G14 (II) Health effects of mercury

Dental amalgam is 50% metallic mercury by weight and mercury vapour continuously evolves from in-place dental amalgam. Increased Hg content with increasing amalgam load is observed in urine, feces, exhaled breath, saliva, blood, and various organs and tissues including the kidney, pituitary gland, liver, and brain. Hg content also increases with maternal amalgam load in amniotic fluid, placenta, cord blood, meconium, various fetal tissues including liver, kidney and brain, in colostrum and breast milk.

Exposure and risks from dental amalgam have not been re-examined for more than 15 years. Based on 2001 to 2004 population statistics for the United States, 181.1 million Americans of all ages carry a grand total of 1.46 billion restored teeth. Based on past dental practice, and recently available data on the relative use of different restorative materials, the majority of these restorations are composed of dental amalgam.

Employing these recent US population-based statistics on body weight and the frequency of dentally restored tooth surfaces in the US population, estimates of Hg exposure from amalgam fillings were determined for 5 age groups of the US population. Children as young as 26 months were recorded as having restored teeth. Four specific exposure scenarios were considered. Based on the least conservative of these scenarios, predicting the lowest levels of exposure, it was estimated that some 67.2 million Americans would exceed the Hg dose associated with the reference exposure level (REL) of 0.3 ug/m³ established by the US Environmental Protection Agency, whereas 122.3 million Americans would exceed the dose associated with the REL of 0.03 ug/m³ established by the California Environmental Protection Agency. Average exposure estimates amount to 0.2 to 0.4 µg/day per filled tooth surface, or 0.5 to 1 µg/day/filled tooth, depending on age and other factors. This work is based on a report used by the US FDA as a centerpiece of its December 2010 Expert Panel review of the safety of dental amalgam.

Purpose: In 1970, mercury contamination from a sodium hydroxide factory was reported in Ontario, Canada, and patients having neurological symptoms were discovered in aboriginal settlements. As same as the Minamata disease cases in Japanese, patients with all or part of Hunter-Russell syndrome have been reported in Canada. But all researchers have not admitted the presence of Minamata disease in Canada. So we did a health survey including neurological symptoms and quantitating sensory measurements and tried to reevaluate the effect by methylmercury in 2010.

Method: In March, 2010, we performed a survey in Grassy-Narrows, Ontario, Canada. We studied subjective symptoms, neurological findings, quantitative sensory measurements including minimal tactile sensation, vibration, position sense, two-point discrimination of 91 residents. Population in Grassy-Narrows settlements is about 800 at present. We classified 80 people who were older than 15 years into two groups. (1)Group CY: 36 residents who were form 16 to 45 years old (M/F=18/18, 34.4+-9.5 years old). (2)Group CO: 44 residents who were from 46 to 76 years old (M/F=19/25, 57.5+-8.1). We compared them to (3)Group JE: 88 methylmercury-exposed people around Minamata district (M/F=38/50, 59.0+-7.5), and (4)Group JC: 164 control residents in non-polluted areas in Japan (M/F=67/97, 58.4+-11.6).

Results: In group CO, most subjective symptoms were as high as group JE and were correlated. Subjective symptoms of group CY were located in the intermediate between group CO and JC. Positive neurological findings were highest in group JE and group CO, and CY were followed. Positive neurological findings were correlated among groups CY, CO, and JE. In quantitative sensory measurements, data of group CO were as poor as group JE. In general, group CY was located in the intermediate between group CO and JC.

Discussion: Nerulogical symptoms and signs observed in the residents in Grassy-Narrows were the same as Japanese Minamata disease patients, and most of them are supposed to have health effects by methylmercury.

Background:
Visual functions are known to be sensitive to toxins such as mercury (Hg) and lead (Pb), while omega-3 fatty acids (FA) and selenium (Se) may be protective. In the Tapajós region of the Brazilian Amazon, all of these elements are present in the local diet.

Objectives:
Examine the associations between near and distant visual acuity, near visual contrast sensitivity and color vision and biomarkers of Hg, Pb, omega-3 FA and Se.

Methods:
Biomarkers of Hg (hair, whole blood, plasma, urine), Pb (whole blood), Se (hair, whole blood, plasma, urine), and omega-3 FA (plasma total phospholipids) were measured. Optometrists carried out complete visuo-ocular examinations. Near and distant visual acuity, near visual contrast sensitivity and color vision were assessed in 242 people (≥15 y) without cataracts or ocular pathologies. Multiple linear and logistic regressions were used to examine the relations between visual functions and the biomarkers, taking into account age, sex, drinking, smoking and examiner.

Results:
Near visual acuity was negatively associated with hair Hg and positively associated with %DHA, with a highly significant LogH-Hg*age interaction term. Stratifying for age showed that while young people presented good acuity, in mid-age people (40-66 y), clinical presbyopia was associated with hair Hg (OR = 3.93 [1.25 – 14.18]) and %DHA (OR = 0.37 [0.11 – 1.11]). A similar age-related pattern was observed for distant visual acuity in relation to blood Pb, but the evidence was weaker. Reduced contrast sensitivity at all spatial frequencies was associated with biomarkers of Hg, with the strongest associations for urinary Hg, while the %EPA+DHA was associated to better visual function. The intermediate spatial frequency of contrast sensitivity (12 cpd) was negatively related to blood Pb and positively related to plasma Se. Acquired color vision loss increased with biomarkers of Hg and decreased with plasma Se and to a lesser extent %EPA+DHA.

Conclusions:
These findings suggest that the local diet of riverside communities of the Amazon contain toxic substance that can have deleterious effects on vision as well as nutrients and essential FA that can improve visual function. The association with U-Hg requires further investigation since it may reflect higher chronic exposures. In this population with little access to eye care, a better knowledge of the nutrient content and health effects of traditional foods would be useful to minimize harmful effects of Hg and Pb exposure.

Methylmercury is a worldwide contaminant found in seafood and freshwater fish. It is a well-established neurotoxicant that can have serious adverse effects on the developing nervous system. Recent evidence has suggested that methylmercury may promote or predispose to the development of heart disease. We examined 713 Faroese residents aged 70-74 years (64% of eligible population) to assess possible adverse effects within a wide range of methylmercury exposures from the consumption of pilot whale meat. Exposure levels were assessed from mercury analysis of whole blood obtained at the time of clinical examination. Outcome measures include heart rate variability (HRV), blood pressure (BP), and common carotid intima-media thickness (IMT). Multiple regression analyses were carried out to determine the confounder-adjusted effect of mercury exposure. Serum long-chain n-3 polyunsaturated fatty acids were also included in the models to adjust for the essential nutrients in fish and seafood which may counteract the adverse effects of mercury. The blood mercury concentrations had a geometric mean of 13.7 µg/L, with a total range of 0.98 to 241 µg/L. The results suggest adverse mercury effects on BP and IMT, although some of the associations were only close to significance. Adjustment with PCB, source of exposure from the consumption of whale blubber, did not substantially change the effects. Further analysis with structural equation models will be performed to take into account the correlations among related outcome measures, categorizing them in groups to derive latent response variables.

The association of mercury with cardiovascular disease is a major public health concern. Fish intake, widely recommended because of beneficial n-3 fatty acids (fish oils), is also a source of methylmercury that may oppose the beneficial effects of fish oils. The evidence base linking mercury to cardiovascular disease is rapidly expanding. Our group, for instance, reported the study of an association between mercury levels in toenails, largely reflecting methylmercury intake from fish, with the risk of myocardial infarctions in 8 European countries and Israel. However, several gaps remain in the evidence base. Additional research is needed to establish the potencial mechanisms responsible for the cardiovascular effects of mercury, as well as the intermediate physiological cardiovascular processes affected by mercury exposure. In terms of population studies, additional evidence is needed to better characterize the association between mercury and cardiovascular disease in women as well as the precise form of the dose-response relationship in the general population. The potential existence of subgroups at particularly high risk from mercury exposure also needs additional investigation. The type of research studies needed to complete our understanding of the cardiovascular effects of mercury will be discussed in the session.

More and more data suggest that the cardiovascular system should be considered a potential target for mercury. For example, work conducted in the Faeroe Islands in children and in Greenland suggests associations between mercury exposure and blood pressure and heart beat variability which are known risk factors for cardiac health. Other studies conducted in Europe suggest association between mercury and increase risk of myocardial infarction. We have studied three large remote fish eating communities in the Arctic, sub Arctic and South Pacific which are exposed to high doses of mercury (3 adults and 1 child cohort) Mercury was measured in blood as well as potential confounding nutritional factors (e.g selenium, n-3 fatty acids) and Paraoxanase (PON) 1 activity. Heart Rate Variability (HRV) and blood pressure were also measured in these 4 cohorts. Mercury concentrations in blood averaged 86, 75, 49 and 81 nmol/L in adults from Nunavik, (Arctic Québec), South Pacific islanders, James Bay Crees Indians and Inuit newborn respectively. In most of these studies we found that mercury exposure was associated with decrease HRV and increase blood pressure. For example, in Inuit adults, we found that a 10 percent increase in blood mercury was associated with an increase of 0.2 mm Hg in systolic blood pressure after controlling for other factors. Concerning biomarkers, our results suggest that Hg exposure exerts an inhibitory effect on PON1 activity, which seems to be offset by selenium intake.Since heart diseases represent the most important causes of death, even a slight negative impact on the cardiovascular system could be of greater public health relevance than any other health effects related to mercury exposure.

The developing fetal brain is the most susceptible organ to methylmercury (MeHg) toxicity and we wished to explore the kinetics of maternal-fetal transfer (in the mouse) under steady-state and "bolus dose" intakes of MeHg by the dams. To do this we dosed animals with MeHg chloride during pregnancy, either by administering a constant dose throughout, or where this constant dose was supplemented by ‘bolus’ doses on two occasions in mid-to-late gestation. This bolus dose approach was an attempt to represent (in this animal model) one example of a human consumption pattern for fish, in pregancy, where the MeHg content (or intake) was elevated. Analysis of MeHg was determined using a new method (and compared to an ICPMS method) which involved application of a head-space micro-extraction technique utilizing isotopic dilution with GC/High resolution mass spectrometry, to measure native and enriched isotopic (202Hg) methylmercury in blood and brain tissues. Data are presented for maternal and new-born blood and brain MeHg concentrations, including data showing the proportion of the total MeHg originating from the two administered bolus doses. The results confirm the previously observed findings that newborn animals have approximately twice the brain concentrations of MeHg compared to their mothers, and also provide additional understanding on the kinetics of methylmercury distribution following intake of bolus doses. The implications of these findings for interpreting how different patterns of consumption in human MeHg exposure affect tissue levels are discussed, as are possible applications of this MeHg isotope tracer method in future kinetic studies.

Evidence of a dose-response relationship between prenatal exposures to methylmercury (MeHg) and neuro-developmental disorders suggests the need for an evaluation of the economic consequences of MeHg-mediated neurotoxicity. The effects of MeHg exposure in children include a reduction of IQ and therefore generate societal costs. The latter have been estimated in some other countries, but not in France. So the purpose of our research was to assess the French health impacts and costs due to MeHg exposure.

We used data on hair-mercury concentrations in French samples of childbearing age women (18-45 years). These data were collected from three sources. The first came from a sample of 126 women at the national level (InVS 2006-2007). The second consisted of two sets of data available from two French coastal regions (n=161 and n=503, respectively). We converted these results into cord blood concentrations that have been used for dose-response relationships. A linear dose response function with a slope of 0.093 [0.059–0.124] IQ points per µg/L increase of the cord-blood mercury concentration was based on the recommendations by the U.S. National Research Council. We used an updated estimate of €₂₀₀₈ 17,363 per IQ point decrement for the calculation of costs. We conducted a sensitivity analysis using three cut off points for MeHg neurotoxicity (2.9, 5, and 12.5 µg/L). We then compared the French national results with those based on regional exposure estimates.

On the basis of national data, we estimated a mean annual economic impact of €0.73 billion, €0.34 billion, €0.02 billion, respectively using the three different points. Above 2.90 µg/L, we estimated mercury-related losses of cognitive function ranging from 0.20, 0.89 and 2.10 IQ points/person and a loss of €3,473, €15,453 and €36,462/person at 5 µg/L, at 12.5µg/L and at the maximum, respectively. Above 5µg/L, we estimated a loss of 0.70 and 1.91 IQ points/person and a loss of €12,154 and €33,163/person at 12.5µg/L and at the maximum, respectively. Above 12.50µg/L, we estimated a loss of 1.21 points/person and a loss of €21,009/person at the maximum.

These results highlight how reduction of exposures to this pollutant could have high social benefits for France. These benefits should be taken into account when considering options for controlling mercury emissions to protect the most highly exposed and vulnerable populations.