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“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.”

“84 patients with oral lichenoid lesions (OLL) were seen in the contact dermatitis clinic. All these patients had reticulate, lacy, plaque-like or erosive lichenoid changes adjacent to amalgam fillings. Patch testing to metallic mercury, 0.1% thimerosal, 1% ammoniated mercury, 0.1% mercuric chloride, and in some cases 0.05% phenylmercuric nitrate and amalgam discs was undertaken. 33 (39%) patients had positive patch test findings. 30/33 patch test positive patients had replacement of their amalgam fillings, with 28 (87%) patients experiencing improvement of symptoms and signs within 3 months. This confirms that mercury allergy is a factor in the pathogenesis of OLL in some cases. In cases where patch test negative patients improve with amalgam replacement, mercury may be acting as an irritant in the pathogenesis of OLL.”

“A 3 1/2-year-old boy presented on three occasions with painful, itchy, oedematous plaques on his limbs. On two occasions he had received hepatitis B vaccination 11-13 days previously, and on the third occasion received triple antigen (DTP) vaccination 10 days earlier. Skin biopsy revealed a prominent infiltrate of eosinophils involving the entire thickness of the dermis. In addition there were prominent ‘flame figures’ consisting of eosinophilic necrotic collagen surrounded by granular basophilic debris. The clinical and histological pictures were consistent with Wells’ syndrome. The eruption settled on the second and third occasions with 0.1% mometasone furoate cream. Subsequent patch testing showed 2+ reaction to preservative thiomersal at 96 hours. This is the first description of Wells’ syndrome with typical clinical and histopathological features associated with thiomersal in two different vaccines.”

“The effect of thimerosal, a reactive oxidant, on cytoplasmic free Ca2+ concentrations ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells was explored by using the Ca2+-sensitive dye fura-2. Thimerosal acted in a concentration-dependent manner with an EC50 of 0.5 microM. The Ca2+ signal comprised a gradual rise and a sustained elevation. Removal of extracellular Ca2+ reduced 80% of the signal. In Ca2+-free medium, the [Ca2+]i rise induced by 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) was completely inhibited by pretreatment with 5 microM thimerosal. The thimerosal (5 microM)-induced Ca2+ release was not changed by inhibition of phospholipase C with 2 microM U73122. Collectively, this study shows that thimerosal induced [Ca2+]i rises in renal tubular cells via releasing store Ca2+ from the endoplasmic reticulum Ca2+ stores in a manner independent of phospholipase C activity.”

“Thiomersal (thimerosal) was a weak inhibitor of the binding of [(3)H]mepyramine to histamine H(1) receptors in guinea-pig cerebellar membranes (11 +/- 1% inhibition at 10 microM, 32 +/- 3% inhibition at 300 microM). However, in the concentration range 3-30 microM, thiomersal enhanced the binding of histamine to the H(1) receptor, as reflected by the displacement of curves of histamine inhibition of [(3)H]mepyramine binding to lower concentrations, without any change in the Hill coefficient. The ratio of the IC50 values (the concentration giving 50% inhibition) in the absence and presence of thiomersal increased from 1.8 with 3 microM to 3.6 with 30 microM thiomersal. There was no consistent effect of thiomersal at concentrations of 30 microM and below on curves of mepyramine inhibition of [(3)H]mepyramine binding. In the presence of 10 microM thiomersal histamine-induced accumulation of inositol phosphates in U373 MG astrocytoma cells was partially inhibited (37 +/- 8% inhibition of the maximum response), without any significant change in the EC50 (the concentration giving the half maximal response) for histamine. Thus although histamine binding was potentiated by thiomersal, there was no potentiation of an H(1) receptor-mediated functional response.”

“In their Perspective article, Bolger and Schwetz1 recommend limiting the intake of mercury by reducing the consumption of mercury-contaminated fish because of possible negative cardiovascular and neurologic effects. We were surprised that they do not mention dental amalgam. Dental amalgam consists of 50 percent elemental mercury, and it is well known that mercury vapor is released from amalgam.”

“The source document upon which this CICAD is based is the Toxicological profile for mercury (update), published by the Agency for Toxic Substances and Disease Registry of the US Department of Health and Human Services (ATSDR, 1999). Data identified as of January 1999 were considered in the source document. Data identified as of November 1999 were considered in the preparation of this CICAD. Information on the availability and the peer review of the source document is presented in Appendix 1. Information on the peer review of this CICAD is presented in Appendix 2. This CICAD was considered at a meeting of the Final Review Board, held in Helsinki, Finland, on 26–29 June 2000 and approved as an international assessment by mail ballot of the Final Review Board members on 27 September 2002. Participants at the Final Review Board meeting are presented in Appendix 3. The International Chemical Safety Cards for elemental mercury and six inorganic mercury compounds, produced by the International Programme on Chemical Safety, have also been reproduced in this document.”

“We were initially highly skeptical that differences in the concentrations of thimerosal in vaccines would have any effect on the incidence rate of neurodevelopmental disorders after childhood immunization. This study presents the first epidemiologic evidence, based upon tens of millions of doses of vaccine administered in the United States, that associates increasing thimerosal from vaccines with neurodevelopmental disorders. Specifically, an analysis of the Vaccine Adverse Events Reporting System (VAERS) database showed statistical increases in the incidence rate of autism (relative risk [RR] = 6.0), mental retardation (RR = 6.1), and speech disorders (RR = 2.2) after thimerosal-containing diphtheria, tetanus, and acellular pertussis (DTaP) vaccines in comparison with thimerosal-free DTaP vaccines. The male/female ratio indicated that autism (17) and speech disorders (2.3) were reported more in males than females after thimerosal-containing DTaP vaccines, whereas mental retardation (1.2) was more evenly reported among male and female vaccine recipients. Controls were employed to determine if biases were present in the data, but none were found. It was determined that overall adverse reactions were reported in similar-aged populations after thimerosal-containing DTaP (2.4 +/- 3.2 years old) and thimerosal-free DTaP (2.1 +/- 2.8 years old) vaccinations. Acute control adverse reactions such as deaths (RR = 1.0), vasculitis (RR = 1.2), seizures (RR = 1.6), ED visits (RR = 1.4), total adverse reactions (RR = 1.4), and gastroenteritis (RR = 1.1) were reported similarly after thimerosal-containing and thimerosal-free DTaP vaccines. An association between neurodevelopmental disorders and thimerosal-containing DTaP vaccines was found, but additional studies should be conducted to confirm and extend this study.”