Blood MeHg Research Articles

KEAP1 polymorphisms and neurodevelopmental outcomes in children with exposure to prenatal MeHg from the Seychelles Child Development Study Nutrition Cohort 2

BackgroundHumans differ in the metabolism of the neurotoxicant methyl mercury (MeHg). This variation may be partially due to variation in genes encoding the transcription factor Nuclear factor E2-related factor 2 (NRF2) and its negative regulator Kelch-like ECH-Associated Protein 1 (KEAP1), which regulate glutathione and related transporter and antioxidant proteins that play a role in the metabolism and neurotoxicity of MeHg. AimTo elucidate a potential risk from genetic variation in NFE2L2 (encoding NRF2) and KEAP1 toward prenatal mercury exposure and child neurodevelopmental outcomes at 20 months and 7 years of age in a population with variable prenatal exposure to MeHg from maternal fish consumption. Material and MethodsNutrition Cohort 2 is a mother–child cohort in the Republic of Seychelles. Children were genotyped for NFE2L2 (rs2364723, rs13001694) and KEAP1 (rs8113472, rs9676881) polymorphisms (N = 1285 after removing siblings). Total mercury (Hg) was measured in cord blood as a biomarker for prenatal MeHg exposure. Child neurodevelopmental outcomes included the Bayley Scales of Infant Development II administered at 20 months of age, and outcomes across multiple neurodevelopmental domains from 14 tests administered in children and 3 instruments completed by parents when children were 7 years of age. ResultsThe mean cord blood MeHg concentration was 34 (95% CI 11, 75) µg/L. None of the four polymorphisms had a significant association (p < 0.05) with either cord MeHg or neurodevelopmental test results at 20 months. There were no significant associations between either NFE2L2 polymorphism and any developmental test scores. At 7 years, children carrying KEAP1 rs8113472 CA showed significantly worse performance on psychomotor function than children with the CC variant (finger tapping, dominant hand: β − 1.19, SE 0.34; finger tapping, non-dominant hand: β − 0.92, SE 0.31) and worse social communication (SCQ Total: β 0.65, SE 0.27). Children carrying rs8113472 AA, versus children with CC, showed significantly better performance on social communication (SRS Total: β − 8.88, SE 3.60). Children carrying KEAP1 rs9676881 AG, versus children with GG, showed significantly worse performance on psychomotor function (trailmaking A time: β 8.66, SE 3.37) and cognition (KBIT Matrices: β − 0.96, SE 0.36). ConclusionNo associations between NFE2L2 and KEAP1 polymorphisms and MeHg concentration were identified. However, at 7 years, KEAP1 polymorphisms were associated with differences in neurodevelopmental outcomes in children from a population with high fish intake.

Total arsenic, dimethylarsinic acid, lead, cadmium, total mercury, methylmercury and hypertension among Asian populations in the United States: NHANES 2011–2018

BackgroundNon-Hispanic Asians (NHA) in USA have been reported with higher arsenic (As), lead (Pb), cadmium (Cd), mercury (Hg) and their specific species levels, comparing with non-NHA. This study aimed to investigate the associations of these metal/metalloid levels with blood pressure levels and prevalence of hypertension among general NHA using the 2011–2018 National Health and Nutrition and Examination Survey (NHANES) data. MethodsThe study included participants aged 20 years and older with determinations of As, Dimethylarsinic acid (DMA), Pb, Cd, Hg and methyl-Hg (MeHg) in blood (n = 10, 177) and urine (n = 5, 175). These metals/metalloid levels were measured by inductively coupled plasma mass spectrometry. Systolic (SBP) and diastolic blood pressure (DBP) levels were examined through a standardized protocol. Censored normal regression model and logistic regression model were employed to explore the associations of As, DMA, Pb, Cd, Hg and MeHg levels with blood pressure levels and prevalence of hypertension respectively, and potential confounders were adjusted in these regression models. Quantile-based g-computation approach was used to analysis joint effect of metals mixture on blood pressure level and hypertension. ResultsFor NHA, urinary As and Hg levels were associated with increased DBP level; Higher blood Hg and MeHg levels were related to increased blood pressure levels and hypertension; However, negative association was observed between urinary Cd and SBP level; Blood metals mixture (including blood Pb, Cd and Hg) was associated with increased DBP level, but not for hypertension. For non-NHA, urinary As and DMA levels were associated with increased SBP level, but not DBP level and prevalence of hypertension; Urinary Pb level was associated with decreased DBP level; Nevertheless, positive associations were observed between blood Pb levels and SBP and prevalence of hypertension; Blood Hg level was associated with decreased DBP level and prevalence of hypertension; Furthermore, blood MeHg level was associated with decreased DBP level; Positive association was observed between blood metals mixture and increased SBP level among non-NHA. ConclusionsHighly exposed to Hg level among NHA was associated with increased blood pressure levels and prevalence of hypertension. Urinary As level was associated with increased DBP level among NHA. Furthermore, blood metals mixture was related to increased DBP level among NHA. Further prospective studies with larger sample size should be performed to warrant the results.

Contribution of child ABC-transporter genetics to prenatal MeHg exposure and neurodevelopment

BackgroundThere is emerging evidence that exposure to prenatal methylmercury (MeHg) from maternal fish consumption during pregnancy can differ between individuals due to genetic variation. In previous studies, we have reported that maternal polymorphisms in ABC-transporter genes were associated with maternal hair MeHg concentrations, and with children’s early neurodevelopmental tests. In this study, we add to these findings by evaluating the contribution of genetic variation in children’s ABC-transporter genes to prenatal MeHg exposure and early child neurodevelopmental tests. MethodsWe genotyped six polymorphisms (rs2032582, rs10276499 and rs1202169 in ABCB1; rs11075290 and rs215088 in ABCC1; rs717620 in ABCC2) in DNA from cord blood and maternal blood of the Seychelles Child Development Study Nutrition Cohort 2. We determined prenatal MeHg exposure by measuring total mercury (Hg) in cord blood by atomic fluorescence spectrometry. We assessed neurodevelopment in children at approximately 20 months using the Bayley Scales of Infant Development (BSID-II). We used linear regression models to analyze covariate-adjusted associations of child genotype with cord MeHg and BSID-II outcomes (Mental Developmental and Psychomotor Developmental Indexes). We also evaluated interactions between genotypes, cord MeHg, and neurodevelopmental outcomes. All models were run with and without adjustment for maternal genotype. ResultsOf the six evaluated polymorphisms, only ABCC1 rs11075290 was associated with cord blood MeHg; children homozygous for the T-allele had on average 29.99 µg/L MeHg in cord blood while those homozygous for the C-allele had on average 38.06 µg/L MeHg in cord blood (p < 0.001). No polymorphisms in the children were associated with either subscale of the BSID. However, the association between cord MeHg and the Mental Developmental Index (MDI) of the BSID differed significantly across the three genotypes of ABCB1 rs10276499 (2df F-test, p = 0.045). With increasing cord MeHg, the MDI decreased (slope=−0.091, p = 0.014) among children homozygous for the rare C-allele. ConclusionsThese findings support the possibility that child ABC genetics might influence prenatal MeHg exposure.

Mercury, legacy and emerging POPs, and endocrine-behavioural linkages: Implications of Arctic change in a diving seabird

Arctic species encounter multiple stressors including climate change and environmental contaminants. Some contaminants may disrupt hormones that govern the behavioural responses of wildlife to climatic variation, and thus the capacity of species to respond to climate change. We investigated correlative interactions between legacy and emerging persistent organic pollutants (POPs), mercury (Hg), hormones and behaviours, in thick-billed murres (Uria lomvia) (N = 163) breeding in northern Hudson Bay (2016–2018). The blood profile of the murres was dominated by methylmercury (MeHg), followed by much lower levels of sum (∑) 35 polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB) and p,p'-dichlorodiphenyltrichloroethylene (DDE), polybrominated diphenyl ethers (PBDEs) BDE-47, -99 and BDE-100; all other measured organochlorine pesticides and replacement brominated flame retardants had low concentrations if detected. Inter-annual variations occurred in MeHg, circulating triiodothyronine (T3), thyroxine (T4), and the foraging behaviours of the murres, identified using GPS-accelerometers. Compared to the 50-year mean date (1971–2021) for 50% of sea-ice coverage in Hudson Bay, sea-ice breakup was 1–2 weeks earlier (2016, 2017) or comparable (2018). Indeed, 2017 was the earliest year on record. Consistent with relationships identified individually between MeHg and total T3, and T3 and foraging behaviour, a direct interaction between these three parameters was evident when all possible interactions among measured chemical pollutants, hormones, and behaviours of the murres were considered collectively (path analysis). When murres were likely already stressed due to early sea-ice breakup (2016, 2017), blood MeHg influenced circulating T3 that in turn reduced foraging time underwater. We conclude that when sea-ice breaks up early in the breeding season, Hg may interfere with the ability of murres to adjust their foraging behaviour via T3 in relation to variation in sea-ice.

Total Blood Mercury Predicts Methylmercury Exposure in Fish and Shellfish Consumers

Many studies evaluating methylmercury (MeHg) toxicity rely on whole blood total mercury (THg) measurements to estimate MeHg exposure. However, whole blood THg includes other forms of mercury (Hg), such as inorganic Hg, which have different exposure sources and toxicological effects than MeHg. Therefore, estimating the whole blood MeHg/THg ratio is critical to predicting MeHg exposure and, subsequently, efforts to establish an exposure–response relationship for use in risk assessment. A large, representative dataset (National Health and Nutrition Examination Survey (NHANES) 2011–2016) was used to determine the whole blood MeHg/THg ratio among (a) self-reported fish and shellfish consumers, ≥ 15 years of age (the “full adult” population (N = 5268 training dataset; N = 2336 test dataset)) and (b) female fish and shellfish consumers, 15–44 years of age (the “women of reproductive age” population (N = 1285 training dataset; N = 560 test dataset)). Unadjusted and adjusted linear and spline models with direct measurements for both THg and MeHg were evaluated. The mean whole blood MeHg/THg ratio was 0.75 (95% confidence interval (CI): 0.74, 0.75). This ratio was significantly higher among those with higher THg concentrations. All models exhibited excellent fit (adjusted R2 from 0.957 to 0.982). Performance was slightly improved in spline versus linear models. For the full adult population and women of reproductive age, the unadjusted spline model predicted whole blood MeHg concentrations of 5.65 µg/L and 5.55 µg/L, respectively, when the THg concentration was 5.80 µg/L. These results suggest that whole blood THg is a good predictor of whole blood MeHg among fish and shellfish consumers.

Serum cytokines are associated with n-3 polyunsaturated fatty acids and not with methylmercury measured in infant cord blood in the Seychelles child development study

BackgroundMaternal fish consumption increases infant methylmercury (MeHg) exposure and polyunsaturated fatty acid (PUFA) concentrations. The n-3 PUFA are regulators of inflammation while MeHg may impact the cord cytokine profile and, subsequently, contribute to immune mediated outcomes. This study aimed to investigate associations between infant MeHg exposure and cord cytokine concentrations while adjusting for cord PUFA. MethodsWe studied participants in the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2), a large birth cohort in a high fish-eating population. Whole blood MeHg, serum PUFA and serum cytokine concentrations (IFN-γ, IL-1β, IL-2, IL-12p70, TNF-α, IL-4, IL-10, IL-13, IL-6 and IL-8) were measured in cord blood collected at delivery (n = 878). Linear regression examined associations between infant MeHg exposure and cord cytokines concentrations, with and without adjustment for cord PUFA. An interaction model examined cord MeHg, cytokines and tertiles of the n-6:n-3 ratio (low/medium/high). ResultsThere was no overall association between cord MeHg (34.08 ± 19.98 μg/L) and cytokine concentrations, with or without adjustment for PUFA. Increased total n-3 PUFA (DHA, EPA and ALA) was significantly associated with lower IL-10 (β = −0.667; p = 0.007) and lower total Th2 (IL-4, IL-10 and IL-13) (β = −0.715; p = 0.036). In the interaction model, MeHg and IL-1β was positive and significantly different from zero in the lowest n-6:n-3 ratio tertile (β = 0.002, p = 0.03). ConclusionMethylmercury exposure from fish consumption does not appear to impact markers of inflammation in cord blood. The association of cord n-3 PUFA with lower IL-10 and total Th2 cytokines suggests that they may have a beneficial influence on the regulation of the inflammatory milieu. These findings are important for public health advice and deserve to be investigated in follow up studies.

Children with Amalgam Dental Restorations Have Significantly Elevated Blood and Urine Mercury Levels.

Human exposure to organic mercury (Hg) as methylmercury (MeHg) from seafood consumption is widely considered a health risk because pure methylmercury is extremely neurotoxic. In contrast, the clinical significance of Hg exposure from amalgam (AMG) dental restorations, the only other major nonoccupational source of Hg exposure, has long been debated. Here, we examined data from the two most recent National Health and Nutrition Examination Surveys (NHANES) on 14 181 subjects to assess the contributions of seafood consumption versus AMG to blood total mercury (THg), inorganic mercury (IHg), and methyl mercury (MeHg) and to urine creatinine corrected mercury (UTHg). All subjects were also classified as to their self-reported qualitative consumption of seafood (59% fish and 44% shellfish). Subjects with restorations were grouped into three groups (0) those without AMG (64.4%), (1) those with 1-5 dental AMG restorations (19.7%), (2) those with more than five AMG (16%). Seafood consumption increased total mercury in urine (UTHg) and total mercury (THg) and methyl mercury (MeHg) in blood, but unlike AMG, seafood did not increase blood inorganic mercury (IHg). Using stratified covariate (ANOVA) and multivariate (GLM) analyses revealed a strong correlation of blood (THg and IHg) and urine (UTHg) levels with the number of AMGs. In a subpopulation without fish consumption, having more than five AMG restorations raised blood THg (103%), IHg (221%), and urine UTHg (221%) over the group without AMG. The most striking difference was noted in classification by age: subjects under 6 years old with more than five AMG restorations had the highest blood IHg and urine UTHg among all age groups. Elevation of bivalent IHg on a large scale in children warrants urgent in-depth risk assessment with specific attention to genetic- and gender-associated vulnerabilities.

Methylmercury Detection in Maternal Blood Samples by Liquid Chromatography with Inductively Coupled Plasma Mass Spectrometry

Methylmercury (MeHg) is one type of mercury (Hg) species known to be very toxic to humans, especially pregnant women and their fetuses. This study aims to obtain and validate the optimum condition of liquid chromatography with inductively coupled plasma mass spectrometry (LC-ICP-MS) to test MeHg concentration. To date, there is limited research that is focused on the maternal blood MeHg samples using LC-ICP-MS in Malaysia. Before analysis, collected blood (500 µL) was placed into a 15 mL polypropylene test tube, followed by the addition of extractant solution [0.10% (v/v) HCl + 0.05% (m/v) L-cysteine + 0.10% (v/v) 2-mercaptoethanol] to the sample and sonicated for 15 minutes. The MeHg level was detected from the sample solution using the LC with Zorbax Eclipse XDB-C18 (4.6 x 12.5 mm, 5 µm) (Agilent Technologies) guard column and analytical column (4.6 x 150 mm, 5 µm) and was quantified by using the ICP-MS. The recovery of MeHg was in the range of 106 to 112% with RSD of less than 10%, followed by the LOD and LOQ values of 0.216 and 0.766 µg/L, respectively. The MeHg appeared at a retention time of fewer than 5 minutes. The results reported that the median (IQR) of maternal blood MeHg level in Malaysian pregnant women was 1.70 (8.90) µg/L, which is 9.7% lower than the LOD value and 11.2% higher than the guideline value of 3.5 µg/L of MeHg in maternal blood.

Mercury in blood, hair, and feces from subsistence fish-eating riverines of the Madeira River Basin (Western Amazon)

BackgroundThe Madeira River (Amazon Basin) has been impacted by activities related to artisanal and small-scale gold mining (ASGM), deforestation and burning (for timber, agriculture, and hydroelectric dam projects). All these activities contribute to environmental mercury (Hg) release and cycling into the Amazon ecosystem and thus to changing lifestyles. MethodWe assessed exposure to total and MeHg in two small riverine communities of the Madeira River (Amazon): Lago Puruzinho (LP, n = 26 families) and São Sebastião do Tapurú (SST, n = 31 families). Samples of human hair (n = 137), blood (n = 39), and feces (n = 41) were collected from adults and children (0–15 years of age). ResultsIn women of childbearing age from LP village, the mean blood total-Hg (THg) (45.54 ± 24.76 μg.L−1) and MeHg (10.79 ± 4.36 μg.L−1) concentrations were significantly (p = 0.0024; p < 0.0001, respectively) higher than in women from SST village (THg: 25.32 ± 16.75 μg.L−1; MeHg: 2.32 ± 1.56 μg.L−1) village; the trend in hair-Hg persisted but was statistically significant (p < 0.0145) only for THg (LP, 11.34 ± 5.03 μg. g−1; SST, 7.97 ± 3.51 μg. g−1). In women, the median hair:blood ratio of total Hg was 269. In children, the mean hair THg concentrations were 6.07 ± 3.60 μg. g−1 and 6.47 ± 4.16 μg. g−1 in LP and SST; thus, not significantly different (p = 0.8006). There was a significant association (p < 0.001) between hair-Hg concentrations of mothers and their respective children. The excretion of Hg in feces of women (0.52 μg. g−1 dw) was not significantly different from children (0.49 μg. g−1 dw). The only statistically significant correlation between Hg in feces and in hair was found in children, (n = 16, rs = 0.38, p = 0.005). Significant relationship was seen between the levels of THg in blood and hair of women from LP and SST. Based on hair-Hg concentrations, fish consumption rate ranged from 94.5 to 212.3 g.day−1. ConclusionWomen and children excrete THg in feces in comparable concentrations. However, the mean fish consumption rate and blood MeHg are higher in the most remote villagers. Mother`s hair-Hg concentration is a good predictor of children’s hair-Hg.

Variation in Methylmercury Metabolism and Elimination in Humans: Physiological Pharmacokinetic Modeling Highlights the Role of Gut Biotransformation, Skeletal Muscle, and Hair.

The biological half-life (t1/2) of methylmercury (MeHg) shows considerable individual variability (t1/2 < 30 to > 120 days), highlighting the importance of mechanisms controlling MeHg metabolism and elimination. Building on a prior physiologically based pharmacokinetic (PBPK) model, we elucidate parameters that have the greatest influence on variability of MeHg t1/2 in the human body. Employing a dataset of parameters for mean organ volumes and blood flow rates appropriate for man and woman (25-35 years) and child (4 - 6 years), we demonstrate model fitness by simulating data from our prior controlled study of MeHg elimination in people. Model predictions give MeHg t1/2 of 46.9, 38.9, and 31.5 days and steady-state blood MeHg of 2.6, 2.6, and 2.3 µg/l in man, woman, and child, respectively, subsequent to a weekly dose of 0.7 µg/kg body weight. The major routes of elimination are biotransformation to inorganic Hg in the gut lumen (73% in adults, 61% in child) and loss of MeHg via excretion within growing hair (13% in adults, 24% in child). Local and global sensitivity analyses of model parameters reveal that variation in biotransformation rate in the gut lumen, and rates of transport between gut lumen and gut tissue, have the greatest influence on MeHg t1/2. Volume and partition coefficients for skeletal muscle (SM) and gut tissue also show significant sensitivity affecting model output of MeHg t1/2. Our results emphasize the role of gut microbiota in MeHg biotransformation, transport kinetics at the level of the gut, and SM mass as moderators of MeHg kinetics in the human body.

Mercury Speciation in Whole Blood and Dried Blood Spots from Capillary and Venous Sources.

There is interest in measuring total mercury (THg) and methylmercury (MeHg) in dried blood spots (DBS) though more research is required to evaluate mercury (Hg) speciation in DBS and to validate the agreement between blood sources (venous vs capillary) and matrices (whole blood vs DBS). Therefore, the present study aimed to develop, evaluate, and validate a DBS-based method to assess MeHg and inorganic mercury (InHg) exposure in human population studies. First, we used volume-controlled (40 μL) paired DBS-whole blood samples to develop an analytical method that involved the extraction and quantification of MeHg and InHg with gas chromatography-cold vapor atomic fluorescence spectrometry (GC-CVAFS). Next, we carried out a validation study using paired DBS-whole blood samples from venous and capillary sources from 49 volunteers with Hg exposures similar to background populations (i.e., MeHg in venous whole blood ranged from 0.2 to 3 μg/L with a median value of 0.8). The limits of detection were higher for InHg (1.9 and 1.1 μg/L in DBS and whole blood, respectively) than MeHg (0.3 and 0.2 μg/L in DBS and whole blood, respectively). The MeHg concentrations among blood sources and matrices were highly correlated (r ranged from 0.85 to 0.95), with no constant bias (intercept ranged from -0.05 to 0.13 μg/L) and small proportional bias (slopes ranged from 0.92 to 1.08). Bland-Altman plots indicated little bias between MeHg measurements with 82-98% of the cases meeting the analytical acceptance criterion of 35% maximum allowed difference. Our results indicate that measures of MeHg in capillary DBS reflect concentrations in the gold standard (i.e., venous whole blood) and that DBS is a suitable tool for assessing MeHg exposure in human population studies, but that more work is required to assess InHg exposures.

Association of blood mercury levels with nonmelanoma skin cancer in the U.S.A. using National Health and Nutrition Examination Survey data (2003-2016).

Some studies have reported increased incidence or mortality of lung and brain cancers associated with occupations involving potential mercury exposure. Epidemiological evidence related to skin cancer is also limited. To investigate the association between blood mercury (Hg) levels and nonmelanoma skin cancer (NMSC). We used National Health and Nutrition Examination Survey data from 2003 to 2016. The exposures were blood total (tHg), inorganic (iHg) and methylmercury (MeHg). The outcome was a self-reported diagnosis of NMSC. We included participants aged ≥ 20 years who had information on blood mercury and sociodemographic factors. We conducted a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of NMSC associated with quartiles of blood Hg, after adjusting for the sociodemographic factors and survey year. The number of participants was 29 413; mean age was 49 years and 52% were female. Compared with those with a tHg ≤ 0·47 μg L-1 (Q1), those with a tHg > 1·74 μg L-1 (Q4) had nearly double the odds of NMSC (OR 1·79, 95% CI 1·19-2·71; Ptrend = 0·004). Similarly, those in the highest quartile of MeHg (> 1·44 μg L-1 ) had 1·7 times greater odds of NMSC (OR 1·74, 95% CI 1·13-2·70; Ptrend = 0·01) than those in the lowest quartile (≤ 0·21 μg L-1 ). iHg levels were nonsignificantly positively associated with NMSC (Ptrend = 0·08). We found that higher blood tHg and MeHg levels were associated with a higher prevalence of NMSC. Linked Comment:Taylor. Br J Dermatol 2020; 183:413-414.

Effects of Gintonin-Enriched Fraction on Methylmercury-Induced Neurotoxicity and Organ Methylmercury Elimination.

Gintonin is a newly discovered ingredient of ginseng and plays an exogenous ligand for G protein-coupled lysophosphatidic acid receptors. We previously showed that gintonin exhibits diverse effects from neurotransmitter release to improvement of Alzheimer’s disease-related cognitive dysfunctions. However, previous studies did not show whether gintonin has protective effects against environmental heavy metal. We investigated the effects of gintonin-enriched fraction (GEF) on methylmercury (MeHg)-induced neurotoxicity and learning and memory dysfunction and on organ MeHg elimination. Using hippocampal neural progenitor cells (hNPCs) and mice we examined the effects of GEF on MeHg-induced hippocampal NPC neurotoxicity, on formation of reactive oxygen species (ROS), and on in vivo learning and memory functions after acute MeHg exposure. Treatment of GEF to hNPCs attenuated MeHg-induced neurotoxicity with concentration- and time-dependent manner. GEF treatment inhibited MeHg- and ROS inducer-induced ROS formations. Long-term treatment of GEF also improved MeHg-induced learning and memory dysfunctions. Oral administration of GEF decreased the concentrations of MeHg in blood, brain, liver, and kidney. This is the first report that GEF attenuated MeHg-induced in vitro and in vivo neurotoxicities through LPA (lysophosphatidic acids) receptor-independent manner and increased organ MeHg elimination. GEF-mediated neuroprotection might achieve via inhibition of ROS formation and facilitation of MeHg elimination from body.

Comment on "Traditional Tibetan Medicine Induced High Methylmercury Exposure Level and Environmental Mercury Burden in Tibet, China".

Highly elevated concentrations of total mercury (THg) and methylmercury (MeHg) were found in the municipal sewage in Tibet. Material flow analysis supports the hypothesis that these elevated concentrations are related to regular ingestion of Hg-containing Traditional Tibetan Medicine (TTM). In Tibet in 2015, a total of 3600 kg of THg was released from human body into the terrestrial environment as a result of TTM ingestion, amounting to 45% of the total THg release into the terrestrial environment in Tibet, hence substantially enhancing the environmental Hg burden. Regular ingestion of TTM leads to chronic exposure of Tibetans to inorganic Hg (IHg) and MeHg, which is 34 to 3000-fold and 0–12-fold higher than from any other known dietary sources, respectively. Application of a human physiology model demonstrated that ingestion of TTM can induce high blood IHg and MeHg levels in the human body. Moreover, 180 days would be required for the MeHg to be cleared out of the human body and return to the initial co...

Association of blood mercury levels with non-melanoma skin cancer in the United States using NHANES data from 2003-2016

PDS 63: Chemicals and metals: health effects, Exhibition Hall (PDS), Ground floor, August 27, 2019, 10:30 AM - 12:00 PM Background/Aim: Some studies have reported that mercury is associated with an increased risk of lung and esophageal cancers. However, few epidemiological studies investigated mercury exposure in relation to skin cancer risk. Mercury inactivates glutathione peroxidase (GPX) and lower GPX activity is associated with increased risk of skin cancer. Therefore, we investigated the association between blood mercury levels and skin cancer. Methods: We used National Health and Nutrition Examination Survey (NHANES) data from 2003 through 2016. Our exposures of interest were blood total (tHg), inorganic (iHg), and methyl mercury (MeHg). The main outcome was a reported diagnosis of non-melanoma skin cancer. We included participants aged ≥18 having information on exposures, outcome, and covariates (age, sex, race, BMI, smoking history, and income). We conducted logistic regression analysis adjusting for above covariates and survey year. Results: Among 30,103 participants, the median age was 48, 52% were female, 46% Non-Hispanic White, and 21% Non-Hispanic Black. A total of 477 subjects reported diagnosis of non-melanoma skin cancer; 95% of whom were Non-Hispanic White. Median levels of tHg and MeHg were 0.9 µg/L and 0.6 µg/L, respectively. A 1 µg/L increase in blood tHg was associated with 6% increased odds of non-melanoma skin cancer (OR: 1.06; 95% CI: 1.02, 1.09). Compared to subjects with tHg ≤ 0.46 µg/L, subjects with tHg >1.72 µg/L had approximately double the odds of non-melanoma skin cancer (OR: 1.93, 95% CI: 1.31, 2.84). Similarly, subjects with MeHg > 1.43 µg/L had 1.8 times greater odds of non-melanoma skin cancer (OR: 1.82, 95% CI: 1.18, 2.79) compared to subjects with MeHg ≤ 0.21 µg/L. Conclusions: We found that higher blood tHg and MeHg levels were associated with higher prevalence of non-melanoma skin cancer. Our findings add to the limited evidence from epidemiologic studies supporting the role of mercury exposures in skin cancer.

Mercury speciation in meconium and associated factors

Meconium is formed early in gestation and it is normally not excreted until after birth. Thus it may provide a longer and cumulative record of exposure to mercury (Hg). The present study aims to speciate Hg in meconium samples (N = 488) from Slovenian and Croatian new-borns prenatally exposed to low levels of methyl-Hg (MeHg) from maternal seafood intake and to Hg0 from maternal dental amalgam fillings. We had complete data of total Hg (THg) and MeHg in meconium and THg in maternal hair (MH), while THg and MeHg in maternal blood (MB) were available only for Croatian mothers. Personal data namely maternal seafood intake, age, pre-pregnancy BMI, parity, smoking, estimated gestational age at birth, sex, and birth weight were available for the majority of participants, except the number of dental amalgams which was in most cases missing for Croatian mothers. The median THg concentration in meconium was 11.1 (range: 0.41–375.2) ng/g and inorganic Hg (Hg(II)) presented 98.8% (range: 82%–100%, CV: 2%) of THg. We observed significant correlation between meconium and MH Hg levels, with the highest correlation between hair THg and meconium MeHg. Correlation analysis including MB (available only for Croatian population) showed a significant positive correlation between THg in meconium and THg in MB (Rs = 0.642). Additionally, MeHg from MB was correlated with MeHg in meconium (Rs = 0.898), while the correlation between Hg(II) in MB and meconium was positive, but not significant. Maternal seafood intake was significantly correlated with meconium MeHg (Rs = 0.498) and Hg(II) (Rs = 0.201). Multiple linear regression (performed on the Slovenian population, N = 143) confirmed a positive association between meconium MeHg and seafood intake. Furthermore, meconium Hg(II) was positively associated with the number of maternal dental amalgam fillings, but linear regression models did not confirm correlation between seafood intake and meconium Hg(II) levels. We assume that Hg0 released from maternal dental amalgam fillings and MeHg from seafood intake were both transported through the placental barrier and portioned between different foetal compartments including meconium. Weak correlation between maternal seafood intake and Hg(II) levels in meconium suggests that there is certain evidence of MeHg demethylation. However, because this correlation was not confirmed by the multiple regression, MeHg demethylation during prenatal life cannot be neither confirmed nor excluded. Further investigations at higher level of exposure are needed to confirm this observations. We can conclude that meconium is a suitable biomarker for MeHg and Hg0 exposure during pregnancy. However, comparability of the results reported in meconium in different studies is hindered by a lack of standardized sampling protocols, storage, and analysis.

Mercury speciation in prenatal exposure in Slovenian and Croatian population – PHIME study

In recent years, several studies have addressed the issue of prenatal exposure to methylmercury (MeHg); however, few have actually analysed MeHg blood concentrations. Our study population included mothers and their new-borns from Slovenia (central region; N = 584) and Croatia (coastal region; N = 234). We have measurements of total Hg (THg) and MeHg in maternal hair, maternal peripheral blood, and cord blood. Cord blood Hg concentrations were low to moderate (median THg = 1.84 ng/g and MeHg = 1.69 ng/g). The proportion of THg as MeHg (%MeHg) in maternal and cord blood varied between 4% and 100% (coefficient of variation, CV = 32%) and between 8% and 100% (CV = 20%), respectively. Our data shows that variability of %MeHg was higher at lower blood THg levels. Concentrations of MeHg in maternal blood and cord blood were highly correlated (Rs = 0.943), in the case of inorganic Hg correlation was significant but weaker (Rs = 0.198). MeHg levels in maternal blood and cord blood were positively associated with seafood intake, maternal age, and negatively associated with pre-pregnancy BMI. Additionally, MeHg in maternal blood was positively associated with plasma selenium levels, and cord blood MeHg was negatively associated with parity. The results of multiple linear regression models showed that speciation analysis provides more defined estimation of prenatal exposure in association modelling. Associations between Hg exposure and cognitive performance of children (assessed using Bayley Scales of Infant and Toddler development) adjusted for maternal or child Apolipoprotein E genotypes showed higher model R2 and lower p-values when adjusted for MeHg compared to THg. This study demonstrates that Hg speciation improves the association between exposure and possible negative health effects.

Concentration of mercury species in hair, blood and urine of individuals occupationally exposed to gaseous elemental mercury in Asturias (Spain) and its comparison with individuals from a control group formed by close relatives

Between November 19th, 2012 and December 3rd, 2012, 50 workers were intoxicated with gaseous Hg in San Juan de Nieva (Asturias, Spain) during the maintenance of a heat exchanger of a zinc manufacturer. We have quantified the concentration of methylmercury (MeHg), ethylmercury (EtHg) and Hg(II) in blood, hair and urine samples of those individuals taken three years after the accident. Blood, hair and urine of their closest relatives were also analyzed to assess whether the mercury burden present in the intoxicated individuals was due to the occupational exposure or to environmental or lifestyle-related factors. The determination of the mercury species in the samples was carried out applying multiple spiking Isotope Dilution GC-ICP-MS. This procedure corrects for possible interconversion reactions between the Hg species during the sample preparation procedure. Linear correlations were observed for both groups when plotting MeHg in blood vs MeHg in hair, and MeHg in hair vs Hg (II) in urine. The concentrations of Hg species in the intoxicated individuals were not significantly different from those obtained in the control group except for MeHg in blood. Significantly higher levels of MeHg in blood were obtained in some of the intoxicated individuals who had not consumed fish or seafood since the accident. A different correlation between MeHg in hair and MeHg in blood was obtained for these individuals compared to the control group who showed a hair-to-blood ratio consistent with the reported value for people exposed to Hg via fish consumption. Our results suggest that ingested MeHg followed the same pathway of deposition in hair in exposed and non-exposed individuals. However, the exposed individuals with high MeHg levels in blood showed a significantly different extent of MeHg deposition in hair compared to the control group.

Total, methyl and inorganic mercury concentrations in blood and environmental exposure sources in newcomer women in Toronto, Canada

Measurements of total blood Hg (tHg), often used as a proxy for methyl Hg (MeHg) concentrations, are most commonly the focus of population-based studies. Data on Hg species in biomarkers can allow for a more nuanced characterization of environmental exposure sources and risk but their availability is limited, especially for newcomer populations. The purpose of the Metals in Newcomer Women (MNW) study was to address existing data gaps on metal concentrations and exposure sources in newcomer women (19–45 years) and to examine tHg, MeHg and inorganic Hg (iHg) in the blood of East and South Asian women recently arrived to Toronto. Study participants were recruited in 2015 (n = 211). Total Hg concentrations were determined using both ICP-Q-MS and isotope dilution (ID)-SPME-GC-ICP-MS. A sample subset (n = 76) was chosen for the analysis of blood MeHg and iHg concentrations (also using ID-SPME-GC-ICP-MS). Hierarchical regression models were used to assess associations between blood tHg concentrations and environmental exposure factors for MNW participants. For the sample subset, a log-linear model was used to examine associations between blood iHg and MeHg concentrations and fish consumption patterns. The geometric mean (GM) blood tHg concentration was 1.05 µg/L (95% CI: 0.88–1.25), which was elevated compared to Canadian-born women (GM: 0.57 µg/L; 95% CI: 0.49–0.66), in a specialized data analysis of the Canadian Health Measures Survey (CHMS). GM concentrations for iHg and MeHg were 0.21 µg/L (95% CI: 0.16–0.28) and 2.66 µg/L (95% CI: 2.00–3.55), respectively. Significant distal determinants associated with blood tHg concentrations were: level of educational attainment, having lived in a coastal/fishing community prior to arrival, and global region of origin. Use of iron supplements and consumption of higher mercury fish species were also associated with tHg concentrations in the fully adjusted model. The study results demonstrate that blood Hg concentrations in newcomer women are slightly elevated, with some individuals in exceedance of recommended concentrations for women of reproductive age. The consumption of fish species low in Hg is recommended for newcomer women, especially those who consume fish frequently.

Method Development and Validation of Dried Blood Spots as a Tool for Mercury Exposure Assessment

Dried blood spots (DBS) provide a minimally invasive collection method with potential to be used as a field-based research tool for exposure to environmental contaminants such as mercury (Hg). Even though previous studies provided novel techniques to measure Total Mercury (THg) and Methylmercury (MeHg) in residual DBS from newborn screening programs, a range of limitations remains including challenges with detection limit, lack of mercury speciation, and validation with paired DBS-Blood samples collected under laboratory conditions. This study follows our previous work on the matter and specifically evaluates the suitability of DBS to assess methylmercury (MeHg) and THg exposure in human and fish blood samples. It focuses on paired DBS-blood samples from venous and capillary sources of 49 human volunteers, and 10 fish (Artic Char) samples. Paired DBS-blood, reference material and venous blood from one volunteer, was used to develop the analytical method. We used a GC-CVAFS to analyze MeHg and a Dual-Stage Gold Preconcentration for THg. Method development results based on EPA1630 guidelines, wet spikes and the use of blood reference materials showed that the measurement of MeHg in whole blood and DBS was both accurate (95-107%) and precise (2-11%). Initial results showed a high correlation for DBS-blood (r2&amp;#61;0.83) for MeHg (average 0.96 &amp;#177; 0.73 µg/L) for human samples, as well as for DBS-blood fish samples MeHg (r2&amp;#61;0.94), (average 919.46 &amp;#177; 492.97µg/L). When coupled with other recent work in this area, there is growing confidence in the use of DBS samples to measure MeHg exposure.