Mercury from maternal “silver” tooth fillings in sheep and human breast milk

Neonatal uptake of mercury (Hg) from milk was examined in a pregnant sheep model, where radioactive mercury (Hg²⁰³)/silver tooth fillings (amalgam), were newly placed. A crossover experimental design was used in which lactating ewes nursed foster lambs. In a parallel study, the relationship between dental history and, breast milk concentration of Hg was also examined in 33 lactating women. Results from the animal studies showed that, during pregnancy, a primary fetal site of amalgam Hg concentration is the liver, and, after delivery, the neonatal lamb kidney receives additional amalgam Hg from mother's milk. In lactating women with aged, amalgam fillings, increased Hg excretion in breast milk and urine correlated with the number of fillings or Hg vapor concentration levels in mouth air. It was concluded that Hg originating from maternal amalgam tooth fillings transfers across the placenta to the fetus, across the mammary gland into milk ingested by the newborn, and ultimately into neonatal body tissues. Comparisons are made to the U.S. minimal risk level recently established for adult Hg exposure. These findings suggest, that placement and removal of “silver” tooth fillings in pregnant and lactating humans will subject the fetus and neonate to unnecessary risk of Hg exposure.     

Urinary mercury after administration of 2,3-dimercaptopropane-1-sulfonic acid: correlation with dental amalgam score.

There is considerable controversy as to whether dental amalgams may cause systemic health effects in humans because they liberate elemental mercury. Most such amalgams contain as much as 50% metallic mercury. To determine the influence of dental amalgams on the mercury body burden of humans, we have given volunteers, with and without amalgams in their mouth, the sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS), a chelating agent safely used in the Soviet Union and West Germany for a number of years. The diameters of dental amalgams of the subjects were determined to obtain the amalgam score. 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. Linear regression analysis indicated a highly significant positive correlation between the mercury excreted in the urine 2 h after DMPS administration and the dental amalgam scores. DMPS can be used to increase the urinary excretion of mercury and thus increase the significance and reliability of this measure of mercury exposure or burden, especially in cases of micromercurialism.     

Dental amalgam affects urinary selenium excretion

Selenium may have a protective effect against mercury toxicity. The aim of the present study was to investigate if selenium excretion in urine was affected in persons with dental amalgam fillings. The reason for this study is that dental amalgam is the most important source of inorganic mercury exposure in the general population, although the potential toxic effects of this exposure remain a subject for debate. The chelating agent 2,3 dimercaptopropane-1-sulfonate (DMPS) was injected intravenously (2 mg/kg) to provoke metal excretion. Urine samples were subsequently collected at intervals over a 24-h period. Selenium concentration was determined by hydride-generation atomic absorption spectrometry. The study was comprised of 20 persons who claimed symptoms from dental amalgam and 21 healthy persons with amalgam fillings. There were two control groups without amalgam. One control group had amalgam replaced because of concern about illness resulting from mercury release (n=20), whereas the other control group never had amalgam (n=19). Individuals with amalgam excreted less selenium (36.4 μg, median value) over 24 hours than those without amalgam (47.5 μg) (p=0.016). There was no difference in selenium excretion between groups with (42.4 μg) and without (39.4 μg) amalgam-related symptoms (p=0.15). The findings indicate that individuals exposed to low levels of elemental mercury from dental amalgam excrete less selenium to urine than unexposed individuals.     

Mercury Exposure and Risks from Dental Amalgam in Canada: The Canadian Health Measures Survey 2007–2009

Dental amalgam is 50% metallic mercury (Hg⁰) by weight and causes Hg exposure. The first assessment of Hg exposure and risk from dental amalgam in Canada was published in 1996. Recent data provided the opportunity to update that assessment. During the Canadian Health Measures Survey (CHMS; 2007 to 2009) the number of tooth surfaces specifically restored with dental amalgam was recorded. Data were also collected on the concentration of Hg in urine of survey participants. These data were employed to determine Hg exposures in the Canadian population. Also determined was the number of amalgam-restored tooth surfaces that would not result in exposure exceeding the dose associated with Canada's reference exposure level (REL) for Hg⁰. Based on the CHMS data, 17.7 million Canadians aged ≥6 years collectively carry 191.1 million amalgam surfaces, representing 76.4 million amalgam-restored teeth. Average Hg exposures were: Children—0.065 μg Hg/kg-day; Teens—0.032 μg/kg-day; Adults—0.033 μg/kg-day; and Seniors—0.041 μg/kg-day. Of Canadians with dental amalgam restorations, 80.4% experience a daily dose of Hg that exceeds the Canadian REL-associated dose. The number of amalgam surfaces that will not result in exceeding the REL-associated dose varied from two amalgam surfaces (children, both sexes) to seven surfaces (adult males).     

Dental amalgam mercury exposure in rats

The aim of this study was to measure the distribution of mercury, in tissues of rats exposed to amalgam over a two months period. Possible interaction of mercury with copper and zinc in organs was also evaluated. Rats were either exposed to mercury from 4 dental amalgams, or fed the diet containing powdered amalgam during two months. Mercury was measured in the kidney, liver and brain, copper in kidney and brain and zinc in kidney. The results showed significantly higher concentrations of mercury in the kidneys and the brains of rats in both exposed groups compared to control. Even after two months of exposure to mercury brain mercury concentration in rats with amalgam fillings was 8 times higher than in the control and 2 times higher than in rats exposed to amalgam supplemented diet. The highest mercury concentration in the latter group was found in the kidneys and it was 5 times higher than in the control group. We found no significant differences between mercury levels in exposed and control rat's liver. Exposure to mercury from dental amalgams did not alter the concentrations of copper and zinc in the tissues. Histopathological analyses of rats tissues did not show any pathological changes. These results support previously proposed nose-brain transport of mercury released from dental amalgam fillings.     

Mercury and selenium concentrations in maternal and neonatal scalp hair: relationship to amalgam-based dental treatment received during pregnancy

Mercury and selenium concentrations were determined in scalp hair samples collected postpartum from 82 term pregnancy mothers and their neonates. Maternal mercury and selenium had median concentrations of 0.39 μg/g (range 0.1–2.13 μg/g) and 0.75 μg/g (range 0.1–3.95 μg/g), respectively, and corresponding median neonatal values were 0.24 μg/g (range 0.1–1.93 μg) and 0.52 μg/g (range (0.1–3.0 μg/g). Amalgam-based restorative dental treatment received during pregnancy by 27 mothers (Group I) was associated with significantly higher mercury concentrations in their neonates (p<0.0001) compared to those born to 55 mothers (Group II) whose most recent history of such dental treatment was dated to periods ranging between 1 and 12 yr prior to pregnancy. In the Group I mother/neonate pairs, amalgam removal and replacement in 10 cases was associated with significantly higher mercury concentrations compared to 17 cases of new amalgam emplacement. Selenium concentrations showed no significant integroup differences. However, the selenium/mercury molar ratio values were lowest in the Group I neonates, compared to their mothers and to the Group II mother/neonate pairs. This ratio decreased as mercury concentration increased, and this interrelation was statistically significant in both groups of mother/neonate pairs. 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.     

Alzheimer disease: mercury as pathogenetic factor and apolipoprotein E as a moderator

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.     

Elimination of mercury from amalgam in rats.

The aim of this study was to measure the urinary mercury excretion in rats exposed to amalgam over a two months period. Animals were either exposed to mercury from 4 dental amalgams or fed the diet containing powdered amalgams. The results showed significantly higher mercury amount in urine of both exposed groups than in control. Even two months after the amalgam had been placed in rats teeth, the amount of mercury in the urine remained 4-5 times higher than in control, and 4 times higher than in rats exposed to diet containing powdered amalgam. The elevated urinary Hg amount was accompanied by an increased level of total protein in urine. In the same exposure period the excretion of total protein in urine of rats with amalgam fillings was 2 times higher than in control and 1.5 times higher than in rats exposed to amalgam through diet. Concentrations of mercury in the sera of all groups were below the detection limit of the method. The results show that amount of mercury and protein in the urine of rats were related to the mercury release from dental malgam.     

Increased mercury emissions from modern dental amalgams

All types of dental amalgams contain mercury, which partly is emitted as mercury vapor. All types of dental amalgams corrode after being placed in the oral cavity. Modern high copper amalgams exhibit two new traits of increased instability. Firstly, when subjected to wear/polishing, droplets rich in mercury are formed on the surface, showing that mercury is not being strongly bonded to the base or alloy metals. Secondly, high copper amalgams emit substantially larger amounts of mercury vapor than the low copper amalgams used before the 1970s. High copper amalgams has been developed with focus on mechanical strength and corrosion resistance, but has been sub-optimized in other aspects, resulting in increased instability and higher emission of mercury vapor. This has not been presented to policy makers and scientists. Both low and high copper amalgams undergo a transformation process for several years after placement, resulting in a substantial reduction in mercury content, but there exist no limit for maximum allowed emission of mercury from dental amalgams. These modern high copper amalgams are nowadays totally dominating the European, US and other markets, resulting in significant emissions of mercury, not considered when judging their suitability for dental restoration.     

Mercury resistance among clinical isolates of Escherichia coli

The use of organomercurials in liquid detergents and disinfectants promoted resistance to mercury among bacteria. Dental amalgam and industries using mercury are the main source of human exposure to mercury vapor. Release of mercury from dental amalgam contributes to the enrichment of the intestinal flora with mercury resistance plasmids which may be associated with antibiotic resistance. The aim of our study was to evaluate the frequency of E. coli strains resistant to mercury and other antimicrobial agents currently used in therapy. The bacterial mercury and ampicillin, cephalexin, cefotaxime, gentamicin, tetracycline and chloramphenicol resistance was tested against 363 E. coli strains obtained from faeces and urine between 1999-2000. According to the guidelines suggested by NCCLS (1998), minimum inhibitory concentrations (MICs) were determined on Mueller-Hinton agar, using the dilution technique with an inoculum of about 10(5) CFU. The MICs were read after 18 h incubation at 37 degrees C as the lowest concentration that inhibited the development of visible growth. Plasmids in enterobacteria may carry genes encoding resistance to both mercury and antibiotics. 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.     

Whole-body imaging of the distribution of mercury released from dental fillings into monkey tissues

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.     

Effects of small concentrations of mercury on the contractile activity of the rat ventricular myocardium

Personal exposure to mercury vapor and the release of mercury from or during removal of amalgam dental fillings increases its blood and plasma concentration. However, it is not known if these very small amounts affect cardiac function. The effects of continuous exposure to 5 and 20 nM of HgCl(2) on the cardiac contractility were investigated in isometric and tetanic contractions of right ventricular strips and in Langendorff perfused rat hearts. The continuous exposure for 2 h produced a small but significant reduction of the isometric twitch force and time to peak tension shortened. Relative post-rest potentiation was not affected by this concentration of HgCl(2) suggesting a lack of action of the metal on the sarcoplasmic reticulum activity. Tetanic tension, in contrast to twitch force, was intensively reduced suggesting an important depressant action on the activity of contractile proteins. In perfused hearts beating spontaneously, isovolumic systolic pressure reduced progressively and the diastolic pressure increased. Although occurring heart rate reduction, it was similar for both controls and mercury treated hearts. Also, time dependent changes in coronary perfusion pressure were similar to controls. Results suggested that cardiac effects may be observed after continuous exposure to very small concentrations of mercury, probably as a result of the cell capacity to concentrate mercury. These results also indicate that continuous professional exposure to mercury followed by its absorption might have toxicological consequences affecting cardiac function, and being considered hazardous.     

Linkage of a novel mercury resistance operon with streptomycin resistance on a conjugative plasmid in Enterococcus faecium

It has been shown that the mercury in dental amalgam and other environmental sources can select for mercury resistant bacteria and that this can lead to an increase in resistance to antibiotics. To understand more about this linkage we have investigated the genetic basis for mercury and antibiotic resistance in a variety of oral bacteria. In this study we have cloned and sequenced the mer operon from an Enterococcus faecium strain which was resistant to mercury, tetracycline, and streptomycin. This strain was isolated, in a previous investigation, from a cynomolgus monkey post-installation of amalgam fillings. The mer operon was contained within a putative transposon (Tnmer1) of the ISL3 family. This element was located on a streptomycin resistant plasmid, pPPM1000, which shares homology with pRE25.     

Aggravated neuromuscular symptoms of mercury exposure from dental amalgam fillings

Dental amalgam fillings are widely used all over the world. However, their mercury content can lead to various side effects and clinical problems. Acute or chronic mercury exposure can cause several side effects on the central nerve system, renal and hepatic functions, immune system, fetal development and it can play a role on exacerbation of neuromuscular diseases. In this case, we will present a patient with vacuolar myopathy whose symptoms were started and aggravated with her dental amalgam fillings.     

Comparison of hair, nails and urine for biological monitoring of low level inorganic mercury exposure in dental workers.

Creatinine-corrected urine mercury measurements in spot urine samples are routinely used in monitoring workers exposed to inorganic mercury. However, mercury measurement in other non-invasive biological material has been used in some epidemiological studies. 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). The geometric mean and 90th percentile mercury concentrations in the urine samples from dentists were 1.7 and 7.3 micromol mol(-1) creatinine, respectively, with only one sample having a value at around the UK's Health and Safety Executive biological monitoring health guidance level of 20 micromol mol(-1) creatinine. Receiver operator characteristic analyses suggested that the ability of the biological material to discriminate between dentists and referents were fingernails>urine approximately equal to toenails>pubic hair approximately equal to head hair. Further investigation is warranted as to why fingernails appear to be such a good discriminator, possibly reflecting some contribution of direct finger contact with amalgam or contaminated surfaces rather than systemic incorporation of mercury into growing nails. Good correlation between head hair and pubic hair mercury levels in all subjects was obtained (r=0.832), which was significantly improved when hair samples weighing <10 mg were excluded (r=0.868). Therefore, under these exposure conditions and using the described pre-analytical washing steps, there is little influence from atmospheric contamination on the level of mercury content of head hair. The choice of non-invasive biological materials for mercury analysis depends on a number of considerations. These include the toxicokinetics of urinary mercury excretion, the growth rates of hair and nail, the nature and time-frame of exposure, and the fact that urine mercury may not reflect the body burden level from dietary methyl mercury. However, the data from this study suggests that urine mercury remains the most practical and sensitive means of monitoring low level occupational exposure to inorganic mercury.     

Biochemical changes in rat kidney on exposure to elemental mercury vapor: effect on biosynthesis of metallothionein.

Evidence is presented that exposure of rats to elemental mercury vapor results in increased amounts of a metallothionein-like protein in kidney tissue but not in liver. After three or more daily exposures, each of 2 h duration, to elemental mercury vapor, more than 50% of the mercury in kidney tissue is bound to a protein having a molecular weight (mol. wt.) of about 10 000 as determined by Sephadex G-75 gel filtration chromatography. Cystine is incorporated into a 10 000 mol. wt. protein fraction from kidneys of rats which were injected with [U-14C] cystine after five daily 2-h exposures to mercury vapor. In contrast, no significant incorporation of [U-14C] cystine into this protein fraction was observed in kidneys of control rats or in livers of both control and mercury vapor-exposed rats. The in vivo incorporation of 109Cd into the fraction followed the same pattern as that of [14C] cystine in rats injected with tracer doses of CdCl2 labeled with radioactive 109Cd isotope. This 10 000 mol. wt. protein, newly synthesized in response to repeated exposures to mercury vapor, exhibited identical properties to metallothionein, namely in its subcellular localization, molecular weight, heat stability and isoelectric points. A significant incorporation of [U-14C]-cystine into this protein in rat kidney alone on exposure to mercury vapor confirms its induced biosynthesis in the kidney.     

Dental "silver" tooth fillings: a source of mercury exposure revealed by whole-body image scan and tissue analysis

Mercury (Hg) vapor is released from dental "silver" tooth fillings into human mouth air after chewing, but its possible uptake routes and distribution among body tissues are unknown. This investigation demonstrates that when radioactive 203Hg is mixed with dental Hg/silver fillings (amalgam) and placed in teeth of adult sheep, the isotope will appear in various organs and tissues within 29 days. Evidence of Hg uptake, as determined by whole-body scanning and measurement of isotope in specific tissues, revealed three uptake sites: lung, gastrointestinal, and jaw tissue absorption. Once absorbed, high concentrations of dental amalgam Hg rapidly localize in kidneys and liver. Results are discussed in view of potential health consequences from long-term exposure to Hg from this dental material.     

Has the mist been peered through? Revisiting the building blocks of human health risk assessment for electronic cigarette use

Electronic cigarettes, battery-powered nicotine delivery devices, have been increasingly used in the past decade. This critical review provides a qualitative research synthesis of the human health risks associated with E-vapor inhalation in the peer-reviewed literature and our own preliminary experimental results. E-cigarettes may be as efficient as traditional cigarettes in nicotine delivery, especially for experienced users, and studies suggest lower emissions of air toxics from E-cigarette vapor and lower second- and third-hand vapor exposures. Some toxic emissions may however surpass those of traditional cigarettes, especially under high voltage vaping conditions. Experimentally, E-vapor/E-liquid exposures reduce cell viability and promote pro-inflammatory cytokine release. User vulnerability to concomitant environmental agent exposures, such as viruses and bacteria, may potentially be increased. While evidence to date suggests that E-cigarettes release fewer toxins and carcinogens compared to cigarettes, E-vapor is not safe and might adversely affect human immune functions. Major knowledge gaps hinder risk quantification and effective regulation of E-cigarette products including: lack of long-term exposure studies, lack of understanding of biological mechanisms associated with exposure, and lack of integration of exposure and toxicity assessments. Better data are needed to inform human health risk assessments and understand the public health impact of E-vapor exposures.     

The toxicology of mercury and its compounds

A concentrated review on the toxicology of inorganic mercury together with an extensive review on the neurotoxicology of methylmercury is presented. The challenges of using inorganic mercury in dental amalgam are reviewed both regarding the occupational exposure and the possible health problems for the dental patients. The two remaining “mysteries” of methylmercury neurotoxicology are also being reviewed; the cellular selectivity and the delayed onset of symptoms. The relevant literature on these aspects has been discussed and some suggestions towards explaining these observations have been presented.     

Treatment of mercury vapor toxicity by combining deferasirox and deferiprone in rats

The hypothesis that combination of deferasirox and deferiprone chelators might be more efficient as combined therapy than single therapy in removing mercury from the body was considered. Male Wistar rats were exposed to mercury vapor for 2 weeks. After mercury administration some abnormal clinical signs such as red staining around the eyes, greenish mottling on the liver, weakness, loss of hair and weight, were observed in animals. Chelators were given orally after mercury vapor application for 2 weeks. Mercury toxicity symptoms in rats decreased after drug administration. After chelation therapy, these rats were anesthetized with ether vapor and immobilized by cervical dislocation and then their heart, liver, kidneys, intestine, spleen and testicles were sampled for determination of mercury and iron concentration. The combined chelation therapy results showed that these chelators are able to remove mercury from the body and toxicity symptoms decreased.