Mercury

The question of whether and to what extent dental materials may be hazardous to patients, the environment, and dental personnel has become of increasing public concern. The very emotional discussion in the public media about amalgam has significantly contributed to this dispute. In addition, reports about potential health risks in relation to other dental materials, such as resins and dental alloys, have generated an increased public and professional interest in this topic. One consequence of this tendency is that dental materials are now the subject of special regulations and directives in almost all countries of the world, intended to guarantee efficiency, safety, and quality and to make sure that only biocompatible materials are brought on the market. Basically, manufacturers are responsible for the safety and quality of their medical devices. It is, however, the responsibility of the dentist to fulfill distinct assignments in this context: The dentist is thus responsible for choosing the most suitable material for each specific indication in an individual patient. Furthermore, the dentist is the primary contact person for patients who have questions about the biocompatibility of the applied materials and is therefore an important part of the market surveillance system, with the responsibility to report adverse effects to the relevant authorities.

“Earlier, we reported that mercury, the environmental risk factor for cardiovascular diseases, activates vascular endothelial cell (EC) phospholipase D (PLD). Here, we report the novel and significant finding that calcium and calmodulin regulated mercury-induced PLD activation in bovine pulmonary artery ECs (BPAECs). Mercury (mercury chloride, 25 microM; thimerosal, 25 microM; methylmercury, 10 microM) significantly activated PLD in BPAECs. Calcium chelating agents and calcium depletion of the medium completely attenuated the mercury-induced PLD activation in ECs. Calmodulin inhibitors significantly attenuated mercury-induced PLD activation in BPAECs. Despite the absence of L-type calcium channels in ECs, nifedipine, nimodipine, and diltiazem significantly attenuated mercury-induced PLD activation and cytotoxicity in BPAECs. This study demonstrated the importance of calcium and calmodulin in the regulation of mercury-induced PLD activation and the protective action of L-type calcium channel blockers against mercury cytotoxicity in vascular ECs, suggesting mechanisms of mercury vasculotoxicity and mercury-induced cardiovascular diseases.”

“OBJECTIVE:
Thimerosal, a mercury compound used as a preservative in vaccines administered during infancy, has been suspected to affect neuropsychological development. We compared the neuropsychological performance, 10 years after vaccination, of 2 groups of children exposed randomly to different amounts of thimerosal through immunization.

METHODS:
Children who were enrolled in an efficacy trial of pertussis vaccines in 1992-1993 were contacted in 2003. Two groups of children were identified, according to thimerosal content in vaccines assigned randomly in the first year of life (cumulative ethylmercury intake of 62.5 or 137.5 microg), and were compared with respect to neuropsychological outcomes. Eleven standardized neuropsychological tests, for a total of 24 outcomes, were administered to children during school hours. Mean scores of neuropsychological tests in the domains of memory and learning, attention, executive functions, visuospatial functions, language, and motor skills were compared according to thimerosal exposure and gender. Standard regression coefficients obtained through multivariate linear regression analyses were used as a measure of effect.

RESULTS:
Nearly 70% of the invited subjects participated in the neuropsychological assessment (N = 1403). Among the 24 neuropsychological outcomes that were evaluated, only 2 were significantly associated with thimerosal exposure. Girls with higher thimerosal intake had lower mean scores in the finger-tapping test with the dominant hand and in the Boston Naming Test.

CONCLUSIONS:
Given the large number of statistical comparisons performed, the few associations found between thimerosal exposure and neuropsychological development might be attributable to chance. The associations found, although statistically significant, were based on small differences in mean test scores, and their clinical relevance remains to be determined.”

“BACKGROUND:

Urinary porphyrins are diagnostic of various metabolic disorders and xenobiotic exposures, but comprehensive normative data for urinary porphyrin concentrations in children are currently unavailable.

METHODS:

Subjects were participants in a prospective, randomized, controlled clinical trial of dental materials safety, 8 to 12 y at inception, who were followed longitudinally for 7 y after baseline with an extensive battery of neurobehavioral, neurological, renal function and urinary porphyrin assessments. Porphyrins were quantified by HPLC. Linear regression analyses were used to measure associations of porphyrin levels with age and gender.

RESULTS:

Mean concentrations, 95% confidence intervals, and 10th, 50th, and 90th percentiles for all 5 typically excreted urinary porphyrins are presented by year of age and by gender. Unadjusted urinary concentrations (microg/l) of all 5 porphyrins remained relatively constant throughout the age range of 8-18 y for both males and females. In contrast, creatinine-adjusted urinary porphyrin concentrations (microg/g) declined significantly throughout this age range in both genders. Boys had significantly higher pentacarboxyl- and copro-porphyrin levels compared with girls both before and after creatinine adjustment.

CONCLUSIONS:

Normative longitudinal data provided herein may facilitate the clinical assessment of pediatric metabolic disorders and may be of particular relevance in evaluating porphyrin changes as a biological indicator of disease or xenobiotic exposures among children and adolescents.”

“This study investigated the relationship of children’s autism symptoms with their toxic metal body burden and red blood cell (RBC) glutathione levels. In children ages 3-8 years, the severity of autism was assessed using four tools: ADOS, PDD-BI, ATEC, and SAS. Toxic metal body burden was assessed by measuring urinary excretion of toxic metals, both before and after oral dimercaptosuccinic acid (DMSA). Multiple positive correlations were found between the severity of autism and the urinary excretion of toxic metals. Variations in the severity of autism measurements could be explained, in part, by regression analyses of urinary excretion of toxic metals before and after DMSA and the level of RBC glutathione (adjusted R(2) of 0.22-0.45, P < .005 in all cases). This study demonstrates a significant positive association between the severity of autism and the relative body burden of toxic metals.”

“Thimerosal (THIM), an organomercury preservative added to many child vaccines is a suspected factor in pathogenesis of neurodevelopmental disorders. We examined the pharmacokinetics of Hg in the brain, liver and kidneys after i.m. THIM injection in suckling rats and we tested THIM effect on nociception. THIM solutions were injected to Wistar and Lewis rats in a vaccination-like mode on PN days 7, 9, 11 and 15 in four equal doses. For Wistar rats these were: 12, 48, 240, 720, 1440, 2160, 3000 microg Hg/kg and for Lewis: 54, 216, 540 and 1080 microg Hg/kg. Pharmacokinetic analysis revealed that Hg from THIM injections accumulates in the rat brain in significant amounts and remains there longer than 30 days after the injection. At the 6th week of age animals were examined for pain sensitivity using the hot plate test. THIM treated rats of both strains and sexes manifested statistically significantly elevated pain threshold (latency for paw licking, jumping) on a hot plate (56 degrees C). Wistar rats were more sensitive to this effect than Lewis rats. Protracted THIM-induced hypoalgesia was reversed by naloxone (5 mg/kg, i.p.) injected before the hot plate test, indicative of involvement of endogenous opioids. This was confirmed by augmented catalepsy after morphine (2.5 mg/kg, s.c.) injection. Acute THIM injection to 6-week-old rats also produced hypoalgesia, but this effect was transient and was gone within 14 days. Present findings show that THIM administration to suckling or adult rats impairs sensitivity to pain, apparently due to activation the endogenous opioid system.”

“Environmental and predisposing genetic factors are known to play a crucial role in the development of systemic autoimmune diseases. With respect to the role of environmental factors, it is not known how and to what extent they contribute to the initiation and exacerbation of systemic autoimmunity. In the present study, I considered this issue and asked if environmental factors can induce autoimmunity in the absence of specific susceptible genes. The development of genetically controlled mercury- and silver-induced B cell activation and anti-nucleolar autoantibodies (ANolA) production in genetically heterozygous outbred Institute of Cancer Research (ICR), Naval Medical Research Institute (NMRI) and Black Swiss mouse stocks were analysed. Four weeks of treatment with both mercury and silver induced a strong B cell activation characterized by increased numbers of splenic antibody-secreting cells of at least one or more immunoglobulin (Ig) isotype(s) in all treated stocks. The three stocks also exhibited a marked increase in the serum IgE levels in response to mercury, but not silver. More importantly, in response to mercury a large numbers of ICR (88%), NMRI (96%) and Black Swiss (100%) mice produced different levels of IgG1 and IgG2a ANolA (a characteristic which is linked strictly to the H-2 genes). Similarly, but at lower magnitudes, treatment with silver also induced the production of IgG1 and IgG2a ANolA in 60% of ICR, 75% of NMRI and 100% of Black Swiss mice. Thus, the findings of this study suggest that long-term exposure to certain environmental factors can activate the immune system to produce autoimmunity per se, without requiring specific susceptible genes.”

“Effects of thimerosal and its metabolites, ethyl mercury and thiosalicylate, on the expression of metallothionein (MT) mRNAs in mouse cerebellum microglia cell line, C8-B4 cells, were studied. The level of MT-1 mRNA significantly decreased at early hours and recovered time-dependently 24h after thimerosal was added to the C8-B4 cells. However, MT-2 and MT-3 mRNA expressions did not change from the control group. In contrast, the expression of MT-1 mRNA increased in a mouse neuroblastoma cell line 6h after incubation with thimerosal. In addition, the level of MT-1 mRNA decreased in C8-B4 cells 6h after the addition of thiosalicylate, but ethyl mercury induced MT-1 mRNA expression. When cell viability was compared with thimerosal, thiosalicylate, and ethyl mercury, the viability of C8-B4 cells decreased dose-dependently 24h after either thimerosal or ethyl mercury was added; however, the viability increased dose-dependently until 15 microM thiosalicylate was added. From the present results, it is concluded that the expression of MT-1 mRNA may be mediated by different factors than the expression of MT-2 mRNA in C8-B4 cells. The reduction of MT-1 mRNA level by thiosalicylate may affect the proliferation of C8-B4 cells.”

“BACKGROUND:

Information on the impact of genetic predisposition on metal toxicokinetics in the human body is limited. There is increasing evidence that certain genetic polymorphisms modify lead and mercury toxicokinetics. This called for analysis of further candidate genes.

OBJECTIVES:

Medical students (N=324) were examined in order to detect potential associations between lead exposure and polymorphisms in HFE, VDR, ALAD, and MT genes, as well as between mercury exposure and GSTT1, GSTM1, GSTA1, GSTP1, GCLC, and MT polymorphisms.

METHODS:

The levels of lead and mercury exposure of students were determined by blood, urine, and hair analyses (ICP-MS, CV-AAS). Genotyping of common polymorphisms was examined by MALDI-TOF MS and the TaqMan methodology. Associations between lead and mercury exposures and genetic background were examined by bivariate analysis, and by categorical regression analysis (CATREG) controlled by metal- and matrix-specific variables.

RESULTS:

Lead and mercury levels in urine, blood, and hair indicated low exposures. VDR polymorphism and joint presence of VDR/ALAD polymorphisms were significantly and independently associated with urine lead concentrations (CATREG P<0.05). Polymorphisms in GSTP1-114 and MT4 genes as well as dual gene combinations including GSTP1, GCLC, GSTT1, and GSTM1 polymorphisms were independent variables related to mercury body burdens (CATREG P<0.05). GSTP1-114/GSTT1 and GSTP1-105/GCLC combinations showed synergistic effects on hair mercury levels compared to single-gene variants.

CONCLUSIONS:

We found evidence that certain genetic backgrounds were associated with lead and mercury metabolism, suggesting gene-environment and gene-gene-environment interactions. The modes of interaction remain to be evaluated.”

BACKGROUND:
Contact allergy to dental materials is poorly understood; clinical manifestations are heterogeneous.

OBJECTIVE:
To analyse positive patch test reactions to metals (as their alloys or salts) used in dentistry together with clinical symptoms and possible relevance to dental fillings.

METHODS:
We retrospectively analysed 206 patients who underwent patch testing with metals used in dentistry because of suspected contact allergy to them.

RESULTS:
Twenty-eight of 206 patients had positive patch test reactions to metals used in dentistry. The number of positive patch test reactions was highest for gold sodium thiosulfate, palladium chloride, and nickel sulfate (n = 10, respectively), followed by amalgam, ammoniated mercury, and cobalt chloride (n = 4, respectively) and amalgam-mixed metals (including copper, tin, zinc, and silicon), and ammonium tetrachloroplatinate (n = 1). Only 14 (7%) of 206 patients had a clinically relevant contact allergy with conditions of the oral mucosa (n = 7 with lichen planus and n = 7 with stomatitis) and positive patch test reactions to dental metals containing the suspected allergen. Improvement of symptoms was assessed in one patient with amalgam contact allergy 2 weeks after removal of dental fillings.

CONCLUSIONS:
Clinically relevant contact allergies to dental metals are infrequent. Gold sodium thiosulfate and palladium chloride presented the most frequent contact allergens.