“The memory of playing with the silvery substance that escaped from a childhood thermometer is all that most adults know of mercury. But rising concerns about this toxic element have once again brought ‘quicksilver’ into the consciousness of citizens around the globe.”
“Methylmercury (Met-Hg) and ethylmercury (Et-Hg) are powerful toxicants with a range of harmful neurological effects in humans and animals. While Met-Hg is a recognized trigger of oxidative stress and an endocrine disruptor impacting neurodevelopment, the developmental neurotoxicity of Et-Hg, a metabolite of thimerosal (TM), has not been explored. We hypothesized that TM exposure during the perinatal period impairs central nervous system development, and specifically the cerebellum, by the mechanism involving oxidative stress. To test this, spontaneously hypertensive rats (SHR) or Sprague-Dawley (SD) rat dams were exposed to TM (200 ?g/kg body weight) during pregnancy (G10-G15) and lactation (P5-P10). Male and female neonates were evaluated for auditory and motor function; cerebella were analyzed for oxidative stress and thyroid metabolism. TM exposure resulted in a delayed startle response in SD neonates and decreased motor learning in SHR male (22.6%), in SD male (29.8%), and in SD female (55.0%) neonates. TM exposure also resulted in a significant increase in cerebellar levels of the oxidative stress marker 3-nitrotyrosine in SHR female (35.1%) and SD male (14.0%) neonates. The activity of cerebellar type 2 deiodinase, responsible for local intra-brain conversion of thyroxine to the active hormone, 3′,3,5-triiodothyronine (T3), was significantly decreased in TM-exposed SHR male (60.9%) pups. This coincided with an increased (47.0%) expression of a gene negatively regulated by T3, Odf4 suggesting local intracerebellar T3 deficiency. Our data thus demonstrate a negative neurodevelopmental impact of perinatal TM exposure which appears to be both strain- and sex-dependent.”
“Thimerosal generates ethylmercury in aqueous solution and is widely used as preservative. We have investigated the toxicology of Thimerosal in normal human astrocytes, paying particular attention to mitochondrial function and the generation of specific oxidants. We find that ethylmercury not only inhibits mitochondrial respiration leading to a drop in the steady state membrane potential, but also concurrent with these phenomena increases the formation of superoxide, hydrogen peroxide, and Fenton/Haber-Weiss generated hydroxyl radical. These oxidants increase the levels of cellular aldehyde/ketones. Additionally, we find a five-fold increase in the levels of oxidant damaged mitochondrial DNA bases and increases in the levels of mtDNA nicks and blunt-ended breaks. Highly damaged mitochondria are characterized by having very low membrane potentials, increased superoxide/hydrogen peroxide production, and extensively damaged mtDNA and proteins. These mitochondria appear to have undergone a permeability transition, an observation supported by the five-fold increase in Caspase-3 activity observed after Thimerosal treatment.”
“We examined the effect of mercury (Hg) associated with dental amalgam fillings on biomarkers of renal and oxidative stress in children between the ages of 5-15.5 years. Urine samples were analyzed for N-acetyl-β-D-glucosaminidase (NAG), α(1)-microglobulin (α(1)-MG), β(2)-microglobulin (β(2)-MG), retinol binding protein (RBP), albumin (ALB), 8-hydroxy-2-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). The level of urinary Hg (UHg-C) was calculated as μg/g creatinine. Multiple regression analyses revealed that the excretion of urinary NAG was significantly associated with the presence of dental amalgam fillings (β=0.149, P=0.03) and the levels of UHg-C (β=0.531, P=0), with an interaction between the two (P=0). The increase in urinary NAG in relation to UHg-C levels had a dose-effect pattern. The lowest observed effect was seen at UHg-C levels above 1.452 μg/g creatinine, which is lower than previously reported. In contrast, α(1)-MG was negatively associated with the presence of dental amalgam fillings (β=-0.270, P=0), but positively with UHg-C levels (β=0.393, P=0). There were 7 children without, and one child with, dental amalgam fillings with urinary α(1)-MG levels above the reference limit of >7 mg/g creatinine. Even though α(1)-MG seems to be a reliable biomarker for early changes in renal functions, it might exert its effect only at a higher level of exposure. An inverse relationship was also observed between urinary 8-OHdG levels and the presence of dental amalgam fillings. This might suggest that the dental amalgam does not increase DNA damage but reduces the capacity to repair DNA, leading to lower urinary excretion of 8-OHdG. On the other hand, we found that Hg affected the excretion of urinary 8-OHdG in a dose-related pattern that was mostly associated with long-term exposure to low Hg levels. Urinary NAG levels were positively associated with urinary MDA levels (β=0.516, P=0) but not with 8-OHdG (β=0.134, P=0.078) after adjustment for potential confounders. Both UHg-C and the presence of dental amalgam fillings remained predictors of the NAG model. Our data provide evidence that low exposure to Hg from dental amalgam fillings exerts an effect on kidney tubular functions in children. Oxidative stress may have played a role in this mechanism. The results of this study would also suggest that urinary NAG is the most sensitive of all the investigated renal biomarkers. These results should be confirmed with further investigation.”
“BACKGROUND:
Despite the common use of Thimerosal as a preservative in childhood vaccines since the 1930s, there are not many studies on ethylmercury toxicokinetics and toxicodynamics in infants. The knowledge of ethylmercury’s potential adverse effects is derived mostly from parallel methylmercury research or from animal and theoretical models.
AIM OF THE STUDY:
This study was designed to examine the relationship between neonatal exposure to Thimerosal-containing vaccine (TCV) and child development.
MATERIAL AND METHODS:
The study sample consisted of 196 infants born between January 2001 and March 2003 to mothers attending ambulatory prenatal clinics in the first and second trimesters of pregnancy in Krakow. Vaccination history (date and the type of the vaccine) was extracted from physicians’ records. Child development was assessed using the Bayley Scales of Infant Development (BSID-II) measured in one-year intervals over 3years. General Linear Model (GLM) and Generalized Estimating Equation (GEE) models adjusted for potential confounders were used to assess the association.
RESULTS:
An adverse effect of neonatal TCV exposure was observed for the psychomotor development index (PDI) only in the 12th and 24th months of life (?=-6.44, p<0.001 and ?=-5.89, p<0.001). No significant effect of neonatal TCV exposure was found in the 36th month. The overall deficit in the PDI attributable to neonatal TCV exposure measured over the course of the three-year follow-up (GEE) was significantly higher in TCV group (?=-4.42, p=0.001). MDI scores did not show the adverse association with neonatal TCV exposure.”
Autoimmune diseases (AID) are a collection of many complex disorders of unknown etiology resulting in immune responses to self-antigens and are thought to result from interactions between genetic and environmental factors. Here we review the epidemiologic evidence for the role of environmental factors in the development of human AID, the conclusions that can be drawn from the existing data, critical knowledge gaps, and research needed to fill these gaps and to resolve uncertainties. We specifically summarize the state of knowledge and our levels of confidence in the role of specific agents in the development of autoimmune diseases, and we define the areas of greatest impact for future investigations. Among our consensus findings we are confident that: 1) crystalline silica exposure can contribute to the development of several AID; 2) solvent exposure can contribute to the development of systemic sclerosis; 3) smoking can contribute to the development of seropositive rheumatoid arthritis; and 4) an inverse association exists between ultraviolet radiation exposure and the risk of development of multiple sclerosis. We suggest that more studies of phenotypes, genotypes, and multiple exposures are needed. Additional knowledge gaps needing investigation include: defining important windows in the timing of exposures and latencies relating to age, developmental state, and hormonal changes; understanding dose-response relationships; and elucidating mechanisms for disease development. Addressing these essential issues will require more resources to support research, particularly of rare AID, but knowledge of the risks conferred by environmental factors in specific genetic contexts could pave the way for prevention of AID in the future.
Children’s blood-lead concentration (B-Pb) is well studied, but little is known about cadmium (B-Cd) and mercury (B-Hg), in particular for central Europe. Such information is necessary for risk assessment and management. Therefore, we here describe and compare B-Pb, B-Cd and B-Hg in children in six European, and three non-European cities, and identify determinants of these exposures. About 50 school children (7-14 years) from each city were recruited (totally 433) in 2007-2008. Interview and questionnaire data were obtained. A blood sample was analyzed: only two laboratories with strict quality control were used. The European cities showed only minor differences for B-Cd (geometric means 0.11-0.17 μg/L) and B-Pb (14-20 μg/L), but larger for B-Hg (0.12-0.94 μg/L). Corresponding means for the non-European countries were 0.21-0.26, 32-71, and 0.3-3.2 μg/L, respectively. For B-Cd in European samples, traffic intensity close to home was a statistically significant determinant, for B-Hg fish consumption and amalgam fillings, and for B-Pb sex (boys higher). This study shows that European city children’s B-Cd and B-Pb vary only little between countries; B-Hg differs considerably, due to varying tooth restoration practices and fish intake. Traffic intensity seemed to be a determinant for B-Cd. The metal concentrations were low from a risk perspective but the chosen non-European cities showed higher concentrations than the cities in Europe.
OBJECTIVE:
The objective of this study is to evaluate the awareness of patients with dental fillings about the toxicity of mercury in dental amalgam.
MATERIALS AND METHODS:
Adult patients having at least one amalgam filling in their mouth were recruited in the Oral Diagnosis Department of OAUTHC, Ile-Ife Dental Hospital. Participants were recruited consecutively as they report in the clinic. Data were collected using a structured questionnaire developed based on standard questions from relevant publications. They were asked to indicate the type of filling material in their mouth, ingredients of the material, previous knowledge of mercury in dental amalgam and ailments due to mercury. They were to indicate their level of agreement with filling their cavities with dental amalgam despite prior information about its mercury content.
RESULTS:
There were about 446 respondents analyzed; male, 194 (43.5%); female 252 (56.5%). Six (1.4%) and 21 (4.7%) respondents were primary and secondary schools students respectively; 15(3.4%) had no formal education while about 410 (91.9%) were either undergraduate or graduate. All of them had at least one amalgam filling. 249 (55%) participants know the type of filling on their teeth; 156 (34.5%) had the knowledge of the presence of mercury in dental amalgam while 26.1% believed mercury can cause problems in human beings. About 90 (19.9%) participants claimed to have heard about adverse reactions to dental amalgams and 34 (7.5%) of them have heard about people recovering from an illness after removal of their filling. The level of agreement with filling their cavities with amalgam despite prior knowledge of its mercury content was 74% while 60% was observed for allowing just any material to be placed on their teeth.
CONCLUSION:
Awareness of toxicity of mercury in dental amalgam was slightly low among the respondents studied. This may be suggested to be a reflection of nonexistent of global amalgam controversy in Nigeria.
“Resin-based composite dental restoration materials may release bisphenol-A, an endocrine-disrupting chemical. Using secondary analysis of a randomized clinical safety trial of amalgam vs. composites, we tested the hypothesis that dental restoration materials affect children’s growth. Children (N = 218 boys, N = 256 girls) aged 6 to 10 yrs at baseline with ≥ 2 decayed posterior teeth were randomized to amalgam or composites (bisphenol-A-diglycidyl-dimethacrylate composite for permanent teeth, urethane-dimethacrylate compomer for primary teeth) for treatment of posterior caries throughout follow-up. Primary outcomes for this analysis were 5-year changes in BMI-for-age z-scores, body fat percentage (BF%), and height velocity; exploratory analyses (n = 113) examined age at menarche. Results showed no significant differences between treatment assignment and changes in physical development in boys [(composites vs. amalgam) BF%, 4.9 vs. 5.7, p = 0.49; (BMI-z-score) 0.13 vs. 0.25, p = 0.36] or girls (8.8 vs. 7.7, p = 0.95; 0.36 vs. 0.21, p = 0.49). Children with more treatment on primary teeth had greater increases in BF% regardless of material type. Girls assigned to composites had lower risk of menarche during follow-up (hazard ratio = 0.57, 95% CI 0.35-0.95). Overall, there were no significant differences in physical development over 5 years in children treated with composites or amalgam. Additional studies examining these restoration materials in relation to age at menarche are warranted (clinicaltrials.gov number NCT00065988).”
Resin-based dental restorations may intra-orally release their components and bisphenol A. Gestational bisphenol A exposure has been associated with poorer executive functioning in children.
To examine whether exposure to resin-based composite restorations is associated with neuropsychological development in children.
Secondary analysis of treatment level data from the New England Children’s Amalgam Trial, a 2-group randomized safety trial conducted from 1997 to 2006. Children (N=534) aged 6-10 y with ≥2 posterior tooth caries were randomized to treatment with amalgam or resin-based composites (bisphenol-A-diglycidyl-dimethacrylate-composite for permanent teeth; urethane dimethacrylate-based polyacid-modified compomer for primary teeth). Neuropsychological function at 4- and 5-year follow-up (N=444) was measured by a battery of tests of executive function, intelligence, memory, visual-spatial skills, verbal fluency, and problem-solving. Multivariable generalized linear regression models were used to examine the association between composite exposure levels and changes in neuropsychological test scores from baseline to follow-up. For comparison, data on children randomized to amalgam treatment were similarly analyzed.
With greater exposure to either dental composite material, results were generally consistent in the direction of slightly poorer changes in tests of intelligence, achievement or memory, but there were no statistically significant associations. For the four primary measures of executive function, scores were slightly worse with greater total composite exposure, but statistically significant only for the test of Letter Fluency (10-surface-years β=-0.8, SE=0.4, P=0.035), and the subtest of color naming (β=-1.5, SE=0.5, P=0.004) in the Stroop Color-Word Interference Test. Multivariate analysis of variance confirmed that the negative associations between composite level and executive function were not statistically significant (MANOVA, P=0.18). Results for greater amalgam exposure were mostly nonsignificant in the opposite direction of slightly improved scores over follow-up.
Dental composite restorations had statistically insignificant associations of small magnitude with impairments in neuropsychological test change scores over 4- or 5-years of follow-up in this trial.”