G14 (III) Health effects of mercury

Different forms of mercury have different behaviors, target organs and biochemical effects on the human body. While methylmercury often gets the press and research spotlight for toxicity due to the easy assimilation from fish and ready crossing of the blood brain barrier, inorganic mercury is a more cytotoxic form due to its multiple binding sites and higher ligand affinities. In fact, recent environmental data is showing inorganic mercury more clearly correlating with toxic effects of mercury in wildlife. People with dental amalgams are exposed to a steady stream of this form of mercury often for many decades.

Despite the obvious potential problem associated with chronic low-level exposure to mercury vapor and corrosion products from the amalgams, relatively little attention has been paid to measuring this exposure separately from methylmercury exposure from fish. Conventional analytical techniques have always had difficulty separating the effects of fish consumption from dental amalgam exposure, and urine levels have always been difficult to correlate with blood total mercury levels.

Automated mercury speciation analysis of blood provides a comprehensive view into levels of exposure of both inorganic and methylmercury, which clearly need separate measurement and separate reference ranges. Comparison of blood inorganic mercury to urinary mercury output provides a very intriguing and clinically useful measure of retention of this form of mercury and helps resolve one of the dilemmas of urinary markers – i.e. why do urinary levels not correlate with toxicity measures?

We will review the analytical system used for this and present data from close to 1000 patients analyzed with this method, with focus on clinical expression of health problems and cases that would have been missed with conventional analytical techniques.

Exposure to methylmercury from fish and marine mammal consumption continues to present a public health concern in Canada and elsewhere. Recently, Health Canada proposed revised interim blood methylmercury guidance values in order to reflect the increased sensitivity of vulnerable populations to methylmercury toxicity. The revised Health Canada guidance value of 8µg meHg/L is applicable to children ≤18 years, pregnant women and women of child-bearing age, while the existing blood methylmercury guidance value of 20µg meHg/L is applicable to males >18 years and females ≥50 years.

The Canadian Health Measures Survey (CHMS) is a national health survey that collects data on the general health and lifestyles of Canadians in order to provide information on chronic and infectious disease, physical fitness, nutrition, and other factors that influence health. As part of the survey, blood samples were collected from participants and analysed for levels of environmental chemicals, including total mercury. Total blood mercury values for the general Canadian population are presented as geometric mean, 10^th percentile, and 95^th percentile, with associated 95% confidence intervals. Statistical analyses were based on weighted data. Data were analysed according to age-sex categories that correspond to the newly revised interim blood methylmercury guidance values.

The geometric mean total blood mercury values in females from 6-18 years, females from 19-49 years, and males ≤18 years were 0.31µg/L, 0.77µg/L, and 0.27µg/L, respectively. The geometric mean total blood mercury values in females ≥50 years and males >18 years were 0.91µg/L and 0.82µg/L, respectively.

The CHMS provides the first national estimates of blood mercury concentrations in Canada. Combined with Health Canada’s revised interim blood methylmercury guidance values, these data allow us to better identify those population groups who are at increased risk of health effects.

A framework is proposed to reduce mercury accumulation in infants’ brains from all sources of mercury exposure to pregnant mothers. The risk science concerning mild mental retardation in children from exposure to mercury will be detailed and interventions proposed to reduce these mercury exposures using the McLaughlin framework for population health risk assessment. Mild mental retardation in children has occurred as a result of foetal exposure to mercury through transport of mercury across the placenta from pregnant mothers with mercury levels previously considered safe. The general public’s highest exposure to mercury is from mercury dental amalgam fillings, while methylmercury in fish is the greatest exposure for subgroups that eat contaminated fish as their primary source of protein. Elucidation of the biological mechanism of absorption of mercury, and its subsequent transport and metabolism, explains how inorganic mercury accumulates in the brain following exposure to any species of mercury. The developing brain of a foetus is especially susceptible. In 1999, the US EPA mandated the removal of thimerosal, a mercury containing preservative, from all vaccines given during early childhood to protect healthy development of the brain in children. However, pregnant women and young children are still exposed to other forms of mercury that could result in similar levels of mercury in the brain and thus have the potential to damage brain development of infants. The interventions proposed in this study would reduce mercury exposures from all sources to women who are planning to become pregnant and to young children. Screening would be used to identify the susceptible subgroups, those with higher blood mercury levels or having the mercury sensitive APOEe4 genotype. Those in the susceptible subgroups would have their mercury exposure reduced through removal of mercury fillings, through recommendation to have only the mercury-free flu vaccine, and advice to avoid eating fish with high mercury content, such as tuna. This study presents an economic analysis of the costs and benefits of interventions to reduce mercury exposures in women who are planning to become pregnant in order to reduce the occurrence of mild mental retardation in children exposed to mercury in-utero.

Zinc smelting and chlor-alkali production were both major sources of mercury (Hg) contamination to the environment, potentially leading to serious impacts on the health of the local population. Huludao, northeast of China has been heavily contaminated by Hg due to a long-term zinc smelting and chlor-alkali production. The aim of this work was to analyze the effect of Hg exposure to human due to diet and dust in Huludao. The investigation included: (a) Hg accumulation in diet, dust and hair (b) Hg intake through diet and dust, and (c) assessment of potential health effects of Hg exposure associated with total mercury (T-Hg) concentrations in human hair. T-Hg concentrations in hair of the human population varied from 0.05 to 3.25 mg kg^-1 (average 0.43 mg kg^-1). Age is an important factor influencing T-Hg concentrations in hair, although no significant correlation between age and T-Hg in hair (r=0.024, p>0.05) was observed. The highest mean value for T-Hg concentration was 0.51 mg kg^-1, and occurred in the 26~45 age group. T-Hg levels in females are higher than in males. There was no significant difference between THg in hair from different districts based on T test (P>0.05). In general, food consumption was identified as the major pathway of human exposure, accounting for > 90% compared to other ways of exposure such as inhalation and dermal contact. The Hg intakes due to dust and diet were 0.0004-0.003 and 0.038-0.050µg kg^-1 day^-1. The adults and children in Huludao will not be presented with a significant potential health risk by the intake Hg from diet. The frequency of paraesthesia to most inhabitants in Huludao was estimated to be lower than 5%, with only one person rated at 50%. A trivial adverse health effect of Hg exposure to the inhabitants of Huludao, despite of the serious Hg contamination in the environment.

Methylmercury (MeHg) is an environmental neurotoxicant.In general, human exposure to MeHg occurs primarily through the consumption of fish. Because the developmental effects of prenatal exposure are of special concern, the tolerable weekly intake for pregnant women (TWI, 2.0 µg/kg BW/week) was proposed in Japan. However, the validity of the TWI is influenced by assumptions such as the biological half-life of mercury and the ratio of its concentration in hair to that in blood. To endorse the validity of TWI, it would be crucial to clarify the kinetics of MeHg in human blood and hair in details. We conducted an intervention study of MeHg exposure to scrutinize the variation of the ratio of the hair-to-blood mercury concentration. Twenty-seven healthy volunteers were exposed to MeHg at the provisional tolerable weekly intake for Japanese adult (3.4 µg/kg BW/week) through bigeye tuna and swordfish consumption during the initial 14-week period, and after that, observation continued for another 15 weeks.

Blood was collected every 1 or 2 weeks. Hair was cut every 4 weeks, and full-length hair was also cut at the 21st week. The full-length hair samples of the eight female subjects were cut into 3 ~ 6 mm segments corresponding to 1 ~ 2 weeks of growth. Total mercury (T-Hg) content of blood and hair were analyzed by CVAAS and CVAFS, respectively.

The T-Hg levels of blood and hair changed significantly with time (p < 0.001). The peak levels of T-Hg were 26.9 ± 6.8 ng/g in blood, and 8.8 ± 2.0 µg/g in hair.

The calculated biological half-lives of T-Hg were 94.1 ± 22.6 days in blood, and 102.2 ± 30.8 days in hair. The mean ratio of the hair-to-blood T-Hg for entire period was 345 ± 102 (range 123 ~ 617). The time lag for the transition from blood to hair was between 1 and 3 weeks. Various patterns of the change of the ratio of segmental hair-to-blood T-Hg were observed. It was suggested that the ratio of hair-to-blood T-Hg was influenced by the time lag or elimination speed, and that large individual variations existed. For this reason, the uncertainty factor may have to become larger than the previously used ones to endorse the safety level in calculating the TWI of MeHg.

Objectives: In small-scale gold mining areas in many developing countries, mercury (Hg) is used to extract gold from ore.

Methods: Data of 1278 participants from Indonesia, Mongolia, Philippines, Tanzania, and Zimbabwe were combined to analyze the relation between exposure in small-scale gold mining areas and body burden.

Four groups were selected relating to their intensity of contact with mercury: (i) a non exposed control group; (ii) a low exposed group with participants only living in mining areas, but not working as miners; (iii) a medium exposed group, miners living in exposed areas and working with mercury without smelting amalgam; and (iv) a high exposed group, miners living in exposed areas and smelting amalgam. The Kruskal–Wallis was used to test for possible differences over all groups for the amount of mercury between the various exposed groups. Furthermore, the Mann-Whitney U test was performed to compare the different exposure groups to the control group.

Results: Compared to the non-exposed control group, participants living and/ or miners working in highly exposed areas have significant higher values of mercury in urine, hair and blood. (p-value < 0.001) The median mercury value in urine in the control group is < 0.2 µg/l. In the high exposed group of amalgam smelters, the median in urine is 11.9 µg/l (max. 5240 µg/l). The median in blood in the control group is < 0.91 µg/l. The median level in blood of the high exposed group is 7.61 µg/l (max. 429 µg/l). The median for total mercury in hair samples from the control group is 0.21 µg/g. In the high exposed group the median hair concentrations are 2.43 µg/g (max. 239 µg/g). The levels differ as well considerably between the countries, reflecting a diverse background burden due to different fish eating habits and different work place methods.

Conclusions: Compared to threshold values a high percentage of exposed participants had levels above threshold values. These high levels of mercury are likely to be related with serious health problems.

Over the last three decades there has been increasing global concern against mercury toxicity over the public health impacts attributed to environmental pollution, in particular, the global burden of diseases. Mercury pollution is one such major area of concern. It is one of the most widely diffused and hazardous organ-specific environmental contaminant. Organic mercury, a systemic poison is posing a serious health problem. Its toxicity first came to public attention by way of the Minamata and Iraqi tragedies. It is one of the most common heavy metal, which is used for more then 3000 years in medicine, industries and used therapeutically as a cathartic, diuretic, in dental amalgam as well as folk remedies. It is a potent neurotoxin that can bind to many enzymes by crossing of blood brain barrier. Present investigation was conducted to assess the protective effects of NAC along with Zn/Se against DMM. Acute mercury exposure revealed elevation in AST, ALT, ALP, LDH activities, however, changes were noticed in LPO, GSH, AH, AND, AChE variables. Chronic DMM exposure produced alterations in LPO, GSH, GR, GPx, G-6-PDH, AChE, ATPase, mercury concentration. To further enhance the efficacy of NAC, it was supplemented with Zn & Se. In which, NAC+ Zn+ Se proved to be most efficacious in mercury mobilization, recoupment in biochemical variables. Histopathological, ultrastructural/ DNA damage observations substantiated above findings.

Selenium is an essential element, with clearly shown benefits to health, and, if in deficiency, is connected with ill health and vulnerability to diseases. However, selenium is toxic in higher doses, and the actual margin between deficiency and toxicity onset very narrow. Therefore, caution is advised in selenium administration, especially in its inorganic form.

Selenium has also been shown to counteract toxicity of mercury and methylmercury in animals, as for example in rats exposed to different doses of methylmercury.

[1] It is suggested that ingestion of selenium has an antagonistic effect and counteracts toxicity, for example when methylmercury is taken up via marine fish.
[2] Recent research suggests that not the mercury or methylmercury concentration is the determining factor for the onset and severity of methylmercury’s toxic action, but rather the molar Hg:Se ratio. [3]

These studies have been mainly concern with animals, and carnivorous diet in humans. Rice has also been shown to be a potential source of dietary methylmercury when grown in contaminated paddy fields. Rice grains can contain substantial amounts of methylmercury, and in some areas rice is the main source for methylmercury exposure to humans. [4]

In the presented research we exploit whether Selenium, if supplemented to the irrigation water, influences the toxicity of mercury in rice plants. We report on EC 50 values obtained for plant growth under the influence of mercury, with and without supplement of selenium to the nutrient solution, and the uptake of mercury and selenium into the plants investigated.

[1] Ralston et al., NeuroToxicology, 29, 802, 2008
[2] Ralston, EcoHealth, 5, 442, 2008
[3] Khan and Wang, Environmental Toxicity and Chemistry, 28, 1567, 2009
[4] Zhang et al., Environmental Health Perspectives, 118, 1183, 2010