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“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.”

“The main objectives of our study were to estimate the impact of a mercury cell chlor-alkali (MCCA) complex in Rosignano Solvay (Tuscany, Italy) on the local environment and to assess mercury exposure of inhabitants living near the plant. Measurement campaigns of atmospheric Hg near the MCCA plant showed that the impact of the emitted Hg from the industry on the terrestrial environment is restricted to a close surrounding area. Total gaseous mercury concentrations in ambient air of inhabited area around the MCCA plant were in the range of 8.0-8.7 ng/m3 in summer and 2.8-4.2 ng/m3 in winter. Peaks of up to 100 ng/m3 were observed at particular meteorological conditions. Background levels of 2 ng/m3 were reached within a radius of 3 km from the plant. Reactive gaseous mercury emissions from the plant constituted around 4.2% of total gaseous mercury and total particulate mercury emission constituted around 1.0% of total gaseous mercury emitted. Analysis of local vegetables and soil samples showed relatively low concentrations of total mercury (30.1-2919 microgHg/kg DW in the soil; <0.05-111 microgHg/kg DW in vegetables) and methylmercury (0.02-3.88 microgHg/kg DW in the soil; 0.03-1.18 microgHg/kg DW in vegetables). Locally caught marine fish and fresh marine fish from the local market had concentrations of total Hg from 0.049 to 2.48 microgHg/g FW, of which 37-100% were in the form of methylmercury. 19% of analysed fish exceeded 1.0 microgHg/g FW level, which is a limit set by the European Union law on Hg concentrations in edible marine species for tuna, swordfish and shark, while 39% of analysed fish exceeded the limit of 0.5 microgHg/g FW set for all other edible marine species. Risk assessment performed by calculating ratio of probable daily intake (PDI) and provisional tolerable daily intake (PTDI) for mercury species for various exposure pathways showed no risks to human health for elemental and inorganic mercury, except for some individuals with higher number of amalgam fillings, while PDI/PTDI ratio for methylmercury and total mercury exceeded the toxicologically tolerable value due to the potential consumption of contaminated marine fish.”

“INTRODUCTION:

The property of mercury to amalgamate with other metals is used to create a material for filling teeth. This material remains the cheapest and most efficient in tooth restoration. Mercurial toxicity has been documented since Antiquity but the metal remains widely used in some countries. This study compared mercury impregnation in dentists and dental assistants in Monastir (Tunisia) to another population not exposed professionally.

SUBJECTS AND METHODS:

A cross-sectional study was made on 52 dentists and dental assistants working in private offices and in the stomatology unit of the Monastir teaching hospital, with a control group of 52 physicians and nurses working in the Monastir Fattouma Bourguiba hospital. The groups were paired according to age and gender. The study lasted three months. A questionnaire investigated the socioprofessional features of the study population, non professional mercury exposure, work environment, the various amalgam handling and preparation techniques, and preventive hygiene measures. Urinary and salivary sampling was performed so as to prevent any accidental mercurial contamination. Mercury level was assessed by atomic absorption spectroscopy in an automatic sampler, urine creatinine with Jaffé’s colorimetric reaction. The results of mercury level assessment were expressed in microg/g of creatinine, salivary mercury in mug/l. The statistical analysis was made with the Epi.info 6 software. Khi(2) and Fisher tests were used to compare qualitative variables. The ANOVA test was used to compare averages with a statistic significance threshold at 0.05.

RESULTS:

Sixty-one percent of individuals with risk exposure worked in a dental clinic. Bruxism and onychophagia were more important in the control group with a significant statistical difference (respectively, p=0.01 and p<0.0001). The urinary and salivary mercury levels were significantly increased in the exposed group, with respective values of 20.4+/-42.4microg/g of creatinine and 10.6+/-13.02microg/l versus 0.04+/-0.3microg/g of creatinine and 0microg/l in the control group. Disposing of amalgam waste was inadequate in 94% of the cases. The variation of mercury in urine was significantly influenced by the presence of fabric curtains (p=0.04). Eating lunch at meals at the work place was also linked to a significant increase of mercury levels in urine (p=0.04). The storage mode of mercury in open containers was a significant factor for variation of mercury level (p=0.03).

DISCUSSION:

Most dentists’ private offices in Monastir do not comply or comply weakly with prevention measures linked to risk of mercury poisoning. Awareness campaigns were launched as well as actions for the improvement of work conditions: efficient aspiration of offices containing fixed sources of mercury, adequate storage of mercury and waste, and compliance to occupational hygiene rules.”

“The Food and Drug Administration (FDA) has developed this guidance as the special control to support the classification of dental amalgam into Class II (special controls), the reclassification of dental mercury1 from Class I to Class II, and the current classification of amalgam alloy in Class II. The three devices are now classified in a single regulation, Dental Amalgam, Mercury, and Amalgam Alloy, 21 CFR 872.3070. Mercury is elemental mercury, supplied as a liquid in bulk, sachet, or predosed capsule form, intended to be combined with amalgam alloy for the direct filling of carious lesions or structural defects in teeth. Amalgam alloy is composed primarily of silver, tin, and copper, supplied as a powder in bulk, tablet, or predosed capsule form, and is intended to be combined with mercury for the direct filling of carious lesions or structural defects in teeth. Dental amalgam consists of a combination of mercury and amalgam alloy, and is intended for the direct filling of carious lesions or structural defects in teeth. FDA is issuing this guidance in conjunction with a Federal Register (FR) notice announcing the final rule classifying dental amalgam, mercury, and amalgam alloy into Class II (special controls). The classification regulation designates this guidance document as the special control for these three devices.”

“SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule classifying dental amalgam into class II, reclassifying dental mercury from class I to class II, and designating a special control to support the class II classifications of these two devices, as well as the current class II classification of amalgam alloy. The three devices are now classified in a single regulation. The special control for the devices is a guidance document entitled, ‘Class II Special Controls Guidance Document: Dental Amalgam, Mercury, and Amalgam Alloy.’ This action is being taken to establish sufficient regulatory controls to provide reasonable assurance of the safety and effectiveness of these devices. Elsewhere in this issue of the FEDERAL REGISTER, FDA is announcing the availability of the guidance document that will serve as the special control for the devices.”