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“There has long been an undercurrent within the dental profession of anti-amalgam sentiment, a ‘mercury-free’ movement. To assess whether anything is or is not scientifically wrong with amalgam, one must look to the vast literature on exposure, toxicology, and risk assessment of mercury. The subject of risk assessment goes straight to the heart of the debate over whether amalgam is safe, or not, for unrestricted use in dentistry in the population at large.”

“Methylmercury-associated effects on the cardiovascular system have been documented though discrepancies exist, and most studied populations experience elevated methylmercury exposures. No paper has investigated the impact of low-level elemental (inorganic) mercury exposure on cardiovascular risk in humans. The purpose of this study was to increase understanding of the association between mercury exposure (methylmercury and elemental mercury) and blood pressure measures in a cohort of dental professionals that experience background exposures to both mercury forms. Dental professionals were recruited during the 2010 Michigan Dental Association Annual Convention. Mercury levels in hair and urine samples were analyzed as biomarkers of methylmercury and elemental mercury exposure, respectively. Blood pressure (systolic, diastolic) was measured using an automated device. Distribution of mercury in hair (mean, range: 0.45, 0.02-5.18 µg/g) and urine (0.94, 0.03-5.54 µg/L) correspond well with the US National Health and Nutrition Examination Survey. Linear regression models revealed significant associations between diastolic blood pressure (adjusted for blood pressure medication use) and hair mercury (n=262, p=0.02). Urine mercury results opposed hair mercury in many ways. Notably, elemental mercury exposure was associated with a significant systolic blood pressure decrease (n=262, p=0.04) that was driven by the male population. Associations between blood pressure and two forms of mercury were found at exposure levels relevant to the general population, and associations varied according to type of mercury exposure and gender.”

“Human exposure to methylmercury (MeHg) and elemental mercury vapor (Hg(0)(g)) are often estimated using total Hg concentrations in hair and urine, respectively. We investigated whether Hg stable isotopes could be used to better distinguish between exposure to Hg(0)(g) versus MeHg. We found that hair from North American dental professionals was characterized by high positive ?(199)Hg values (mean = 1.86‰, 1 SD = 0.12‰, n = 11). This confirms that among people who regularly consume fish, total Hg concentrations in hair reflect exposure to MeHg. In contrast, we found that urine from the same individuals was characterized by a range of ?(199)Hg values (0.29 to 1.77‰, 2 SD = 0.06‰, n = 12) that were significantly correlated to the number of dental amalgams in each individual’s mouth. We hypothesize that fish-derived MeHg is demethylated within the body, causing mass-dependent fractionation and the excretion of inorganic Hg in urine. Mercury in urine therefore represents a mixture of demethylated fish-derived MeHg and amalgam-derived inorganic Hg. We estimate that the majority (>70%) of Hg in urine from individuals with <10 dental amalgams is derived from ingestion of MeHg in fish. These data suggest that within populations that consume fish, urine total Hg concentrations may overestimate Hg exposure from personal dental amalgams.”

“Methylmercury (MeHg) toxicity may vary widely despite similar levels of exposure. This is hypothetically related to genetic differences in enzymes metabolizing MeHg. MeHg causes oxidative stress in experimental models but little is known about its effects on humans. The aims of the present study was to evaluate the effects of polymorphisms in glutathione (GSH)-related genes (GSTM1, GSTT1, GSTP1 and GCLM) on Hg concentrations in blood and hair, as well as MeHg-related effects on catalase (CAT) andglutathione-peroxidase (GPx) activity and GSH concentrations. Study subjects were from an Amazonian population in Brazil chronically exposed to MeHg from fish. Hg in blood and hair were determined by ICP-MS, CAT, GPx and GSH were determined by spectrophotometry, and multiplex PCR (GSTM1 and GSTT1) and TaqMan assays (GSTP1 and GCLM) were used for genotyping. Mean Hg concentrations in blood and hair were 48±36 μg/L and 14±10 μg/g. Persons with the GCLM-588 TT genotype had lower blood and hair Hg than did C-allele carriers (linear regression for Hg in blood β=-0.32, p=0.017; and hair β=-0.33; p=0.0090; adjusted for fish intake, age and gender). GSTM1*0 homozygous had higher blood (β=0.20; p=0.017) and hair Hg (hair β=0.20; p=0.013). Exposure to MeHg altered antioxidant status (CAT: β=-0.086; GSH: β=-0.12; GPx: β=-0.16; all p<0.010; adjusted for gender, age and smoking). Persons with GSTM1*0 had higher CAT activity in the blood than those with GSTM1. Our data thus indicate that some GSH-relatedpolymorphisms, such as GSTM1 and GCLM may modify MeHg metabolism and Hg-related antioxidant effects.”

“BACKGROUND:

Administration of mercury at nontoxic doses induces systemic autoimmune disease in Brown Norway (BN) rats. The pathogenesis of lupus-like oral mucosal lesion by mercury-induced autoimmunity is still unclear, even though the oral mucosa is observed to be commonly affected in mercury-treated BN rats. In this study, we investigated the immunopathology of lupus-like oral mucosal lesions in a model of mercury-induced systemic autoimmunity.

METHODS:

Brown Norway male rats were injected subcutaneously with either phosphate-buffered saline (control) or mercury at a dose of 1.0 mg per kilogram of body weight on days 0, 3, 5, and 7. Blood, kidney, and tongue samples were taken at various timepoints for evaluation by immunohistochemistry, RT-PCR, and lupus band test (LBT).

RESULTS:

Oral mucosal lesions were classified according to three consecutive temporal phases on the basis of infiltration of immunocompetent cells as follows: (phase I) infiltration of MHC class II+ dendritic cells (DC) and macrophages; (phase II) addition of ED1+ macrophage infiltrates; and (phase III) focal infiltration of pan T cells following increased infiltration of DC and macrophages. Dense infiltration of DC and macrophages was observed in the basement membrane (BM) zone of the oral epithelium. Tissue expression of IL-4 mRNA was detected in early lesions (phase I), suggesting that locally produced IL-4 may be responsible for Th2-mediated immune response. A linear and continuous smooth pattern of fluorescence was observed in the oral epithelial BM in addition to renal glomeruli, indicating immune complex deposits.

CONCLUSIONS:

Local autoimmune responses are involved in the pathogenesis of mercury-induced lupus-like lesions of the oral mucosa.”

“Various forms of mercury possess different rates of absorption, metabolism and excretion, and consequently, toxicity. Methylmercury (MeHg) is a highly neurotoxic organic mercurial. Human exposure is mostly due to ingestion of contaminated fish. Ethylmercury (EtHg), another organic mercury compound, has received significant toxicological attention due to its presence in thimerosal-containing vaccines. This study was designed to compare the toxicities induced by MeHg and EtHg, as well as by their complexes with cysteine (MeHg-S-Cys and EtHg-S-Cys) in the C6 rat glioma cell line. MeHg and EtHg caused significant (p<0.0001) decreases in cellular viability when cells were treated during 30min with each mercurial following by a washing period of 24h (EC50 values of 4.83 and 5.05?M, respectively). Significant cytotoxicity (p<0.0001) was also observed when cells were treated under the same conditions with MeHg-S-Cys and EtHg-S-Cys, but the respective EC50 values were significantly increased (11.2 and 9.37?M). l-Methionine, a substrate for the l-type neutral amino acid carrier transport (LAT) system, significantly protected against the toxicities induced by both complexes (MeHg-S-Cys and EtHg-S-Cys). However, no protective effects of l-methionine were observed against MeHg and EtHg toxicities. Corroborating these findings, l-methionine significantly decreased mercurial uptake when cells were exposed to MeHg-S-Cys (p=0.028) and EtHg-S-Cys (p=0.023), but not to MeHg and EtHg. These results indicate that the uptake of MeHg-S-Cys and EtHg-S-Cys into C6 cells is mediated, at least in part, through the LAT system, but MeHg and EtHg enter C6 cells by mechanisms other than LAT system.”

“Reports from human case studies indicate a half-life for inorganic mercury in the brain in the order of years-contradicting older radioisotope studies that estimated half-lives in the order of weeks to months in duration. This study systematically reviews available evidence on the retention time of inorganic mercury in humans and primates to better understand this conflicting evidence. A broad search strategy was used to capture 16,539 abstracts on the Pubmed database. Abstracts were screened to include only study types containing relevant information. 131 studies of interest were identified. Only 1 primate study made a numeric estimate for the half-life of inorganic mercury (227-540days). Eighteen human mercury poisoning cases were followed up long term including autopsy. Brain inorganic mercury concentrations at death were consistent with a half-life of several years or longer. 5 radionucleotide studies were found, one of which estimated head half-life (21days). This estimate has sometimes been misinterpreted to be equivalent to brain half-life-which ignores several confounding factors including limited radioactive half-life and radioactive decay from surrounding tissues including circulating blood. No autopsy cohort study estimated a half-life for inorganic mercury, although some noted bioaccumulation of brain mercury with age. Modelling studies provided some extreme estimates (69days vs 22years). Estimates from modelling studies appear sensitive to model assumptions, however predications based on a long half-life (27.4 years) are consistent with autopsy findings. In summary, shorter estimates of half-life are not supported by evidence from animal studies, human case studies, or modelling studies based on appropriate assumptions. Evidence from such studies point to a half-life of inorganic mercury in human brains of several years to several decades. This finding carries important implications for pharmcokinetic modelling of mercury and potentially for the regulatory toxicology of mercury.”

“The American Dental Association (ADA) strongly objects to the recent segment about dental amalgam, broadcast on a March 28 segment of ‘The Dr. Oz Show’ and its reliance on sensationalism while ignoring sound science.”

“This background catalyzed a December 2012 workshop organized by the International Association for Dental Research (IADR) and King’s College London (KCL), co-sponsored by the World Health Organization (WHO), United Nations Environmental Programme (UNEP), and the FDI World Dental Federation. The objectives of the workshop were to identify knowledge gaps in our current choices of dental restorative materials, identify promising areas of materials research that could be applied to restorative dentistry, and develop a prioritized research and advocacy agenda and action plan to address individual and population-level needs for restorative materials with environmental compatibility and economic feasibility. Expert information and insight were provided by researchers and innovators, including materials scientists from within the dental community and from outside dentistry, policy-makers, and clinicians, along with representatives from industry, funding agencies, regulatory bodies, and professional organizations.”