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Objectives: This cross-sectional study aimed to explore the association between methyl mercury (MeHg) level and latent tuberculosis infection (LTBI) risk based on the data from National Health and Nutrition Examination Survey (NHANES 2011-2012)., Methods: A total of 5243 participants with 20 variables were enrolled. The importance of these variables on TB infection was first ranked by XGBoost and Random Forest methods. Then the association between MeHg level and infection risk was evaluated by restricted cubic spline, threshold effect, and generalized linear regression analyses. We also explored the factors correlated with the difference in MeHg level and finally conducted a mediation analysis to assess the mediating effect of MeHg in LTBI., Results: 521 participants were experiencing the LTBI, and 12 variables showed the differences between infection and non-infection groups (all P < 0.05). Of them, MeHg presented the highest importance on the LTBI. Restricted cubic spline (RCS) next revealed a significant non-linear correlation of MeHg with LTBI (all P < 0.05). Adjusted regression models further indicated their independent association (all P < 0.05), and infection risk increased with the increase of MeHg (P for trend < 0.05). We also found a significant turning point, and their association was significantly observed when MeHg > 5.75 µg/L (P < 0.05). In addition, asthma history was related to the difference in MeHg levels between LTBI and non-LTBI groups. Mediation analysis found that MeHg level partially mediated the association of asthma and LTBI risk (all P < 0.05)., Conclusions: Our study identified MeHg as an independent risk factor for LTBI risk. Their causal relationship needs more investigation to verify., (© 2024. The Author(s).)

Background: Humans 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., Aim: To 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 Methods: Nutrition 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., Results: The 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)., Conclusion: No 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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tanzy M. Love, Gene E. Watson, Sally W. Thurston, Alison J. Yeates, Maria S. Mulhern, Emeir M. McSorley, J.J. Strain, Conrad F. Shamlaye, G.J. Myers, Matthew D. Rand, and Edwin van Wijngaarden report financial support was provided by the National Institutes of Health. Helena Korres de Paulaa, Tanzy M. Love, Daniela Pineda, Gene E. Watson, Alison J. Yeates and, Karin Broberg report financial support was provided by The Swedish Research Council for Health, Working Life and Welfare (FORTE), the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS), and the Karolinska Institutet. Conrad Shamlaye reports in kind support from the Government of Seychelles., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Some authors have reported that low-level exposure to methylmercury (MeHg) adversely impacts measures of auditory function. These reports, however, are not consistent in their findings. Consequently, we examined auditory function in a population exposed to low-level methylmercury (MeHg) exposure from fish consumption and to mercury vapor (Hg 0 ) from dental amalgams. We analyzed their associations with the participants hearing acuity, absolute and interwave ABR latencies, and otoacoustic emissions (distortion product/DPOAE and click evoked/CEOAE)., Design: We administered an audiometry test battery to 246 participants from the Seychelles Child Development Study (SCDS) Nutrition Cohort 1 (NC1) at 9 years of age. The test battery included standard pure-tone audiometry, tympanometry, Auditory Brainstem Responses (ABR) and Distortion Product and Click Evoked Otoacoustic Emissions (DPOAE and CEOAE) testing. We measured prenatal MeHg exposure in maternal hair and postnatal MeHg in children's hair. We approximated prenatal Hg 0 exposure using maternal amalgam surface area and postnatal Hg 0 using children amalgam surface area. Complete exposure records and audiometric data were available on 210 participants and in them we analyzed the association of MeHg and Hg 0 exposures with auditory outcomes using covariate-adjusted linear regression models adjusted for sex and tympanometric pressure., Results: Hg exposures were similar for both sexes. Seven of the 210 evaluable participants examined had either a mild (5) or moderate (2) hearing loss. Four had a mild monaural hearing loss and 3 had either a mild (1) or moderate (2) bilateral hearing loss. No participant had greater than a moderate hearing loss in either ear. Hg exposures were higher in participants with either a mild or moderate hearing loss, but these differences were not statistically significant. Among the 210 with complete data, neither prenatal nor postnatal MeHg nor Hg 0 exposure was statistically significantly associated with any of the ABR endpoints (p > 0.05 for all 72 associations). Neither prenatal nor postnatal Hg 0 exposure was associated with any of the OAE endpoints (p > 0.05). MeHg exposure was statistically associated with 6 of the 56 DPOAE endpoints (p-values between 0.0001 and 0.023), but none of the 40 CEOAE endpoints. Two of the associations occurred with prenatal MeHg exposures and 1 of those would suggest a beneficial effect. Four of the other associations occurred with postnatal MeHg exposures with only 2 found in left ears of both males and females and the other 2 in the left and right ear of females at only one frequency., Conclusion: Overall, these data do not present a clear and consistent pattern to suggest that the auditory system is negatively affected by low-level methylmercury exposure due to dietary consumption of oceanic fish or mercury vapor exposure from dental amalgams., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The risk to human health from exposure to certain pollutants through the consumption of fruits, tubers, and fish were evaluated in a settlement located in a Colombian area highly impacted by gold mining activities. The concentrations of mercury (Hg) and arsenic (As) in edible food tissues and methylmercury (MeHg) in fish were determined for risk assessment. A questionnaire-based dietary survey was answered by 178 residents of three population groups: children (CHD), women of childbearing age (WCBA), and the rest of the population (RP). The estimated weekly intake (EWI) of MeHg presented values of 1.9 and 2.4 times higher than the provisional tolerable weekly intake (1.6 μg/kg BW/week) recommended by the FAO/WHO for CH and WCBA, respectively. The results of the HQ values of As and Hg for different food were above the safety level (HQ < 1) for most of the groups. For Hg, the highest HQ values correspond to fish, whereas for As in most of the food, but specially in fruits. The total target hazard quotients (HI) were higher than 1, in all the groups (except for CHD that consume tubers) indicating potential non-carcinogenic health risks. The values of carcinogenic risk (CR) for As through exposure to food ranged from 1.2·10 -4 to 7.7·10 -4 , well above than the safety level of US EPA risk (10 -4 -10 -6 ), suggesting the probability of carcinogenic risk for the entire population via ingestion. Therefore, safety control mechanisms and environmental education strategies should be applied to address food intake, associated with good agricultural practices to provide solutions to protect the health of the residents in areas affected by gold mining activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Background: There 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., Methods: We 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., Results: Of 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., Conclusions: These findings support the possibility that child ABC genetics might influence prenatal MeHg exposure., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Mercury (Hg) is a toxic heavy-metal element, which can be enriched in fauna and flora and transformed into methylmercury (MeHg). MeHg is a widely distributed environmental pollutant that may be harmful to fish-eating populations through enrichment of aquatic food chains. The central nervous system is a primary target of MeHg. Embryos and infants are more sensitive to MeHg, and exposure to MeHg during gestational feeding can significantly impair the homeostasis of offspring, leading to long-term neurodevelopmental defects. At present, MeHg-induced neurodevelopmental toxicity has become a hotspot in the field of neurotoxicology, but its mechanisms are not fully understood. Some evidence point to oxidative damage, excitotoxicity, calcium ion imbalance, mitochondrial dysfunction, epigenetic changes, and other molecular mechanisms that play important roles in MeHg-induced neurodevelopmental toxicity. In this review, advances in the study of neurodevelopmental toxicity of MeHg exposure during pregnancy and the molecular mechanisms of related pathways are summarized, in order to provide more scientific basis for the study of neurodevelopmental toxicity of MeHg.

Background/aim: The ingestion of contaminated seafood by MeHg is considered the main route of human exposure, turning the salivary gland one important target organ. The salivary glands play critical roles in maintaining oral health homeostasis, producing saliva that maintains the oral microbiota, initiation of the digestion of macromolecules, and being essential in maintaining the integrity of the adjacent soft tissues and teeth. Thus, this study aimed to investigate the effects of MeHg exposure on human salivary gland cells line., Methods: Cells were exposed to 1-6 μM of MeHg for 24 h, and analysis of toxicity was performed. Based on these results, the LC50 was calculated and two concentrations were chosen (0.25 and 2.5 μM MeHg) to evaluate intracellular mercury (Hg) accumulation (THg), metabolic viability and oxidative stress parameters (GSH:GSSG ratio, lipid peroxidation, protein oxidation and DNA damage)., Results: The results demonstrated accumulation of THg as we increased the MeHg concentrations in the exposure and, the higher the dose, the lower is the cell metabolic response. In addition, the 2.5 μM MeHg concentration also triggered oxidative stress in human salivary gland cells by depleting the antioxidant competence of GSH:GSSG ratio and increasing lipid peroxidation and proteins carbonyl levels, but no damages to DNA integrity., Conclusion: In conclusion, although these two elected doses did not show lethal effects, the highest dose triggered oxidative stress and new questionings about long-term exposure models are raised to investigate furthers cellular damages to human salivary gland cells caused by MeHg exposure to extrapolate in a translational perspective., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Methyl mercury (MeHg) is a neurotoxicant that with sufficient exposure can seriously impair the central nervous system and cause mental retardation, cerebral palsy, and neuromotor dysfunction. The level of exposure needed to adversely affect the nervous system is unknown. Human exposure to low levels of MeHg is common from consumption of fish. We examined the relationship between MeHg exposure and development of articulatory-phonologic speech skills in children whose mothers consumed a diet high in fish during pregnancy to determine whether any adverse associations could be detected. A total of 544 children from the Republic of Seychelles were given a speech assessment when they were 66 months of age. Exposure level was determined by measuring MeHg in maternal hair growing during pregnancy. No adverse associations between articulatory- phonologic speech skills and prenatal MeHg exposure were detected. The findings of this investigation are compatible with previous developmental assessments of Seychellois children that have indicated no adverse effects of prenatal MeHg exposure from fish consumption., (Copyright © 2021. Published by Elsevier B.V.)

This review examines the role of nutrients in child development and outlines the key nutrients identified as potentially important to neurodevelopment among high fish consumers in the Seychelles Child Development Nutrition Study (SCDNS). It describes the clinical assessment of these nutrients in the blood and breast milk samples collected from the cohort of 300 pregnant women who were recruited, at their first antenatal visit, on the SCDNS. These key nutrients include the long chain polyunsaturated fatty acids (LCPUFA), docosohexaenoic acid (DHA) and arachidonic acid (AA), both of which may affect neurodevelopment in the later stages of fetal growth. Only DHA, however, is strongly associated with fish consumption, the predominant source of the neurotoxicant methyl mercury (MeHg). Any benefits of increased selenium status on neurodevelopment are likely to accrue via detoxification of MeHg during fetal growth, while benefits of optimal iodine or thyroid status are likely to be directly related to neurodevelopment during late fetal growth. Unlike LCPUFA, Se, and I, the status of the B vitamins, folate, vitamin B12, vitamin B6, and riboflavin are unlikely to be closely related to fish consumption but the status of each of these B vitamins is likely to impinge on overall status of choline, which is expected to have direct effects on neurodevelopment both prenatally and postnatally and may also impact on MeHg toxicity. Choline status, together with the status of two other candidate nutrients, zinc and copper, which are also likely to have effects on neurodevelopment prenatally and postnatally, are expected to have some correlation with fish consumption., (Copyright © 2021. Published by Elsevier B.V.)

Epidemiological studies to determine the impact of low level toxic exposure on child development are important in guiding clinical and public health action. However, carrying out such studies and interpreting their findings presents a number of significant challenges to the investigators. First, they must find a cohort with suitable exposure, select a biomarker that will accurately determine the level of exposure and determine the endpoints that are most likely to detect subtle differences in neurodevelopment. Following that, the logistics of the study must be organised and collaboration established with the local population and health authorities. To accurately interpret the data, they must also accurately determine covariates that impact child development. After the data are collected, interpreting the findings presents a further challenge. Throughout this process, the study must adhere to fundamental epidemiological principles and clearly defined statistical approaches. This paper discusses those principles and uses the Seychelles Child Development Study to show how one epidemiological study addressed them., (Copyright © 2021. Published by Elsevier B.V.)

Methyl mercury (MeHg) is a potent neurotoxin. Methyl mercury exposure took place at Niigata in the late 1950s and early 1960s due to industrial pollution of the Agano River. We studied adults who were exposed in utero or as children during that epidemic to determine their long-term outcomes. We contacted individuals with known exposure. Those who consented completed a questionnaire and then were interviewed. Thirty-nine subjects agreed to participate. Twenty-six subjects had health problems during their childhood and difficulties with schoolwork. As adults, some had difficulty with employment, but most led fairly normal family and social lives. Five subjects were considered to be socially maladjusted and eight others had social adjustment problems. Although some exposed subjects had health problems, many have been able to lead fairly normal lives., (Copyright © 2021. Published by Elsevier B.V.)

The Seychelles Child Development Study is a longitudinal cohort study following a group of 779 children exposed prenatally to methyl mercury (MeHg) through a maternal diet high in fish. The cohort has been examined six times beginning in infancy with no consistent evidence of adverse effects. In fact, their performance resembles what would be expected from normal children of comparable ages growing up in western cultures. During a neurodevelopment assessment at 66 months, the children were tested for scholastic achievement using the Woodcock Johnson Tests of Achievement. Their reading scores were depressed relative to US norms while arithmetic scores were within normal limits. This disparity was not evident at 107 months; in fact, reading achievement scores far exceeded expected performance relative to US norms, with over 75% of the cohort obtaining scores at or above the 90th percentile. This study reports a secondary analysis of the scholastic achievement data to test the hypothesis that the results obtained in the primary analysis were probably due to the onset of the primary school curriculum between the first and second testing, and not to inherent cognitive deficits among the children at 66 months. The results suggest that a combination of reading instruction and characteristically consistent letter-sound relationships in Creole, the language spoken at home by the majority of Seychellois families, probably accounted for the high achievement scores at 107 months., (Copyright © 2021. Published by Elsevier B.V.)

Methyl mercury (MeHg) is an organic highly toxic compound that is transported efficiently via the human placenta. Our previous data suggest that MeHg is taken up into placental cells by amino acid transporters while mercury export from placental cells mainly involves ATP binding cassette (ABC) transporters. We hypothesized that the ABC transporter multidrug resistance-associated protein (MRP)1 (ABCC1) plays an essential role in mercury export from the human placenta. Transwell transport studies with MRP1-overexpressing Madin-Darby Canine Kidney (MDCK)II cells confirmed the function of MRP1 in polarized mercury efflux. Consistent with this, siRNA-mediated MRP1 gene knockdown in the human placental cell line HTR-8/SVneo resulted in intracellular mercury accumulation, which was associated with reduced cell viability, accompanied by increased cytotoxicity, apoptosis, and oxidative stress as determined via the glutathione (GSH) status. In addition, the many sources claiming different localization of MRP1 in the placenta required a re-evaluation of its localization in placental tissue sections by immunofluorescence microscopy using an MRP1-specific antibody that was validated in-house. Taken together, our results show that (1) MRP1 preferentially mediates apical-to-basolateral mercury transport in epithelial cells, (2) MRP1 regulates the GSH status of placental cells, (3) MRP1 function has a decisive influence on the viability of placental cells exposed to low MeHg concentrations, and (4) the in situ localization of MRP1 corresponds to mercury transport from maternal circulation to the placenta and fetus. We conclude that MRP1 protects placental cells from MeHg-induced oxidative stress by exporting the toxic metal and by maintaining the placental cells' GSH status in equilibrium.

Human exposure to methylmercury (MeHg) due to contaminated fish intake as part of a high-fat (HFD), high-carbohydrate diets is a reality today for many populations. HFD is associated with hypertension and hyperlipidemia, primary cardiovascular disease (CVD) risk factors. Some studies suggest that MeHg induces those risk factors. We evaluated the effect of MeHg exposure in mice fed with HFD or control diet for eight weeks. In the last experimental 15 days, the half group received a MeHg solution (20 mg/L) replacing water. Blood pressure (BP), heart rate, lipoprotein concentrations, and paraoxonase activity were evaluated. Liver cholesterol, triacylglycerol, and IBA-1+ cells, as well as transcriptional levels of genes related to lipid metabolism and inflammatory response, were also assessed. HFD and both MeHg groups presented increased BP and total cholesterol (TC). In the liver, HFD but not MeHg was related to an increase in TC. Also, MeHg intoxication reduced paraoxonase activity regardless of diet. MeHg intoxication and HFD increased steatosis and the number of IBA-1+ cells and modified some gene transcripts associated with lipid metabolism. In conclusion, we demonstrated that MeHg effects on CVD risk factors resemble those caused by HFD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The exposure of methylmercury (MeHg) has become a public health concern because of its neurotoxic effect. Various neurological symptoms were detected in Minamata disease patients, who got intoxicated by MeHg, including paresthesia, ataxia, gait disturbance, sensory disturbances, tremors, visual, and hearing impairments, indicating that MeHg could pass the blood-brain barrier (BBB) and cause impairment of neurons and other brain cells. Previous studies have reported some expected mechanisms of MeHg-induced neurotoxicity including the neuroinflammation pathway. It was characterized by the up-regulation of numerous pro-inflammatory cytokines expression. Therefore, the use of anti-inflammatories such as N-acetyl-l-cysteine (NAC) may act as a preventive compound to protect the brain from MeHg harmful effects. This mini-review will explain detailed information on MeHg-induced pro-inflammatory cytokines activation as well as possible preventive strategies using anti-inflammation NAC to protect brain cells, particularly in in vivo and in vitro studies.

Background: 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., Objectives: To investigate the association between blood mercury (Hg) levels and nonmelanoma skin cancer (NMSC)., Methods: 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., Results: 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; P trend = 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; P trend = 0·01) than those in the lowest quartile (≤ 0·21 μg L -1 ). iHg levels were nonsignificantly positively associated with NMSC (P trend = 0·08)., Conclusions: 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., (© 2020 British Association of Dermatologists.)

The population of Hawai'i has traditionally been high in average fish consumption when compared to the national average. However, information is lacking on patterns of fish consumption among subpopulations. Data on fish consumption in the last 30 days from 11,293 adults was collected with the use of the Hawai'i Health Survey (an annual telephone survey of households and household members) during the years 2007 and 2008 and weighted to represent the adult population of Hawai'i. The US Department of Agriculture's, Environmental Protection Agency, and the United States Food and Drug Administration, recommend 8-12 ounces of fish per week for associated health benefits. Present estimates of fish consumption were skewed to the right (mean 10.5 and median 7.9 ounces) with some adults eating large amounts of fish per day and frequently. It may be of concern, given high amounts of methylmercury in select fish, that 13.7% of adults were eating fish 20 or more times per month. In addition, the serving size increased with increasing number of times per week fish was eaten. The subpopulation variables examined included age, sex, marital status, education, ethnicity, poverty, and demographics representing the adults of Hawai'i. The prevalence of adults consuming 8 or more ounces was highest for other than Honolulu counties, men, ages 18-74, married, with at least one year of college, Filipino and Native Hawaiian ethnicities (White, Japanese, Chinese, and All Others were also examined), employed, and adults living with higher income levels (lower poverty). However, only an estimated 46.9% of adults in Hawai'i were eating the eight or more ounces of fish weekly. Prevalence was lowest for women, Chinese, age >74 years, and the City and County of Honolulu. Adults who rated their general health better (excellent/good compared to fair/poor) were more likely to consume 8 or more ounces of fish per week, significantly for men. Men who rated their physical health higher and their mental health higher (via Optum SF™ Health Surveys) were associated with higher prevalence of consuming 8 or more ounces of fish per week. Higher consumption of the beneficial omega-3 fatty acids associated with fish low in methylmercury needs to be encouraged for those not meeting the recommended ounces of fish per week, particularly women, Chinese, older age groups, and adults living below the poverty level., Competing Interests: None of the authors identify any conflict of interest., (©Copyright 2020 by University Health Partners of Hawai‘i (UHP Hawai‘i).)

Background: Health risks linked with dioxin in fish remain a complex policy issue. Fatty Baltic fish contain persistent pollutants, but they are otherwise healthy food. We studied the health benefits and risks associated with Baltic herring and salmon in four countries to identify critical uncertainties and to facilitate an evidence-based discussion., Methods: We performed an online survey investigating consumers' fish consumption and its motivation in Denmark, Estonia, Finland, and Sweden. Dioxin and methylmercury concentrations were estimated based on Finnish studies. Exposure-response functions for several health endpoints were evaluated and quantified based on the scientific literature. We also quantified the infertility risk of men based on a recent European risk assessment estimating childhood dioxin exposure and its effect on sperm concentration later in life., Results: Baltic herring and salmon contain omega-3 fatty acids and vitamin D, and the beneficial impact of these fishes on cardiovascular diseases, mortality, and the risk of depression and cancer clearly outweighs risks of dioxins and methylmercury in people older than 45 years of age and in young men. Young women may expose their children to pollutants during pregnancy and breast feeding. This study suggests that even in this critical subgroup, the risks are small and the health benefits are greater than or at least similar to the health risks. Value of information analysis demonstrated that the remaining scientific uncertainties are not large. In contrast, there are several critical uncertainties that are inherently value judgements, such as whether exceeding the tolerable weekly intake is an adverse outcome as such; and whether or not subgroup-specific restrictions are problematic., Conclusions: The potential health risks attributable to dioxins in Baltic fish have more than halved in the past 10 years. The new risk assessment issued by the European Food Safety Authority clearly increases the fraction of the population exceeding the tolerable dioxin intake, but nonetheless, quantitative estimates of net health impacts change only marginally. Increased use of small herring (which have less pollutants) is a no-regret option. A more relevant value-based policy discussion rather than research is needed to clarify official recommendations related to dioxins in fish.

The objective of this study was to identify geographic, dietary, and other predictors for childhood exposure to perfluoroalkyl substances (PFASs), polychlorinated biphenyls (PCBs), and methylmercury in Greenlandic children. The study includes cross-sectional data from 367 Greenlandic children aged 7 to 12 years examined during 2012-2015. A parent or guardian participated in a structured interview, and a blood sample from the child was analysed for PFASs, PCBs and total mercury. Predictors for the environmental exposures were identified using linear regression. Area of residence was found to have the strongest explanatory power, accounting for 24% to 68% of the variance in the serum concentrations. Information about diet was available for two-thirds of the children, and among these, consumption of traditional Greenlandic food accounted for 2% to 10% of the variance in the biomarker concentrations. Models including all predictors associated with at least one of the environmental chemicals explained 19% to 54% of the total variance. In conclusion, area is a likely proxy for a traditional marine diet, and together area and diet constitute the most important predictors of exposure to methylmercury, PCBs and PFASs among Greenlandic children.

Methylmercury (MeHg) is an extremely important environmental toxicant posing serious health risks to human health and a big source of environmental pollutant. Numerous evidence available showing a link between nervous system toxicity and MeHg exposure. Other forms of mercury are reason of metabolic toxic effects and alteration of DNA in the human body. The sources of exposure could be occupational or other environmental settings. In the present study MeHg was orally gavaged to mice, at doses of 2.5, 5, and 10 mg/kg for 4 weeks. Fasting hyperglycemia, activity of hepatic phoshphoenolpyruvate carboxykinase and glucose 6-phoshphate were reported high as compared to control group. Inflammatory markers like, tumor necrosis factor α, the actual end product of inflammatory mediators' cascade pathway was also raised in comparison to control group. Hyperinsulinemia observed in serum showed clear understanding of mercury induced insulin resistance. Moreover, tissue damage due to increased oxidative stress markers like, hepatic lipid peroxidation, 8-deoxygunosine, reactive oxygen species, and carbonyl groups was significantly higher as compared to control group. MeHg caused a significant reduction in antioxidant markers like ferric reducing antioxidant power and total thiol molecules. The present study highlighted that activity of key enzymes involved in glucose metabolism is changed, owing to MeHg induced toxicity in the liver. Induction of similar toxic effects assumed to be stimulated by the production of high quantity free radicals., (© 2019 Wiley Periodicals, Inc.)

Objective: Long-chain omega-3 polyunsaturated fatty acids (PUFA) from fish have been inversely associated with coronary heart disease (CHD) risk. Fish may also contain methylmercury, which has been associated with higher CHD risk and may diminish the cardioprotective effect of long-chain omega-3 PUFA. We investigated the associations of serum long-chain omega-3 PUFA and hair mercury with the odds for myocardial ischaemia during exercise., Methods: A total of 2199 men from the Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 years were studied in 1984-89. Of the 2199 men, 342 had history of CHD. The men performed a maximal symptom-limited exercise stress test using an electrically braked bicycle ergometer. ORs for exercise-induced myocardial ischaemia were estimated with logistic regression., Results: In the multivariable analysis, those in the highest versus lowest serum long-chain omega-3 PUFA quartile had 33% lower odds of myocardial ischaemia (OR 0.67, 95% CI 0.51 to 0.87, p-trend=0.006). The association was stronger among those with CHD history (OR 0.10, 95% CI 0.03 to 0.39, p-trend <0.001), than among those without (OR 0.80, 95% CI 0.57 to 1.12, p-trend=0.17) (p-interaction=0.01). Higher hair mercury concentration was associated with increased odds for myocardial ischaemia in the entire population (OR 1.62, 95% CI 1.22 to 2.14, p-trend=0.002)., Conclusion: Higher circulating concentrations of the long-chain omega-3 PUFAs, a marker for fish consumption, were associated with lower occurrence of exercise-induced myocardial ischaemia, but only among men with CHD history. Hair mercury concentration was directly associated with the occurrence of exercise-induced myocardial ischaemia in the entire study population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The methylation of mercuric mercury (Hg 2+ ) in the aquatic sediments produces methylmercury (CH 3 Hg + ), which is biomagnified along the food chain. The ingestion of piscivorous fish or aquatic mammals by pregnant women is of concern because it can cause long-lasting neurobehavioral deficits in their offspring.

Mercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular mechanism of MeHg-induced neurotoxicity are pivotal to the understanding of its toxic effects and the development of preventive measures. Post-translational modifications (PTMs) of proteins, such as phosphorylation, ubiquitination, and acetylation are essential for the proper function of proteins and play important roles in the regulation of cellular homeostasis. The rapid and transient nature of many PTMs allows efficient signal transduction in response to stress. This review summarizes the current knowledge of PTMs in MeHg-induced neurotoxicity, including the most commonly PTMs, as well as PTMs induced by oxidative stress and PTMs of antioxidant proteins. Though PTMs represent an important molecular mechanism for maintaining cellular homeostasis and are involved in the neurotoxic effects of MeHg, we are far from understanding the complete picture on their role, and further research is warranted to increase our knowledge of PTMs in MeHg-induced neurotoxicity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Epidemiologic evidence of an adverse association between exposure to methylmercury (MeHg) from consuming fish and heart rate variability (HRV) is inconclusive. We aimed to evaluate MeHg exposure in relation to HRV parameters in a large cohort of young adults from a high fish consuming population in the Republic of Seychelles. Main Cohort participants in the Seychelles Child Development Study were evaluated at a mean age of 19 years. Prenatal MeHg exposure was determined in maternal hair growing during pregnancy and recent exposure in participant's hair taken at the evaluation. The evaluation consisted of short (~2 h) and long (overnight) Holter recordings obtained in 514 and 203 participants, respectively. Multivariable analyses examined the association of prenatal and recent MeHg exposure (in separate models) with time-domain and frequency-domain HRV parameters in different physiologic circumstances: supine position, standing position, mental stress when undergoing a mathematics test, sleep, and long recording. Prenatal MeHg exposure was not associated with any of the 23 HRV parameters studied after adjustment for multiplicity. The recent MeHg showed a trend toward significance only for few variables in the primary model. However, after additional adjustment for activity levels, polyunsaturated fatty acids, and multiplicity none were significant after a Bonferroni adjustment. In conclusion, prenatal and recent MeHg exposure had no consistent pattern of associations to support the hypothesis that they are adversely associated with heart rate variability in this study population that consumes large amounts of fish., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Methylmercury is an organic form of mercury that is well recognized for its bioaccumulation in aquatic species. Consumption of fish contaminated with methylmercury poses a toxicological health risk to both humans and animals. Salmon is an increasingly common ingredient in commercial pet foods because of manufacturers' interest in unconventional protein sources and inclusion of omega-3 polyunsaturated fatty acids. Previous studies have measured total mercury, but not methylmercury, in commercial pet foods. The purpose of this study was to evaluate total mercury and methylmercury concentrations in commercially available salmon-containing and nonsalmon-containing canine diets and to estimate risk of chronic exposure in dogs fed these diets long term. Total mercury was detected in 3 of 24 diets evaluated (12.5%), 2 of which did not contain any ingredients from fish. The single salmon-containing diet that contained total mercury was the lowest of the 3 but was also the only sample positive for methylmercury. None of the 3 mercury-containing diets contained fish oil. Concentrations of total mercury were similar to most data previously reported for pet foods. Using expected calorie intake for dogs of 2 body weights, the mercury concentrations determined in this study were applied to theoretical chronic exposure calculations to assess risk of toxicosis to dogs. Total mercury and methylmercury were uncommonly identified in the commercially available canine diets sampled in this study and were found in concentrations unlikely to pose risk to healthy adult dogs. Common sources of mercury in pet foods remain unknown and are not reliably of seafood origin., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Methylmercury is an environmental pollutant that causes specific and serious damage to the central nervous system. We have previously shown that C-C motif chemokine ligand 4 (CCL4) protects cultured neural cells from methylmercury toxicity and expression of CCL4 is specifically induced in mouse brain by methylmercury. In this study, we examined the transcriptional regulatory mechanism that induces CCL4 expression by methylmercury using C17.2 mouse neural stem cells. The promoter region of the CCL4 gene was analyzed by a reporter assay, revealing that the region up to 50 bp upstream from the transcription start site was necessary for inducing expression of CCL4 by methylmercury. Nine transcription factors that might bind to this upstream region and be involved in the induction of CCL4 expression by methylmercury were selected, and the induction of CCL4 expression by methylmercury was suppressed by the knockdown of serum response factor (SRF). In addition, the nuclear level of SRF was elevated by methylmercury, and an increase in the amount bound to the CCL4 gene promoter was also observed. Furthermore, we examined the upstream signaling pathway involved in the induction of CCL4 expression by SRF, and confirmed that activation of p38 and ERK, which are part of the MAPK pathway, are involved. These results suggest that methylmercury induces the expression of CCL4 by activating SRF via the p38 and ERK signaling pathway. Our findings are important for elucidating the mechanism involved in the brain-specific induction of CCL4 expression by methylmercury.

Methylmercury (MeHg) is an environmental neurotoxicant that induces neuropathological changes. In this study, we established chronic MeHg-intoxicated rats. These rats survived, and sustained MeHg-induced axonal degeneration, including the dorsal root nerve and the dorsal column of the spinal cord; these changes persisted 12 weeks after MeHg withdrawal. We demonstrated for the first time the restorative effect of Fasudil, a specific inhibitor of Rho-associated coiled coil-forming protein kinase, on axonal degeneration and corresponding neural dysfunction in the established chronic MeHg-intoxicated rats. To investigate the mechanism of this restorative effect, we focused on the expression of Rho protein families. This was supported by our previous study, which demonstrated that cotreatment with Fasudil prevented axonal degeneration by mitigating neurite extension/retraction incoordination caused by MeHg-induced suppression of Rac1 in vitro and in subacute MeHg-intoxicated rats. However, the mechanism of the restorative effect of Fasudil on axonal degeneration in chronic MeHg-intoxicated rats differed from MeHg-mediated neuritic extension/retraction incoordination. We found that the restorative effect of Fasudil was caused by the Fasudil-induced change of microglial phenotype, from proinflammatory to anti-inflammatory; moreover, Fasudil suppressed Rho-associated coiled coil-forming protein kinase activity. Treatment with Fasudil decreased the expression of proinflammatory factors, including tumor necrosis factor-α, inducible nitric oxide synthase, interleukin-1β, and interleukin-6; furthermore, it inactivated the nuclear factor kappa-light-chain-enhancer of activated B cells pathway. Additionally, Fasudil treatment was associated with increased levels of anti-inflammatory factors arginase-1 and interleukin-10. These results suggest that Rho-associated coiled coil-forming protein kinase inhibition may recover MeHg-mediated axonal degeneration and neural dysfunction in chronic MeHg intoxication., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The mercury-related central nervous system disorders have been extensively studied on animal models and human beings. However, clinical evidences of which neurological changes are in fact associated with mercury exposure remains controversial. This systematic review (Prospero registration under the number CRD42016041760) aimed to elucidate the association of methylmercury (MeHg) exposure with neurological alteration in populations living in MeHg-endemic risk area. A systematic search was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis criteria using available databases PubMed, LILACS, Scopus, Web of Science, The Cochrane Library, OpenGrey and Google Scholar. A search of the following terms: "methylmercury compounds", "organomercury compounds", "neurologic manifestations", "memory disorders", "neurobehavioral manifestations" and "communication disorders" were performed in a systematic way. Studies focusing on MeHg exposure and subsequent neurological alteration on humans (>13 years) were included. Evaluation of methodological quality and risk of bias as well as the level of evidence was performed. Our results have identified 470 studies and six articles were eligible for systematic review inclusion criteria. The studies suggested alterations related to the psychosensory, motor and coordination system, as well as motor speech, hearing, visual impairment, mood alterations and loss of intelligent quotient. Of all the six studies, two presented a high risk of bias, with methodological problems related to the confounding factors and all studies presented evidence level ranged from very low to low. In this way our results revealed that a definitive demonstration of an association of MeHg and neurological alterations in human beings is still a pending subject. Future studies in this topic should take into consideration more confident and reliable methods to answer this question., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: Awareness of Listeriosis and Methylmercury toxicity recommendations are associated with decreased intake of high-risk foods. Whether awareness of the recommendations affect dietary quality of pregnant women in Australian is unknown., Aim: To evaluate awareness of Listeriosis and Methylmercury toxicity recommendations during pregnancy and its impact on dietary quality., Methods: Pregnant women (n=81) were recruited from antenatal clinics. Awareness of Listeriosis and Methylmercury toxicity recommendations and high-risk foods consumption were assessed via questionnaire at 10-23 weeks gestation. Diet quality was measured using the 2005 Healthy Eating Index using a validated food frequency questionnaire at 10-23 and 34-36 weeks gestation., Findings: A higher proportion of women were aware of Methylmercury toxicity compared with Listeriosis recommendations (75.3 vs. 59.2%, p<0.001). The proportion of women who decreased or avoided consumption of certain high-risk Listeriosis foods were higher in those who were aware compared with those who were unaware of Listeriosis recommendations [raw fish (96.0 vs 69.2%, p=0.046), soft-serve ice cream (93.9 vs 58.3%, p=0.004) and alfalfa/bean sprouts (68.7 vs 28.5%, p=0.006)]. A large proportion of women (96.8%) met recommendations for limiting consumption of high Methylmercury fish. There was no difference in the change in dietary quality over pregnancy regardless of women's awareness of the recommendations., Discussion and Conclusions: Awareness of Listeriosis and Methylmercury toxicity recommendations has little impact on dietary quality of pregnant women in this small study. Further research in a large representative population of pregnant women is needed to confirm our findings and to optimise dietary quality during pregnancy., (Copyright © 2018 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Methylmercury (MeHg) is a contaminant present in fish which exerts a severe impact on health predominantly exhibiting neurotoxicity that might irreversibly affect fetal neurodevelopment. Fish consumption in Portugal is the third highest in the world, particularly high in regions with fishing tradition such as the Madeira Archipelago. Therefore, this study aimed at assessing the risk of exposure to MeHg in a population of pregnant women residing in Madeira. Blood samples from pregnant women (533) and umbilical cord (194) were collected from volunteer participants collected at primary health services in Madeira (Portugal) and analyzed for total mercury (HgT) level. A food-frequency questionnaire was used to estimate exposure and indices of risk while HgT in blood were correlated with estimated exposure. Analysis of HgT levels in blood indicated that 30% of pregnant women surpassed the maximum safe level of 10 µg/L recommended by the WHO, which was derived from the consumption of predatory fish, rich in MeHg. In addition, HgT levels in cord blood were 1.3 fold higher than in maternal blood, indicating the high risk of exposure to MeHg in this population. It is thus important to provide nutritional advice concerning fish consumption as a food choice in order to reduce fetal exposure and potential neurologic damage.

The notion that adverse health effects produced by exposure to environmental contaminants (EC) may be modulated by the presence of non-chemical stressors is gaining attention. Previously, our lab demonstrated that cross-fostering (adoption of a litter at birth) acted as a non-chemical stressor that amplified the influence of developmental exposure to EC on the glucocorticoid stress-response in adult rats. Using liver from the same rats, the aim of the current study was to investigate whether cross-fostering might also modulate EC-induced alterations in hepatic gene expression profiles. During pregnancy and nursing, Sprague-Dawley dams were fed cookies laced with corn oil (control, C) or a chemical mixture (M) composed of polychlorinated biphenyls (PCB), organochlorine pesticides (OCP), and methylmercury (MeHg), at 1 mg/kg/day. This mixture simulated the contaminant profile reported in maternal human blood. At birth, some control and M treated litters were cross-fostered to form two additional groups with different biological/nursing mothers (CC and MM). The hepatic transcriptome was analyzed by DNA microarray in male offspring at postnatal days 21 and 78-86. Mixture exposure altered the expression of detoxification and energy metabolism genes in both age groups, but with different sets of genes affected at day 21 and 78-86. Cross-fostering modulated the effects of M on gene expression pattern (MM vs M), as well as expression of energy metabolism genes between control groups (CC vs C). In conclusion, while describing short and long-term effects of developmental exposure to EC on hepatic transcriptomes, these cross-fostering results further support the consideration of non-chemical stressors in EC risk assessments.

We determined concentrations of eicosapentaenoic and docosahexaenoic acids (EPA + DHA), Σomega-3, polyunsaturated fatty acids (ΣPUFA), selenium, methylmercury, and selenium:methylmercury (Se:Hg) ratios in native and northward-redistributing sub-Arctic marine fish and invertebrates from low, mid-, and high Canadian Arctic latitudes. There was no clear latitudinal trend in nutrient or contaminant concentrations. Among species, EPA + DHA concentrations in native Arctic cod (Boreogadus saida) were similar to concentrations in sub-Arctic capelin (Mallotus villosus) and sand lance (Ammodytes spp.) (444-658 mg.100 g -1 ), and higher than in most other species. Concentrations of EPA + DHA were related to lipid content, but to a greater extent for higher trophic position species (R 2  = 0.83) than for species at lower trophic positions (R 2  = 0.61). Selenium concentrations were higher in sand lance (1.15 ± 0.16 μg g -1 ) than in all other species (0.30-0.69 μg g -1 ), which was significantly, but weakly, explained by more pelagic feeding in sand lance. Methylmercury concentrations were similar (and Se:Hg ratios were higher) in capelin, sand lance, and Arctic cod (0.01-0.03 μg g -1 wet weight (ww)) and lower than in other prey (0.12-0.26 μg g -1 ww), which was significantly explained by the smaller size of these species and more pelagic feeding habits than other fish. These results suggested that a shift in prey fish composition from Arctic cod to capelin and/or sand lance is unlikely to reduce the food quality of the prey available to marine predators at least with respect to concentrations of essential fatty acids, selenium, and Se:Hg ratios., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Although high or repeated exposure to different forms of Hg can have serious health consequences, the most important toxicity risk for humans is as methylmercury (MeHg) which exposure is mainly through consumption of fish. Generally, more than the 80% of Hg in hair is as MeHg, which is taken up by hair follicles as MeHg-cysteine complexes. In this context, hair samples were collected from 200 children (7 years) living in a coastal site in the North-East (A) of Italy and from 299 children (6-11 years) living in a urban area of South of Italy (B) to determine the levels of MeHg. Considering the neurotoxicity of MeHg, children were subjected to cognitive and neuropsychological tests. The hair values of Hg in the children population groups were comparable with data reported in other international surveys. On the other hand, combining results of the neurological tests with Hg levels, a possible relationship between Hg and an increase of the errors average reported in some neurological tests has been noted. Although the Hg levels were not elevated, a possible neurological influence in children, a population more susceptible than adults, might not be excluded, but the influence on neurological performances of the children could be also due to the family environment (socio economic status, educational level, etc.)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Problem: Maternal methylmercury (MeHg) exposure may be associated with immune response during pregnancy., Method of Study: In the high fish-eating Seychelles Child Development Study Nutrition Cohort 2, we examined the association between maternal MeHg, polyunsaturated fatty acids (PUFA), and immune markers (Th1:Th2; TNF-α, IL-1β, IFN-γ, IL-2, IL-4, IL-5, IL-10, MCP-1, TARC, sFlt-1, VEGF-D, CRP and IL-6) at 28 weeks' gestation. Linear regression examined associations between MeHg exposure and immune markers with and without adjustment for PUFA., Results: In all models, as MeHg concentrations increased, the Th1:Th2 ratio, total Th1 and individual Th1 (IL-1β, IL-2, TNF-α) concentrations decreased. MeHg was not associated with total Th2 cytokines but was associated with a decrease in IL-4 and IL-10. MeHg was positively associated with TARC and VEGF-D and negatively associated with CRP. There was a significant interaction between MeHg and the n-6:n-3 ratio, with MeHg associated with a larger decrease in Th1:Th2 at higher n-6:n-3 PUFA ratios. The n-3 PUFA were associated with lower CRP, IL-4 and higher IFN-γ. The n-6 PUFA were associated with higher IL-1β, IL-2, TNF-α, IL-4, IL-10, CRP and IL-6., Conclusion: Maternal MeHg was associated with markers of immune function at 28 weeks' gestation. A significant interaction between MeHg and the n-6:n-3 ratio on the Th1:Th2 ratio suggests that the n-3 PUFA may mitigate any immunosuppressive associations of MeHg. The n-3 and n-6 PUFA were associated with suppressive and stimulatory immune responses, respectively. Overall, the associations were of small magnitude, and further research is required to determine the clinical significance., (© 2018 The Authors. American Journal of Reproductive Immunology Published by John Wiley & Sons Ltd.)

In a previous study, we pointed out that the neurotoxic action evoked by methylmercury (MeHg), a potent environmental pollutant responsible for fatal food poisoning, is associated with alterations of cellular excitability by irreversible blockade of sodium and calcium currents. Here, we investigated the MeHg effects on synaptic transmission and neuronal plasticity using extracellular field recording in CA1 area of rat hippocampal slices. MeHg caused a fast and drastic depression of evoked field excitatory postsynaptic potentials (fEPSPs) in a concentration-dependent manner with an IC 50 of 25.7 μM. This depression was partially caused by the irreversible reduction of axon recruitment deduced from the decrement of the fiber volley (FV) amplitude. Nevertheless, this MeHg-induced synaptic depression represents a true reduction of synaptic efficacy, as judged by input/output curves. In addition, a reduction on presynaptic release of glutamate was detected with the paradigm of paired-pulse facilitation during MeHg application. Moreover, MeHg also reduced population spike (PS) ampxlitude, and this effect was more prominent when the PS was evoked by ortodromic stimulation than by antidromic stimulation. Interestingly, despite these strong effects of MeHg on synaptic transmission and excitability, this compound did not modify the induction of long-term synaptic potentiation (LTP). The effects described here for MeHg were irreversible or very slowly reversible after drug wash-out. In summary, the blockade of sodium and calcium channels by MeHg affects synaptic transmission and cellular excitability but not synaptic plasticity.

The objective of this study was to quantify total mercury in highly popular Amazonian fish pacu, curimatã, jaraqui, and sardinha from the Madeira River and to estimate the exposure to methylmercury from fish consumption. The samples were obtained from two locations - Puruzinho Igarapé and Santa Rosa - near Humaitá, Amazonia, Brazil in two seasons of 2015 (high and low waters). The fish were identified, weighed and measured, and lipids were quantified. Total mercury was determined by gold amalgamation-atomic absorption spectrometry. Mean levels were used to calculate exposure of Amazonian and riverine populations. There was significant correlation (p < 0.05) between length × weight for all fish; length × lipid and weight × lipid were significant only for pacu. Total mercury levels varied along muscle tissue for the fish, except for sardinha; therefore muscle from the dorsal area along the fish were sampled, homogenized and used for analysis. The levels of total mercury varied from 0.01 to 0.46 mg/kg, with higher median levels in sardinha (0.24 mg/kg), followed by curimatã (0.16 mg/kg), jaraqui (0.13 mg/kg) and pacu (0.04 mg/kg), corresponding with the respective feeding habits along the trophic chain. Total mercury levels were not affected by the location of fish capture and by high and low waters seasons. Total mercury correlated significantly with length and weight for jaraqui and with length for sardinha (negative correlation). Total mercury levels in fish complied with legislation; however, exposures to methylmercury from fish consumption overpassed the safe intake reference dose for sardinha for Amazonians; however, for the riverine communities, all of the fish would cause potential health risk, mainly for children and women of childbearing age., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Land exploitation that follows deforestation and mining can result in soil erosion and the release of mercury to the waters of rivers in the Amazon Basin. Inorganic mercury is methylated by bacteria that are present in the environment and it serves as a source of human contamination through fish consumption in the form of methylmercury. Long-term exposure to low-level methylmercury in the riverside populations can lead to nervous system alterations, some of which are visual impairments such as loss of luminance contrast sensitivity, restricted visual fields and color vision defects. The present study sought to examine color vision in a group of adults living in the central Brazilian Amazon who were exposed to low-levels of methylmercury. Total Hg concentrations were measured from hair collected at the time of the testing. The D15d and FM100 color vision arrangement tests were applied in a population of 36 (22 males) and 42 (25 males), respectively. Controls were healthy volunteers from the cities of São Paulo for the D15d and Belém for the FM100. There was a statistically significant difference in performance between those who were exposed and controls for both tests (p < 0.01 and p < 0.0001, respectively, Mann-Whitney U test), meaning that adults living in this region of the Amazon made more mistakes on both tests when compared to controls. A linear regression was performed using Hg concentrations and test scores. Hg concentrations accounted for 7% and 2% of color D15d and FM100 arrangement test errors, respectively. Although other studies have previously found color vision impairment in the Amazon, they tested inhabitants on the east side of the Amazon, while this study was conducted in the central Amazon region and it is the first study in a population with no direct contact with the Hg source of contamination. These results suggest that long-term exposure to low-level methylmercury in riverside populations is more widely spread in the Amazon Basin than previously reported. This information is needed to implement public health policies that will ensure a safer environment for the Amazonian population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Methylmercury causes behavioural and reproductive effects in adult mammals via early developmental exposure. Similar studies in birds are limited and mostly focussed on aquatic systems, but recent work has reported high blood mercury concentrations in terrestrial, passerine songbirds. We used the zebra finch (Taeniopygia guttata) as a model to explore the long-term effects of early developmental exposure to methylmercury exposure. Chicks were dosed orally with either the vehicle control, 0.0315 µg Hg/g bw/day, or 0.075 µg Hg/g bw/day throughout the nestling period (days 1-21 post-hatching). We then measured (a) short-term effects on growth, development, and behaviour (time to self-feeding, neophobia) until 30 days of age (independence), and (b) long-term effects on courtship behaviour and song (males) and reproduction (females) once methylmercury-exposed birds reached sexual maturity (90 days post-hatching). High methylmercury treated birds had mean blood mercury of 0.734 ± 0.163 µg/g at 30 days post-hatching, within the range of values reported for field-sampled songbirds at mercury contaminated sites. However, there were no short-term effects of treatment on growth, development, and behaviour of chicks, and no long-term effects on courtship behaviour and song in males or reproductive performance in females. These results suggest that the nestling period is not a critical window for sensitivity to mercury exposure in zebra finches. Growing nestlings can reduce blood mercury levels through somatic growth and depuration into newly growing feathers, and as a result they might actually be less susceptible compared to adult birds receiving the same level of exposure.

In ecotoxicology, transcriptomics is an effective way to detect gene expression changes in response to environmental pollutants. Such changes can be used to identify contaminants or contaminant classes and can be applied as early warning signals for pollution. To do so, it is important to distinguish contaminant-specific transcriptomic changes from genetic alterations due to general stress. Here we present a first step in the identification of contaminant class-specific transcriptome signatures. Embryos of zebrafish (Danio rerio) were exposed to three substances (methylmercury, chlorpyrifos and Aroclor 1254, each from 24 to 48 hpf exposed) representing sediment typical contaminant classes. We analyzed the altered transcriptome to detect discriminative genes significantly regulated in reaction to the three applied contaminants. By comparison of the results of the three contaminants, we identified transcriptome signatures and biologically important pathways (using Cytoscape/ClueGO software) that react significantly to the contaminant classes. This approach increases the chance of finding genes that play an important role in contaminant class-specific pathways rather than more general processes.

Mercury and its compounds are classified into three main groups: metallic mercury (Hg 0 ), inorganic mercury (Hg 2+ ), and organic mercury (methyl mercury: CH 3 Hg + , etc.). Metallic mercury is the only metal that is liquid at ambient temperature and normal pressure, which readily forms an amalgam with other metals. Therefore, mercury has long been used for refining various metals, and mercury amalgam has been used for dental treatment. Mercury has also been used in measuring instruments such as thermometers, barometers and blood pressure monitors, as well as electric appliances such as lighting equipment and dry batteries. Large amounts of metallic mercury are still used in other countries as a catalyst in the production of caustic soda by electrolysis. In addition, mercury compounds have been used in various chemicals such as mercurochrome, agricultural chemicals, and mildew-proofing agents. However, the use of mercury has also caused health problems for people. Minamata disease in Japan is a typical example. Also, since mercury is highly volatile, it is discharged as a product of industrial activities or derived from volcanoes, and it has been concluded on the basis of the findings of the United Nations Environment Program (UNEP) that it is circulating globally. Therefore, with the aim of establishing an internationally legally binding treaty for the regulation of mercury use to reduce risk, an intergovernmental negotiating committee was established in 2009. Japan actively contributed to this negotiation owing to its experience with Minamata disease, which led to the Convention on the regulation of mercury use being discharged as the "Minamata Convention on Mercury" and the treaty came into force on August 16, 2017. In this review, we introduce 1) the Global Mercury Assessment by UNEP; 2) mercury kinetics, exposure assessment and toxicity of different chemical forms; 3) large-scale epidemics of methylmercury poisoning; 4) methylmercury exposure assessment and health survey in whale-eating populations; 5) elemental mercury exposure assessment and health survey of mercury mine workers in China.

The ecotoxicological effects of methylmercury (MeHg) exposure have been intensively described in literature. Yet, it is still unclear how marine biota will respond to the presence of MeHg under climate change, namely ocean warming. The present study aimed to investigate, for the first time, fish condition [Fulton's K index (K), hepatosomatic index (HIS) and brain-to-body mass ratio (BB-ratio)] and several stress-related responses in an ecologically and commercially important fish species (Dicentrachus labrax) exposed for 28days to dietary MeHg (8.0mg kg-1 dw) and temperature increase (+4°C). Results showed significant impairments on fish condition, i.e. up to 34% decrease on K, >100% increase on HIS and 44% decrease on BB-ratio, compared to control conditions. Significant changes on tissue biochemical responses were observed in fish exposed to both stressors, acting alone or combined, evidencing the relevance of assessing possible interactions between different environmental stressors in ecotoxicological studies. For instance, muscle showed to be the least affected tissue, only revealing significant alterations in GST activity of MeHg-enriched fish. On the other hand, liver exhibited a significant induction of GST (>100%) and CAT (up to 74%) in MeHg-enriched fish, regardless of temperature exposure, as well as decreased SOD activity (19%) and increased HSP70/HSC70 content (87%) in fish exposed to warming alone. Brain showed to be affected by temperature (69% of GST inhibition and >100% of increased CAT activity), MeHg (>100% of increased CAT activity, 47% of SOD inhibition and 55% of AChE inhibition), as well as by the combination of both (GST, SOD and AChE inhibition, 17%, 48% and 53%, respectively). Hence, our data provides evidences that the toxicological aspects of MeHg ca be potentiated by warmer temperatures, thus, evidencing the need for further research combining contaminants exposure and climate change effects, to better forecast ecological impacts in the ocean of tomorrow., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Very little is known about the relationship between postnatal methylmercury concentrations (via toenails as bioindicator) and behavioural characteristics of Pacific Island children living in New Zealand. The aim of this study was to explore the association between total mercury exposure and different domains of behavioural problems in Pacific children., Materials and Methods: A sample of nine-year-old Pacific Island children resident in Auckland, New Zealand participated in this study. Total mercury was determined in biological samples (toenail clippings) on behavioural problems as identified by mothers (using the child behaviour checklist). Specific behavioural domains, particularly aggression, rule breaking, attention and social problems were studied in relation to mercury exposure using toenails. The determination of mercury concentration in toenail clippings, after acid digestion was carried out using inductively coupled plasma mass spectrometry., Results: The observational study was conducted between July 2010 and July 2011 in which 278 eligible nine-year-old Pacific Island children were enrolled (Girls n=58%; boys n=42%)., Findings: showed that 21% of the children had total toenail mercury concentrations (1.5μg/g to 6μg/g) higher than the United State Environmental Protection Agency recommended levels (RfD; 1μg/g Hg) for optimal health in children. Aggressive behaviour was associated with total toenail mercury exposure after adjusting for gender, ethnicity and income levels (OR: 2.15 95% CI 1.45, 3.18 p-value <0.05; OR 1.38 95% CI 0.83, 1.2 p value <0.05, respectively)., Conclusions: Overall, this research contributes to the understanding of total toenail mercury concentrations for Pacific people in New Zealand using toenail clippings as biomarkers in terms of associations with child behavioural problems. Mercury in toenails demonstrated a moderate association with a specific behavioural domain - aggressive behaviour., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Fish contain nutrients essential to the developing fetal brain, but they are contaminated with methylmercury. The Tohoku Study of Child Development, now underway in the Sanriku coastal area of Miyagi prefecture, Japan, follows mother-child pairs to examine the risks and benefits of fish consumption during pregnancy, especially the effects of prenatal exposures to methylmercury, selenium, and docosahexaenoic acid (DHA) on child neurodevelopment. Children aged 18 months were administered the Bayley Scales of Infant Development second edition (BSID-II) and Kyoto Scale of Psychological Development (KSPD) in 2004-2008. Complete data of cord-blood total mercury (THg), cord-plasma selenium, maternal-plasma DHA, the above test scores, and confounders for 566 mother-child pairs were available. The median cord-blood THg level was 15.7 (range, 2.7-96.1) ng/g. Since the BSID-II and KSPD scores were significantly lower in the 285 boys than in the 281 girls, analyses were conducted separately. The Psychomotor Development Index (PDI) of BSID-II was significantly correlated with cord-blood THg only in the boys, and significance of the association remained unchanged after adjusting for possible confounders; i.e., a 10-fold increase in cord-blood THg was associated with a 8.3-point decrease in the score of the PDI. Other significant correlations of THg were not seen in the boys or girls. Selenium and DHA showed no significant correlations with the BSID-II or KSPD scores in either sex. In conclusion, intrauterine methylmercury exposure may affect psychomotor development, and boys appear to be more vulnerable to the exposure than girls.

Background: The effects of prenatal exposures to polychlorinated biphenyls (PCBs), methylmercury, and lead on birth weight remain disputable. The aim of this study was to investigate whether these chemicals affect birth weight of Japanese newborns, with special emphasis on determining whether these effects differ between males and females., Methods: The subjects from Tohoku Study of Child Development, which was designed to examine the developmental effects of prenatal exposures to such hazardous chemicals, were 489 mother-newborn pairs with complete data including smoking habit during pregnancy., Results: The mean birth weight of all newborns was 3083 (range, 2412-4240) g. The median values of biomarkers in cord blood were 46.0 (5th and 95th percentiles, 18.6-113.8) ng/g-lipid for total PCBs, 10.1 (4.3-22.4) ng/g for total mercury (THg), and 1.0 (0.6-1.7) μg/dL for lead. The birth weight was significantly heavier in the 252 male newborns than in the 237 female ones. A negative association between total PCBs and birth weight was observed in both male and female newborns, even after adjusting for possible confounders. However, a negative association of THg with birth weight was found only in the male newborns. There was no significant relationship between lead and birth weight in both groups., Conclusion: Birth weight appears to be affected by prenatal PCB exposure in Japanese male and female newborns, and the effect of methylmercury exposure on male fetal growth may be stronger than that for females. This implication is that the effects on fetal growth should be assessed in males and females separately.

Putative protective effects of selenium (Se) against methylmercury (MeHg) toxicity have been examined but no conclusion has been reached. We recently reported the lack of serious neurological symptoms in a Japanese fish-eating population with high intakes of MeHg and suggested a potential protective role for Se. Here, relationships between levels of Hg and Se in the blood and plasma samples, with a quantitative evaluation of Se-containing proteins, obtained from this population were examined. While levels of the whole-blood Hg (WB-Hg) and plasma Se (P-Se) showed a positive correlation, stratified analysis revealed that they correlated only in samples with higher (greater than the median) levels of MeHg. A food frequency questionnaire showed that consumption of fish/whales correlated with WB-Hg, but not with P-Se, suggesting that the positive correlation between WB-Hg and P-Se might not be the result of co-intake of these elements from seafood. Speciation of plasma Se revealed the differences in the responses of two plasma selenoproteins, glutathione peroxidase (GPx) and selenoprotein P (SePP), in relation to Hg exposure. In the high-Hg group, SePP showed a positive correlation with WB-Hg, but GPx did not. In the low-Hg group, neither SePP nor GPx showed any correlation with WB-Hg. These observations suggest that the increase in P-Se in the high-Hg group might be associated with an increase in SePP, which may, in turn, suggest an increased demand for one or more selenoproteins in various organs, for which SePP supplies the element., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)