3e: Human exposure and health effects of mercury: epidemiology and population studies

Introduction: In artisanal small-scale gold mining (ASGM), a chronic exposure to metallic mercury vapor results from the use of mercury during gold extraction. Health effects such as tremors, erethisms, sleep disorders and many other may occur. The information on health-related quality of life of people suffering from chronic metallic mercury vapor intoxication (CMMVI) is limited. This project analyzed the severity of CMMVI in comparison to other health states.

Methods: International experts, identified by a PubMed search, were invited to participate in a pretested online survey. The questionnaire contained pairwise comparison questions asking if a person with a defined health state is healthier as another person with another health state. Eighteen health states were examined including moderate and severe CMMVI. Data was analyzed with probit regression. Based on the regression coefficients, it was possible to classify the health states according to their severity.

Results: The questionnaire was completed by 105 individuals with expertise in public health, epidemiology and burden of disease among others. Respondents from all continents were reached; however, three-quarters of participants came from Europe. The order of the health states from the lowest (1) to the highest severity (18) was: (1) mild vision disorder, (2) deafness, (3) breast cancer (clinically disease-free stage without permanent sequelae), (4) problems of alcohol drinking, (5) severe asthma, (6) chronic low back pain, (7) HIV/AIDS (seropositive, asymptomatic), (8) mild dementia, (9) diabetes mellitus (uncomplicated/poorly controlled), (10) manifest alcoholism, (11) coronary heart disease/severe stable angina, (12) moderate CMMVI, (13) colorectal cancer (stage of diagnosis/primary therapy), (14) stroke (moderate impairments), (15) severe depression, (16) delirium caused by excessive alcohol intake, (17) quadriplegia, (18) severe CMMVI.

Conclusions: The survey results confirm the appraisal of a high severity for both, moderate (rank 12) and severe CMMVI (rank 18) in comparison to other health states. The severe CMMVI, which description contained a worst case scenario of CMMVI, was evaluated as the most severe condition in comparison to the other 17 health states; ranking even higher than severe depression and quadriplegia. The results confirm the necessity to avoid the health impairing exposure to mercury in ASGM. The results can directly be transformed into disability weights to quantify the burden of disease, which will be useful for policy decision making.

This work has received funding from Pure Earth, Bielefeld University, and the European Unions Seventh Programme for research, technological development and demonstration under grant agreement No 603946 (HEALS).

Pharmaceuticals & personal care products (PPCPs), while intended to improve health, may have unintended health effects and are emerging contaminants of concern. One potential example which has received limited attention is the effect of PPCPs on the risks associated with exposure to common environmental contaminants such as mercury (Hg). Here, the objective was to understand if pharmaceutical use can be associated with biomarkers of Hg exposure (total blood Hg). We analyzed prescription drug use and Hg biomarker data from the U.S. National Health and Nutrition Examination Survey (NHANES) 2009-2010 (n=7990), accounting for age, sex, income, race/ethnicity, red blood cell count, hemoglobin, and fish consumption. Preliminary two-sample t-tests suggested that subjects taking any prescription drug had significantly higher blood Hg concentrations (~1.5 µg/l) than those not taking any prescription drugs (~1.1 µg/l). Preliminary t-tests on broad categories of drugs indicated that subjects taking cardiovascular agents had higher blood Hg concentrations (~1.7 µg/l) compared to those not taking cardiovascular agents (~1.2 µg/l), while no difference was found between those taking vs. not taking central nervous system agents or psychotherapeutic agents. In multiple regression analyses, overall prescription drug use was not a significant predictor of blood Hg. More multiple regression analyses revealed that cardiovascular agents (β = -0.166), central nervous system agents (β = -0.186), and psychotherapeutic agents (β = -0.151) were significant predictors of lower blood Hg, after accounting for fish consumption. These results suggest that exposure to certain PPCPs commonly utilized by society may mediate exposures to contaminants such as Hg, though future work is needed to determine the hazards associated with such real-world exposures to chemical mixtures.

Abstract not available

We examined correlations among Hg concentration in scalp hair and stable isotope ratios of carbon (d13C) and nitrogen (d15N) of the constituent amino acids in the scalp hair from heavy fish-eaters. Positive correlations were found between the bulk d13C and bulk d15N values (p<0.01) and between the bulk d15N value and Hg concentration (p<0.01) in the hair samples, while no correlation was found between bulk d13C value and Hg concentration. The d15N values for all trophic amino acids (Ala, Val, Leu, Ile, Pro, Asx and Glx) increased with increases in Hg concentration (p<0.01), while the d15N value for Thr decreased (p<0.01). The difference in d15N values between Glx and Thr was positively correlated with Hg concentration, showing the highest correlation coefficient (R2=0.773, p<0.01) among the various combinations for amino acids. Thus, the difference in d15N values between Glx and Thr appear to be the best proxies for the estimation of Hg concentration in scalp hair. In contrast, the d13C values for Val and Glx increased with increases in Hg concentraion (p<0.01), while those for Met and Ile decreased (p<0.01). No correlation between bulk d13C and Hg concentraion could reflect inverse changes of d13C in amino acids constituting the scalp hair.

Dried blood spots (DBS) are collected and archived from newborns shortly after birth in many jurisdictions worldwide and thus potentially represent a cost-effective biomarker to gauge developmental exposures to methylmercury (MeHg). The objective of this study was to: 1) develop a method to accurately and precisely measure MeHg in DBS; and 2) apply the method to characterize MeHg exposures in newborns by analyzing DBS archived in the Michigan Biotrust. Using DBS created in-house with human blood MeHg standard reference material (SRM) from the Institut National de Sant Publique du Qubec (INSPQ), a method was developed to quantify MeHg in as few as two 1/8 DBS punches. The analytical precision of the method, in terms of assaying the SRMs, was generally less than 10% and accuracy was similarly strong when using SRM-based standard curves. Next, we quantified MeHg in 675 DBS samples obtained from the Michigan Biotrust for Health, which is the States newborn screening biobank initiative. In doing so we calculate a median MeHg concentration of 3.7 ug/L with an inter-quartile range (25th-75th) that spans 2.7 to 4.9 ug/L. To our knowledge there is no robust dataset on newborn blood MeHg values to make comparisons with, and as such the results are compared to MeHg measurements taken on cord blood and show some similarities. This study shows that MeHg can be measured in DBS samples, and that the method can be scaled-up to analyze DBS archived from newborn screening programs thus representing a potentially cost-effective means to biomonitoring MeHg.

Background: The Asian population in the U.S. has elevated blood mercury compared with the non-Asian population due to higher frequency of fish consumption. Methyl mercury (MeHg) crosses the placenta and has been shown to affect neurodevelopment as well as cardiovascular risk in adults. East and Southeast Asians in Chicago, Illinois are a growing population that may have elevated health risks from fish consumption

Methods: We conducted a community assessment of Chinese, Koreans and Vietnamese in Chicago consisting of an in person survey of fish consumption and other cultural dietary practices, hair sampling for total mercury, and analysis of fish purchased in Chicago markets for mercury and PCBs.

Results: To date, 282 of 375 planned participants have been enrolled. On average, participants lived in the US for 12.3 years; 96% of the participants were born outside of the US, and 49% spoke only non-English at home. Mean age was 45 years (range 19, 80), 83% were female, 64% were married, and 49% had an annual income of <$20,000. Fish consumption rates differed significantly by ethnic group, with 61% of Koreans consuming fish 3 or more days/week compared to 38% of Vietnamese and Chinese participants. Most of the fish consumed was purchased, but 30% ate locally caught fish at least annually, although less than 50% of those were able to identify the body of water from which the fish was caught. Seafood consumption preferences varied among the ethnic groups and included species with a range of contaminant levels. Tilapia, salmon, bass, pompano, croaker and sole were the most popular among Chinese; while salmon, pompano, catfish, mackerel, and blue fish, and anchovies, mackerel, salmon, tuna and croaker were top choices among the Vietnamese and Korean, respectively. In our previous work we found that 28% of Chicago Asians tested had hair Hg mercury > 1ppm. Hair sample analysis for the current study is on-going and will be presented. Risk factors for elevated hair mercury that will be analyzed include age, sex, ethnicity, BMI, acculturation metrics and seafood consumption rates. We will also evaluate species of fish and cultural fish consumption practices that affect the risk of elevated hair mercury.

Conclusion: This study characterized risk factors for potential adverse health effects to Chicago Asian communities from fish consumption practices. These findings will be used to develop messages to decrease exposure to contaminants while maintaining consumption of healthy nutrients in fish.

Artisanal small-scale gold mining (ASGM) is the largest anthropogenic source of mercury contamination globally, presenting a risk to environmental quality and human health. Intensive ASGM activity in the Madre de Dios region of Peru results in the release of an estimated 50 tons Hg/year into the environment. Once in the environment, Hg may be biochemically converted to methylmercury (MeHg), which bioaccumulates in aquatic organisms and biomagnifies in fish commonly consumed by local populations. Previous studies report elevated Hg exposure in the human population of Madre de Dios, includin residents of native communities and mining communities. This is the first study to focus on Hg exposure and risk factors in women of childbearing age, a population of concern, living throughout Madre de Dios. After obtaining informed consent, hair samples, a common MeHg biomarker, were collected from 200 women living in six communities throughout Madre de Dios. All study participants were between 18 and 49 years of age and had not moved in the six months prior to sampling. Each study participant also responded to a survey, which collected information on age, diet (including fish consumption), occupation, level of education, and other risk factors. The survey also included questions regarding knowledge of health risks associated with Hg. Hair samples were analyzed for total Hg (THg) concentration following U.S. EPA Method 7473. The mean hair THg concentration was 2.25 ± 2.54 µg/g (range: 0.01 – 30.12 µg/g) and 67 subjects (33.5%) had levels above the 2.2 µg/g exposure limit established by the World Health Organization (WHO). Mercury exposure was not significantly associated with age, educational attainment, residence time, or frequency of fish consumption. Residents of Pilcopata, located at the headwaters of the Madre de Dios River basin and far upstream from ASGM activity, had significantly lower Hg exposure than residents of other all other communities. This suggests that conditions downstream from Pilcopata, such as intensive ASGM activity or eroded soils from disturbed sites, may account for human Hg exposure. Further research is needed to determine the sources of mercury contamination in the Madre de Dios River watershed. Furthermore, the elevated levels of Hg exposure among women of childbearing age indicate that a public health response is urgently needed. Most study participants expressed concern about Hg contamination, but the majority had limited understanding of the health risks associated with Hg exposure.

The lawsuit of Niigata Minamata Disease filed by victims in 2007 is currently underway in the Tokyo High Court. The Niigata District Court ruling was that only the plaintiffs who have a officially certified patient in their families should be officially recognized as victims and compensated. However, the diagnosis criteria of Minamata Disease established by the government are too strict for many individuals with symptoms of methylmercury poisoning to be recognized. Uncertified patients are not eligible to receive proper compensation. Although the Supreme Court ruled that the criteria should be relaxed in 2004, the Japanese Government has yet to make a change.

In Niigata, two surveys were conducted regarding inhabitants of the Agano River basin in June of 1965. As a result of this, 26 patients were diagnosed with Minamata Disease. The range of mercury levels in their hair was between 52 ppm and 570 ppm. The current WHO neurological risk standard for adult exposure (hair mercury level: 50 ppm) was based partly on evidence gleaned from these surveys. The Japanese Government also claims that 50 ppm is the threshold level of mercury in hair to cause methylmercury poisoning, and denies patients who have lower levels. However, another study conducted in Niigata showed that patients with less than 50 ppm still exhibit neurological signs related to methylmercury poisoning. Despite the above facts, the Japanese Government has not conducted further investigations, nor compensated patients. Thus, Uncertified patients have no choice but file a lawsuit.

The purpose of this study was to develop a new human hair reference material supporting human biomonitoring for mercury speciation. The requirement for certified reference materials for assessing mercury is on high with an increasing number of survey research to evaluate the effectiveness of the Minamata Convention. We collected human scalp hair from Vietnamese males from a barber shop in Hanoi in 2016. Special attention was paid to avoid contamination from grinding vessel during the preparation procedure. We prepared 1000 bottles of hair, each containing 3 g, after sieving and blending of the hair powder. Value for total mercury and methylmercury, as well as other trace elements (Cu, Zn, As, Se) will be presented.

Background: Mercury is a global pollutant with potential for multiple adverse health implications. Studies have reported inconsistent findings for the relation of mercury exposure and blood pressure in human populations.

Objective: To conduct a systematic review and meta-epidemiological analysis to explore: (1) The relation of mercury on blood pressure, and (2) Dose-response relationship and threshold for effect.

Methods: A search with relevant keywords was conducted in Pubmed to identify studies. Abstracts and full texts were screened to identify studies for inclusion. Inclusion criteria were human adult populations, mercury exposure, outcome of systolic or diastolic blood pressure or hypertension, and English language. Data were extracted and assessed for quality by two reviewers. Meta-regression and dose-response meta-analyses were performed to explore the impact of study characteristics, mercury dose, population baseline mercury exposure, matrix of mercury measurement, type of effect estimate (i.e. odds ratio, mean difference, correlation coefficient) and exposure estimate (i.e. log-transformed vs. untransformed).

Results: A total of 34 studies were included. These studies were primarily of cross-sectional design and also included case-control and cohorts. Populations exposed to higher levels of mercury were the Inuit from Canada and Greenland, fishermen in Japan and Indigenous groups of the Amazon in Brazil. Lower exposure to mercury occurred mainly in general populations of the United States, Europe, and South Korea. Mercury was measured in various matrices including blood (N = 15), hair (N = 11), and toenail (N = 4). The outcome was defined as either systolic/diastolic blood pressure as continuous measurements or hypertension defined based on blood pressure threshold. The relation of mercury on blood pressure differed by baseline mercury exposure level. The exploration of dose-response and threshold has several methodological uncertainties and limitations due to inadequate reporting.

Conclusion: Considerable amount of data are available on the relation between mercury and blood pressure in adult populations around the world. The association between mercury and blood pressure varies by study characteristics and levels of exposure. Improvement in reporting and advances in methodology will improve the accuracy of dose-response and threshold estimates. These considerations are applicable to many other environmental contaminants and health outcomes.

CHAPTER 7 in Springers February 2016 publication Epigenetics, the Environment, and Childrens Health Across Lifespans

All dental amalgam fillings contain approximately 50 % elemental mercury by weight. Concerns about health risks due to continual emissions of mercury vapor from this tooth restorative material have been addressed by dentists, scientists, and government authorities worldwide and have resulted in a range of recommended practices and regulations. By reviewing articles collected by a literature search of the International Academy of Oral Medicine and Toxicology (IAOMT) database and the PubMed database, we identify health risks associated with dental mercury amalgam. We present the science of potential harm as applicable to the general population, pregnant women, fetuses, children, and dental professionals. We specifically address genetic predispositions, mercury allergies, Alzheimers disease, multiple sclerosis, amyotrophic lateral sclerosis, and other health conditions pertinent to dental mercury exposure and its toxicity. We conclude that reviews and studies of dental amalgam mercury risk should assess biocompatibility with special consideration for all populations and all risk factors.

Millions of dentists around the world continue to routinely use dental amalgam, often referred to as silver fillings, as a filling material in decayed teeth. As a result, 67 million Americans aged two years and older exceed the intake of mercury vapor considered safe by the U.S. EPA or over 122 million Americans exceed the intake of mercury vapor considered safe by the California EPA. Mercury is a known neurotoxin that can cause harm to humans, especially children, pregnant women, and fetuses. Furthermore, the use of dental amalgam results in substantial quantities of toxic mercury released annually into the environment. Once in the environment, mercury pollution damages animals, plants, and the entire ecosystem, while creating hotspots that last for centuries.

Except for the USA, numerous countries have taken protective actions against this dental material ranging from a general ban in Norway and Sweden to restrictions on its use in selected populations in Denmark, Estonia, Finland, Italy, Japan, Switzerland, France, Austria, Canada, Finland, and Germany. In December 2016, three EU institutions (the European Parliament, the European Commission and the Council of the European Union) reached a provisional agreement to ban dental amalgam fillings for children under 15 and pregnant and breastfeeding women as of July 1, 2018.

The high levels of methylmercury into the human body there is most often due to eating fish and seafood. The local population of the Vologda region traditionally eat a lot of fish from local lakes and rivers. Fish methylmercury levels were high in the last decade in the North-West of the European Russia including the Vologda region. Therefore the local people are at the highest risk of mercury exposure.

Women living in a large industrial city – Cherepovets (n=53) and workers settlement Vokhtoga (n=45) have been screened (the Vologda region) to assess the content of methyl mercury in human hair. The level of mercury in the hair of pregnant women (geometric mean of 0.296 µg/g, the 95th percentile of 1.078 µg/g) in this population is above the average value obtained in the Moscow region (n=120) geometric mean 1.4 exceeds and twice exceeds that on 95th percentile. In this sample, the threshold value recommended by the WHO and the US exceeded with 2.2% and 5.8% of the participants.

The occurrence of fires can substantially increase the emissions of mercury (Hg) into the atmosphere. Due to its toxicity Hg Emissions from fires has the potential for increased population exposures, put firefighters at risk, as well as influencing the global Hg budget. Despite the high frequency of fire in Australia little focus has been given to understanding Hg emissions and dispersion from Australian bushfires and the potential health impacts. A recent study carried out in the Commonwealth Science and Industry Research Organization (CSIRO) Pyrotron facility involved measurement of Hg emissions from vegetation concurrent with CO and CO2 in order to quantify Hg emission factors (EF) and emission ratios (ER) from Australian vegetation. These Hg EFs and ERs were used to determine the exposure of firefighters and local populations to Hg. Firefighter exposure to Hg was determined using a data base of personal CO monitors collected over the past two years from prescribed burns. An average hourly exposure of 8.0 ng m-3 with a max 1 min peak value of 683.4 ng m-3 was calculated. Exposure of populations from prescribed and wild fires was determined using a CSIRO Chemical Transport Model (CMT) modified to incorporate the Hg emission factor calculated from the pyrotron experiments. A number of case studies of different fire intensities were run to determine the transport, amount of Hg emitted and the subsequent exposure limits. Local population exposures in closest proximity to the fire source showed inhalation exposures to be well below WHO standards. Populations are mostly at risk from indirect exposure caused by the redistribution of mobilised Hg and methylation within the environments.

Fish consumption is associated with elevated blood levels of methylmercury (meHg). The developing nervous system is especially vulnerable to exposure to meHg. Messages about safe fish consumption are complex because fish are also a source of beneficial nutrients. Health care providers are sources of credible information to their patients. Screening at a health care clinic for high mercury (Hg) exposure through biomonitoring is not currently feasible. Instituting screening in the form of brief intake question(s) is possible and explored in this work.

Four hundred ninety-nine women age 16-50 from an area in Minnesota with a cultural connection to fishing completed a health care clinic visit which included: brief screening questions, a detailed questionnaire of fish consumption, and blood collection for Hg analysis. Sensitivity and specificity in predicting high blood mercury Hg were calculated for screening and detailed fish consumption questions, and accuracy was examined using receiver operating characteristic (ROC) curves.

Screening questions on meals of total fish and local fish with moderate levels of mercury had high sensitivity but lower sensitivity. Combining responses to both questions increased sensitivity, but decreased specificity. Responses from the detailed questionnaire were more accurate than screening questions in predicting elevated Hg, and accuracy was slightly improved with a question that excluded salmon, fish sticks and tilapia from total fish consumption.

A brief set of questions that assess total and moderate Hg fish meals can be an effective tool in predicting which individuals are likely to be at risk of an elevated blood Hg, and allow for targeted education by health care providers. Biomonitoring is the most accurate test for determining risk among those frequently consuming fish, however, incorporation into clinical practice would require changes in current health care systems.

Mercury (Hg) and methylmercury (MeHg) in diet pose health risks for populations. Based on abundant measurements from previous studies in recent years and Monte Carlo simulation, we carried out a Hg and MeHg human exposure study in China. Results showed that rice consumption was the primary pathway of total mercury (THg) exposure for most populations in China due to its large consumption, but the critical pathway of MeHg intake was fish consumption (including marine fish and freshwater fish), especially in North (49% of total MeHg intake), Northeast (69%), East (57%) and South China (52%) due to its high MeHg concentration. Rice was the most important pathway of MeHg exposed in Central (54%) and Southwest China (65%). In Northwest China, wheat was the critical pathway of both THg (45%) and MeHg (64%) intake. Totally, 43% and 10% of Chinese population exceeded the MeHg reference dose of U.S. EPA and JACFA, respectively, and fish consumption contributed the most. Physiologically Based Pharmacokinetic Model (PBPK) for THg and MeHg was applied to evaluate the impact of diet to human body. Although the amount of fish consumption is lower than other main food, higher concentration of MeHg in fish, especially in marine fish, can drive not only higher MeHg exposure but also higher MeHg/THg ratio in blood. As a more toxic form of Hg, intake of MeHg from fish consumption should be paid more attention, while the aquatic environment has been threatened by the anthropogenic pollution in China.

Mercury poses public health risks to populations worldwide. National surveys in North America, such as the Canadian Health Measures Survey and the National Health and Nutrition Examination Survey monitor population baseline levels over time. However, in many remote communities where fish is frequently consumed, such as in the Northwest Territories, such baseline levels are largely unknown. There have been numerous fish consumption advisories related to mercury issued over the past decade in this region, potential increasing the health risks posed by dietary transition away from traditional foods. This research is providing human baseline levels of several contaminants, including mercury, and is investigating the role of the consumption of locally-harvested fish on mercury exposure and risk. It is part of a four-year community based biomonitoring project with the aim to investigate the role of country foods for contaminant exposure using a risks and benefits approach.

This Northern Contaminant Program funded project will collect samples in up to 13 Indigenous communities in the Northwest Territories, Canada. The project includes: 1) a participatory approach with communities, 2) hair, blood, and urine collection, 3) dietary questionnaires, and 4) the analysis of numerous contaminants (including mercury) and nutrients (including selenium and healthy fatty acids EPA+DHA) in biological samples. The results herein are based on pilot sampling completed in 2016 in a single community in the Mackenzie Valley of the Northwest Territories (n=21). Despite an extended fish consumption among participants, and the presence of several consumption advisories on nearby lakes, whole blood mercury (GM 0.69 g/L) and hair mercury (GM 0.40 g/g) of participants were well below the relevant Health Based Tissue Guidelines. However, the plasma EPA+DHA levels (GM 67 mg/L) were also relatively low among participants. In contrast, selenium levels among participants appeared moderately higher than the Canadian general population, respectively for 15% and 20% of participants in whole blood and urine. Interestingly, a negative trend was observed between urine selenium and blood mercury. Future investigations will characterize the drivers of mercury, selenium, and EPA+DHA levels among participants.

In the next year, the participation of additional communities will augment these results so they can be used in community-led initiatives that promote traditional food consumption in manners that keeps mercury exposures low while improving nutrition. This project will facilitate future analyses of temporal trends and will shed light on the effectiveness of various policies for the protection of public health against the harmful effects of mercury.

Since 2000, mining industry has been developing progressively and environmental degradation, pollution has become problematic issues in Mongolia. It has been drawing our attention to that information about people who living in the near mercury polluted mining area has consumed river fish extensively. We carried out determination of total mercury concentration in the maternal urine, hair and cord blood of 265 women who delivered birth in 2016. They were recruited from the area of substantial fish consumption and mining. The geometric mercury concentration in the cord blood of the mothers (n=210) who never consuming river fish was 0.16 ng/ml, the mothers (n=40) who consuming once per quarter was 0.24 ng/ml, the mothers (n=15) who consuming at least once per month was 0.38 ng/ml. In the cord blood of the mothers (n=160) who never consuming canned fish was 0.15 ng/ml, the mothers (n=54) who consuming once per quarter was 0.20 ng/ml, the mothers (n=51) who consuming at least once per month was 0.25 ng/ml. In the cord blood of the mothers (n=156) who never consuming seaweed was 0.16 ng/ml, the mothers (n=75) who consuming once per month was 0.19 ng/ml, the mothers (n=34) who consuming at least once per week was 0.25 ng/ml. We observed that there were statistically significantly differences between cord blood total mercury concentration and river fish or seaweed consumption (p<0.01). The geometric mercury concentration in the cord blood of the mothers (n=227) who never consuming river fish during the last 3 months were 0.16 ng/ml and hair concentration was 19.5 ng/g. The mothers (n=28) who consuming less than once per month during the last 3 months were 0.31 ng/ml, in the hair was 33.9 ng/g. The mothers (n=10) who consuming at least once per month during the last 3 months were 0.49 ng/ml, in the hair was 89.6 ng/g. In the other hand, there were statistically significantly differences between river fish consumption during the last 3 months and total mercury in the cord blood, and hair (p<0.01). Therefore, we need to take part further investigation on organic mercury concentration in the biological samples of people who living higher fish consumption area.

Apart from traditional gold mining, other factors, such as river damming, may show the potential to facilitate mercury accumulation in the Amazonian environment. An increased number of dams are in different development or operational stages, occupying about 100,000 km2 (or 3% of Brazil’s Amazon forest) and both mercury methylation and bioaccumulation may be increased by submerging terrestrial areas (peatlands, upland soils, and vegetation). Yet, studies of human exposure to mercury in dam areas in the Amazon are scarce. One of the largest dams ever built in the Amazon recently attracted our attention: the Tucuruí Dam in Tocantins River basin, East Amazon, because high methylmercury concentrations has been found in Tucunaré fishes (Cichla sp.) by Rodríguez et al. (2014). Leino and Lodenius (1995) revealed 20 years ago that 45 people living at the main reservoir presented median levels of mercury (up to 51 μg/g) in hair, well above the safe limit (10 μg/g) established by the World Health Organization (WHO). However, no other evaluation with human populations has been carried out to date in this area.

Therefore, the aim of this work has been to assess the mercury exposure of this population and its potential harmful effects. For this purpose, hair has been selected as the study sample since it has been described as a good indicator of mercury levels in the body and it can be easily collected, transported and stored. Strict exclusion/inclusion criteria were applied for the selection of participants avoiding those with altered hepatic and/or renal functions. Mercury species and total mercury content were determined. Interestingly, the levels were relatively higher than those currently shown for human populations highly influenced by gold mining areas in the Amazonian region. The median level of mercury in hair was above the WHO safety limit, with values up to 75 µg/g (about 90% as methylmercury). Although additional studies are needed to confirm the possible magnification of mercury by the dams in the Amazon, our data already support the importance of adequate impact studies and continuous monitoring.

In recent decades the rapid growth of illegal artisanal and small scale gold mining (ASGM) in the Peruvian department of Madre de Dios has had serious impacts on its ecosystems and people. Recent studies have linked massive releases of mining related mercury into the regions atmosphere and waterways (~40 tonnes / yr) with elevated hair mercury levels in an estimated 60-75% percent of the population - with native populations showing the highest levels of contamination. In May 2016, this public health crisis was formally recognized by the declaration of a Regional State of Emergency due to this mercury contamination. However, despite recent increased awareness of these environmental health risks, government response to recognize and mitigate this public health crisis has been has been slow and limited. This paper describes the development of an innovative strategy centered on the establishment of a state-level multi-sectoral technical advisory group to 1) improve the quality of scientific information on mercury to support regional and municipal level decision-making; 2) support public sector technical response to the mercury state of emergency; and 3) the development of effective activities to mitigate the effects of mercury on local populations. A key success stories include active participation of primary and secondary level teachers to incorporate information on mercury related health risks and students into lesson plans throughout the public school system. This strategy has resulted in measurable increases in the number and quality of government actions and policies resulting in greater public health impact in local populations. Given the strong economic power of ASGM in similar rural sectors in Amazonia combined with weak governance, these experiences can serve as a reference for local actors to provoke and improve environmental and public health policies using integrative and multidisciplinary approaches.

[Background] Very few epidemiological or clinical studies have been carried out around Minamata since the discovery of the disease in 1956. Due to this lack of precise clinical and epidemiological examinations, it has always been assumed that Minamata disease was restricted to the seacoast area around Minamata. After October 2004, our group of doctors have been examining residents outside the government’s designated area and found they, the residents, had the same symptoms as Minamata disease victims in Minamata city. Only now has the true spread of Minamata disease becoming clearer.

[Methods] Since 2004 we were carried out studies in almost all areas of the Yatsushiro seashore. We studied 10196 medical records (M/F=4846/5350, mean age=62.7±12.0) who had already been examined for Minamata disease between November 2004 and March 2016. 214 residents of a non-polluted area were selected as a control group (M/F=91/123, average age=52.7±15.0). We classified the data of the polluted area by difference in residential area, occupation, age, and so on, and analyzed them. We also compared the data before and after July 31, 2012, when the application for relief of Minamata disease was closed.

[Results and Discussion] The symptoms of Minamata disease which were prevalent in records we studied: numbness of the hands (polluted area about 86-93% / control area 3%), unsteady tandem gait (50-65% / 9%), narrowing of the visual field (21-30% / 1%) in all area. Symptoms of subjects who had moved from polluted area to other areas were the same as those who lived in the polluted area. There were little differences of symptoms among different districts along the Yatshshiro seashore. There were also little differences of symptoms between fishermen and non-fishermen. It is because, as for dietary habits in the polluted period from 1950 to 1970, fish food was prevalent everywhere. There were little differences in symptoms between before and after deadline for the relief, which means that there were still a lot of Minamata disease patients, who had not been diagnosed or not been relieved.

[Conclusion] The spread of Minamata disease is greater than has been supposed up until now.

Huancavelica, Peru is among the worlds most mercury-contaminated cities due to 400 years of cinnabar mining and refining associated with the nearby Santa Brbara mine. Located southeast of Lima at 12,000 ft. in the Andes, Huancavelica is the capitol of its namesake department, which is the poorest in Peru. Several assessments using community-based participatory research have identified mercury two orders of magnitude above risk-based screening levels in earthen walls and floors in 75% of the homes studied. This extrapolates to about 3,800 homes in Huancavelica that could be contaminated above risk based screening levels. The predominant manner of release is likely due to historic emissions of both vapor and dust from refining cinnabar in the city. Local surface soil is contaminated with mercury and other heavy metals, and such soil has been used as construction material for over half the homes in the city. Mercury concentrations in wall and floor material, as well as indoor vapor, are above USEPA and World Health Organization standards for chronic exposure and in many cases above USEPA interim removal action levels. Since 2009, community members have been engaged in research design and conduct, educational initiatives, and the remedial alternative pilot study of 2015-2016. This pilot study ranked sixty assessed homes on the basis of level of contamination, and covered the walls with stucco and poured concrete floors in 9 of the most contaminated homes. Vapor concentrations in six homes was measured using a Lumex RA-915 mercury vapor monitor before and after encapsulation. Vapor concentrations decreased on average approximately 60% after completing the remedial action. In addition, encapsulation of heavy metal-contaminated earthen materials significantly decreased the risk of exposure through incidental ingestion of contaminated dust, which also contains arsenic and lead above screening levels. Stucco walls and concrete floors are moderately inexpensive and are a culturally relevant remedy.

INTRODUCTION: Apolipoprotein E (ApoE, gene APOE) is a lipid binding plasma glycoprotein with central roles in lipid metabolism and neurobiology. Some studies point on its antioxidative, metal-binding and immunomodulatory/anti-inflammatory properties. It has three major isoforms (ApoE2, ApoE3 and ApoE4) encoded by alleles ε2, ε3 and ε4. A large number of studies estimated, that isoform ε4 allele can be associated with different age related disadvantages. Individuals with ε4 variant are supposed to be more susceptible to metal toxicity, including MeHg known to be neurotoxic especially early in life. The purpose of present work was to estimate relations between ApoE polymorphisms and concentrations of selected metal(loid)s (Hg, MeHg, As and Se) in mothers and their newborns, chronically exposed to low or moderate amounts of Hg, mostly through fish consumption during pregnancy.
METHODS: We used samples and metal concentration data-set of Croatian mothers (n=209, aged 19-44y, sampling in 3rd trimester) and their newborns (n=176, sampling at delivery) from a wider prospective birth cohort study PHIME (‘Public Health Impact of long-term, low-level, mixed element exposure in susceptible population strata'; EU project 2006-2011). Database consisted of total Hg, MeHg, Se, As, Pb, Cd, Cu and Zn levels in maternal urine, breast milk, hair, peripheral and cord blood, and child urine. Archived DNA extracts from maternal leukocytes and cord tissue were used for APOE genotypisation by TaqMan pre-designed SNP assay for rs429358 and rs7412.
RESULTS: Mothers and newborns were divided in Apo ε4 carriers (genotypes ε3/ε4 and ε4/ε4) and ε4 non-carriers (genotypes ε3/ε3, ε3/ε2 and ε2/ε2). We identified 17% and 20% ε4 carriers among mothers and newborns, respectively. Mothers with allele ε4 have significantly higher concentrations of: i) blood Se, total Hg, MeHg and As; ii) plasma Se, iii) hair Hg. For Se only, the observed associations persisted after taking into account the influence of possible cofounders like seafood consumption, parity, age, body mass index, education, alcoholic beverages and presence of other metals. The same associations will be estimated for cord blood as well, with special interest on MeHg, because of its suggested neurodevelopmental effects.
CONCLUSION: Observed superior Se status in healthy pregnant females with genotypes Apo ε3/ε4 and ε4/ε4 in comparison with Apo ε3/ε3, ε3/ε2 and ε2/ε2 group could be linked to Apo ε4 ‘beneficial effects early in life’. The presence of detrimental metals in maternal blood did not affect plasma Se level in sense of its decrease.

Mercury (Hg) is a well-known neurotoxin, and has been more recently studied specifically as an immunotoxin. In experimental and a few epidemiologic studies, Hg has been associated with distinct cytokine profiles and antinuclear antibody (ANA) positivity, though patterns at lower levels of exposure, typical of seafood consumers with a western diet, are not well characterized.

Seafood consumers (n=287) recruited on Long Island, NY completed food frequency and health questionnaires and provided blood for analysis of Hg, poly-unsaturated fatty acids (omega-3 and omega-6 fatty acids), selenium (Se), ANA, and several cytokines (IL-1β, IL-4, IL-10, TNF-α, IL-17, IFN-γ, and IL-1ra). Logistic and linear regression analyses were conducted to evaluate associations between serum Hg and cytokines and ANA. Adjusted models accounted for gender, age, ethnicity, income, education, smoking, BMI, selenium, omega-3 fatty acids, omega-6 fatty acids, omega-3/omega-6 ratio, and fish intake. Sex-stratified models were also generated with the expectation that immune profiles would differ between women and men.

Median blood Hg was 4.58 µg/L with 90th %ile =19.8 µg/L. Nine individuals displayed ANA positivity at serum titers above 1:80; many of the cytokines were below detection limits, and the ability to detect was used in the logistic regression analyses. In linear and logistic regression analyses, Hg was not significantly associated with any of the seven investigated cytokines or with ANA-positivity.

Therefore, Hg was not associated with altered immune profiles in this population of seafood consumers.

The exposure to mercury in the Amazon has always been surrounded by numerous questions that have not yet been clarified. Studies carried out in the region over the last 40 years showed the existence of populations with median levels of total mercury in blood upper to the levels found in other regions of the planet. Between these were also frequently found average levels above the biological tolerance limit recommended by the World Health Organization. However, epidemiological and clinical studies in these individuals did not show signs of mercurialism. On the other hand, other studies indicates that a diet rich in selenium would have a protective effect on mercury, since selenium would have the capacity to reduce the toxicity of mercurial compounds from an equimolar proportion. In this study, the molar ratio of selenium and mercury of individuals from five riverside communities located in the Amazonian estuary (Vila do Beja, Vila do Conde, Vila de Itupanema, Curuperê and Ilha São João) was evaluated. Blood sampling was performed in 2013 and followed all ethical recommendations. The analyzes were performed by Induced Plasma Coupled Mass Spectrometry (ICP-MS). The results showed higher mean levels of total mercury in Ilha São João (6.155 μg.L-1), noting that the highest weekly frequency of fish consumption was also recorded. Total selenium levels ranged from 459.882 to 802.199 μg.L-1. The equimolar ratio showed that the amount of selenium atoms absorbed was 238 to 469 times greater than the amount of mercury. It should be noted that the mean levels of total mercury in the blood of these communities were lower than in other areas of the Amazon, a fact that may be associated with greater proximity to the estuary and greater distance from the gold mining areas in Brazil and in border countries. Considering that blood represents a recent absorption of selenium and mercury associated with dietary habit this equimolar ratio was indicative that the diet of these individuals is as rich in selenium as in mercury. This discussion could be extended to evaluate the equimolar ratio of selenium and mercury in other areas of the Amazon and could contribute to a better understanding of mercury exposure in the region.

Mineral exploration in the Amazon is old and was intensified in the 70's and 80's. At that time, artesanal gold mining was initially predominant, and soon afterwards large mineral plants were set up to exploit aluminum, copper, iron and manganese. In parallel, large hydroelectric dams were built and industrial poles created to promote regional development. All of these great ventures were always tied to major conflicts of land use and intense migratory processes. The margins of any planning, these industrial areas have settled alongside communities, some of these traditional ones (riverine, quilombola and indigenous), and others have been created over the years, as it happened in the industrial area of Barcarena, located in Amazonian estuary. Industrial production generates atmospheric pollutants containing metal contaminants such as mercury (Hg), causing the environmental exposure of people living near, depending on factors such as the proximity of the ventures and direction of the winds. This study aims to analyze the concentration of total mercury in human blood close to the industrial area and was carried out in the human population of five communities located in the municipality of Barcarena, Pará State, Brazil, in the year 2013. The study was epidemiological and laboratorial and complied with all ethical principles involving human research. The total mercury (THg) analyzes were performed by mass spectrometry coupled with induced plasma (ICP-MS). The THg median levels in the Bairro Industrial, Dom Manoel, Acuí, Bairro Canaã and Laranjal were, respectively, 8.6 μg.L-1, 6.2 μg.L-1, 3.7 μg.L-1, 2.3 μg.L-1 and 0.8 μg.L-1. The increase in HgT values ​​in the communities was positively related to their proximity to the industrial area of Barcarena. The Bairro Industrial and Dom Manoel are communities close to the kaolin industries and coke production, while other communities are further away from sources of pollution. Highlighting the occurrence of low weekly frequency of fish consumption among all communities (1 or 2 times per week). In the industrial processes of extraction and production are released particles easily carried by the air, and these can reach long distances. As evidenced by the significant Hg levels in the communities Acuí and Bairro do Canaã that are further away from the companies in question. The data showed another form of environmental exposure to mercury in the Amazon associated with the proximity of communities of industrial areas.

Human exposure to toxic and harmful metals occurs naturally and anthropic for thousands of years. These toxic metals are present in soils and rocks, but also as constituents of industrialized products used in our daily lives. The Amazonian riverside populations present a diet based on fish consumption and through this bioaccumulate mercury. Thus, these individuals are environmentally exposed to mercury. The study area comprised the cities of Abaetetuba and Barcarena, located in the Pará State, Northern Brazil. The method was epidemiological and laboratorial. In the year of 2013, blood samples were collected in six riverside communities. All ethical criteria were met and epidemiological forms were completed. Mercury (Hg) was quantified by cold vapor atomic absorption spectrometry (CV-AAS) and mass spectrometry coupled with induced plasma (ICP-MS). Mean blood Hg levels were highest in the Maranhão (10.350 μg.L-1) and Ilha São João (6.155 μg.L-1) communities. In these communities there is a higher weekly frequency of fish consumption (more than 5 times per week). In other communities, such as Vila do Conde, Itupanema, Curuperê and Vila do Beja, Hg levels were similar. In these, for the majority of the population, the weekly frequency of fish consumption is small (at most 2 times a week). The fish of the Amazon region are known for the high concentration of mercury, especially predators. Therefore, when it is consumed by these populations, the tendency is that the levels of Hg in the blood are higher, according to the observed results. The data showed that there is a greater environmental exposure to mercury associated with higher consumption of fish and there is a need for establishing public policies to guide the populations of the region.

Natural and anthropogenic processes represent the sources of mercury that can reach living organisms, including humans, through exposure routes. The mercury levels in individuals from areas affected by anthropogenic sources may exceed reference values ​​for biological tolerance to the toxic agent; however, some areas without anthropogenic sources present mercury levels in populations above the reference limit for non-exposed individuals. This is the case of cities in the Acre State in Brazilian Amazon such as Manoel Urbano, where a preliminary study in the first half of the 2000s indicated the possibility of high exposure to mercury in these individuals. This city is located near the border of countries like Peru and Bolivia. To confirm or not the mercury exposure in this city on the bank of the Purus River, a study approved by the research ethics committee was carried out in 2012, which included an epidemiological survey (n = 276) with sampling of human blood and hair and also fish muscle from the Purus River, for analyzes of total mercury and methylmercury, which were developed by Cold Vapor Atomic Absorption Spectrometry and Gas Chromatography with electron capture detector, respectively. The results confirmed a broad spectrum of mercury exposure in the population, ranging from 0.49 to 138.64 μg.L-1 (median of 9.61 μg.L-1) in blood and 0.10 to 41.82 μg.g-1 (mean 2.90) in Hair, associated with fish consumption, age and length of dwelling. Methylmercury levels ranged from 0.37 to 134.19 μg.L-1 (median of 9.45 μg.L-1) in blood and 0.68 to 36.24 μg.g-1 (median 5.63 μg.g-1) in hair. The total mercury levels in fish varied from 0.034 μg.g-1 in non-carnivorous to 6.371 μg.g-1 in carnivorous species. The results indicate the environmental availability of mercury in fish as a way of exposing the population and highlight the importance of transboundary circulation of mercury through international rivers such as the Purus and the contribution of the diversity of mercury sources in the region. Other studies are under way to assess the dynamics of this exposure and to intensify health surveillance actions.

In most Brazilian cities the solid urban waste is not segregated and disposed on the ground forming open dumps. On the action of intemperic factors are generated liquid effluents rich in contaminants and pathogens. Between this contaminants are toxic metals such as mercury (Hg). The leachate penetrates the soil, contaminating the underground aquifers or are spill into the rivers. In the Belém Metropolitan Region (BMR) for almost 30 years all garbage produced was deposited in the Aurá dump. Near is located the watershed of the Aurá river where a riverine community resides. The Aurá river basin receives both the slurry load and the sewage from nearby districts. In this study, mercury levels were evaluated in surface waters of 5 points of the river Aurá and its tributaries and for control 2 points in the Uriboquinha river and 3 points in the Uriboca river. The samplings were performed quarterly between the period of October / 2014 to July / 2016. The total mercury (THg) analyzes were performed by mass spectrometry coupled with induced plasma (ICP-MS). The results showed that the THg average levels in the surface waters of the Aurá river were higher when compared to the other rivers evaluated. The highest mean value of HgT was recorded in the Santana do Aurá Igarapé (0.32 μg.l-1), the nearest point and impacted by the leachate from the open dump, the lowest value was recorded on the Uriboca river (0.20 μg. L-1), a point distant about 6 km from the source of anthropic pollution. These results show the susceptibility of riparian communities, even from urban centers, to water pollution due to the lack of planning for the proper disposal of solid urban waste.