indicator of Hg exposure; Lack of control groups unexposed to Hg (amalgam free) for epidemiologic investigations of health problems; Contribution of dental mercury to environmental pollution. In conclusion, a lack of interdisciplinary research and of a critical approach to established clinical routine appears to be the reason for the failure of the dental profession to protect the patient from Hg exposure when saving the tooth.

Does mercury from amalgam restorations constitute a health hazard? Weiner JA, Nylander M, Berglund F. Sci Total Environ. 1990 Dec 1; 99(1-2):1-22. 2270464 PubMed. Amalgam restorations continuously emit mercury vapour, which is absorbed in considerable quantities via the lungs. A comparison with dose-effect relationships, obtained in occupational studies, for certain effects on the kidneys and central nervous system (CNS), suggests that individuals with unusually high emission of mercury from amalgam fillings are at risk. It is unclear whether or not clinically significant effects could be expected. The limited sensitivity of available occupational studies, together with insufficient knowledge of possible host factors affecting resistance to mercury, implies that other more severe effects in susceptible individuals cannot be excluded. Information on long-term effects on organs other than brain or kidney is sparse. Animal studies suggest the possibility of immune system reactions to mercury, i.e. development of autoimmunity, that are not primarily dose-dependent, but rather depend on genetic susceptibility. From a toxicological point of view, amalgam is an unsuitable material for dental restorations.

Environmental exposure to mercury and its toxicopathologic implications for public health. Tchounwou PB, Ayensu WK, Ninashvili N, Sutton D. Environ Toxicol. 2003 Jun; 18(3):149-75. 12740802 PubMed. Its creeping neurotoxicity is highly devastating, particularly in the central and peripheral nervous systems of children. Central nervous system defects and erethism as well as arrythmias, cardiomyopathies, and kidney damage have been associated with mercury exposure. Necrotizing bronchitis and pneumonitis arising from inhalation of mercury vapor can result in respiratory failure. Mercury is also considered a potent immunostimulant and -suppressant, depending on exposure dose and individual susceptibility, producing a number of pathologic sequelae including lymphoproliferation, hypergammaglobulinemia, and total systemic hyper- and hyporeactivities. In this review we discuss the sources of mercury and the potential for human exposure; its biogeochemical cycling in the environment; its systemic, immunotoxic, genotoxic/carcinogenic, and teratogenic health effects; and the dietary influences on its toxicity; as well as the important considerations in risk assessment and management of mercury poisoning.

Environmental medicine, part three: long-term effects of chronic low-dose mercury exposure. Crinnion WJ. Altern Med Rev. 2000 Jun;5(3):209-23. 10869102 PubMed. Mercury is ubiquitous in the environment, and in our mouths in the form of "silver" amalgams. Once introduced to the body through food or vapor, mercury is rapidly absorbed and accumulates in several tissues, leading to increased oxidative damage, mitochondrial dysfunction, and cell death. Mercury primarily affects neurological tissue, resulting in numerous neurological symptoms, and also affects the kidneys and the immune system. It causes increased production of free radicals and decreases the availability of antioxidants. It also has devastating effects on the glutathione content of the body, giving rise to the possibility of increased retention of other environmental toxins.

Influence of amalgam fillings on Hg levels and total antioxidant activity in plasma of healthy donors. Pizzichini M, Fonzi M, Gasparoni A, Mencarelli M, Rocchi G, Kaitsas V, Fonzi L. Bull Group Int Rech Sci Stomatol Odontol. 2001 May-Sep; 43(2):62-7. 11799720 PubMed. In order to evaluate the influence of mercury (Hg) levels on antioxidant power in human plasma, 26 healthy people were evaluated by a dentist and their plasma analyzed for Hg content by atomic absorption and total antioxidant activity (TAA) by FRAP method. Hg plasma concentration correlated with number of amalgam restorations, suggesting that Hg released from fillings is a source of Hg in non-occupational exposed people. Fish consumption, in fact, showed no influence on Hg plasma levels, perhaps because Italian subjects examined in the present group used low quantity of fish at week or kinds of fish with light contamination. TAA negatively correlated with Hg plasma revealing a pro-oxidant role of Hg released from amalgam fillings.

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Mercury exposure and early effects: an overview. Kazantzis G. Med Lav. 2002 May-Jun; 93(3):139-47. 12197264 PubMed. In an uncontaminated environment the general population is exposed to mercury vapour from the atmosphere and from dental amalgam, while the diet, mainly from fish, is the principal source for methyl mercury absorption. Mercury vapour release from amalgam fillings increases with chewing, with absorption and uptake by the brain and kidneys. Infants exposed to phenyl mercury from treated diapers and young children ingesting mercurous chloride in teething powders have developed acrodynia (pink disease), and Kawasaki disease and the use of mercurial skin lightening creams has been followed by the development of the nephrotic syndrome. Both mercury compounds and mercury vapour have given rise to contact dermatitis in the general population. Epidemics of mercury poisoning have followed release of mercury into the environment from industrial activity, with uptake of methyl mercury from fish eating in Minamata Bay and uptake of both inorganic and methyl mercury following release of mercury vapour and deposition into waterways from gold recovery procedures in the Amazon basin. The ingestion of wheat and barley seed treated with an alkyl mercury fungicide for sowing, by a largely illiterate population in Iraq, led to a major outbreak of poisoning with a high fatality rate. Following exposure to mercury vapour, the earliest clinically observed adverse effects at urine mercury levels of the order of 30-100 mg/g creatinine, are objectively detectable tremor, psychological disorder and impaired nerve conduction velocity in sensitive subjects, with subjective symptoms of irritability, fatigue and anorexia. At these and at lower levels, proteinuria has also been observed. Both glomerular and tubular damage may occur at exposure levels lower than those giving rise to central nervous system effects. An immunological effect has also been observed in studies on clinically asymptomatic workers with low level exposure. CONCLUSIONS: As mercury can give rise to allergic and immunotoxic reactions which may be genetically regulated, in the absence of adequate dose-response studies for immunologically sensitive individuals, it has not been possible to set a level for mercury in blood or urine below which mercury related symptoms will not occur.

Mercury exposure from "silver" tooth fillings: emerging evidence questions a traditional dental paradigm. Lorscheider FL, Vimy MJ, Summers AO. FASEB J. 1995 Apr; 9(7):504-8. 7737458 PubMed. For more than 160 years dentistry has used silver amalgam, which contains approximately 50% Hg metal, as the preferred tooth filling material. During the past decade medical research has demonstrated that this Hg is continuously released as vapor into mouth air; then it is inhaled, absorbed into body tissues, oxidized to ionic Hg, and finally covalently bound to cell proteins. Animal and human experiments demonstrate that the uptake, tissue distribution, and excretion of amalgam Hg is significant, and that dental amalgam is the major contributing source to Hg body burden in humans. Current research on the pathophysiological effects of amalgam Hg has focused upon the immune system, renal system, oral and intestinal bacteria, reproductive system, and the central nervous system. Research evidence does not support the notion of amalgam safety. (10 micrograms of mercury into the body (i.e. 3,000,000,000,000,000 (3 quadrillion) mercury atoms per day), more than 2/3 of the excretable mercury in humans is derived from amalgams)


Organic mercury compounds: human exposure and its relevance to public health. Risher JF, Murray HE, Prince GR. Toxicol Ind Health. 2002 Apr; 18(3):109-60. 12974562 PubMed. Humans may be exposed to organic forms of mercury by either inhalation, oral, or dermal routes, and the effects of such exposure depend upon both the type of mercury to which exposed and the magnitude of the exposure. In general, the effects of exposure to organic mercury are primarily neurologic, while a host of other organ systems may also be involved, including gastrointestinal, respiratory, hepatic, immune, dermal, and renal. While the primary source of exposure to organic mercury for most populations is the consumption of methylmercury-contaminated fish and shellfish, there are a number of other organomercurials to which humans might be exposed. The antibacterial and antifungal properties of organomercurials have resulted in their long use as topical disinfectants (thimerosal and merbromin) and preservatives in medical preparations (thimerosal) and grain products (both methyl and ethyl mercurials). Phenylmercury has been used in the past in paints, and dialkyl mercurials are still used in some industrial processes and in the calibration of certain analytical laboratory equipment. The effects of exposure to different organic mercurials by different routes of exposure are summarized in this article.

Side-effects: mercury contribution to body burden from dental amalgam. Reinhardt JW. Adv Dent Res. 1992 Sep; 6:110-3. 1292449 PubMed. 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 dental amalgam issue. A review. Hanson M, Pleva J. Experientia. 1991 Jan 15; 47(1):9-22. 1999251 PubMed. Using an interdisciplinary approach, the current position in the dental amalgam controversy and the potential impact of amalgam mercury on human health are reviewed. Aspects of materials science, corrosion, mercury exposure, toxicology, neurology and immunology are included. New data on mercury exposure from corroded amalgam fillings in vivo are presented. The exposure can reach levels considerably over known threshold limit values. Also, measurements of mercury absorption from intraoral air are presented. The vital importance of avoiding a galvanic amalgam-gold coupling is emphasized. The symptomatology of a disabled patient, who recovered after amalgam removal, has been included. It is concluded that discussion of the dental amalgam issue has suffered from the lack of an interdisciplinary approach. It would be wise to learn from the lesson of acrodynia, and consider amalgam mercury among other possible factors in neurological and immunological diseases of unclear etiology.

The relationship between mercury concentration in human organs and different predictor variables. Weiner JA, Nylander M. Sci Total Environ. 1993 Sep 30; 138(1-3):101-15. 8259485 PubMed. An effect of a number of tooth surfaces with amalgam was seen in occipital lobe cortex, abdominal muscle and pituitary gland, but not in kidney cortex. In occipital lobe cortex and abdominal muscle, concentrations of mercury increased with age. Explanations discussed include: that a significant fraction of the mercury retained from amalgam fillings has a very long biological half-life; a decreasing capacity of mercury excretion with age; or higher fish consumption in the older individuals. In kidney cortex mercury concentrations decreased with age. The reason for this remains unclear, but it might indicate a decreasing capacity of mercury excretion with age.

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The toxicology of mercury. Clarkson TW. Crit Rev Clin Lab Sci. 1997 Aug; 34(4):369-403. 9288445 PubMed. The health effects of mercury vapor have been known since ancient times. Severe exposure results in a triad of symptoms, erethism, tremor, and gingivitis. Today, we are concerned with more subtle effects such as preclinical changes in kidney function and behavioral and cognitive changes associated with effects on the central nervous system. Methylmercury is a neurological poison affecting primarily brain tissue. In adults, brain damage is focal affecting the function of such areas as the cerebellum (ataxia) and the visual cortex (constricted visual fields). Methylmercury also at high doses can cause severe damage to the developing brain. Today the chief concern is with the more subtle effects arising from prenatal exposure such as delayed development and cognitive changes in children.

Toxic Teeth: The Chronic Mercury Poisoning of Modern Man. Vimy MJ. Chemistry Industry. 14-7, 1995. By Dr. Murray J. Vimy DMD. Clinical Associate Professor Faculty of Medicine, University of Calgary. http://www.testfoundation.org/toxicteeth.htm Web

Toxicity of mercury. Langford N, Ferner R. J Hum Hypertens. 1999 Oct;13(10):651-6. 10516733 PubMed. The new laws have been passed because of worries about mercury poisoning. Yet you can drink metallic mercury and come to no harm. What does it all mean? There are three forms of mercury from a toxicological point of view: inorganic mercury salts; organic mercury compounds; and metallic mercury. Inorganic mercury salts are water soluble, irritate the gut, and cause severe kidney damage. Organic mercury compounds, which are fat soluble, can cross the blood brain barrier and cause neurological damage. Mercury metal poses two dangers. It can be vaporised: the vapour pressure at room temperature is about 100 times the safe amount, so poisoning can occur if mercury metal is spilled into crevices or cracks in the floorboards. Dentists are occasionally poisoned this way. Mercury easily crosses into the brain, and causes tremor, depression, and behavioural disturbances. A second danger from metallic mercury is that it is biotransformed into organic mercury, by bacteria at the bottom of lakes. This can be passed along the food chain and eventually to man.

Whole-body imaging of the distribution of mercury released from dental fillings into monkey tissues. Hahn LJ, Kloiber R, Leininger RW, Vimy MJ, Lorscheider FL. FASEB J. 1990 Nov; 4(14):3256-60. 2227216 PubMed. The fate of mercury (Hg) released from dental "silver" amalgam tooth fillings into human mouth air is uncertain. A previous report about sheep revealed uptake routes and distribution of amalgam Hg among body tissues. The present investigation demonstrates the bodily distribution of amalgam Hg in a monkey whose dentition, diet, feeding regimen, and chewing pattern closely resemble those of humans. When amalgam fillings, which normally contain 50% Hg, are made with a tracer of radioactive 203Hg and then placed into monkey teeth, the isotope appears in high concentration in various organs and tissues within 4 wk. Whole-body images of the monkey revealed that the highest levels of Hg were located in the kidney, gastrointestinal tract, and jaw. The dental profession's advocacy of silver amalgam as a stable tooth restorative material is not supported by these findings.

Transportation

Mechanisms of hepatic methylmercury uptake. Ballatori N, Truong AT. J Toxicol Environ Health. 1995 Nov; 46(3):343-53. 7473862 PubMed. The mechanism by which methylmercury is cleared from hepatic portal blood was examined in isolated rat livers perfused single-pass with Krebs-Henseleit buffer. [203Hg]Methylmercury (0.24-24 microM) was infused over a 30-min interval, followed by a 30-min washout, as a complex with the endogenous ligands L-cysteine (CH3Hg-L-cys), glutathione (CH3Hg-SG), and serum albumin (CH3Hg-albumin), or as a complex with dithiothreitol (CH3Hg-DTT), chloride (CH3HgCl), and the D-enantiomer of cysteine (CH3Hg-D-cys). The sulfhydryl-containing compounds were added at a 10-fold molar excess. When administered as the albumin complex, only a small fraction of the [203Hg]methylmercury was cleared from perfusate (approximately 8%) and excreted into bile (0.7%). Hepatic uptake and biliary excretion of methylmercury was considerably higher for the other complexes: The percent of the dose recovered in liver tissue and bile was, respectively, CH3Hg-albumin, 6.9 and 0.7; CH3Hg-L-cys, 15.7 and 2.3; CH3Hg-D-cys, 27.1 and 2.8; CH3Hg-SG, 17.7 and 2.1; CH3HgCl, 66.5 and 3.2; and CH3Hg-DTT, 70.1 and 19.8. For the dithiothreitol complex, hepatic extraction of methylmercury was nearly complete during single-pass perfusion. A comparison of hepatic removal of increasing doses of CH3Hg-L-cys and CH3Hg-D-cys revealed little difference in uptake between these two enantiomers. Moreover, the fraction of methylmercury removed was similar when infused at concentrations of 0.24, 2.4, and 24 microM, indicating no saturability of uptake within this dose range. Methylmercury was not hepatotoxic at concentrations up to 24 microM if administered as a mercaptide; however, the chloride complex (CH3HgCl) produced cholestasis and an increase in perfusion pressure at a concentration of only 0.24 microM. These findings indicate that hepatic methylmercury uptake and toxicity are dependent on the chemical form in blood plasma. Uptake was faster when methylmercury was present as a cysteine or glutathione complex, as compared to the albumin complex; however, the lack of stereoselectivity indicates that the uptake process may be relatively unselective.

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Methylmercury transport across the blood-brain barrier by an amino acid carrier. Kerper LE, Ballatori N, Clarkson TW. Am J Physiol. 1992 May; 262(5 Pt 2):R761-5. 1590471 PubMed. The mechanism by which methylmercury (MeHg) crosses the blood-brain barrier was examined in the rat. Previous studies demonstrated that intravenous injection of L-cysteine with MeHg accelerates MeHg uptake into brain. Since the complex of MeHg with L-cysteine is structurally similar to L-methionine, a substrate for the L (leucine-preferring) amino acid transport system, this carrier may be involved in MeHg uptake. To examine this hypothesis, the rapid carotid infusion technique was used in the anesthetized rat. The concentration dependence of 203Hg uptake into brain after injection of Me203Hg-L-cysteine complex was nonlinear, exhibiting characteristics of saturable transport (apparent Michaelis constant 0.39 mM, vmax 33 nmol.min-1.g-1). A slower, nonsaturable uptake was seen after MeHg-L-cysteine uptake was inhibited by methionine and the amino acid analogue 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH), an L system substrate, but not by alpha-methylaminoisobutyric acid, an alanine-preferring system substrate. Furthermore, L-[14C]methionine transport was inhibited by MeHg-L-cysteine but not by MeHgCl. There was a significant amount of uptake of 203Hg when injected as Me203Hg-glutathione, and this was inhibited by L-methionine and BCH but not D-methionine. S-ethylglutathione also inhibited 203Hg uptake after administration as Me203Hg-glutathione but had no effect on Me203Hg-L-cysteine uptake. These results suggest that MeHg may enter the brain as a cysteine complex via the L system and that plasma MeHg-glutathione serves as a source of MeHg-cysteine.

Transport of the glutathione-methylmercury complex across liver canalicular membranes on reduced glutathione carriers. Dutczak WJ, Ballatori N. J Biol Chem. 1994 Apr 1; 269(13):9746-51. 8144567 PubMed. Methylmercury transport across liver canalicular membranes into bile, a major route of excretion of this toxic compound, is dependent upon intracellular GSH, and a glutathione-methylmercury complex (CH3Hg.SG) has been detected in liver tissue and bile. To examine whether the CH3Hg.SG complex is itself transported across the canalicular membrane and to identify the transport system involved, studies were performed in isolated rat liver canalicular plasma membrane vesicles. Uptake of CH3(203)Hg.SG (10 microM) into an osmotically active space was temperature-sensitive and unaffected by either ATP (5 mM) or an inwardly directed Na+ gradient (100 mM); however, CH3Hg.SG uptake was enhanced by a valinomycin-induced K+ diffusion potential (inside-positive) indicating that its transport was electrogenic. Transport of CH3Hg.SG exhibited saturation kinetics with both high affinity (Km = 12 +/- 2 microM, Vmax = 0.23 +/- 0.02 nmol.mg-1.20 s-1) and low affinity (Km = 1.47 +/- 0.22 mM, Vmax = 1.23 +/- 0.14 nmol.mg-1.20 s-1) components. Uptake of this complex was inhibited by GSH, the GSH analog ophthalmic acid, S-methyl, S-ethyl, S-butyl, S-hexyl, S-octyl, and S-dinitrophenyl glutathione, but not by GSSG, bile acids, amino acids, and P-glycoprotein inhibitors. Furthermore, GSH competitively inhibited (Ki = 83 microM) and trans-stimulated CH3Hg.SG uptake into the canalicular vesicles. These studies provide the first kinetic characterization of a transport system for glutathione-mercaptides and indicate that CH3Hg.SG is not a substrate for the ATP-dependent, canalicular GSSG or glutathione S-conjugate carriers, but appears to be a substrate for canalicular carriers that also transport GSH. Because efflux systems for GSH are found in all mammalian cells, transport of glutathione-metal complexes by such carriers may be a common mechanism for the removal of methylmercury and possibly other metals from cells.

Transport of toxic metals by molecular mimicry. Ballatori N. Environ Health Perspect. 2002 Oct; 110 Suppl 5:689-94. 12426113 PubMed. Intracellular concentrations of essential metals are normally maintained within a narrow range, whereas the nonessential metals generally lack homeostatic controls. Some of the factors that contribute to metal homeostasis have recently been identified at the molecular level and include proteins that mediate import of essential metals from the extracellular environment, those that regulate delivery to specific intracellular proteins or compartments, and those that mediate metal export from the cell. Some of these proteins appear highly selective for a given essential metal; however, others are less specific and interact with multiple metals, including toxic metals. For example, DCT1 (divalent cation transporter-1; also known as NRAMP2 or DMT1) is considered to be a major cellular uptake mechanism for Fe(2+) and other essential divalent metals, but this protein also mediates uptake of Cd(2+), Pb(2+), and possibly of other toxic divalent metals. The ability of nonessential metals to interact with binding sites for essential metals is critical for their ability to gain access to specific cellular compartments and for their ability to disrupt normal biochemical or physiological functions. Another major mechanism by which metals traverse cell membranes and produce cell injury is by forming complexes whose overall structures mimic those of endogenous molecules. For example, it has long been known that arsenate and vanadate can compete with phosphate for transport and metabolism, thereby disrupting normal cellular functions. Similarly, cromate and molybdate can mimic sulfate in biological systems. Studies in our laboratory have focused on the transport and toxicity of methylmercury (MeHg) and inorganic mercury. Mercury has a high affinity for reduced sulfhydryl groups, including those of cysteine and glutathione (GSH). MeHg-l-cysteine is structurally similar to the amino acid methionine, and this complex is a substrate for transport systems that carry methionine across cell membranes. Once MeHg has entered the cell, some of it binds to GSH, and the resulting MeHg-glutathione complex appears to be a substrate for proteins that mediate cellular export of glutathione S-conjugates, including the apically located MRP2 (multidrug resistance-associated protein 2) transporter, a member of the adenosine triphosphate-binding cassette protein superfamily. Because other toxic metals also form complexes with endogenous molecules, comparable mechanisms may be involved in their membrane transport and disposition.

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Types of Amalgam Fillings

Effect of selenium on mercury vapour released from dental amalgams: an in vitro study. Psarras V, Derand T, Nilner K. Swed Dent J. 1994;18(1-2):15-23. 8052947 PubMed. High copper, non- gamma 2- amalgams, released more mercury vapour than the conventional one throughout the experiment.

Mercury vaporization from amalgams with varied alloy compositions. Ferracane JL, Adey JD, Nakajima H, Okabe T. J Dent Res. 1995 Jul; 74(7):1414-7. 7560393 PubMed. The results showed a strong negative correlation between the log of total mercury released and the amount of tin in the gamma 1.

WHO: No Safe Level of Mercury

World Health Organization (WHO), Environmental Health Criteria 118: Inorganic Mercury, pp, 28-33, 84- 113, Geneva, 1991.

WHO Geneva. 1991. ISBN 92 4 157118 7. In the 1940s, "pink disease" (acrodynia) was reported in children below 5 years of age as a result of the use of mercurous chloride in teething powder and oinments. Affected children became irritable and generally miserable and had difficulty in sleeping. Profuse sweating, photophobia, and generalized rash followed. The extremities became cold, painful, red, and swollen, and the skin desquamated. NEITHER the occurrence of this disease nor its severity was DOSE RELATED... After the withdrawal of teething powder preparations by the main United Kingdom manufacturers in 1953, there was a dramatic decline in the occurence of pink disease.  

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