Mercury

RESULTS:
At the initial examination, 964 (15.2 percent) of amalgam restorations and 199 (17.4 percent) of resin-based composite restorations required re-treatment. Of those judged clinically acceptable, 14.2 percent of amalgam and 16.7 percent of resin-based composite restorations required replacement during the observation period. The authors found significant increases in replacement rates for resin-based composite restorations compared with amalgam restorations for replacement due to all causes (adjusted hazard ratio, 1.28; P < .05), as well as for replacement due to restoration failure (adjusted hazard ratio, 1.64; P < .01).

CONCLUSIONS:
About 30 percent of posterior restorations required replacement, either at the initial examination or during the subjects’ first years of military service. In a young military population, significantly more resin-based composite restorations in place at the initial examination will require replacement than will amalgam restorations. Multi-surface restorations had higher rates of replacement than did one-surface restorations, and subjects at high caries risk experienced significantly higher replacement rates than did those at low caries risk.

CLINICAL IMPLICATIONS:
The number of surfaces restored and subjects’ caries risk status may influence the longevity of resin-based composite and amalgam restorations.

“PURPOSE:

A scientific review panel for the US Food and Drug Administration (FDA) recently identified the need for more data on the health risk of mercury exposure from dental amalgam among susceptible populations. We evaluated impacts of low-level mercury exposure on renal function and neurobehavioral and neuropsychological performance among children.

METHODS:

Dental histories for 403 children aged 7-11 years in five schools from Xuhui, Shanghai were checked by dentists. Of them, 198 with confirmed amalgam fillings were recruited (exposure group). Reference children (N=205) were those who never had dental amalgam treatment. In May 2004, each child provided a urine sample for measurements of total mercury, N-acetyl-beta-D-glucosaminidase activity, microalbumin, and creatinine (Cr). The Child Behavior Checklist, Eysenck Personality Questionnaire, and an intelligence screening test were administered.

RESULTS:

The geometric mean urinary mercury concentration was 1.6 microg/g Cr for children with and 1.4 microg/g Cr for children without amalgam fillings. No differences were found between children with and without fillings for either renal function biomarker, or on neurobehavioral, neuropsychological, or intelligence tests.

CONCLUSIONS:

Although urinary mercury concentration was slightly elevated among children with amalgam fillings, we found no evidence of adverse effects on the outcomes evaluated. These results agree with those from recent trials in developed countries.”

“OBJECTIVE:
We evaluated the association between infant hair-Hg and Gesell schedules (GS).

BACKGROUND:
Longitudinal assessment of prenatal and postnatal Hg exposure during the first 60 months.

METHODS:
We used hair-Hg as a marker of postnatal Hg exposure (inorganic and methyl-Hg from breast milk, and ethyl-Hg from thimerosal) and GS measured at 6, 36, and 60 months.

RESULTS:
Hair-Hg at 6 months responded to events related to Hg exposure and breastfeeding. However, most neurodevelopment delays observed at 6 months were overcome with infant growth; at 60 months 87% of children showed adequate GS (>85). Length of lactation and hair-Hg were each significantly correlated with GS, but in opposite ways: length of lactation was positive and significantly correlated with all GS at 60 months; hair-Hg concentrations were negative and significantly correlated with GS at 6 months (r=-0.333; P=0.002) and 60 months (r=-0.803; P=0.010), but not at 36 months. Multiple regression models showed that the GS outcome at 60 months depended on GS at 36 months that in turn was influenced by infants’ developmental and Hg exposure variables. GS at 6 months was significantly influenced by prenatal (maternal and infant hair-Hg at birth) and postnatal Hg exposure at 6 months.

CONCLUSIONS:
Until there is more refined approach to recognize children sensitive to Hg exposure, and in situations of uncertainty (EtHg exposure), the neurodevelopment benefit of breastfeeding should be recommended.”

“Dental offices are known to be one of the largest users of inorganic mercury. It is well documented that dentists and dental personnel who work with amalgam are chronically exposed to mercury vapour, which accumulates in their bodies to much higher levels than for most non-occupationally exposed. Adverse health effects of this exposure including neurological effects have also been well documented that affect most dentists and dental assistants, with measurable effects among those in the lowest levels of exposure.”

“The effect of thimerosal on cytosolic free Ca(2+) concentrations ([Ca(2+)](i) ) in human oral cancer cells (OC2) is unclear. This study explored whether thimerosal changed basal [Ca(2+)](i) levels in suspended OC2 cells using fura-2. Thimerosal at concentrations between 1and 50 microM increased [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was reduced partly by removing extracellular Ca( 2+). Thimerosal-induced Ca(2+) influx was not blocked by L-type Ca(2+) entry inhibitors and protein kinase C modulators (phorbol 12-myristate 13-acetate [PMA] and GF109203X). In Ca(2+)-free medium, 50 microM thimerosal failed to induce a [Ca(2+)](i) rise after pretreatment with thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). Inhibition of phospholipase C with U73122 did not change thimerosal-induced [Ca(2+)](i) rises. At concentrations between 5 and 10 microM, thimerosal killed cells in a concentration-dependent manner. The cytotoxic effect of 8 muM thimerosal was potentiated by prechelating cytosolic Ca(2+) with the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetate/acetomethyl (BAPTA/ AM). Flow cytometry data suggested that 1-7 microM thimerosal-induced apoptosis in a concentration-dependent manner. Collectively, in OC2 cells, thimerosal-induced [Ca(2+)](i) rises by causing phospholipase C-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) influx through non-L-type Ca(2+) channels. Thimerosal killed cells in a concentration-dependent manner through apoptosis.”

“Research into the metabolic phenotype of autism has been relatively unexplored despite the fact that metabolic abnormalities have been implicated in the pathophysiology of several other neurobehavioral disorders. Plasma biomarkers of oxidative stress have been reported in autistic children; however, intracellular redox status has not yet been evaluated. Lymphoblastoid cells (LCLs) derived from autistic children and unaffected controls were used to assess relative concentrations of reduced glutathione (GSH) and oxidized disulfide glutathione (GSSG) in cell extracts and isolated mitochondria as a measure of intracellular redox capacity. The results indicated that the GSH/GSSG redox ratio was decreased and percentage oxidized glutathione increased in both cytosol and mitochondria in the autism LCLs. Exposure to oxidative stress via the sulfhydryl reagent thimerosal resulted in a greater decrease in the GSH/GSSG ratio and increase in free radical generation in autism compared to control cells. Acute exposure to physiological levels of nitric oxide decreased mitochondrial membrane potential to a greater extent in the autism LCLs, although GSH/GSSG and ATP concentrations were similarly decreased in both cell lines. These results suggest that the autism LCLs exhibit a reduced glutathione reserve capacity in both cytosol and mitochondria that may compromise antioxidant defense and detoxification capacity under prooxidant conditions.”

“Mercury compounds versatility explains their numerous applications in diverse areas of industry. The growing use of this metal has resulted in a significant increase of environment contamination and episodes of human intoxication, arousing the concern of international organisms. Meanwhile, consequences of these intoxication outbreaks are still not fully understood, especially if we consider long-term effects of chronic exposure to relatively low levels of mercury compounds. In the present manuscript, studies about the genotoxicity of mercury compounds, performed in vitro, in vivo, and/or including epidemiologic studies of human populations were reviewed. Some mercury compounds are known as teratogenic agents, especially affecting the normal development of the central nervous system; however, the connection between mercury exposure and carcinogenesis remains controversial. Since 1990s, epidemiological studies have begun to include an increasing number of human subjects, making the results more reliable: thus, increased genotoxicity was demonstrated in human populations exposed to mercury through diet, occupation or by carrying dental fillings. In fact, concentrations of methylmercury causing significant genotoxic alterations in vitro below both safety limit and concentration were associated with delayed psychomotor development with minimal signs of methylmercury poisoning. Based on mercury’s known ability to bind sulfhydryl groups, several hypotheses were raised about potential molecular mechanisms for the metal genotoxicity. Mercury may be involved in four main processes that lead to genotoxicity: generation of free radicals and oxidative stress, action on microtubules, influence on DNA repair mechanisms and direct interaction with DNA molecules. All data reviewed here contributed to a better knowledge of the widespread concern about the safety limits of mercury exposure.”

“Thimerosal (TMR), an ethylmercury-containing preservative in pharmaceutical products, was recently reported to increase intracellular Zn(2+) concentration. Therefore, some health concerns about the toxicity of TMR remain because of physiological and pathological roles of Zn(2+). To reveal the property of TMR-induced increase in intracellular Zn(2+) concentration, the effect of TMR on FluoZin-3 fluorescence, an indicator of intracellular Zn(2+), of rat thymocytes was examined. TMR at concentrations ranging from 0.3 microM to 10 microM increased the intensity of FluoZin-3 fluorescence in a concentration-dependent manner under external Ca(2+)- and Zn(2+)-free condition. The threshold concentration was 0.3-1 microM. The increase in the intensity was significant when TMR concentration was 1 microM or more. N,N,N’,N’-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a chelator for intracellular Zn(2+), completely attenuated the TMR-induced augmentation of FluoZin-3 fluorescence. Hydrogen peroxide (H(2)O(2)) and N-ethylmaleimide, reducing cellular thiol content, significantly increased FluoZin-3 fluorescence intensity and decreased 5-chloromethylfluorescein (5-CMF) fluorescence intensity, an indicator for cellular thiol. The correlation coefficient between TMR-induced augmentation of FluoZin-3 fluorescence and attenuation of 5-CMF fluorescence was -0.882. TMR also attenuated the 5-CMF fluorescence in the presence of TPEN. Simultaneous application of H(2)O(2) and TMR synergistically augmented the FluoZin-3 fluorescence. It is suggested that TMR increases intracellular Zn(2+) concentration via decreasing cellular thiol content.”

“There are four published reference exposure levels (RELs) for Hg(0), ranging from 0.09microg/m(3) to 1microg/m(3). All RELs were derived from the same toxicological database, predominantly of male chloralkali workers. Some key factors are apparent which make the use of that database questionable for REL derivation. Occupational studies of chloralkali workers are not an appropriate basis for a REL for Hg(0). Concomitant exposure to chlorine gas (Cl(2)) diminishes uptake and effects of Hg(0) exposure. There are gender differences in Hg(0) uptake, distribution and excretion, with females at potentially greater risk from Hg(0) exposure than males. Studies of chloralkali workers focused almost exclusively on adult males. Recent investigations of dental professionals (dentists, technicians, assistants) have failed to define a threshold in the dose-response relationship linking Hg(0) with neurobehavioural outcomes, an observation generally ignored in Hg(0) REL development. Finally, there is a growing database on genetic predisposition to health effects associated with Hg(0) exposure. Based on these considerations, we propose a different key study for REL derivation, one that involved male and female dental professionals without concomitant Cl(2) exposure. Adjusting the LOEAL to continuous exposure and applying appropriate UF values, we propose a Canadian REL for Hg(0) of 0.06microg/m(3).”

“Thimerosal (ethylmercurithiosalicylic acid), an ethylmercury (EtHg)-releasing compound (49.55% mercury (Hg)), was used in a range of medical products for more than 70 years. Of particular recent concern, routine administering of Thimerosal-containing biologics/childhood vaccines have become significant sources of Hg exposure for some fetuses/infants. This study was undertaken to investigate cellular damage among in vitro human neuronal (SH-SY-5Y neuroblastoma and 1321N1 astrocytoma) and fetal (nontransformed) model systems using cell vitality assays and microscope-based digital image capture techniques to assess potential damage induced by Thimerosal and other metal compounds (aluminum (Al) sulfate, lead (Pb)(II) acetate, methylmercury (MeHg) hydroxide, and mercury (Hg)(II) chloride) where the cation was reported to exert adverse effects on developing cells. Thimerosal-associated cellular damage was also evaluated for similarity to pathophysiological findings observed in patients diagnosed with autistic disorders (ADs). Thimerosal-induced cellular damage as evidenced by concentration- and time-dependent mitochondrial damage, reduced oxidative-reduction activity, cellular degeneration, and cell death in the in vitro human neuronal and fetal model systems studied. Thimerosal at low nanomolar (nM) concentrations induced significant cellular toxicity in human neuronal and fetal cells. Thimerosal-induced cytoxicity is similar to that observed in AD pathophysiologic studies. Thimerosal was found to be significantly more toxic than the other metal compounds examined. Future studies need to be conducted to evaluate additional mechanisms underlying Thimerosal-induced cellular damage and assess potential co-exposures to other compounds that may increase or decrease Thimerosal-mediated toxicity.”