Mercury

“Thimerosal is a widely used preservative in health care products, especially in vaccines. Due to possible adverse health effects, investigations on its metabolism and toxicity are urgently needed. An in vivo study on chronic toxicity of thimerosal in rats was inconclusive and reports on genotoxic effects in various in vitro systems were contradictory. Therefore, we reinvestigated thimerosal in the cytochalasin B block micronucleus test. Glutathione S-transferases were proposed to be involved in the detoxification of thimerosal or its decomposition products. Since the outcome of genotoxicity studies can be dependent on the metabolic competence of the cells used, we were additionally interested whether polymorphisms of glutathione S-transferases (GSTM1, GSTT1, or GSTP1) may influence the results of the micronucleus test with primary human lymphocytes. Blood samples of six healthy donors of different glutathione S-transferase genotypes were included in the study. At least two independent experiments were performed for each blood donor. Significant induction of micronuclei was seen at concentrations between 0.05-0.5 micro g/ml in 14 out of 16 experiments. Thus, genotoxic effects were seen even at concentrations which can occur at the injection site. Toxicity and toxicity-related elevation of micronuclei was seen at and above 0.6 micro g/ml thimerosal. Marked individual and intraindividual variations in the in vitro response to thimerosal among the different blood donors occurred. However, there was no association observed with any of the glutathione S-transferase polymorphism investigated. In conclusion, thimerosal is genotoxic in the cytochalasin B block micronucleus test with human lymphocytes. These data raise some concern on the widespread use of thimerosal.”

“Similar to many complex autoimmune diseases, genetic and environmental factors including diet, infection and xenobiotics play a critical role in the development of autism. In this study, we postulated that infectious agent antigens such as streptokinase, dietary peptides (gliadin and casein) and ethyl mercury (xenobiotic) bind to different lymphocyte receptors and tissue enzyme (DPP IV or CD26). We assessed this hypothesis first by measuring IgG, IgM and IgA antibodies against CD26, CD69, streptokinase (SK), gliadin and casein peptides and against ethyl mercury bound to human serum albumin in patients with autism. A significant percentage of children with autism developed anti-SK, anti-gliadin and casein peptides and anti-ethyl mercury antibodies, concomitant with the appearance of anti-CD26 and anti-CD69 autoantibodies. These antibodies are synthesized as a result of SK, gliadin, casein and ethyl mercury binding to CD26 and CD69, indicating that they are specific. Immune absorption demonstrated that only specific antigens, like CD26, were capable of significantly reducing serum anti-CD26 levels. However, for direct demonstration of SK, gliadin, casein and ethyl mercury to CD26 or CD69, microtiter wells were coated with CD26 or CD69 alone or in combination with SK, gliadin, casein or ethyl mercury and then reacted with enzyme labeled rabbit anti-CD26 or anti-CD69. Adding these molecules to CD26 or CD69 resulted in 28-86% inhibition of CD26 or CD69 binding to anti-CD26 or anti-CD69 antibodies. The highest % binding of these antigens or peptides to CD26 or CD69 was attributed to SK and the lowest to casein peptides. We, therefore, propose that bacterial antigens (SK), dietary peptides (gliadin, casein) and Thimerosal (ethyl mercury) in individuals with pre-disposing HLA molecules, bind to CD26 or CD69 and induce antibodies against these molecules. In conclusion, this study is apparently the first to demonstrate that dietary peptides, bacterial toxins and xenobiotics bind to lymphocyte receptors and/or tissue enzymes, resulting in autoimmune reaction in children with autism.”

“OBJECTIVES:

The objectives of this study were: (1) to compare the mercury levels in general dentists with the mercury levels in other health professionals using toenail clippings as a biomarker, (2) to identify risk factors associated with high mercury levels, and (3) to compare practice characteristics of dentists with high and low mercury levels.

METHODS:

A sample of 579 men was randomly selected from the 33,737 men participating in the Health Professionals Follow-up Study who had provided toenail samples in 1987. A questionnaire was sent to these male subjects in 1991 to obtain information on fish consumption, toothbrushing frequency, number of teeth, number of amalgam restorations, general practice or specialty status, number of amalgam restorations placed and removed per week, mercury storage and handling procedures, and mercury spillage incidents. A measure of long-term mercury exposure was obtained from toenail samples using neutron activation analysis for the 410 respondents (71% response rate). The 90th percentile mercury level in toenails (0.88 ppm) was selected as the threshold for elevated toenail mercury level.

RESULTS:

No relationship was found between the number of dental amalgams and toenail mercury levels among general dentists, dental specialists, and nondental health professionals. General dentists were found to have more than twice the level of mercury in toenails than nondental health professionals (mean level = 0.94 vs 0.45) and 60 percent higher than dental specialists (mean = 0.59). The combined use of disposable capsules and water storage of scrap amalgam appeared to reduce the risk of elevated mercury levels. Regardless of professional status, consumption of tuna and saltwater fish were the primary exposure factors that were positively associated with toenail mercury levels.

CONCLUSIONS:

As shown by the associations with dental profession and fish consumption, the mercury content of toenails is a stable biomarker of cumulative long-term mercury exposure. The lack of association between nail mercury levels and number of amalgam restorations suggests that avoidance of mercury amalgam restorative materials cannot be justified by the presence of mercury released from dental amalgams.”

“The main threats to human health from heavy metals are associated with exposure to lead, cadmium, mercury and arsenic. These metals have been extensively studied and their effects on human health regularly reviewed by international bodies such as the WHO. Heavy metals have been used by humans for thousands of years. Although several adverse health effects of heavy metals have been known for a long time, exposure to heavy metals continues, and is even increasing in some parts of the world, in particular in less developed countries, though emissions have declined in most developed countries over the last 100 years.”

“The general population is primarily exposed to mercury via food, fish being a major source of methyl mercury exposure, and dental amalgam. The general population does not face a significant health risk from methyl mercury, although certain groups with high fish consumption may attain blood levels associated with a low risk of neurological damage to adults. Since there is a risk to the fetus in particular, pregnant women should avoid a high intake of certain fish, such as shark, swordfish and tuna; fish (such as pike, walleye and bass) taken from polluted fresh waters should especially be avoided. There has been a debate on the safety of dental amalgams and claims have been made that mercury from amalgam may cause a variety of diseases. However, there are no studies so far that have been able to show any associations between amalgam fillings and ill health.”

“Isotopically enriched HgO standards were used to synthesize CH3(200)Hg+ and C2H5(199)Hg+ using Grignard reagents. These species were employed for isotope dilution GC-ICPMS to study uptake and biotransformation of ethylmercury in mice treated with thimerosal, (sodium ethylmercurithiosalicylate) 10 mg L(-1) in drinking water ad libitum for 1, 2.5, 6, or 14 days. Prior to analysis, samples were spiked with aqueous solutions of CH3(200)Hg+, C2H5(199)Hg+, and 201Hg2+ and then digested in 20% tetramethylammonium hydroxide and extracted at pH 9 with DDTC/toluene. Extracted mercury species were reacted with butylmagnesium chloride to form butylated derivatives. Absolute detection limits for CH3Hg+, C2H5Hg+, and Hg2+ were 0.4, 0.2, and 0.6 pg on the basis of 3sigma of five separate blanks. Up to 9% of the C2H5Hg+ was decomposed to Hg2+ during sample preparation, and it is therefore crucial to use a species-specific internal standard when determining ethylmercury. No demethylation, methylation, or ethylation during sample preparation was detected. The ethylmercury component of thimerosal was rapidly taken up in the organs of the mice (kidney, liver, and mesenterial lymph nodes), and concentrations of C2H5Hg+ as well as Hg2+ increased over the 14 days of thimerosal treatment. This shows that C2H5Hg+ in mice to a large degree is degraded to Hg2+. Increased concentrations of CH3Hg+ were also observed, which was found to be due to impurities in the thimerosal.”

In a previous study, a significant increase in serum interleukin-6 (IL-6) was apparent after an acute low-level mercury (Hg) exposure, achieved by removal of amalgam fillings (Loftenius et al., 1998). In the present study, 11 healthy volunteers were exposed to an oral dose of 1 g of pulverized amalgam powder. Hg, IL-6, and C-reactive protein (CRP) levels in plasma were followed before and up to 72 h after exposure. The Hg levels were low and stable prior to exposure and increased rapidly after exposure. The median Hg increase was 12.9 nmol/L, which is considerably higher than in the previous study. No significant change over time was observed for IL-6 and CRP levels. Therefore, it cannot be ruled out that our previous finding of increasing IL-6 levels detected after acute low-level Hg exposure through removal of amalgam fillings was due to the dental treatment per se.

A 61-year-old woman presented with a 2-year history of an abnormal erythematous swelling on the upper lip and cheek. Upon examination there were no other physical findings. Histological examination found discreet sarcoidal granulomas in the lower dermis. Routine laboratory studies, chest radiographs and pulmonary functions were all normal. Clinical presentation and histological findings were, therefore, compatible with the diagnosis of orofacial granulomatosis (OFG). The patient was patch tested with an extended standard series that included metal-salt, dental prosthesis, bakery and corticosteroids series. The patch test was positive (score ++) after 48 and 72 h for mercury in the metal-salt and dental prosthesis series. During the past decade the patient had received amalgam fillings of several dental cavities, including one adjacent to the swollen cheek. The unilateral localization of the soft tissue swelling adjacent to the amalgam tooth fillings, along with the positive patch test for mercury, raised the possibility that the OFG was part of a delayed hypersensitive reaction to the fillings. The patient therefore underwent a total amalgam replacement procedure; complete disappearance of the swelling overlying the right cheek was observed within 7 weeks and the swelling of the upper lip subsided completely within 6 months. We propose that mercury in amalgam tooth fillings is another cause of OFG and suggest appropriate patch testing in patients who do not have an apparent cause of OFG.

A 61-year-old woman presented with a 2-year history of an abnormal erythematous swelling on the upper lip and cheek. Upon examination there were no other physical findings. Histological examination found discreet sarcoidal granulomas in the lower dermis. Routine laboratory studies, chest radiographs and pulmonary functions were all normal. Clinical presentation and histological findings were, therefore, compatible with the diagnosis of orofacial granulomatosis (OFG). The patient was patch tested with an extended standard series that included metal-salt, dental prosthesis, bakery and corticosteroids series. The patch test was positive (score ++) after 48 and 72 h for mercury in the metal-salt and dental prosthesis series. During the past decade the patient had received amalgam fillings of several dental cavities, including one adjacent to the swollen cheek. The unilateral localization of the soft tissue swelling adjacent to the amalgam tooth fillings, along with the positive patch test for mercury, raised the possibility that the OFG was part of a delayed hypersensitive reaction to the fillings. The patient therefore underwent a total amalgam replacement procedure; complete disappearance of the swelling overlying the right cheek was observed within 7 weeks and the swelling of the upper lip subsided completely within 6 months. We propose that mercury in amalgam tooth fillings is another cause of OFG and suggest appropriate patch testing in patients who do not have an apparent cause of OFG.

“The use of dental amalgam as a restorative material has long been a contentious issue because of its elemental mercury component. While microleakage of mercury from amalgam has been conclusively confirmed over the past 30 years intensive research has failed to identify deleterious health outcomes. Mercury, as with other metals entering the body tissues, appears to be tolerated at low levels. Nevertheless, a contrary opinion is held by some professional and lay groups who advocate a zero tolerance for inhaled or ingested elemental mercury. They identify dental amalgam as an aetiological factor for neurological conditions such as chronic fatigue syndrome, multiple sclerosis and Alzheimer’s disease resulting from chronic mercury poisoning. Epidemiological and clinical evidence of widespread chronic mercury toxicity associated with a body burden of amalgam has consistently failed to be established even in populations with a high prevalence of dental amalgam restorations. On current evidence, international consensus heavily supports the statement that amalgam does not constitute a health risk to patients. However, exposure to volatile free mercury in dental clinics should be controlled to eliminate occupational risk. This paper provides a general review of the current situation and issues. It offers a consensus viewpoint for practitioners and lay people in reaching an informed decision on dental amalgam restorations.”

“BACKGROUND:

The pathogenetic relationship between oral lichenoid reactions (OLR) and dental amalgam fillings is still a matter of controversy.

OBJECTIVES:

To determine the diagnostic value of patch tests with amalgam and inorganic mercury (INM) and the effect of amalgam removal in OLR associated with amalgam fillings.

METHODS:

In 134 consecutive patients 467 OLR were classified according to clinical criteria. One hundred and fifty-nine biopsies from OLR lesions were histologically diagnosed according to the World Health Organization criteria for oral lichen planus (OLP) and compared with 47 OLP lesions from edentulous patients without amalgam exposure. One hundred and nineteen patients were patch tested with an amalgam series. In 105 patients (357 of 467 lesions) the amalgam fillings were removed regardless of the patch test results and OLR were re-examined within a follow-up period of about 3 years. Twenty-nine patients refused amalgam removal and were taken as a control group.

RESULTS:

Eleven patients with OLR (8.2%) had skin lesions of lichen planus (LP). Histologically, the lesions in the OLR group could not be distinguished from those seen in the OLP group. Thirty-three patients (27.7%) showed a positive patch test to INM or amalgam. Amalgam removal led to benefit in 102 of 105 patients (97.1%), of whom 31 (29.5%) were cured completely. Of 357 lesions, 213 (59.7%) cleared after removal of amalgam, whereas 65 (18.2%) did not improve. In the control group without amalgam removal (n = 29) only two patients (6.9%) showed an improvement (P < 0.05). Amalgam removal had the strongest impact on lesions of the tongue compared with lesions at other sites (P < 0.05), but had very little impact on intraoral lesions in patients with cutaneous LP compared with patients without cutaneous lesions (P < 0.05). Patients with a positive patch test reaction to amalgam showed complete healing more frequently than the amalgam-negative group (P < 0.05). After an initial cure following amalgam removal, 13 lesions (3.6%) in eight patients (7.6%) recurred after a mean of 14.6 months.

CONCLUSIONS:

Of all patients with OLR associated with dental amalgam fillings, 97.1% benefited from amalgam removal regardless of patch test results with amalgam or INM. We suggest that the removal of amalgam fillings can be recommended in all patients with symptomatic OLR associated with amalgam fillings if no cutaneous LP is present.”