Human neurotoxicity of mercury in the Amazon: A scoping review with insights and critical considerations.

Human exposure to mercury is a major public health concern, causing neurological outcomes such as motor and visual impairment and learning disabilities. Currently, human exposure in the Amazon is among the highest in the world. A recent systematic review (doi:10.1016/j.jtemb.2018.12.001), however, highlighted the lack of high-quality studies on mercury-associated neurotoxicity. There is, therefore, a need to improve research and much to still learn about how exposure correlates with disease. In this review, we discuss studies evaluating the associations between neurological disturbances and mercury body burden in Amazonian populations, to generate recommendations for future studies. A systematic search was performed during July 2020, in Pubmed/Medline, SCOPUS and SCIELO databases with the terms (mercury*) and (Amazon*). Four inclusion criteria were used: original article (1), with Amazonian populations (2), quantifying exposure (mercury levels) (3), and evaluating neurological outcomes (4). The extracted data included characteristics (as year or origin of authorship) and details of the research (as locations and type of participants or mercury levels and neurological assessments). Thirty-four studies, most concentrated within three main river basins (Tapajós, Tocantins, and Madeira) and related to environmental exposure, were found. Mercury body burden was two to ten times higher than recommended and main neurological findings were cognitive, vision, motor, somatosensory and emotional deficits. Important insights are described that support novel approaches to researching mercury exposure and intoxication, as well as prevention and intervention strategies. As a signatory country to the Minamata Convention, Brazil has the opportunity to play a central role in improving human health and leading the research on mercury intoxication.

Prenatal and postnatal methyl mercury exposure in Niigata, Japan: adult outcomes.

Methyl mercury (MeHg) poisoning or Minamata disease (MD) from fish consumption is a public health concern throughout the world because all fish contain small amounts. The lowest exposure level needed to impair children's development is controversial. Actual poisoning with MeHg from fish consumption has been reliably reported only two times. It occurred in Minamata, Japan in the 1950s and then in Niigata, Japan in the 1960s. On each occasion, massive industrial pollution led to local fish having mercury levels as high as 40ppm. In Niigata the pollution was on the Agano River and there were over 2000 commercial fishermen active at that time. We studied adult subjects who had been exposed perinatally to MeHg from fish consumption during the Niigata poisoning to determine the long-term impact of exposure. We identified mothers with elevated levels of exposure during the epidemic and those diagnosed with MeHg poisoning. The subjects of the study were their adult children, born during the epidemic. The evaluation consisted of a questionnaire (administered by interview) focusing on development, symptoms, and current function and a standard medical and neurological examination. The subjects were divided into four groups based upon prenatal levels of mercury in maternal hair or the presence of MD. For Group A the hair mercury levels were 50ppm or more, for Group B the mercury levels were 25-49ppm, and for Group C 10-24ppm. The subjects in Group D were born to mothers diagnosed with MD, but their mercury levels were not measured. Exposure was predominantly prenatal, but some mothers also breast fed their infants. Group A included 13 subjects among whom two were diagnosed with congenital MeHg poisoning and in two others it was suspected. Group B included 10 subjects, of whom three had symptoms compatible with MeHg poisoning. Group C had nine subjects including one with intellectual deficit and another with hearing loss. Group D had eight subjects of whom four had symptoms compatible with MeHg exposure, but only one had abnormal neurological findings. Among the subjects thought to have congenital or childhood MeHg poisoning, intelligence did not appear to have declined over time. More children were affected by prenatal and postnatal MeHg exposure at Niigata than was previously reported.

Principles of studying low-level neurotoxic exposures in children: using the Seychelles Child Development Study of methyl mercury as a prototype.

Epidemiological studies to determine the impact of low level toxic exposure on child development are important in guiding clinical and public health action. However, carrying out such studies and interpreting their findings presents a number of significant challenges to the investigators. First, they must find a cohort with suitable exposure, select a biomarker that will accurately determine the level of exposure and determine the endpoints that are most likely to detect subtle differences in neurodevelopment. Following that, the logistics of the study must be organised and collaboration established with the local population and health authorities. To accurately interpret the data, they must also accurately determine covariates that impact child development. After the data are collected, interpreting the findings presents a further challenge. Throughout this process, the study must adhere to fundamental epidemiological principles and clearly defined statistical approaches. This paper discusses those principles and uses the Seychelles Child Development Study to show how one epidemiological study addressed them.

Temporal trends of infant and birth outcomes in Minamata after severe methylmercury exposure.

Severe methylmercury poisoning occurred in Minamata and neighboring communities in Japan during the 1950s and 1960s, causing what is known as Minamata disease. Although an increase in stillbirths and a reduced male proportion at birth (i.e., reduced sex ratio) have been reported, no studies have evaluated the impact of exposure on an entire set of infant and birth outcomes. We therefore evaluated the temporal trends of these outcomes in the Minamata area from 1950 to 1974. We focused on the spontaneous/artificial stillbirth rate, crude fertility rate, male proportion at birth, male proportion among stillbirths, and infant mortality. We obtained the number of stillbirths, live births, and infant deaths in Minamata City and Kumamoto Prefecture (as a reference) from 1950 to 1974. After plotting annual figures for each outcome, we divided the study period into five intervals and compared them between Minamata City and Kumamoto Prefecture using the chi-squared test. We observed a slightly increased spontaneous stillbirth rate and decreased artificial stillbirth rate in Minamata City, followed by a reduced crude fertility rate. The crude fertility rates in Minamata City during the period 1955-1965 were significantly lower compared with those in Kumamoto Prefecture (p < 0.001). An increase in the male proportion among stillbirths was observed, corresponding to a reduction in the proportion of males at birth in the late 1950s. The impact on infant mortality was equivocal. These descriptive analyses demonstrate a severe regional impact of methylmercury exposure on a series of birth outcomes in the Minamata area.

Intoxicación ocupacional por mercurio y la neurotoxicidad / Occupational intoxication by mercury and neurotoxicity

Introducción: El mercurio es un metal pesado que puede encontrarse en la naturaleza en 3 formas primarias: elemental, orgánico e inorgánico. Metodología: Se describe el caso de un varón de 30 años, profesión calderero, que formo parte de unos de los equipos encargados de sustituir los tubos de acero-carbono del intercambiador por donde circulan gases sulfurosos con restos de mercurio. Los síntomas iniciales fueron diarreas e inflamación de encías, presentando inicialmente una concentración de Hg en orina 939 mcg/L(VN≤30mcg/L), no recibiendo tratamiento hasta después de 6 meses con DMPS en dos oportunidades viendo una reducción de valores urinarios de 1830,47 a 7,38mcg/L. Como clínica, tuvo un eretismo mercurial severo, un trastorno visual complejo y un síndrome diarreico por neuropatía autonómica. Conclusión:Este trabajo pretende advertir sobre las consecuencias de la exposición prolongada a mercurio elemental, especialmente para el sistema nervioso central, así como el diagnóstico precoz y el tratamiento oportuno (AU)

Introduction: Mercury is a heavy metal that can be found in nature in 3 primary forms: elemental; organic and inorganic. Intoxication of occupational origin is widely identified as occupational disease. Methodology: The case of a 30-year-old man, a boilermaker (welder assembler), is described as one of the teams responsible for replacing the carbon steel tubes of the exchanger where sulfur gases with mercury traces circulate. The initial symptoms were diarrhea with mucus and blood and inflammation of the gums, initially presenting a blood Hg concentration of 475.9mcg / L (VN = <10mcg / L) and a concentration of Hg in urine 939mcg / L (VN = <30mcg / L), not receiving treatment until after 6 months with DMPS on two occasions seeing a reduction of urinary values from 1830.47 to 7.38mcg / L. As a clinical result, he had severe mercurial erythemia, a secondary visual complex disorder, and a secondary autonomic neuropathic diarrheal syndrome. Consequently, this fact at the beginning was declared as an occupational accident, however, due to its evolution the INSS, a year later, gave the declaration of professional illness caused by mercury, thus was also given the absolute permanent disability for any profession or trade. Conclusion: The present paper aims to warn about the consequences of prolonged exposure to elemental mercury especially for the central nervous system, as well as early diagnosis and timely treatment. On the other hand, note the importance of adopting an adequate and effective preventive system to protect the health of workers exposed to mercury (AU)

The blood of my veins - mercury, Minamata and the soul of Japan.

The methylmercury contamination of Minamata Bay during the WWII postwar period resulted in thousands of Japanese citizens suffering horrific neurological injury. Fear and miscommunication destroyed and changed family and social structure. In addition, the Minamata poisoning caused momentous changes in the civic discourse in Japan and was an instrumental event in the democratization of the country. This manuscript describes the effects that the environmental contamination and human poising had in the transition of Japan from a feudal society to a democratic one.

Signs and symptoms of mercury-exposed gold miners.

OBJECTIVES: Gold miners use mercury to extract gold from ore adding liquid mercury to the milled gold-containing ore. This results in a mercury-gold compound, called amalgam. Miners smelt this amalgam to obtain gold, vaporizing it and finally inhaling the toxic mercury fumes. The objective was to merge and analyze data from different projects, to identify typical signs and symptoms of chronic inorganic mercury exposure. MATERIAL AND METHODS: Miners and community members from various artisanal small-scale gold mining areas had been examined (Philippines, Mongolia, Tanzania, Zimbabwe, Indonesia). Data of several health assessments were pooled. Urine, blood and hair samples were analyzed for mercury (N = 1252). Questionnaires, standardized medical examinations and neuropsychological tests were used. Participants were grouped into: Controls (N = 209), living in an exposed area (N = 408), working with mercury as panners (N = 181), working with mercury as amalgam burners (N = 454). Chi2 test, linear trend test, Mann-Whitney test, Kruskal-Wallis test, correlation coefficient, Spearman's rho, and analysis of variance tests were used. An algorithm was used to define participants with chronic mercury intoxication. RESULTS: Mean mercury concentrations in all exposed subgroups were elevated and above threshold limits, with amalgam burners showing highest levels. Typical symptoms of chronic metallic mercury intoxication were tremor, ataxia, coordination problems, excessive salivation and metallic taste. Participants from the exposed groups showed poorer results in different neuropsychological tests in comparison to the control group. Fifty-four percent of the high-exposed group (amalgam burners) were diagnosed as being mercury-intoxicated, compared to 0% within the control group (Chi2 p < 0.001). CONCLUSIONS: Chronic mercury intoxication, with tremor, ataxia and other neurological symptoms together with a raised body burden of mercury was clinically diagnosed in exposed people in artisanal small-scale mining areas. The mercury exposure needs to be urgently reduced. Health care systems need to be prepared for this emerging problem of chronic mercury intoxication among exposed people. Int J Occup Med Environ Health 2017;30(2):249-269.

[Food Sanitation Act and Minamata Disease].

Immediately after the official recognition of Minamata disease (1956.5.l) a study group at Kumamoto University suggested that Minamata disease was caused by food poisoning. The next year, this suggestion was accepted by the Ministry of Health and Welfare (MHW). Prior to the decision to apply the Food Sanitation Act (FSA), the local government asked MHW for the application of FSA. Soon after, the chief of the Public Health Bureau replied to the local government that the application of FSA to the Minamata area was impossible. Epidemiological investigations of residents and polluted areas, therefore, were not carried out. Data essential for the screening for exposed residents were unavailable. The criteria for the screening were presented. The Environmental Agency (EA) presented the criteria in the form of notice in 1971, which were revised in 1977. Notwithstanding the clear difference between the original and revised criteria, EA insisted that these two sets of criteria were quite similar. This insistence by EA and the absence of epidemiological data on residents and polluted area resulted in the present confusion about Minamata disease. The application of FSA was stopped by bureaucrats who had no interest in the environmental problems and by several scientists patronized by stakeholders (Chisso, Japanese Association of Chemical Industries, MHW and EA). Stakeholders suppressed science.

[Epidemiology of Minamata Disease--Focus on the Clinical Features Related to the 1977 Diagnostic Criteria].

Large-scale food poisoning caused by methylmercury was identified in Minamata, Japan, in the 1950s (Minamata Disease). Although the diagnostic criteria for the disease was controversial and difficult during that time, we, the Kumamoto University Study Group, carried out a large-scale study to assess the clinical features in 1972-1973. The author tried to reassess the results of that study to appraise the diagnostic criteria established in 1977 on the basis of those results. A substantial number of residents in the exposed area exhibited neurologic signs, especially paresthesia of only the extremities, namely, the male residents of Minamata City showed a positive predictive value of 0.73 and a negative predictive value of 0.23. The relative risks of paresthesia only were 2.6 (2.0-3.3) and 1.2 (0.9-1.5), in Minamata and Goshonoura related to Ariake (control), respectively. At least until 1977, the diagnostic criteria remained valid, although it was inadequate. Nevertheless, presently, a follow-up study of the certified patients may lead to the development of efficient new diagnostic criteria.

Methylmercury exposure and neurological outcomes in Taiji residents accustomed to consuming whale meat.

Methylmercury (MeHg) is a major environmental neurotoxicant that causes damage to the central nervous system. In Japan, industrial emission of MeHg has resulted in MeHg intoxication in Minamata and Niigata, the so-called Minamata disease. Humans are exposed to MeHg derived from natural sources, primarily fish and fish predators. Therefore, MeHg continues to be an environmental risk to human health, particularly in susceptible populations that frequently consume substantial amounts of fish or fish predators such as whale. This study aimed to investigate the health effects of MeHg exposure in adults. The subjects were 194 residents (117 males, 77 females; age 20-85 years) who resided in the coastal town of Taiji, the birthplace of traditional whaling in Japan. We analyzed hair for mercury content and performed detailed neurological examinations and dietary surveys. Audiometry, magnetic resonance imaging, and electromyography were performed to diagnose neurological defects. Whole blood mercury and selenium (Se) levels were measured in 23 subjects. The geometric mean of the hair mercury levels was 14.9 µg/g. Twelve subjects revealed hair mercury levels >50 µg/g (NOAEL) set by WHO. Hair mercury levels significantly correlated with daily whale meat intake. These results suggested that residents in Taiji were highly exposed to MeHg by ingesting MeHg-contaminated whale meat. Multivariate regression analysis demonstrated no significant correlations between hair mercury levels and neurological outcomes, whereas some of the findings significantly correlated with age. A significantly positive correlation between whole blood mercury and Se levels was observed and the whole blood mercury/Se molar ratios of all subjects were <1. These findings suggested that sufficient Se intake might be one of causes of the absence of adverse effects of MeHg exposure in this study.

Association between social group participation and perceived health among elderly inhabitants of a previously methylmercury-polluted area.

OBJECTIVE: This study attempted to clarify the association between participation in a social group and perceived health among elderly residents of a previously methylmercury-polluted area in Japan. METHODS: We conducted a cross-sectional study using eligible subjects from the Shiranui Sea coastal area, where mercury poisoning due to daily intake of fish and shellfish had previously caused some residents to develop the neurological disorder "Minamata disease (MD)." In the present study, we selected subjects aged ≥65 years who had never been diagnosed with MD or applied for medical treatment compensation. RESULTS: A logistic regression model after adjusting for confounding factors showed that membership in a hobby or volunteer group was associated with good perceived health (odds ratio 1.97, 95 % confidence interval 1.02-3.80). CONCLUSION: Our results showed that the effects of membership in social groups on perceived health were not equal across all social groups, with only hobby- or volunteer-related groups having a positive effect on perceived health. Our findings suggested that promoting participation in a social group such as hobby- or volunteer-related groups can help improve perceived health among elderly individuals who had experienced environmental pollution incidents.

Estado actual sobre la exposición alimentaria al mercurio durante el embarazo y la infancia, y recomendaciones en salud pública / Current dietary exposure to mercury during pregnancy and childhood, and public health recommendations

La exposición a dosis altas de mercurio durante periodos vulnerables (como el embarazo y la infancia) puede tener serias consecuencias para el desarrollo cognitivo, tal como se ha constatado tras los episodios de envenenamiento agudo ocurridos en Japón e Irak. El consumo de ciertos tipos de pescado es la fuente principal de exposición a mercurio de la población general. Existe una creciente preocupación por los posibles efectos neurotóxicos del mercurio, especialmente a edades tempranas en poblaciones donde el consumo de pescado es moderado-alto. La evidencia científica hasta el momento no es concluyente. En el ámbito español, el Proyecto INMA (Infancia y Medio Ambiente) ha proporcionado información sobre los niveles de exposición prenatal a mercurio de 1800 recién nacidos de Valencia, Sabadell, Asturias y Guipúzcoa. En general, los niveles resultaron elevados, con un 24% de los niños con niveles superiores a las dosis recomendadas por la Organización Mundial de la Salud y un 64% por encima de la recomendación de la Agencia de Protección Ambiental de Estados Unidos. Los resultados en el segundo año de vida, sin embargo, no muestran un incremento en el riesgo de efectos adversos en el desarrollo cognitivo de los niños. Diversas agencias han desarrollado recomendaciones de consumo de pescado dirigidas a mujeres embarazadas y población infantil, debido a la presencia de mercurio. No obstante, sería conveniente reforzar estas recomendaciones, teniendo en cuenta el pescado como fuente de nutrientes esenciales para el desarrollo en las fases tempranas de la vida, consensuadas para todas las comunidades autónomas y la administración estatal (AU)

Exposure to high levels of mercury during vulnerable periods (such as pregnancy and childhood) may have serious consequences for cognitive development, as observed after acute poisoning episodes in Japan and Irak. The main source of mercury exposure in the general population is consumption of certain types of fish. There is growing concern about the possible neurotoxic effects of mercury, especially in younger children in populations where fish intake is moderate to high. The scientific evidence to date is inconclusive. In Spain, the Childhood and Environment (Infancia y Medio Ambiente [INMA]) project has provided information on levels of prenatal exposure to mercury among 1800 newborns from Valencia, Sabadell, Asturias and Guipúzcoa. In general, levels were high, being above the World Health Organization's recommended dose in 24% of children and above the recommended levels of the U.S. Environmental Protection Agency in 64%. However, the results did not indicate a significant association between prenatal mercury exposure and delayed cognitive development during the second year of life. Various agencies have developed recommendations on fish consumption for pregnant women and children, due to the presence of mercury. These recommendations should be strengthened, since there is general consensus among all regional and national public administrations that fish is an essential source of nutrients for development in the early stages of life (AU)

Critical appraisal of the 1977 diagnostic criteria for Minamata disease.

Large-scale food poisoning caused by methylmercury was identified in Minamata, Japan, in the 1950s (Minamata disease). Although the diagnostic criteria for the disease remain current, few studies have been carried out to assess the diagnostic accuracy of the criteria. From a 1971 population-based investigation, data from 2 villages were selected: Minamata (high-exposure area; n = 779) and Ariake (low-exposure area; n = 755). The authors examined the prevalence of neurologic signs characteristic of methylmercury poisoning and the validity of the criteria. A substantial number of residents in the exposed area exhibited neurologic signs even after excluding officially certified patients. Using paresthesia of the extremities as the gold standard of diagnosis, the criteria had a sensitivity of 66%. The current diagnostic criteria as well as the official certification system substantially underestimate the incidence of Minamata disease.

Neurodevelopmental effects of low-level prenatal mercury exposure from maternal fish consumption in a Mediterranean cohort: study rationale and design.

BACKGROUND: Mercury is a neurotoxic environmental pollutant. However, the literature on the neurodevelopmental effect of low-level prenatal mercury exposure from maternal fish intake is inconsistent. We assessed the association between prenatal mercury exposure and infant neurodevelopment in coastal areas of 4 Mediterranean countries. METHODS: This was a prospective cohort study that planned to enroll approximately 1700 mother-infant pairs. Pregnant women and their newborn children were recruited in selected hospitals of the study areas. Biological samples, including maternal hair and cord blood, were collected from mothers and children, and the concentrations of mercury and other elements were measured. Exposures to lifestyle, environmental, and social factors were assessed through questionnaires. The main outcome was child neurodevelopment at 18 months, as measured by the Bayley Scales of Infant and Toddler Development, Third Edition. CONCLUSIONS: This cohort has a number of strengths. First, mercury concentration was measured in several biological samples, which allows for a better understanding of mercury kinetics and is useful for sensitivity analyses. Therefore, we expect to be able to adjust for the potential confounding effects of lifestyle and social factors and for the effects of other elements that were measured in the biological samples. Finally, this is a multinational study and thus permits assessment of the relation between mercury and child neurodevelopment in different populations.

Lower urinary tract symptoms in patients with Niigata Minamata disease: a case-control study 50 years after methyl mercury pollution.

OBJECTIVES: To clarify the prevalence of lower urinary tract symptoms and overactive bladder in patients with chronic methyl mercury poisoning. METHODS: A total of 151 patients (61 men and 90 women; mean age 72.1 years) with Niigata Minamata disease were enrolled. An age- and sex-matched group of 150 participants was used as control. Patients reported their International Prostate Symptom Score and overactive bladder symptom score. RESULTS: In men, the total, storage and voiding International Prostate Symptom Score scores were higher in the Niigata Minamata disease group than in the control group (10.6 ± 7.8 vs 5.0 ± 5.0, 4.5 ± 3.3 vs 2.4 ± 2.4 and 6.1 ± 5.1 vs 2.7 ± 3.1, respectively, P < 0.001 in all). In women, these scores were also higher in the Niigata Minamata disease group than in the control group (8.9 ± 7.3 vs 4.0 ± 4.0, 4.4 ± 3.2 vs 2.8 ± 2.4 and 4.5 ± 5.0 vs 1.3 ± 2.0, respectively, P < 0.001 in all). The prevalence of overactive bladder was more frequent in the Niigata Minamata disease group compared with that in the control group (51.7% vs 26.7%, P < 0.001). In both men and women, the overactive bladder symptom score was higher in the Niigata Minamata disease group than in the control group (4.1 ± 3.0 vs 2.4 ± 2.9, P = 0.002 and 4.6 ± 3.6 vs 2.7 ± 2.9, P < 0.001, respectively). The International Prostate Symptom Score and overactive bladder symptom score in the Niigata Minamata disease group were highest in patients aged 60-69 years (P < 0.001 in both), whereas these increased in an age-dependent manner in the control group. CONCLUSIONS: Lower urinary tract symptoms and overactive bladder are severe and highly prevalent conditions among patients with methyl mercury poisoning. The higher prevalence of lower urinary tract symptoms among patients aged 60-69 years might be related to the fact that they were exposed to methyl mercury during their childhood/development.