Low-level Methylmercury Exposure Research Articles

Epigenetic alternations in the SYP and DLG4 genes due to low-level methylmercury exposure during neuronal differentiation in vitro.

Methylmercury (MeHg) is an environmental toxin known to damage the central nervous system. When pregnant women ingest seafood, which may contain accumulated MeHg, fetal development may be affected. The embryonic period, a time of major epigenetic change, is susceptible to epigenetic disruptions due to chemical exposure. Therefore, understanding the molecular mechanism underlying MeHg's effects on neuronal development requires consideration of epigenetic factors. In this study, we investigated epigenetic modifications in the synaptophysin (SYP) and discs large MAGUK scaffold protein 4 (DLG4) genes. LUHMES cells were exposed to 1 nM MeHg for 6 days during days 2-8 of neural differentiation. MeHg exposure significantly reduced the number of spikes observed on day 16 of differentiation. Both mRNA and protein expression levels of SYP and DLG4 were significantly decreased by MeHg exposure. Additionally, MeHg treatment reduced acetyl histone H3 levels associated with transcriptional activity in the SYP gene while increasing histone H3 lysine 27 tri-methylation (H3K27me3) levels related to transcriptional repression. Conversely, regarding the DLG4 gene, MeHg exposure increased H3K27me3 levels. Differential changes in DNA methylation (high and low methylation states) were observed in the SYP and DLG4 genes due to MeHg exposure depending on CpG site position. In conclusion, this study suggests that epigenetic changes, particularly histone modifications, contribute to decreased MeHg exposure-induced SYP and DLG4 expression during neuronal differentiation.

The association of auditory function measures with low-level methylmercury from oceanic fish consumption and mercury vapor from amalgam: The Seychelles Child Development Study Nutrition 1 Cohort

BackgroundSome authors have reported that low-level exposure to methylmercury (MeHg) adversely impacts measures of auditory function. These reports, however, are not consistent in their findings. Consequently, we examined auditory function in a population exposed to low-level methylmercury (MeHg) exposure from fish consumption and to mercury vapor (Hg0) from dental amalgams. We analyzed their associations with the participants hearing acuity, absolute and interwave ABR latencies, and otoacoustic emissions (distortion product/DPOAE and click evoked/CEOAE). DesignWe administered an audiometry test battery to 246 participants from the Seychelles Child Development Study (SCDS) Nutrition Cohort 1 (NC1) at 9 years of age. The test battery included standard pure-tone audiometry, tympanometry, Auditory Brainstem Responses (ABR) and Distortion Product and Click Evoked Otoacoustic Emissions (DPOAE and CEOAE) testing. We measured prenatal MeHg exposure in maternal hair and postnatal MeHg in children’s hair. We approximated prenatal Hg0 exposure using maternal amalgam surface area and postnatal Hg0 using children amalgam surface area. Complete exposure records and audiometric data were available on 210 participants and in them we analyzed the association of MeHg and Hg0 exposures with auditory outcomes using covariate-adjusted linear regression models adjusted for sex and tympanometric pressure. ResultsHg exposures were similar for both sexes. Seven of the 210 evaluable participants examined had either a mild (5) or moderate (2) hearing loss. Four had a mild monaural hearing loss and 3 had either a mild (1) or moderate (2) bilateral hearing loss. No participant had greater than a moderate hearing loss in either ear. Hg exposures were higher in participants with either a mild or moderate hearing loss, but these differences were not statistically significant. Among the 210 with complete data, neither prenatal nor postnatal MeHg nor Hg0 exposure was statistically significantly associated with any of the ABR endpoints (p > 0.05 for all 72 associations). Neither prenatal nor postnatal Hg0 exposure was associated with any of the OAE endpoints (p > 0.05). MeHg exposure was statistically associated with 6 of the 56 DPOAE endpoints (p-values between 0.0001 and 0.023), but none of the 40 CEOAE endpoints. Two of the associations occurred with prenatal MeHg exposures and 1 of those would suggest a beneficial effect. Four of the other associations occurred with postnatal MeHg exposures with only 2 found in left ears of both males and females and the other 2 in the left and right ear of females at only one frequency. ConclusionOverall, these data do not present a clear and consistent pattern to suggest that the auditory system is negatively affected by low-level methylmercury exposure due to dietary consumption of oceanic fish or mercury vapor exposure from dental amalgams.

Molecular Fates of Organometallic Mercury in Human Brain.

Mercury is ubiquitous in the environment, with rising levels due to pollution and climate change being a current global concern. Many mercury compounds are notorious for their toxicity, with the potential of organometallic mercury compounds for devastating effects on the structures and functions of the central nervous system being of particular concern. Chronic exposure of human populations to low levels of methylmercury compounds occurs through consumption of fish and other seafood, although the health consequences, if any, from this exposure remain controversial. We have used high energy resolution fluorescence detected X-ray absorption spectroscopy to determine the speciation of mercury and selenium in human brain tissue. We show that the molecular fate of mercury differs dramatically between individuals who suffered acute organometallic mercury exposure (poisoning) and individuals with chronic low-level exposure from a diet rich in marine fish. For long-term low-level methylmercury exposure from fish consumption, mercury speciation in brain tissue shows methylmercury coordinated to an aliphatic thiolate, resembling the coordination environment observed in marine fish. In marked contrast, for short-term high-level exposure, we observe the presence of biologically less available mercuric selenide deposits, confirmed by X-ray fluorescence imaging, as well as mercury(II)-bis-thiolate complexes, which may be signatures of severe poisoning in humans. These differences between low-level and high-level exposures challenge the relevance of studies involving acute exposure as a proxy for low-level chronic exposure.

DNA methyltransferase- and histone deacetylase-mediated epigenetic alterations induced by low-level methylmercury exposure disrupt neuronal development.

Methylmercury (MeHg) is a chemical substance that causes adverse effects on fetal development. However, the molecular mechanisms by which environmental MeHg affects fetal development have not been clarified. Recently, it has been suggested that the toxic effects of chemicals on fetal development are related alterations in epigenetics, such as DNA methylation and histone modification. In order to analyze the epigenetic effects of low-level MeHg exposure on neuronal development, we evaluated neuronal development both in vivo and in vitro. Pregnant mice (C57BL/6J) were orally administrated 3mg/kg of MeHg once daily from embryonic day 12-14. Fetuses were removed on embryonic day 19 and brain tissues were collected. LUHMES cells were treated with 1nM of MeHg for 6days and collected on the last day of treatment. In both in vivo and in vitro samples, MeHg significantly suppressed neurite outgrowth. Decreased acetylated histone H3 (AcH3) levels and increased histone deacetylase (HDAC) 3 and HDAC6 levels were observed in response to MeHg treatment in both in vivo and in vitro experiments. In addition, increased DNA methylation and DNA methyltransferase 1 (DNMT1) levels were observed in both in vivo and in vitro experiments. The inhibition of neurite outgrowth resulting from MeHg exposure was restored by co-treatment with DNMT inhibitor or HDAC inhibitors. Our results suggest that neurological effects such as reduced neurite outgrowth due to low-level MeHg exposure result from epigenetic changes, including a decrease in AcH3 via increased HDAC levels and an increase in DNA methylation via increased DNMT1 levels.

Prenatal low-level methyl mercury exposure and child development in an Italian coastal area

Environmental studies have identified mercury pollution in the Northern Adriatic Sea (Italy). High- level methyl mercury exposure is a known cause of neurodevelopmental disorders. However, the exposure-effect relation at levels <10ppm is controversial. To assess the possible health effects of prenatal methyl mercury exposure through maternal fish consumption, we conducted an epidemiologic cohort study in a mercury polluted area of the Adriatic Sea. We identified all the children born between 1999 and 2001 to women who were resident in two coastal fishing towns. A comparison group was identified inland. A total of 243 children were enrolled. Their mothers were interviewed approximately two months after delivery to determine a variety of covariates and the type, quantity and origin of fish consumed during pregnancy. Total mercury (THg) and methyl mercury (MeHg) were assessed in maternal hair and breast milk and in the child's hair. The children were evaluated after age 18 months with a physical examination and the Denver Developmental Screening Test II (DDST II). Statistical analyses matched by residential area are not presented since they were not associated with fresh fish consumption, THg or MeHg exposure level or neurodevelopmental outcomes. To date 52 children have been evaluated. After adjustment for a number of potential confounders, preliminary results indicate that the fine motor adaptive score on the Denver Developmental test is inversely related to maternal hair THg. These pilot findings are suggestive of an association between children's fine motor skills and their prenatal methyl mercury exposure from maternal fish consumption. However, only a small number of the cohort have been tested and more extensive testing with more sensitive and specific tests is needed to determine if these findings persist.

Color vision impairment with low-level methylmercury exposure of an Amazonian population – Brazil

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

Low-level methylmercury exposure through rice ingestion in a cohort of pregnant mothers in rural China

BackgroundRice ingestion is an important dietary exposure pathway for methylmercury. There are few studies concerning prenatal methylmercury exposure through rice ingestion, yet the health risks are greatest to the developing fetus, and thus should be investigated. ObjectivesOur main objective was to quantify dietary methylmercury intake through rice and fish/shellfish ingestion among pregnant mothers living in southern China, where rice was a staple food and mercury contamination was considered minimal. MethodsA total of 398 mothers were recruited at parturition, who donated scalp hair and blood samples. Total mercury and/or methylmercury concentrations were measured in biomarkers, in rice samples from each participant's home, and in fish tissue purchased from local markets. Additional fish/shellfish mercury concentrations were obtained from a literature search. Dietary methylmercury intake during the third trimester was equivalent to the ingestion rate for rice (or fish/shellfish)×the respective methylmercury concentration. ResultsDietary methylmercury intake from both rice and fish/shellfish ingestion averaged 1.2±1.8µg/day (median=0.79µg/day, range=0–22µg/day), including on average 71% from rice ingestion (median: 87%, range: 0–100%), and 29% from fish/shellfish consumption (median 13%, range: 0–100%). Median concentrations of hair total mercury, hair methylmercury, and blood total mercury were 0.40µg/g (range: 0.08–1.7µg/g), 0.28µg/g (range: 0.01–1.4µg/g), and 1.2µg/L (range: 0.29–8.6µg/L), respectively, and all three biomarkers were positively correlated with dietary methylmercury intake through rice ingestion (Spearman's rho=0.18–0.21, p≤0.0005), although the correlations were weak. In contrast, biomarkers were not correlated with fish/shellfish methylmercury intake (Spearman's rho=0.04–0.08, p=0.11–0.46). ConclusionsAmong pregnant mothers living in rural inland China, rice ingestion contributed to prenatal methylmercury exposure, more so than fish/shellfish ingestion.

Rice consumption contributes to low level methylmercury exposure in southern China

Fish consumption is considered as the primary pathway of human methylmercury (MeHg) exposure. However, recent studies highlighted that, rice, rather than fish, is the main route of human MeHg exposure in Guizhou, inland China. China is considered as the largest anthropogenic source of mercury (Hg) emission in the world, which has led to serious environmental Hg pollution. But there are no comprehensive studies regarding this environmental health problem to evaluate human Hg exposure and associated health effects. This study aimed to estimate daily MeHg intake and health risk in 7 provinces in southern China, and to assess the relative contribution from rice and fish consumption. The average levels of total mercury (THg) and MeHg in rice samples were generally low at 10.1ng·g−1 and 2.47ng·g−1, respectively. But a total of 36 rice samples (12.7%) had THg concentration exceeding the national limit (20ng·g−1). Generally, rural population had significantly higher Probable Daily Intakes (PDIs) of MeHg than urban population from rice consumption and its relative contribution to MeHg exposure increased significantly from coastal to inland area. The averages of PDIs of MeHg were 0.020μg·kg−1·d−1 and 0.028μg·kg−1·d−1 for urban and rural population in southern China, respectively. Despite the serious environmental Hg pollutions in China, the general population in southern China had low risk of MeHg exposure. But rice is an important route of human MeHg exposure in southern China, especially for the rural population in inland area. The findings indicate that rice consumption should be considered when evaluating MeHg exposure in rice eating population in southern China.

Casting a Wider Net: The Quest for Better Guidance on Seafood Consumption

Vol. 120, No. 6 News | Science SelectionsOpen AccessCasting a Wider Net: The Quest for Better Guidance on Seafood Consumptionis accompanied byEvidence on the Human Health Effects of Low-Level Methylmercury Exposure Kellyn S. Betts Kellyn S. Betts Search for more papers by this author Published:1 June 2012https://doi.org/10.1289/ehp.120-a244bView Article in:中文版AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Fish is the primary dietary source of omega-3 long-chain polyunsaturated fatty acids, which are necessary for healthy prenatal development and linked to reducing cardiovascular disease risk. The type and quantity of seafood that individuals choose to eat can impact both their health and the long-term sustainability of the world’s fisheries. An interdisciplinary team of researchers wants consumers to have clearer and more complete guidance in making informed choices about the seafood they eat. Their review presents a framework for producing guidance based not only on nutritional and contaminant information but also ecologic and economic tradeoffs associated with fish consumption choices [EHP 120(6):790–798; Oken et al.].The review highlights areas of overlap and disagreement in current U.S. guidance regarding what constitutes better choices. The myriad fish consumption advice provided by 21 governmental and nongovernmental entities can leave consumers uncertain how to weigh and reconcile multiple benefits and risks associated with any given fish. For instance, the amount of omega-3 fatty acids provided by different fish varies widely, depending on genetics and diet. And where a fish comes from and what it eats can affect its pollutant load—both wild and farmed fish may be high in toxicants such as methylmercury [also see EHP 120(6):799–806; Karagas et al.].More inclusive fish consumption guides might provide information on ecologic and economic impacts as well as nutritional and contaminant information.© Michael Blann/ThinkstockThe authors posit that fish consumption advice should reflect the reality that both fish farming and the harvesting of wild fish can profoundly affect the health of the oceans. The annual global fish catch exceeds the maximum sustainable yield by three to four times, and some forms of fishing can devastate ocean ecosystems. Aquaculture, the world’s fastest-growing food-production industry, may help ensure adequate fish supplies, but it too has adverse ecological impacts.The authors recommend that countries develop national lists of fish that can be eaten freely or moderately and fish that should be avoided. These lists should consider all the perspectives analyzed, although the authors acknowledge the challenges of doing so. Ideally, basic national messages would consist of simple lists supplemented by links to more detailed resources for those who desire them, which could be adjusted on a regional basis as necessary. The authors also reaffirm the importance of remediation or elimination of sources of fish contamination as well as policies that promote environmentally responsible and economically viable fishing practices.FiguresReferencesRelatedDetailsRelated articlesEvidence on the Human Health Effects of Low-Level Methylmercury ExposureJan 24, 2012, 12:00:00 AMEnvironmental Health Perspectives Vol. 120, No. 6 June 2012Metrics About Article Metrics Publication History Originally published1 June 2012Published in print1 June 2012 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact ehponline@niehs.nih.gov. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Evidence on the Human Health Effects of Low-Level Methylmercury Exposure

Background: Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by bene-ficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited.Objectives: We undertook a synthesis of the current knowledge on the human health effects of low-level MeHg exposure to provide a basis for future research efforts, risk assessment, and exposure remediation policies worldwide.Data sources and extraction: We reviewed the published literature for original human epidemio-logic research articles that reported a direct biomarker of mercury exposure. To focus on high-quality studies and those specifically on low mercury exposure, we excluded case series, as well as studies of populations with unusually high fish consumption (e.g., the Seychelles), marine mammal consumption (e.g., the Faroe Islands, circumpolar, and other indigenous populations), or consumption of highly contaminated fish (e.g., gold-mining regions in the Amazon).Data synthesis: Recent evidence raises the possibility of effects of low-level MeHg exposure on fetal growth among susceptible subgroups and on infant growth in the first 2 years of life. Low-level effects of MeHg on neuro-logic outcomes may differ by age, sex, and timing of exposure. No clear pattern has been observed for cardio-vascular disease (CVD) risk across populations or for specific CVD end points. For the few studies evaluating immunologic effects associated with MeHg, results have been inconsistent.Conclusions: Studies targeted at identifying potential mechanisms of low-level MeHg effects and characterizing individual susceptibility, sexual dimorphism, and non-linearity in dose response would help guide future prevention, policy, and regulatory efforts surrounding MeHg exposure.

The effect of methylmercury exposure on early central nervous system development in the zebrafish (Danio rerio) embryo

Much attention is focused on environmental contamination by heavy metals. The heavy metal mercury is found worldwide and is ranked number 3 on the Comprehensive Environmental Response, Compensation and Liability Act substance list. We examined the effect of low-level methylmercury exposure on central nervous system development of wild-type zebrafish embryos (ZFEs) of the AB strain because methylmercury is the most common form of mercury to which humans are exposed in the environment. ZFEs were exposed to nine different concentrations of methylmercury [0 (negative control), 5, 10, 50, 80, 100, 200, 500 and 1000 parts per billion (μg l(-1) )] starting at 6 h post-fertilization, which is the time the neural tube is first beginning to form. ZFEs were exposed to 2% ethanol as positive controls (100% embryonic death). ZFEs were assessed at 30, 54, 72 and 96 h post-fertilization for changes in embryonic development, mortality, time of hatching and morphological deformities. No abnormalities were observed in ZFEs exposed to 5 μg l(-1) methylmercury. The time of hatching from the chorion was delayed in ZFEs exposed to methylmercury concentrations of 50 μg l(-1) or higher. Significantly more ZFEs exposed to 0, 5 or 10 μg l(-1) methylmercury successfully completed hatching compared with ZFEs exposed to 50 μg l(-1) or higher methylmercury. ZFEs exposed to more than 200 μg l(-1) methylmercury exhibited 100% embryonic mortality. The rate of cell proliferation within the neural tube was significantly decreased in embryos exposed to 10, 50 and 80 μg l(-1) methylmercury and there were no differences between these doses.

メチル水銀毒性に関する疫学的研究の動向

More than fifty years have passed since the outbreak of Minamata disease, and large-scale methylmercury poisoning due to industrial effluents or methylmercury-containing fungicide intoxication has scarcely happened in developed countries. On the other hand, widespread environmental mercury contamination has occurred in gold and mercury mining areas of developing countries. In this article, we provided an overview of recent studies addressing human health effects of methylmercury, which we searched using the PubMed of the US National Library of Medicine. The following suggestions were obtained for low-level methylmercury exposure: (1) In recent years, the proportion of human studies addressing methylmercury has tended to decrease. (2) Prenatal exposure to methylmercury through fish intake, even at low levels, adversely affects child development after adjusting for polychlorinated biphenyls and maternal fish intake during pregnancy, whereas maternal seafood intake has some benefits. (3) Long-term methylmercury exposure through consumption of fish such as bigeye tuna and swordfish may pose a potential risk of cardiac events involving sympathovagal imbalance. (4) In measuring methylmercury levels in preserved umbilical cord collected from inhabitants born in Minamata areas between 1945 and 1989, the elevated concentrations (≥1 mg/g) were observed mainly in inhabitants born between 1947 and 1968, and the peak coincided with the peak of acetaldehyde production in Minamata. (5) Since some developing countries appear to be in similar situations to Japan in the past, attention should be directed toward early recognition of a risky agent and precautions should be taken against it.

Recognizing and Preventing Overexposure to Methylmercury from Fish and Seafood Consumption: Information for Physicians

Fish is a valuable source of nutrition, and many people would benefit from eating fish regularly. But some people eat a lot of fish, every day or several meals per week, and thus can run a significant risk of overexposure to methylmercury. Current advice regarding methylmercury from fish consumption is targeted to protect the developing brain and nervous system but adverse health effects are increasingly associated with adult chronic low-level methylmercury exposure. Manifestations of methylmercury poisoning are variable and may be difficult to detect unless one considers this specific diagnosis and does an appropriate test (blood or hair analysis). We provide information to physicians to recognize and prevent overexposure to methylmercury from fish and seafood consumption. Physicians are urged to ask patients if they eat fish: how often, how much, and what kinds. People who eat fish frequently (once a week or more often) and pregnant women are advised to choose low mercury fish.

Relationship between the prenatal exposure to low-level of mercury and the size of a newborn’s cerebellum

Exposure to methylmercury at any stage of central nervous system development could induce alterations and result in severe congenital abnormalities. Total mercury level in maternal hair during pregnancy correlates well with blood levels of methylmercury and with total mercury levels in fetal brain. A prospective study has been conducted and a total of 137 childbearing women living at the coastal region with term, normal pregnancies were included and their newborns evaluated by ultrasonography. Mothers and their newborns are divided in two groups according to their hair mercury levels; examined group with high body levels of mercury (⩾1 μg/g) and control group with low body levels of mercury (<1 μg/g). Neurosonographic examination was conducted to all newborns. Two dimensions of cerebellum in the sagital-medial plane have been measured: maximum height and width starting from the roof of the fourth chamber. Majority of mothers had hair mercury levels lower than 1 μg/g ( N = 107). Mean value was 0.88 μg/g (SD 1.24), ranging from 0.02 to 8.71 μg/g. There was no significant difference between the two groups when it comes to the width of cerebellum (Mann–Whitney test: Z = 1471; p = 0.141). However, comparison related to the length of cerebellum shows statistically significant smaller cerebellum in newborns whose mother had hair mercury levels higher than 1 μg/g (Mann–Whitney test: Z = 2329; p = 0.019). Our results lead to a conclusion that prenatal exposure to, what we consider to be, low-levels of methylmercury does influence fetal brain development detected as decreased size of newborn’s cerebellum. From a clinical point of view, a question related to the influence of prenatal low-level methylmercury exposure on fetal neurodevelopment remains open. Our further objectives are to direct the research towards performing detailed neuropshychological tests on children at the age of 18 months. Such tests could indicate the presence of subtle neurological or neuropsychological deficits.

Neurophysiological evidence of methylmercury neurotoxicity

A variety of neurophysiological measures are useful in hospital settings for diagnostic and other clinical purposes. Previously, abnormal changes in various sensory evoked potentials (EPs), and heart rate variability (HRV) were observed in patients with acquired and fetal Minamata disease (MD; methylmercury poisoning). In recent years, some of these methods have been used for the risk assessment of low-level methylmercury exposure in asymptomatic children. The objectives of this article were to present an overview of neurophysiological findings involved in methylmercury neurotoxicity and to examine the usefulness of those measures. The reports addressing both neurophysiological measures and methylmercury exposure in humans were identified and evaluated. The neurological signs and symptoms of MD included paresthesias, constriction of visual fields, impairment of hearing and speech, mental disturbances, excessive sweating, and hypersalivation. Neuropathological lesions involved visual, auditory, and post- and pre-central cortex areas. Neurophysiological changes involved in methylmercury, as assessed by EPs and HRV, were found to be in accordance with both clinical and neuropathological observations in patients with MD. EPs and HRV appear to be useful and objective methods for assessing methylmercury neurotoxicity. However, subtle changes due to low-level methylmercury exposure may not necessarily be of clinical relevance, and interpretation of small deviations from expectations must be cautious.

Low-Level Methylmercury Exposure as a Risk Factor for Neurologic Abnormalities in Adults

Methylmercury is a neurotoxicant that bio-accumulates in the aquatic food chain and is present in all fish. Little is known about the effects of long-term low-dose exposure to methylmercury in adults. The aim of this study was to determine whether a dose–response relationship exists between long-term methylmercury exposure and neurological abnormalities in aboriginal Quebec Cree adults for whom fish is a dietary staple. We re-analysed data from a 1977 cross-sectional study conducted by Kofman and collaborators on a group of Quebec Cree individuals claiming ill health from local fish consumption. In the original 1977 study, 306 adult participants aged 18–82 years were assessed for methylmercury exposure. Tremor and other neurologic outcomes were assessed with a clinical examination. The investigators did not find clinical evidence of methylmercury intoxication based on an analysis of covariance. We used ordinal regression to obtain odds ratios for the relationship between total hair mercury levels and neurologic abnormalities. Hair mercury concentrations ranged from 0.5 to 46 ppm (parts per million). A 6 ppm increase in hair mercury was associated with increasing levels of tremor (OR, 2.22; 95%CI, 1.15–4.26) in adults under 40 years of age. There was no association with nine other outcomes considered, nor with tremor among older persons. Odds ratios were not influenced by gender, smoking, alcohol use, or co-morbidity. Conclusion: Dose-dependent effects of methylmercury on tremor may occur below the commonly accepted 50 ppm threshold, particularly in young adults. These effects may be detectable by clinical examination. However, the results should be interpreted with caution given that alcohol use was probably under-reported and that multiple outcomes were studied.

Low level methylmercury exposure affects neuropsychological function in adults.

BackgroundThe neurotoxic effects of methylmercury (MeHg) have been demonstrated in both human and animal studies. Both adult and fetal brains are susceptible to the effects of MeHg toxicity. However, the specific effects of adult exposures have been less well-documented than those of children with prenatal exposures. This is largely because few studies of MeHg exposures in adults have used sensitive neurological endpoints. The present study reports on the results of neuropsychological testing and hair mercury concentrations in adults (>17 yrs) living in fishing communities of Baixada Cuiabana (Mato Grosso) in the Pantanal region of Brazil.MethodsA cross-sectional study was conducted in six villages on the Cuiaba River. Participants included 129 men and women older than 17 years of age. They were randomly selected in proportion to the age range and number of inhabitants in each village. Questionnaire information was collected on demographic variables, including education, occupation, and residence history. Mercury exposure was determined by analysis of hair using flameless atomic absorption spectrophotometry. The neurocognitive screening battery included tests from the Wechsler Memory Scale and the Wechsler Adult Intelligence Scale, Concentrated Attention Test of the Toulouse-Pierron Factorial Battery, the Manual Ability Subtests of the Tests of Mechanical Ability, and the Profile of Mood States.ResultsMercury exposures in this population were associated with fish consumption. The hair mercury concentration in the 129 subjects ranged from 0.56 to 13.6 μg/g; the mean concentration was 4.2 ± 2.4 micrograms/g and the median was 3.7 μg/g. Hair mercury levels were associated with detectable alterations in performance on tests of fine motor speed and dexterity, and concentration. Some aspects of verbal learning and memory were also disrupted by mercury exposure. The magnitude of the effects increased with hair mercury concentration, consistent with a dose-dependent effect.ConclusionsThis study suggests that adults exposed to MeHg may be at risk for deficits in neurocognitive function. The functions disrupted in adults, namely attention, fine-motor function and verbal memory, are similar to some of those previously reported in children with prenatal exposures.

Fatal meningococcal septicaemia with “blebbing” meningococcus

1 Clements CJ, Ball LK, Ball R, Pratt D. Thiomersal in vaccines. Lancet 2000; 355: 1279–80. 2 American Academy of Pediatrics, Committee on Infectious Diseases, and Committee on Environmental Health. Thimerosal in vaccines—An interim report to clinicians. Pediatrics 1999; 104: 570–74. 3 Ball LK, Ball R, Pratt, RD. An assessment of thimerosal use in childhood vaccines. Pediatrics 2001; 107: 1147–54. 4 Cox NH, Forsyth A. Thimerosal allergy and vaccination reactions. Contact Dermatitis 1988; 18: 229–33. 5 Axton JH. Six cases of poisoning after a parenteral organic mercurial compound (merthiolate). Postgrad Med J 1972; 561: 417–21. 6 Fagan DG, Pritchard JS, Clarkson TW, Greenwood MR. Organ mercury levels in infants with omphaloceles treated with organic mercurial antiseptic. Arch Dis Child 1977; 52: 962–64. 7 Matheson DS, Clarkson TW, Gelfand EW. Mercury toxicity (acrodynia) induced by long-term injection of gammaglobulin. J Pediatr 1980; 97: 153–55. 8 Lowell JA, Burgess S, Shenoy S, Curci JA, Peters M, Howard TK. Mercury poisoning associated with high-dose hepatitis-B immune globulin administration after liver transplantation for chronic hepatitis B. Liver Transpl Surg 1996; 2: 475–78. 9 Pfab R, Muckter H, Roider G, Zilker T. Clinical course of severe poisoning with thimerosal. J Toxicol Clin Toxicol 1996; 34: 453–60. 10 Clarkson TW. Mercury: major issues in environmental health. Environ Health Perspect 1992; 100: 31–38. 11 Clarkson TW. The toxicology of mercury. Crit Rev Clin Lab Sci 1977; 34: 369–403. 12 Yess NJ. US food and Drug Administration survey of methylmercury in canned tuna. J AOAC Int 1993; 76: 36–38. 13 Shenker BJ, Guo TL, Shapiro IM. Low-level methylmercury exposure causes human T-cells to undergo apoptosis: evidence of mitochondrial dysfunction. Environ Res 1998; 77: 149–59. 14 Grandjean P, Weihe P, White RF, et al. Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicol Teratol 1997; 6: 417–28. 15 Davidson PW, Myers GJ, Cox C, et al. Effects of prenatal and postnatal methylmercury exposure from fish consumption on neurodevelopment: outcomes at 66 months of age in the Seychelles child development study. JAMA 1998; 280: 701–07. 16 Cernichiari E, Toribara TY, Liang L, et al. The biological monitoring of mercury in the Seychelles study. Neurotoxicology 1995; 16: 613–28. 17 Cernichiari E, Brewer R, Myers GJ, et al. Monitoring methylmercury during pregnancy: maternal hair predicts fetal brain exposure. Neurotoxicology 1995; 16: 705–10. 18 Nielsen JB, Andersen O, Grandjean P. Evaluation of mercury in hair, blood and muscle as biomarkers for methylmercury exposure in male and female mice. Arch Toxicol 1994; 68: 317–21. 19 National Academy of Sciences. Toxicologic effects of methylmercury. Washington DC: National Research Council, 2000. 20 Stajich GV, Lopez GP, Harry SW, Sexson WR. Iatrogenic exposure to mercury after hepatitis B vaccination in preterm infants. J Pediatr 2000; 136: 679–81. ARTICLES

Methylmercury exposure affects motor performance of a riverine population of the Tapajós river, Brazilian Amazon.

Gold mining and deforestation in the Brazilian Amazon are increasing mercury pollution of the extensive water system, exposing riverine populations to organic mercury through fish-eating. The aim of the present study was to evaluate the effect of such exposure on motor performance. This cross-sectional study was carried out in May 1996, in a village located on the banks of the Tapajós river in the Amazonian Basin, Brazil. Information concerning sociodemographics, health, smoking habits, alcohol drinking, dietary habits and work history were collected using an interview-administered questionnaire. Mercury concentrations were measured by cold vapor atomic absorption in blood and hair of each participant, of whom those aged between 15 and 79 years were assessed for motor performance (n = 84). Psychomotor performance was evaluated using the Santa Ana manual dexterity test, the Grooved Pegboard Fine motor test and the fingertapping motor speed test. Motor strength was measured by dynamometry for grip and pinch strength. Following the exclusion of 16 persons for previous head injury, working with mercury in the goldmining sites, or for diabetes, the relationship between performance and bioindicators of mercury was examined using multivariate statistical analyses, taking into account covariables. All participants in the study reported eating fish, which comprised 61.8% of the total meals eaten during the preceding week. The median hair total mercury concentration was 9 microg/g. Organic mercury accounted for 94.4 = 1.9% of the total mercury levels. Multivariate analysis of variance indicated that hair mercury was inversely associated with overall performance on the psychomotor tests, while a tendency was observed with blood mercury. Semipartial regression analyses showed that hair total mercury accounted for 8% to 16% of the variance of psychomotor performance. Neither hair nor blood total mercury was associated with the results of the strength tests in women and men. Although dose-effect relationships were observed in this cross-sectional study, they may reflect higher exposure levels in the past. The findings of this study demonstrated neurobehavioral manifestations of subtle neurotoxic effects on motor functions, associated with low-level methylmercury exposure.

Neurotoxic Effects of Low-Level Methylmercury Contamination in the Amazonian Basin

Many studies have demonstrated mercury contamination in the Amazonian ecosystem, particularly in fish, a dietary mainstay of populations in this region. The present study focused on potential health effects of this low-level methylmercury exposure. The study was carried out in a village on the Tapajós River, a tributary of the Amazon, on 91 adults inhabitants (15–81 years), whose hair mercury levels were inferior to 50 μ/g. Performance on a neurofunctional test battery and clinical manifestations of nervous system dysfunction were examined in relation to hair mercury concentrations. Near visual contrast sensitivity and manual dexterity, adjusted for age, decreased significantly with hair mercury levels (P<0.05), while there was a tendency for muscular fatigue to increase and muscular strength to decrease in women. For the most part, clinical examinations were normal, however, hair mercury levels were signficantly higher (P<0.05) for persons who presented disorganized movements on an alternating movement task and for persons with restricted visual fields. These results suggest dose-dependent nervous system alterations at hair mercury levels below 50 μg/g, previously considered a threshold for clinical effects. The profile of dysfunction in this adult population is consistent with the current knowledge on methylmercury poisoning. The long-term implications of these findings are unknown and need to be addressed.