Exposures of dental professionals to elemental mercury and methylmercury.
ABSTRACT: Mercury (Hg) exposure, a worldwide public health concern, predominantly takes two forms--methylmercury from fish consumption and elemental Hg from dental amalgam restorations. We recruited 630 dental professionals from an American Dental Association meeting to assess Hg body burden and primary sources of exposure in a dually exposed population. Participants described occupational practices and fish consumption patterns via questionnaire. Hg levels in biomarkers of elemental Hg (urine) and methylmercury (hair and blood) were measured with a Direct Mercury Analyzer-80 and were higher than the general US population. Geometric means (95% CI) were 1.28 (1.19-1.37) ?g/l in urine, 0.60 (0.54-0.67) ?g/g in hair and 3.67 (3.38-3.98) ?g/l in blood. In multivariable linear regression, personal amalgams predicted urine Hg levels along with total years in dentistry, amalgams handled, working hours and sex. Fish consumption patterns predicted hair and blood Hg levels, which were higher among Asians compared with Caucasians. Five species contributed the majority of the estimated Hg intake from fish--swordfish, fresh tuna, white canned tuna, whitefish and king mackerel. When studying populations with occupational exposure to Hg, it is important to assess environmental exposures to both elemental Hg and methylmercury as these constitute a large proportion of total exposure.
Project description:Modification of the epigenome may be a mechanism underlying toxicity and disease following chemical exposure. Animal and human data suggest that mercury (Hg) impacts DNA methylation. We hypothesize that methylmercury and inorganic Hg exposures from fish consumption and dental amalgams, respectively, may be associated with altered DNA methylation at global repetitive elements (long interspersed elements, LINE-1) and candidate genes related to epigenetic processes (DNMT1) and protection against Hg toxicity (SEPW1, SEPP1). Dental professionals were recruited at Michigan Dental Association (MDA) meetings in 2009 and 2010. Subjects (n=131) provided survey data (e.g. exposure sources, demographics) and biological samples for Hg measurement and epigenetic analysis. Total Hg was quantified via atomic absorption spectrophotometry in hair and urine, indicative of methylmercury and inorganic Hg exposures, respectively. Global repetitive and candidate gene methylation was quantified via pyrosequencing of bisulfite converted DNA isolated from buccal mucosa. Hair Hg (geometric mean (95% CI): 0.37 (0.31-0.44) µg/g) and urine Hg (0.70 (0.60-0.83) µg/L) were associated with sources of exposure (fish consumption and dental amalgams, respectively). Multivariable linear regression revealed a trend of SEPP1 hypomethylation with increasing hair Hg levels, and this was significant (P<0.05) among males. The trend remained when excluding non-dentists. No significant relationships between urine Hg and DNA methylation were observed. Thus, in a limited cohort, we identified an association between methylmercury exposure and hypomethylation of a potentially labile region of the genome (SEPP1 promoter), and this relationship was gender specific.
Project description:Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione S-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n=515), and total mercury content was measured. Average urine (1.06±1.24 microg/L) and hair mercury levels (0.49±0.63 microg/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5'), or both (SEPP1 3'UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption).
Project description:<h4>Background</h4>Some clinical studies have suggested that ingestion of n-3 polyunsaturated fatty acids (PUFA) has neuroprotective effects on peripheral nerve function. However, few epidemiological studies have examined the effect of dietary n-3 PUFA intake from fish consumption on peripheral nerve function, and none have controlled for co-occurrence of methylmercury exposure from fish consumption.<h4>Objectives</h4>We evaluated the effect of estimated dietary n-3 PUFA intake on peripheral nerve function after adjusting for biomarkers of methylmercury and elemental mercury in a convenience sample of 515 dental professionals.<h4>Methods</h4>We measured sensory nerve conduction (peak latency and amplitude) of the median, ulnar and sural nerves and total mercury concentrations in hair and urine samples. We estimated daily intake (mg/day) of the total n-3 PUFA, n-3 docosahexaenoic acid (DHA), and n-3 eicosapentaenoic acid (EPA) based on a self-administrated fish consumption frequency questionnaire. We also collected information on mercury exposure, demographics and other covariates.<h4>Results</h4>The estimated median intakes of total n-3 PUFA, n-3 EPA, and n-3 DHA were 447, 105, and 179 mg/day, respectively. The mean mercury concentrations in urine (1.05 ?g/L) and hair (0.49 ?g/g) were not significantly different from the US general population. We found no consistent association between n-3 PUFA intake and sensory nerve conduction after adjusting for mercury concentrations in hair and urine although some positive associations were observed with the sural nerve.<h4>Conclusions</h4>In a convenience sample of dental professionals, we found little evidence suggesting that dietary intake of n-3 PUFAs from fish has any impact on peripheral nerve function after adjustment for methylmercury exposure from fish and elemental mercury exposure from dental amalgam.
Project description:BACKGROUND:Mechanistic studies support the potential for mercury (Hg) to alter immunity, including via in utero exposure. As yet, there are few prospective studies of in utero Hg exposure and subsequent immune-related outcomes, especially in infancy. OBJECTIVES:We investigated the association of biomarkers of prenatal Hg exposure and maternal silver-mercury dental amalgams with the occurrence of infant allergy, respiratory infection, and respiratory symptoms in the first year of life. METHODS:The New Hampshire Birth Cohort Study (NHBCS) ascertained information on infant allergies, infections and symptoms through telephone interviews at 4, 8 and 12 months postpartum and measured total Hg in maternal toenails collected at ~28-30 weeks gestation. Information on maternal fish consumption and presence of dental amalgams was obtained from a questionnaire administered at study enrollment at 24-28 weeks. A total of 1321 NHBCS mother-infant pairs had at least one Hg exposure measure (toenail Hg or information on dental amalgams) and information on dietary fish intake. Generalized linear models and generalized estimating equation models with Poisson regression adjusted for potential confounders (maternal age, level of education, parity, smoking, alternative Healthy Eating Index-2010, infant sex, gestational age, feeding mode, and day care attendance) were used to assess the association between infant outcomes and prenatal toenail Hg levels. We subsetted this analysis on mothers who consumed fish (n?=?706) as a measure of in utero methylmercury (MeHg) exposure. Associations between infant outcomes and dental amalgams as a measure of in utero inorganic Hg exposure were assessed among mothers who did not consume fish (n?=?218). RESULTS:Among women who ate fish during pregnancy, higher maternal toenail Hg concentrations were associated with an increased risk of lower respiratory infections and respiratory symptoms requiring a doctor visit among infants age 9-12?months (relative risk (RR) 1.4 (95% CI: 1.1, 1.9) and 1.2 (95% CI: 1.0, 1.4) respectively), whereas a reduced risk of lower respiratory infections was observed among infants 0-4?months of age (RR?=?0.7 (95% CI: 0.5, 1.0). We found little to no evidence of associations of toenail Hg with upper respiratory infections, allergy or eczema at any age to one year. Among infants of mothers who did not consume fish, we found an elevated risk of upper respiratory infections requiring a doctor visit in relation to having dental amalgams during pregnancy (RR?=?1.5 (95% CI: 1.1, 2.1)). Overall, weaker associations were observed with lower respiratory infections, respiratory symptoms, and medically confirmed allergies, and there was no association with eczema. CONCLUSIONS:Our analyses of a US birth cohort, along with prior mechanistic work, raise the possibility that gestational Hg exposure through fish/seafood consumption and dental amalgams may alter respiratory infections and respiratory symptoms in infants.
Project description:Methylmercury (MeHg) exposure via fish in the diet remains a priority public health concern. Individual variation in response to a given MeHg exposure and the biotransformation of MeHg that follows complicate our understanding of this issue. MeHg elimination from the human body occurs slowly (elimination rate (kel) approximately 0.01?day(-1) or approximately 70 days half-life [t1/2]) and is a major determinant of the Hg body burden resulting from fish consumption. The underlying mechanisms that control MeHg elimination from the human body remain poorly understood. We describe here improved methods to obtain a MeHg elimination rate via longitudinal Hg analysis in hair using laser ablation-inductively coupled plasma-mass spectrometry. We measured MeHg elimination rates in eight individuals following the consumption of 3 fish meals in two 75-day trials separated by a 4-month washout period. In addition, since MeHg biotransformation to inorganic Hg (I-Hg) is associated with Hg excretion, we speciated Hg in feces samples to estimate individual MeHg de-methylation status. We observed a wide range of MeHg elimination rates between individuals and within individuals over time (kel?=?0.0163-0.0054?day(-1); estimated t1/2?=?42.5-128.3 days). The ratio of MeHg and I-Hg in feces also varied widely among individuals. While the %I-Hg in feces was likely influenced by dental amalgams, findings with subjects who lacked amalgams suggest that faster MeHg elimination is associated with a higher %I-Hg in feces indicating more complete de-methylation. We anticipate these methods will contribute to future investigations of genetic and dietary factors that influence MeHg disposition in people.
Project description:The main source of mercury (Hg) exposure in the general population is fish. Another possible source is dental amalgam. Here, we compare the levels of Hg and selenium (Se) in samples of maternal and fetal origin collected shortly after childbirth of healthy postpartum women in the coastal (n = 96) and continental (n = 185) areas of Croatia related to maternal seafood/fish consumption. We also evaluated Hg concentrations and maternal serum metallothionein (MT2) concentrations in relation to the number of dental amalgam fillings, and MT2A-5A/G (rs28366003) polymorphism. The levels of Hg and Se in maternal hair and blood/serum, placenta and cord blood/serum increased in relation to increasing fish consumption with the highest values in subjects from the coast. The concentrations of each element and between elements correlated across the matrices. Increasing amalgam number correlated linearly with increased Hg levels in maternal and cord serum and was not associated with serum MT2. No association of MT2A-5A/G polymorphism and Hg or Se levels were found. The results confirmed higher fish consumption in coastal vs. continental Croatia and increases of both Hg and Se related to fish consumption in all analyzed samples. Increased blood Hg reflected the predominant MeHg share from seafood, while increased serum Hg matched exposure from dental amalgams.
Project description:Immune dysregulation associated with mercury has been suggested, although data in the general population are lacking. Chronic exposure to low levels of methylmercury (organic) and inorganic mercury is common, such as through fish consumption and dental amalgams.We examined associations between mercury biomarkers and antinuclear antibody (ANA) positivity and titer strength.Among females 16-49 years of age (n = 1,352) from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, we examined cross-sectional associations between mercury and ANAs (indirect immunofluorescence; cutoff ? 1:80). Three biomarkers of mercury exposure were used: hair (available 1999-2000) and total blood (1999-2004) predominantly represented methylmercury, and urine (1999-2002) represented inorganic mercury. Survey statistics were used. Multivariable modeling adjusted for several covariates, including age and omega-3 fatty acids.Sixteen percent of females were ANA positive; 96% of ANA positives had a nuclear speckled staining pattern. Geometric mean (geometric SD) mercury concentrations were 0.22 (0.03) ppm in hair, 0.92 (0.05) ?g/L blood, and 0.62 (0.04) ?g/L urine. Hair and blood, but not urinary, mercury were associated with ANA positivity (sample sizes 452, 1,352, and 804, respectively), after adjusting for confounders: for hair, odds ratio (OR) = 4.10 (95% CI: 1.66, 10.13); for blood, OR = 2.32 (95% CI: 1.07, 5.03) comparing highest versus lowest quantiles. Magnitudes of association were strongest for high-titer (? 1:1,280) ANA: hair, OR = 11.41 (95% CI: 1.60, 81.23); blood, OR = 5.93 (95% CI: 1.57, 22.47).Methylmercury, at low levels generally considered safe, was associated with subclinical autoimmunity among reproductive-age females. Autoantibodies may predate clinical disease by years; thus, methylmercury exposure may be relevant to future autoimmune disease risk.
Project description:Mercury (Hg) isotopic signatures were characterized in polished rice samples from China, U.S., and Indonesia (n = 45). Hg isotopes were also analyzed in paired hair samples for participants from China (n = 21). For the latter, we also quantified the proportion of methylmercury intake through rice (range: 31-100%), and the weekly servings of fish meals (range: 0-5.6 servings/weekly). For these participants, 29% (n = 6) never ingested fish, 52% (n = 11) ingested fish < twice/weekly, and 19% (n = 4) ingested fish ? twice/weekly. In rice and hair, both mass-dependent fractionation (MDF, reported as ?202Hg) and mass-independent fractionation (MIF, reported as ?199Hg) of Hg isotopes were observed. Compared to rice, hair ?202Hg values were enriched on average (±1 standard deviation) by 1.9 ± 0.61‰, although the range was wide (range: 0.45‰, 3.0‰). Hair ?199Hg was significantly inversely associated with %methylmercury intake from rice (Spearman's rho = -0.61, p < 0.01, n = 21), i.e., as the proportion of methylmercury intake from rice increased, MIF decreased. Additionally, hair ?199Hg was significantly higher for participants ingesting fish ? twice/weekly compared to those who did not ingest fish or ingested fish < twice/weekly (ANOVA, p < 0.05, n = 21); Overall, results suggest that Hg isotopes (especially MIF) in human hair can be used to distinguish methylmercury intake from rice versus fish.
Project description:Mercury (Hg) is a potent toxicant of concern to the general public. Recent studies suggest that several genes that mediate Hg metabolism are polymorphic. We hypothesize that single nucleotide polymorphisms (SNPs) in such genes may underline inter-individual differences in exposure biomarker concentrations.Dental professionals were recruited during the American Dental Association (ADA) 2012 Annual Meeting. Samples of hair, blood, and urine were collected for quantifying Hg levels and genotyping (88 SNPs in classes relevant to Hg toxicokinetics including glutathione metabolism, selenoproteins, metallothioneins, and xenobiotic transporters). Questionnaires were administrated to obtain information on demographics and sources of Hg exposure (e.g., fish consumption and use of dental amalgam). Here, we report results for 380 participants with complete genotype and Hg biomarker datasets. ANOVA and linear regressions were used for statistical analysis.Mean (geometric) Hg levels in hair (hHg), blood (bHg), urine (uHg), and the average estimated Hg intake from fish were 0.62µg/g, 3.75µg/L, 1.32µg/L, and 0.12µg/kg body weight/day, respectively. Out of 88 SNPs successfully genotyped, Hg biomarker levels differed by genotype for 25 SNPs, one of which remained significant following Bonferroni correction in ANOVA. When the associations between sources of Hg exposure and SNPs were analyzed with respect to Hg biomarker concentrations, 38 SNPs had significant main effects and/or gene-Hg exposure source interactions. Twenty-five, 23, and four SNPs showed significant main effects and/or interactions for hHg, bHg, and uHg levels, respectively (p<0.05), and six SNPs (in GCLC, MT1M, MT4, ATP7B, and BDNF) remained significant following Bonferroni correction.The findings suggest that polymorphisms in environmentally-responsive genes can influence Hg biomarker levels. Hence, consideration of such gene-environment factors may improve the ability to assess the health risks of Hg more precisely.
Project description:A dynamic model was developed to project Hg concentrations in common biomarkers of exposure in response to changes in Hg concentrations in predatory fish from local waters. The model predicts biomarkers in susceptible populations for intake rates representing the mean, 90th, 95th, and 99 th percentiles of populations of interest. The biomarkers the model calculates are blood methylmercury, total hair Hg, and fetal blood methylmercury. Decision makers can use the model to determine the degree of reduction in fish tissue Hg levels necessary to protect the health of susceptible populations. Biomarker output was calibrated with literature sources. Output was then compared to additional literature sources to evaluate model function. Projected biomarkers were not different from literature sources. The model can be used as a tool to understand the impact of local fish consumption on susceptible populations.