Mercury

OVERVIEW:
The authors review factors related to office infrastructure and operation that dentists should consider when investing in an amalgam separator. They also provide a cost-analysis worksheet and checklist that may be useful to dentists who are considering purchasing a separator.

CONCLUSIONS AND CLINICAL IMPLICATIONS:
Before purchasing or installing an amalgam separator, dentists should consider factors specific to the available models, including size and maintenance requirements. In addition, office-specific actors should be considered (such as the plumbing configuration, available space for installation and subsequent access to that space for equipment replacement and maintenance). Dentists also should research whether any local or state regulations exist that might influence product selection or installation. Dentists should consider the effect an amalgam separator could have on existing suction equipment. Finally, dentists will want to consider the short- and long-term costs (including maintenance and parts replacement) of the available options.

“The authors employed pharmacy utilization data to evaluate the health status of a representative sample of 600 dentists, matched to control subjects, for gender, age, geographical area, and insurance plan structure. Dentists demonstrated significantly more prescription utilization of specific illness medications than did Controls, for the following disease categories: Neuropsychological, Neurological, Respiratory, and Cardiovascular. The greater majority of pediatric and general practice dentists still use mercury amalgam restorations. This places them at greater risk than the general population for those disorders, as well as threatening the future health of America’s children and adults who continue to receive silver amalgam restorations.”

“Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is the identification of children who may be uniquely susceptible to Hg toxicity because of genetic disposition. We examined the hypothesis that CPOX4, a genetic variant of the heme pathway enzyme coproporphyrinogen oxidase (CPOX) that affects susceptibility to mercury toxicity in adults, also modifies the neurotoxic effects of Hg in children. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of Hg from dental amalgam tooth fillings in children. Subjects were evaluated at baseline and at 7 subsequent annual intervals for neurobehavioral performance and urinary mercury levels. Following the completion of the clinical trial, genotyping assays for CPOX4 allelic status were performed on biological samples provided by 330 of the trial participants. Regression modeling strategies were employed to evaluate associations between CPOX4 status, Hg exposure, and neurobehavioral test outcomes. Among girls, few significant CPOX4-Hg interactions or independent main effects for Hg or CPOX4 were observed. In contrast, among boys, numerous significant interaction effects between CPOX4 and Hg were observed spanning all 5 domains of neurobehavioral performance. All underlying dose-response associations between Hg exposure and test performance were restricted to boys with the CPOX4 variant, and all of these associations were in the expected direction where increased exposure to Hg decreased performance. These findings are the first to demonstrate genetic susceptibility to the adverse neurobehavioral effects of Hg exposure in children. The paucity of responses among same-age girls with comparable Hg exposure provides evidence of sexual dimorphism in genetic susceptibility to the adverse neurobehavioral effects of Hg in children and adolescents.”

“BACKGROUND:
Thimerosal, a mercury-containing preservative, is one of the most widely used preservatives and found in a variety of biological products. Concerns over its possible toxicity have reemerged recently due to its use in vaccines. Thimerosal has also been reported to be markedly cytotoxic to neural tissue. However, little is known regarding thimerosal-induced toxicity in muscle tissue. Therefore, we investigated the cytotoxic effect of thimerosal and its possible mechanisms on mouse C2C12 myoblast cells.

METHODOLOGY/PRINCIPAL FINDINGS:
The study showed that C2C12 myoblast cells underwent inhibition of proliferation and apoptosis after exposure to thimerosal (125-500 nM) for 24, 48 and 72 h. Thimerosal caused S phase arrest and induced apoptosis as assessed by flow cytometric analysis, Hoechst staining and immunoblotting. The data revealed that thimerosal could trigger the leakage of cytochrome c from mitochondria, followed by cleavage of caspase-9 and caspase-3, and that an inhibitor of caspase could suppress thimerosal-induced apoptosis. Thimerosal inhibited the phosphorylation of Akt(ser473) and survivin expression. Wortmannin, a PI3K inhibitor, inhibited Akt activity and decreased survivin expression, resulting in increased thimerosal-induced apoptosis in C2C12 cells, while the activation of PI3K/Akt pathway by mIGF-I (50 ng/ml) increased the expression of survivin and attenuated apoptosis. Furthermore, the inhibition of survivin expression by siRNA enhanced thimerosal-induced cell apoptosis, while overexpression of survivin prevented thimerosal-induced apoptosis. Taken together, the data show that the PI3K/Akt/survivin pathway plays an important role in the thimerosal-induced apoptosis in C2C12 cells.

CONCLUSIONS/SIGNIFICANCE:
Our results suggest that in C2C12 myoblast cells, thimerosal induces S phase arrest and finally causes apoptosis via inhibition of PI3K/Akt/survivin signaling followed by activation of the mitochondrial apoptotic pathway.”

“Mammalian brain development is regulated by the action of thyroid hormone (TH) on target genes. We have previously shown that the perinatal exposure to thimerosal (TM, metabolized to ethylmercury) exerts neurotoxic effects on the developing cerebellum and is associated with a decrease in cerebellar D2 activity, which could result in local brain T3 deficiency. We have also begun to examine TM effect on gene expression. The objective of this study was to expand on our initial observation of altered cerebellar gene expression following perinatal TM exposure and to examine additional genes that include both TH-dependent as well as other genes critical for cerebellar development in male and female neonates exposed perinatally (G10-G15 and P5 to P10) to TM. We report here for the first time that expression of suppressor-of-white-apricot-1 (SWAP-1), a gene negatively regulated by T3, was increased in TM-exposed males (61.1% increase), but not in females; (p<0.05). Positively regulated T3-target genes, Purkinje cell protein 2 (Pcp2; p=0.07) and Forkhead box protein P4 (FoxP4; p=0.08), showed a trend towards decreased expression in TM-exposed males. The expression of deiodinase 2 (DIO2) showed a trend towards an increase in TM-exposed females, while deiodinase 3 (DIO3), transthyretin (TTR), brain derived neurotrophic factor (BDNF) and reelin (RELN) was not significantly altered in either sex. Since regulation of gene splicing is vital to neuronal proliferation and differentiation, altered expression of SWAP-1 may exert wide ranging effects on multiple genes involved in the regulation of cerebellar development. We have previously identified activation of another TH-dependent gene, outer dense fiber of sperm tails 4, in the TM exposed male pups. Together, these results also show sex-dependent differences between the toxic impacts of TM in males and females. Interestingly, the genes that were activated by TM are negatively regulated by TH, supporting our hypothesis of local brain hypothyroidism being induced by TM and suggesting a novel mechanism of action TM in the developing brain.”

“OBJECTIVES:

Intraoral exposure to dental restorations can cause contact allergy that may induce carcinogenesis. We investigated the relationship of intraoral metal contact allergy to epithelial carcinogenesis.

METHODS:

The prevalence of positive patch test reactions to dental restoration metals in 65 prospectively enrolled patients with newly or previously diagnosed oral squamous cell carcinoma (SCC) was compared to that in 48 control patients. The relative risk of oral SCC was estimated by calculating odds ratios for exposure to dental metals resulting in allergy.

RESULTS:

Of the 65 patients with oral SCC, 34% were allergic to at least 1 adjacent metal. They were 1.57 times as likely as control patients to have metal contact allergy (odds ratio, 1.57; 95% confidence interval, 0.65 to 3.80) and more than 3 times as likely to react to mercury (odds ratio, 3.20; 95% confidence interval, 0.42 to 33.20).

CONCLUSIONS:

Patients with oral SCC who have metal dental restorations should undergo patch testing and possible removal of the restorations if their reactions are positive.”

“BACKGROUND:

Dental amalgam is approximately 50% metallic mercury and releases mercury vapor into the oral cavity, where it is inhaled and absorbed. Maternal amalgams expose the developing fetus to mercury vapor. Mercury vapor can be toxic, but uncertainty remains whether prenatal amalgam exposure is associated with neurodevelopmental consequences in offspring.

OBJECTIVE:

To determine if prenatal mercury vapor exposure from maternal dental amalgam is associated with adverse effects to cognition and development in children.

METHODS:

We prospectively determined dental amalgam status in a cohort of 300 pregnant women recruited in 2001 in the Republic of Seychelles to study the risks and benefits of fish consumption. The primary exposure measure was maternal amalgam surfaces present during gestation. Maternal occlusal points were a secondary measure. Outcomes were the child’s mental (MDI) and psychomotor (PDI) developmental indices of the Bayley Scales of Infant Development-II (BSID-II) administered at 9 and 30 months. Complete exposure, outcome, and covariate data were available on a subset of 242 mother-child pairs.

RESULTS:

The number of amalgam surfaces was not significantly (p>0.05) associated with either PDI or MDI scores. Similarly, secondary analysis with occlusal points showed no effect on the PDI or MDI scores for boys and girls combined. However, secondary analysis of the 9-month MDI was suggestive of an adverse association present only in girls.

CONCLUSION:

We found no evidence of an association between our primary exposure metric, amalgam surfaces, and neurodevelopmental endpoints. Secondary analyses using occlusal points supported these findings, but suggested the possibility of an adverse association with the MDI for girls at 9 months. Given the continued widespread use of dental amalgam, we believe additional prospective studies to clarify this issue are a priority.”

“Mercury is a ubiquitous environmental toxicant that causes a wide range of adverse health effects in humans. Three forms of mercury exist: elemental, inorganic and organic. Each of them has its own profile of toxicity. The aim of the present study was to determine the effect of thimerosal, a topical antiseptic and preservative in vaccines routinely given to children, methyl mercury, and mercuric chloride on cellular viability measured by MTT in Jurkat T cells, a human T leukemia cell line. The treatment of Jurkat T cells with thimerosal caused a significant decrease in cellular viability at 1 ?M (25%, p<0.05; IC50: 10 ?M). Methyl mercury exhibited a significant decrease in cellular viability at 50 ?M (33%, p<0.01; IC50: 65 ?M). Mercuric chloride (HgCl2) did not show any significant change in cellular survival. Our findings showed that contrary to thimerosal and methyl mercury, mercuric chloride did not modify Jurkat T cell viability.”

“While its use has essentially been eliminated in many countries, dental amalgam is now being considered for a global phase-out in the ongoing mercury treaty negotiations1 and in the European Union (BIO 2012) because of significant environmental concerns. The negative effects of mercury releases related to amalgam use are widely recognized in countries where its use has been prevalent: it is often the largest source of mercury in municipal wastewater as well as an increasing source of mercury air pollution from crematoria. On the other hand, high-quality mercury-free alternatives have long been available. While most dental professionals charge lower prices for amalgam fillings than for mercury-free alternatives, this paper shows that when factoring in “external” environmental and societal costs,2 amalgam is a higher-priced dental material by far (Hylander and Goodsite 2006). Ultimately, society pays for mercury releases related to amalgam use through additional pollution control costs, the loss of common (public-owned) resources, and the health effects associated with mercury releases and contamination (MPP 2008).”

“The health and environmental risks associated with mercury (Hg) are well known and have led the Commission to adopt an EU Mercury Strategy in 2005(1), with the aim to ‘reduce mercury levels in the environment and human exposure, especially from methylmercury in fish’. The review of the Strategy’s implementation(2), in 2010, acknowledged the progress made with regard to a number of actions proposed in 2005 such as the adoption of the Mercury Export Ban Regulation(3), the phase-out of mercury use in certain measuring devices under the REACH Regulation4, the submission of additional mercury use restriction proposals under REACH, and the EU’s contribution to the progress of international negotiations on the global mercury treaty. The review also highlighted areas for further improvement, among which the remaining uses of mercury in several applications where Hg-free alternatives exist and are already used to some extent; this concerns in particular dental amalgam and button cell batteries, which are the subject of the present study.”