Methylmercury Effects on Birds: A Review, Meta-Analysis, and Development of Toxicity Reference Values for Injury Assessment Based on Tissue Residues and Diet.

Birds are used as bioindicators of environmental mercury (Hg) contamination, and toxicity reference values are needed for injury assessments. We conducted a comprehensive review, summarized data from 168 studies, performed a series of Bayesian hierarchical meta-analyses, and developed new toxicity reference values for the effects of methylmercury (MeHg) on birds using a benchmark dose analysis framework. Lethal and sublethal effects of MeHg on birds were categorized into nine biologically relevant endpoint categories and three age classes. Effective Hg concentrations where there was a 10% reduction (EC10) in the production of juvenile offspring (0.55 µg/g wet wt adult blood-equivalent Hg concentrations, 80% credible interval: [0.33, 0.85]), histology endpoints (0.49 [0.15, 0.96] and 0.61 [0.09, 2.48]), and biochemical markers (0.77 [<0.25, 2.12] and 0.57 [0.35, 0.92]) were substantially lower than those for survival (2.97 [2.10, 4.73] and 5.24 [3.30, 9.55]) and behavior (6.23 [1.84, >13.42] and 3.11 [2.10, 4.64]) of juveniles and adults, respectively. Within the egg age class, survival was the most sensitive endpoint (EC10 = 2.02 µg/g wet wt adult blood-equivalent Hg concentrations [1.39, 2.94] or 1.17 µg/g fresh wet wt egg-equivalent Hg concentrations [0.80, 1.70]). Body morphology was not particularly sensitive to Hg. We developed toxicity reference values using a combined survival and reproduction endpoints category for juveniles, because juveniles were more sensitive to Hg toxicity than eggs or adults. Adult blood-equivalent Hg concentrations (µg/g wet wt) and egg-equivalent Hg concentrations (µg/g fresh wet wt) caused low injury to birds (EC1) at 0.09 [0.04, 0.17] and 0.04 [0.01, 0.08], moderate injury (EC5) at 0.6 [0.37, 0.84] and 0.3 [0.17, 0.44], high injury (EC10) at 1.3 [0.94, 1.89] and 0.7 [0.49, 1.02], and severe injury (EC20) at 3.2 [2.24, 4.78] and 1.8 [1.28, 2.79], respectively. Maternal dietary Hg (µg/g dry wt) caused low injury to juveniles at 0.16 [0.05, 0.38], moderate injury at 0.6 [0.29, 1.03], high injury at 1.1 [0.63, 1.87], and severe injury at 2.4 [1.42, 4.13]. We found few substantial differences in Hg toxicity among avian taxonomic orders, including for controlled laboratory studies that injected Hg into eggs. Our results can be used to quantify injury to birds caused by Hg pollution. Environ Toxicol Chem 2024;43:1195-1241. Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Accumulation and risk assessment of mercury in soil as influenced by mercury mining/smelting in Tongren, Southwest China.

To investigate the influence of mercury (Hg) mining/smelting on the surrounding soil environment, ninety soil samples were collected around Hg mining/smelting areas in Tongren city, Guizhou Province, Southwest China. The total mercury (THg), methylmercury (MeHg), bioavailability and fractions of Hg in the soil and their potential risk were evaluated. The results showed that Hg mining/smelting significantly increased the soil pH and decreased the soil organic matter content (p < 0.05). The THg content in the surrounding soil was much higher than that at the control site, with almost all the samples exceeding the national standard in China (3.4 mg/kg, GB15618-2018). Similarly, the concentrations of MeHg (0.09-2.74 µg/kg) and bioavailable Hg (0.64-62.94 µg/kg) in these soil samples were also significantly higher than those in the control site. However, the MeHg/THg ratio was significantly lower in mining/smelting influenced soils (0.01-0.68%) than in control soils (0.60-3.72%). Fraction analysis revealed that residual (RES-Hg) and organic matter-bounded (OM-Hg) Hg accounted for more than 50% of the THg. Ecological risk assessment revealed that the potential ecological risk for most of the Hg mining/smelting-influenced soils (30.16 ≤ Er ≤ 2280.02) were higher than those at the control site (15.12 ≤ Er ≤ 27.1). In addition, these Hg mining/smelting-influenced soils posed acceptable noncarcinogenic risks to adults (except for two soil samples), with hazard indices (HIs) ranging from 0.04 to 1.11 and a mean HI of 0.44. However, children suffer serious noncarcinogenic risks, with HIs ranging from 0.34 to 7.43 and a mean HI of 3.10.

Multi-biomarker Assessment in a Native Species Psalidodon eigenmanniorum Under Inorganic Mercury and Recovery Scenarios.

The increasing contamination of water bodies with mercury raises concerns about its possible effects on aquatic organisms. The combined use of several biomarkers allows researchers to study the impact of a chemical at different levels of biological organization. In the present work, we determined the response of histological (gills and liver), somatic (condition factor and hepato-somatic index), and behavioral (predator-prey relationship, through the presentation of a computer-animated image) biomarkers in the native species Psalidodon eigenmanniorum exposed to 100 µg L-1 of inorganic Hg (IHg) during 96 h. We also assessed whether there was a change in the biomarkers analyzed after 7 days in Hg-free water compared with those exposed to IHg. In exposed fish, IHg caused damage to the gills and liver tissues. The condition factor showed no difference between IHg-exposed organisms and control organisms, while the hepato-somatic index was lower in IHg-exposed fish. As for the behavioral analyses, it was observed that the presentation of a stimulus induced changes in the behavioral responses of fish exposed to IHg, which showed a heightened state of alertness with respect to control. On the other hand, after 7 days in Hg-free water, the organisms generally showed no changes in biomarkers compared with IHg-exposed fish. Our results contribute new data on IHg toxicity in a native species and provide information on the plasticity of damage to reverse itself. Furthermore, this work provides baseline information for environmental assessments in water bodies where mercury is present.

Seasonal trends of mercury bioaccumulation and assessment of toxic effects in Asian clams and microbial community from field study of estuarine sediment.

This study investigated seasonal trends in bioaccumulation potential and toxic effects of mercury (Hg) in Asian clams (Corbicula fluminea) and microbial community. For this, a clam-exposure experiment was performed during summer, fall, and winter seasons in four different sites (HS1: control/clean site; HS2, HS3, and HS4: contaminated sites) of Hyeongsan River estuary, South Korea. Total mercury (THg) and methylmercury (MeHg) in whole sediments were highest at HS4 site during fall, sustained similar levels during winter, but decreased during summer. Unlike whole sediment, pore water reported higher levels in summer, and gradually declined during fall and winter. Asian clams from HS4 site collected during summer presented highest bioaccumulations of THg (521.52 µg/kg, dry weight) and MeHg (161.04 µg/kg, dry weight), which also correlated with the higher levels of Hg present in pore water in the same season. Moreover, biota-sediment-pore water accumulation factor (BSpAF) were comparatively greater in clams collected from HS2∼HS4 compared to HS1 sites, suggesting that porewater was a better indicator of accumulation of Hg. Upregulation of biomarker genes responsible for detoxifying process (gsts1), scavenging oxidative stress (cat), and protein reparation (hsp70 and hsp90) were observed in clams collected from HS2∼HS4. The overexpression of these biomarkers implied that Asian clams can be considered as promising warning tools for Hg-contamination. Both bacterial and metabolic diversities were negatively affected by higher levels of THg and MeHg. Phylum Proteobacteria was enriched in HS2∼HS4 compared to HS1. In contrast, phylum Bacteroidetes showed a reverse trend. The metabolic profile was highest in HS1 and lowest in HS4, revealing higher stress of Hg in HS4 site. Overall, the outcomes of this field study broaden the information on seasonal trends of bioaccumulation of Hg and its toxic effects. These findings may be helpful in Hg monitoring and management programs in other river systems.

Altered Larval Yellow Perch Swimming Behavior Due to Methylmercury and PCB126 Detected Using Hidden Markov Chain Models.

Fish swimming behavior is a commonly measured response in aquatic ecotoxicology because behavior is considered a whole organism-level effect that integrates many sensory systems. Recent advancements in animal behavior models, such as hidden Markov chain models (HMM), suggest an improved analytical approach for toxicology. Using both new and traditional approaches, we examined the sublethal effects of PCB126 and methylmercury on yellow perch (YP) larvae (Perca flavescens) using three doses. Both approaches indicate larvae increase activity after exposure to either chemical. The middle methylmercury-dosed larvae showed multiple altered behavior patterns. First, larvae had a general increase in activity, typically performing more behavior states, more time swimming, and more swimming bouts per second. Second, when larvae were in a slow or medium swimming state, these larvae tended to switch between these states more often. Third, larvae swam slower during the swimming bouts. The upper PCB126-dosed larvae exhibited a higher proportion and a fast swimming state, but the total time spent swimming fast decreased. The middle PCB126-dosed larvae transitioned from fast to slow swimming states less often than the control larvae. These results indicate that developmental exposure to very low doses of these neurotoxicants alters YP larvae overall swimming behaviors, suggesting neurodevelopment alteration.

An Assessment of Health Outcomes and Methylmercury Exposure in Munduruku Indigenous Women of Childbearing Age and Their Children under 2 Years Old.

In line with the 1000-day initiative and the Sustainable Development Goals (SDG) 2 and 3, we present a cross-sectional analysis of maternal health, infant nutrition, and methylmercury exposure within hard-to-reach indigenous communities in the state of Pará, Brazilian Amazon. We collected data from all women of childbearing age (i.e., 12-49) and their infants under two years old in three Munduruku communities (Sawré Muybu, Sawré Aboy, and Poxo Muybu) along the Tapajos River. We explored health outcomes through interviews, vaccine coverage and clinical assessment, and determined baseline hair methylmercury (H-Hg) levels. Hemoglobin, infant growth (Anthropometric Z scores) and neurodevelopment tests results were collected. We found that 62% of women of childbearing age exceeded the reference limit of 6.0 µg/g H-Hg (median = 7.115, IQR = 4.678), with the worst affected community (Sawré Aboy) registering an average H-Hg concentration of 12.67 µg/g. Half of infants aged under 24 months presented with anemia. Three of 16 (18.8%) infants presented H-Hg levels above 6.0 µg/g (median: 3.88; IQR = 3.05). Four of the 16 infants were found to be stunted and 38% of women overweight, evidencing possible nutritional transition. No infant presented with appropriate vaccination coverage for their age. These communities presented with an estimated Infant Mortality Rate (IMR) of 86.7/1000 live births. The highest H-Hg level (19.6 µg/g) was recorded in an 11-month-old girl who was found to have gross motor delay and anemia. This already vulnerable indigenous Munduruku community presents with undernutrition and a high prevalence of chronic methylmercury exposure in women of childbearing age. This dual public health crisis in the context of wider health inequalities has the potential to compromise the development, health and survival of the developing fetus and infant in the first two critical years of life. We encourage culturally sensitive intervention and further research to focus efforts.

Health Risk Assessment of Mercury Exposure from Fish Consumption in Munduruku Indigenous Communities in the Brazilian Amazon.

Fish serves as the principal source of animal protein for the indigenous people of the Amazon, ensuring their food and nutritional security. However, gold mining causes mercury (Hg) contamination in fish, and consequently increases health risks associated with fish consumption. The aim of this study was to assess the health risk attributed to the consumption of mercury-contaminated fish by Munduruku indigenous communities in the Middle-Tapajós Region. Different fish species were collected in the Sawré Muybu Indigenous Land to determine mercury levels. The health risk assessment was carried out according to the World Health Organization (WHO 2008) methodology and different scenarios were built for counterfactual analysis. Eighty-eight fish specimens from 17 species and four trophic levels were analyzed. Estimates of Hg ingestion indicated that the methylmercury daily intake exceeds the U.S. EPA (United States Environmental Protection Agency) (2000) reference dose from 3 to 25-fold, and up to 11 times the FAO (Food and Agriculture Organization)/WHO (2003) dose recommendation. In all situations analyzed, the risk ratio estimates were above 1.0, meaning that the investigated Munduruku communities are at serious risk of harm as a result of ingestion of mercury-contaminated fish. These results indicate that, at present, fish consumption is not safe for this Munduruku population. This hazardous situation threatens the survival of this indigenous population, their food security, and their culture.

Human Methylmercury Exposure and Potential Impacts in Central Tibet: Food and Traditional Tibetan Medicine.

Methylmercury presents potent neurotoxicity to humans. Fish consumption is the leading source of human exposure to methylmercury worldwide. However, the exposure source in Tibet remains poorly understood because of the scarcity of observational data on most Tibetan foods, although high mercury levels were recently detected in some traditional Tibetan medicines. Here, the results of field investigations show that the joint consumption of traditional Tibetan medicines (TTMs), fish, and rice constitutes a primary exposure pathway to methylmercury in Tibetans and that the probable daily intake of methylmercury is close to that for many coastal regions. People who are young and high-income may have higher methylmercury exposure levels mainly because of economic development and cultural exchanges among regions. Our analysis indicates that a large proportion of the Tibetan population are likely to face a high methylmercury exposure risk and that mercury-susceptible populations in Tibet should be attentive to consuming TTMs with fish.

The burden of disease of three food-associated heavy metals in clusters in the Danish population - Towards targeted public health strategies.

Lifestyle and sociodemographics are likely to influence dietary patterns, and, as a result, human exposure to chemical contaminants in foods and their associated health impact. We aimed to characterize subgroups of the Danish population based on diet and sociodemographic indicators, and identify those bearing a higher disease burden due to exposure to methylmercury (MeHg), cadmium (Cd) and inorganic arsenic (i-As). We collected dietary, lifestyle, and sociodemographic data on the occurrence of chemical contaminants in foods from Danish surveys. We grouped participants according to similarities in diet, lifestyle, and sociodemographics using Self-Organizing Maps (SOM), and estimated disease burden in disability-adjusted life years (DALY). SOM clustering resulted in 12 population groups with distinct characteristics. Exposure to contaminants varied between clusters and was largely driven by intake of fish, seafood and cereal products. Five clusters had an estimated annual burden >20 DALY/100,000. The cluster with the highest burden had a high proportion of women of childbearing age, with most of the burden attributed to MeHg. Individuals belonging to the top three clusters had higher education and physical activity, were mainly non-smokers and lived in urban areas. Our findings may facilitate the development of preventive strategies targeted to the most affected subgroups.

Exposure assessment of methylmercury in samples of the BfR MEAL Study.

The BfR MEAL Study is the first German total diet study and will establish a representative and comprehensive database for dietary exposure assessment in Germany. The present study reports first results of the BfR MEAL Study regarding methylmercury in fish, seafood and mushrooms. In total, 34 MEAL foods were purchased nationally or regionally according to a defined sampling plan, prepared in a representative way for German households, pooled into 49 samples, homogenized and subjected to ICP-MS analysis. Dogfish, tuna, ocean perch, halibut and eel were the fish species with highest MeHg concentrations, while levels in mushrooms and mushroom products had markedly lower MeHg levels. Exposure was estimated by matching the present results with consumption data at appropriate levels of food group aggregation. MeHg exposure for adult high consumers (P 95) exceeded the tolerable weekly intake recommended by the European Food Safety Authority in two age groups (14-17 and 18-24 years). In children, no age group exceeded the recommended tolerable weekly intake. Regional samples differed only slightly in MeHg levels. The differences in exposure found in four regions of Germany were influenced by consumption habits rather than MeHg level in the investigated food.

New approach for reproductive toxicity assessment: chromatoid bodies as a target for methylmercury and polychlorinated biphenyls in prepubertal male rats.

This study investigated the reproductive toxicity of methylmercury (MeHg) and Aroclor (Sigma-Aldrich), alone or in combination, following exposure of prepubertal male rats considering the chromatoid body (CB) as a potential target. The CB is an important molecular regulator of mammalian spermatogenesis, primarily during spermatid cytodifferentiation. Male Wistar rats were exposed to MeHg and/or Aroclor , according the following experimental design: control group, which was administered in corn oil (vehicle) only; MeHg-treated group, which was administered 0.5mg kg-1 day-1 MeHg; Aroclor-treated group, which was administered 1mg kg-1 day-1 Aroclor; Mix-LD, group which was administered a low-dose mixture of MeHg (0.05mg kg-1 day-1) and Aroclor (0.1mg kg-1 day-1); and Mix-HD group, which was administered a high-dose mixture of MeHg (0.5mg kg-1 day-1) and Aroclor (1.0mg kg-1 day-1). MeHg was diluted in distilled water and Aroclor was made up in corn oil (volume 1mL kg-1). Rats were administered the different treatments from PND23 to PND53 by gavage, . The morphophysiology of CBs was analysed, together with aspects of steroid hormones status and regulation, just after the last treatment on PND53. In addition, the long-term effects on sperm parameters were assessed in adult animals. MeHg exposure increased mouse VASA homologue (MVH) protein levels in seminiferous tubules, possibly affecting the epigenetic status of germ cells. Aroclor produced morphological changes to CB assembly, which may explain the observed morphological defects to the sperm flagellum and the consequent decrease in sperm motility. There were no clear additive or synergistic effects between MeHg and Aroclor when administered in combination. In conclusion, this study demonstrates that MeHg and Aroclor have independent deleterious effects on the developing testis, causing molecular and morphological changes in CBs. To the best of our knowledge, this is the first study to show that CBs are targets for toxic agents.

Trends in neurodevelopmental disability burden due to early life chemical exposure in the USA from 2001 to 2016: A population-based disease burden and cost analysis.

Endocrine disrupting chemicals are known to cause neurodevelopmental toxicity through direct and indirect pathways. In this study we used data from the National Health and Nutrition Examination Surveys, along with known exposure-disease relationships, to quantify the intellectual disability burden attributable to in utero exposure to polybrominated diphenyl ethers (PBDEs), organophosphates, and methylmercury and early life exposure to lead. We also estimated the cost of the IQ points lost and cases of intellectual disability. PBDE exposure was the greatest contributor to intellectual disability burden, resulting in a total of 162 million IQ points lost and over 738,000 cases of intellectual disability. This was followed by lead, organophosphates, and methylmercury. From 2001 to 2016, IQ loss from PBDEs, methylmercury, and lead have decreased or remained stagnant. Organophosphate exposure measurements were only available up to 2008 but did show an increase in organophosphate-attributable IQ loss. Although most of these trends show benefit for children's neurodevelopmental health, they may also point towards the use of potentially harmful substitutions for chemicals that are being phased out.

In Vitro Assessment of the Efficacy of a Macrocyclic Chelator in Reversing Methylmercury Toxicity.

Methylmercury (MeHg) is a highly neurotoxic compound to which human populations are exposed via fish consumption. Once in cells, MeHg actively binds thiols and selenols, interfering with the activity of redox enzymes such as thioredoxin (Trx) and the selenoenzyme thioredoxin reductase (TrxR) which integrate the thioredoxin system. In fact, it has been shown that inhibition of this system by MeHg is a critical step in the unfolding of cell death. Current clinical approaches to mitigate the toxicity of MeHg rely on the use of chelators, such as meso-2,3-dimercaptosuccinic acid (DMSA) which largely replaced British anti-Lewisite or 2,3-dimercapto-1-propanol (BAL) as the prime choice. However, therapeutic efficacy is limited and therefore new therapeutic options are necessary. In this work, we evaluated the efficacy of a macrocyclic chelator, 1-thia-4,7,10,13-tetraazacyclopentadecane ([15]aneN4S), in preventing MeHg toxicity, namely by looking at the effects over relevant molecular targets, i.e., the thioredoxin system, using both purified enzyme solutions and cell experiments with human neuroblastoma cells (SH-SY5Y). Results showed that [15]aneN4S had a similar efficacy to DMSA and BAL in reversing the inhibition of MeHg over purified TrxR and Trx by looking at both the 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) reduction assay and insulin reduction capability. In experiments with cells, none of the chelating agents could reverse the inhibition of TrxR by MeHg, which corroborates the high affinity of MeHg to the selenol in TrxR active site. [15]aneN4S and BAL, unlike DMSA, could prevent inhibition of Trx, which allows the maintenance of downstream functions, although BAL showed higher toxicity to cells. Overall these findings highlight the potential of using [15]aneN4S in the treatment of MeHg poisoning and encourage further studies, namely in vivo.

Corn (Zea mays L.): A low methylmercury staple cereal source and an important biospheric sink of atmospheric mercury, and health risk assessment.

In mercury (Hg) contaminated areas of Asia, human exposure to toxic methyl-Hg (MeHg) through a rice-based diet of locally produced crop may pose a health threat. Alternative cropping system to rice in such areas would be most desirable. In this study, corn, the leading cereal source in the world with large biomass, was demonstrated to accumulate an insignificant amount of MeHg from the soil in its edible portion compared to that in rice, suggesting corn being a very competitive alternative crop. By examining Hg stable isotope composition, Hg in the aerial parts of corn was found to be mostly from the atmosphere. Maize cropping worldwide is estimated to be a discemible sink of atmospheric Hg with approximately 44 Mg Hg accumulated in each growing season on a yearly basis, most of which is from foliar uptake of atmospheric Hg and this amount is comparable to litterfall Hg observed in North America and Europe. It is thus recommended to use corn as a replacement of rice in highly Hg-contaminated areas for remediation of Hg pollution in the food supply.

Assessment of potential mercury toxicity to native invertebrates in a high-gradient stream.

This study evaluated potential effects of mercury (Hg) on benthic macroinvertebrates in the South River, Virginia, USA. The study used a multiple lines of evidence approach, including spatially and temporally matched sediment chemistry, biological, and toxicological information (Sediment Quality Triad), exposure and effect analysis in bulk and interstitial sediment and interstitial water, and critical body residue analysis. Ten-day Chironomus dilutus and Hyalella azteca toxicity tests established site-specific no-effect concentrations (NOEC) at 18.9 µg/g total Hg (THg) and 102 ng/g methylmercury (MeHg). However, the benthic community at these locations was impaired, with lower mayfly and caddisfly composition. Few locations had concentrations of THg and MeHg that exceeded the NOEC in bulk or interstitial sediment. The THg concentrations in interstitial water were far below concentrations expected to reduce survival in benthic invertebrates, and only a low percentage of samples exceeded sublethal (growth) low-effect concentrations (LOEC) for THg or MeHg. The THg concentrations in invertebrate tissue did not exceed the NOEC or LOEC in the South River, and MeHg concentrations exceeded the LOEC at all locations, including those with no evidence of benthic impairment, illustrating the uncertainty associated with this line of evidence. Finally, statistical modeling that evaluated diversity of sensitive invertebrate species as a function of Hg exposure, geomorphological parameters, and physicochemical variables indicated that physicochemical and geomorphological parameters were most predictive of benthic community; where Hg was indicated, we were unable to distinguish between models with or without interstitial water Hg. Overall, the lines of evidence indicate that Hg, while clearly toxic to invertebrates at sufficiently high exposure concentrations, is not negatively impacting invertebrate communities in the South River. This study illustrates the difficulty of assessing risks to invertebrates using traditional tools of risk assessment and identifies critical gaps in knowledge that complicate the management of Hg risk. Integr Environ Assess Manag 2019;00:000-000. © 2019 SETAC.

The implications of following dietary advice regarding fish consumption frequency and meal size for the benefit (EPA + DHA and Se) versus risk (MeHg) assessment.

Fish contain healthy nutrients, such as ω3 polyunsaturated fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which protect against cardiovascular disease, and selenium (Se), which reduces methylmercury (MeHg) toxicity. Fish are also a dietary source of MeHg. This requires an assessment of the benefits versus risks. A risk-benefit evaluation showed that blue shark regardless of the way it is cooked generated high probabilities of surpassing the MeHg tolerable weekly intake (TWI), >22%. In tuna, boiling and grilling led to higher MeHg risks than canning, 6-37% versus <7%. EPA + DHA contributed for the prevention of coronary disease. With exception of blue shark, Se neutralised MeHg toxicity. Higher MeHg risk was associated with blue shark and boiled and grilled tuna consumption. For tuna, however, high Se content after boiling and grilling may mitigate MeHg risk.

Probabilistic Integrated Human Mixture Risk Assessment of Multiple Metals Through Seafood Consumption.

Inorganic arsenic (iAs), cadmium (Cd), lead (Pb), and methylmercury (MeHg) are toxic metals that cause substantial health concern and are present in various seafood items. This study linked probabilistic risk assessment to the interactive hazard index (HIINT ) approach to assess the human mixture risk posed by the dietary intake of iAs, Cd, Pb, and MeHg from seafood for different age populations, and joint toxic actions and toxic interactions among metals were also considered in the assessment. We found that, in combination, an iAs-Cd-Pb-MeHg mixture synergistically causes neurological toxicity. Furthermore, an iAs-Cd-Pb mixture antagonistically causes renal and hematological effects and additively causes cardiovascular effect. Our results demonstrated that if toxic interactions are not considered, the health risk may be overestimated or underestimated. The 50th percentile HIINT estimates in all age populations for neurological, renal, cardiovascular, and hematological effects were lower than 1; however, the 97.5th percentile HIINT estimates might exceed 1. In particular, toddlers and preschoolers had the highest neurological risk, with 0.16 and 0.19 probabilities, respectively, of neurological HIINT exceeding 1. Saltwater fish consumption was the principal contributor to the health risk. We suggest that regular monitoring of metal levels in seafood, more precise dietary surveys, further toxicological data, and risk-benefit analysis of seafood consumption are warranted to improve the accuracy of human mixture risk assessment and determine optimal consumption.

Screening-level risk assessment of methylmercury for non-anadromous Arctic char (Salvelinus alpinus).

Non-anadromous forms of Arctic char (Salvelinus alpinus), those that are restricted to lakes and rivers, typically have higher mercury (Hg) concentrations than anadromous forms, which migrate to and from the sea. Using tissue burden data from the literature and our own analyses, we performed a screening-level risk assessment of methylmercury (MeHg) for non-anadromous Arctic char. Our assessment included 1569 fish distributed across 83 sites. Site-specific mean total Hg concentrations in non-anadromous Arctic char muscle varied considerably from 0.01 to 1.13 µg/g wet weight, with 21% (17 of 83 sites) meeting or exceeding a threshold-effect level in fish of 0.33 µg/g wet weight, and 13% (11 of 83 sites) meeting or exceeding a threshold-effect level in fish of 0.5 µg/g wet weight. Of the sites in exceedance of the 0.33-µg/g threshold, 7 were located in Greenland and 10 in Canada (Labrador, Nunavut, and Yukon). All but one of these sites were located in interfrost or permafrost biomes. Maximum total Hg concentrations exceeded 0.33 µg/g wet weight at 53% of sites (40 of the 75 sites with available maximum Hg values), and exceeded 0.5 µg/g wet weight at 27% (20 of 75 sites). Collectively, these results indicate that certain populations of non-anadromous Arctic char located mainly in interfrost and permafrost regions may be at risk for MeHg toxicity. This approach provides a simple statistical assessment of MeHg risk to non-anadromous Arctic char, and does not indicate actual effects. We highlight the need for studies that evaluate the potential toxic effects of MeHg in non-anadromous Arctic char, as well as those that aid in the development of a MeHg toxic-effect threshold specific to this species of fish. Environ Toxicol Chem 2019;38:489-502. © 2018 SETAC.

Burden of Mild Mental Retardation attributed to prenatal methylmercury exposure in Amazon: local and regional estimates.

The gold rush in the Amazon Region caused an increase of mercury (Hg) levels in the environment, and, consequently, raised human exposure. Once released into aquatic systems, Hg could generate methylmercury (MeHg), an extremely toxic compound, which is accumulated through trophic chains. Several studies have provided evidences of the brain sensitivity to MeHg, as well as, of the fetus vulnerability during pregnancy. The main objective of this study was to estimate the Mild Mental Retardation (MMR) in Amazonian populations, caused by prenatal exposure to MeHg, using the methodology proposed by Poulin (2008), which quantifies the environmental burden of disease. The estimates of the MMR burden, attributed to prenatal MeHg exposure, were based on the calculation of Disability-Adjusted Life Years (DALY), which were obtained from MMR incidence rate in the studied populations. At the local level, the MMR incidence rate calculations were based on primary data of MeHg exposure of riverine women at childbearing age. The MMR incidence rate was equal to 5.96/1,000 infants, which would result in 2.0 IQ points loss in 34.31% of the newborns. The estimated DALY/1,000 infants was equal to 71.2, while the DALY was 576. For the regional estimates, different exposure scenarios were created. The calculated DALY varied from 3,256 to 65,952 per year.

[Mercury as a Global Pollutant and Mercury Exposure Assessment and Health Effects].

Mercury and its compounds are classified into three main groups: metallic mercury (Hg0), inorganic mercury (Hg2+), and organic mercury (methyl mercury: CH3Hg+, 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.