Human exposure to mercury and its hematological effects: a systematic review.

Mercury is a metal found in the environment from natural and anthropogenic sources. It is highly toxic to ecosystems and living beings. Most human exposures come from ingestion of contaminated seafood, outgassing from dental amalgam or occupational exposure (e.g. gold mining), among other cases. Large populations are exposed to mercury, making it a very important issue from the public health perspective. Adverse health effects are commonly seen in the nervous system, but every organ is a potential target, such as the bone marrow. The main goal of this study was to assess the available evidence on human exposure to mercury and its hematological effects. A search strategy was constructed, including key terms (MeSH, text word and equivalents) for querying 2 repositories of master dissertation and PhD thesis (Fiocruz/ARCA and University of São Paulo) and 4 different electronic databases: BVS/LILACS, MEDLINE/PubMed, Scopus and TOXLINE/NIH, for articles published from 1950 to February 2018. There was no language restriction and a tool (EPHPP) was used to assess the quality of included studies. According to pre-established criteria, 80 studies were retrieved, all of them observational (48 case reports, 24 cross-sectional, 6 case series and 2 cohorts), comprising 9,284 people. Despite the fact that most exposed ones (6,012) had normal blood cell count and mercury hematological effects did not seem very usual (1,914 cases: 14 severe and 29 deaths), three studies reported association (ß) for anemia, lymphopenia, neutrophilia and basophilia. We concluded that the gathered information pointed to mercury hematotoxic effects, some of them may be serious and even fatal.

Mercury Involvement in Neuronal Damage and in Neurodegenerative Diseases.

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis are characterized by a chronic and selective process of neuronal cell death. Although the causes of neurodegenerative diseases remain still unknown, it is now a well-established idea that more factors, such as genetic, endogenous, and environmental, are involved. Among environmental causes, the accumulation of mercury, a heavy metal considered a toxic agent, was largely studied as a probable factor involved in neurodegenerative disease course. Mercury exists in three main forms: elemental mercury, inorganic mercury, and organic mercury (methylmercury and ethylmercury). Sources of elemental mercury can be natural (volcanic emission) or anthropogenic (coal-fired electric utilities, waste combustion, hazardous-waste incinerators, and gold extraction). Moreover, mercury is still used as an antiseptic, as a medical preservative, and as a fungicide. Dental amalgam can emit mercury vapor. Mercury vapor, being highly volatile and lipid soluble, can cross the blood-brain barrier and the lipid cell membranes and can be accumulated into the cells in its inorganic forms. Also, methylmercury can pass through blood-brain and placental barriers, causing serious damage in the central nervous system. This review describes the toxic effects of mercury in cell cultures, in animal models, and in patients with neurodegenerative diseases. In vitro experiments showed that mercury exposure was principally involved in oxidative stress and apoptotic processes. Moreover, motor and cognitive impairment and neural loss have been confirmed in various studies performed in animal models. Finally, observational studies on patients with neurodegenerative diseases showed discordant data about a possible mercury involvement.

Human exposure to mercury and its hematological effects: a systematic review / Exposição humana ao mercúrio e seus efeitos hematológicos: uma revisão sistemática / Exposición humana al mercurio y sus efectos hematológicos: una revisión sistemática

Mercury is a metal found in the environment from natural and anthropogenic sources. It is highly toxic to ecosystems and living beings. Most human exposures come from ingestion of contaminated seafood, outgassing from dental amalgam or occupational exposure (e.g. gold mining), among other cases. Large populations are exposed to mercury, making it a very important issue from the public health perspective. Adverse health effects are commonly seen in the nervous system, but every organ is a potential target, such as the bone marrow. The main goal of this study was to assess the available evidence on human exposure to mercury and its hematological effects. A search strategy was constructed, including key terms (MeSH, text word and equivalents) for querying 2 repositories of master dissertation and PhD thesis (Fiocruz/ARCA and University of São Paulo) and 4 different electronic databases: BVS/LILACS, MEDLINE/PubMed, Scopus and TOXLINE/NIH, for articles published from 1950 to February 2018. There was no language restriction and a tool (EPHPP) was used to assess the quality of included studies. According to pre-established criteria, 80 studies were retrieved, all of them observational (48 case reports, 24 cross-sectional, 6 case series and 2 cohorts), comprising 9,284 people. Despite the fact that most exposed ones (6,012) had normal blood cell count and mercury hematological effects did not seem very usual (1,914 cases: 14 severe and 29 deaths), three studies reported association (β) for anemia, lymphopenia, neutrophilia and basophilia. We concluded that the gathered information pointed to mercury hematotoxic effects, some of them may be serious and even fatal.

O mercúrio é um metal que pode ser encontrado naturalmente no meio ambiente e através de fontes antropogênicas. É altamente tóxico para ecossistemas e seres vivos. A maior parte da exposição humana provém da ingestão de pescados contaminados, da liberação de gases da amálgama dentária ou da exposição ocupacional (p.ex.: extração de ouro). Vastas populações são expostas ao mercúrio, tornando-se uma questão de saúde pública muito importante. Efeitos adversos à saúde são comumente observados no sistema nervoso, mas todos os órgãos são alvos em potencial, como a medula óssea. O principal objetivo do estudo foi avaliar as evidências disponíveis sobre a exposição humana ao mercúrio e seus efeitos hematológicos. Uma estratégia de busca foi realizada, incluindo termos chave (palavras-chave, palavras do texto e equivalentes), para pesquisar dois repositórios de dissertações de mestrado e teses de doutorado (Fiocruz/ARCA e Universidade de São Paulo) e quatro bases de dados eletrônicas: BVS/LILACS, MEDLINE/PubMed, Scopus e TOXLINE/NIH (artigos publicados de 1950 até fevereiro de 2018). Não houve restrições de linguagem e uma ferramenta (EPHPP) foi utilizada para avaliar a qualidade dos estudos incluídos. De acordo com os critérios pré-estabelecidos, foram encontrados 80 estudos, todos observacionais (48 relatos de caso, 24 estudos transversais, 6 séries de casos e 2 coortes), que compreendiam 9.284 pessoas. Apesar do fato de que as pessoas mais expostas (6.012) tinham contagens de células sanguíneas normais, e os efeitos hematológicos do mercúrio não pareciam muito comuns (1.914 casos, 14 graves e 29 mortes), três estudos relataram a associação de (β) anemia, linfopenia, neutrofilia e basofilia. Concluímos que as informações coletadas indicam efeitos hematotóxicos do mercúrio, alguns dos quais podem ser muito graves e até fatais.

El mercurio es un metal que se puede encontrar de forma natural en el ambiente y mediante fuentes antropogénicas. Es altamente tóxico para los ecosistemas y seres vivos. Entre otras, la mayor parte de la exposición humana, proviene de la ingestión de pescado contaminado, liberación de gases de amalgamas dentales o exposición ocupacional (p.ej. extracción de oro). Vastas poblaciones están expuestas al mercurio, convirtiéndolo en un asunto muy importante desde la perspectiva de la salud pública. Los efectos adversos para la salud se observan comúnmente en el sistema nervioso, pero cada órgano es un objetivo potencial, como la médula ósea. El objetivo principal del estudio fue evaluar las evidencias disponibles sobre la exposición humana al mercurio y sus efectos hematológicos. Se realizó una estrategia de búsqueda, incluyendo términos clave (palabras-clave, palabras del texto y equivalentes), se consultaron 2 registros de trabajos finales de máster y tesis de doctorado (Fiocruz/ARCA y Universidad de São Paulo) y 4 bases de datos electrónicas diferentes: BVS/LILACS, MEDLINE/PubMed, Scopus y TOXLINE/NIH, para artículos publicados desde el año 1950, hasta febrero de 2018. No hubo restricciones de lengua y se usó la herramienta (EPHPP) para evaluar la calidad de los estudios incluidos. De acuerdo con los criterios preestablecidos, se recopilaron 80 estudios, todos observacionales (48 informes de casos, 24 estudios transversales, 6 series de casos, y 2 cohortes), que comprendieron a 9.284 personas. A pesar de que la mayoría de los expuestos (6.012) tenían un recuento normal de células sanguíneas y los efectos hematológicos del mercurio no parecían muy comunes (1.914 casos: 14 severos y 29 muertes), tres estudios informaron de la asociación (β) para anemia, linfopenia, neutrofilia y basofilia. Concluimos que la información recabada indicaba los efectos hematotóxicos del mercurio, algunos de los cuales pueden ser muy serios e incluso fatales.

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

Mercury and its compounds are classified into three main groups: metallic mercury (Hg0), inorganic mercury (Hg2+), and organic mercury (methyl mercury: CH3Hg+, etc.). Metallic mercury is the only metal that is liquid at ambient temperature and normal pressure, which readily forms an amalgam with other metals. Therefore, mercury has long been used for refining various metals, and mercury amalgam has been used for dental treatment. Mercury has also been used in measuring instruments such as thermometers, barometers and blood pressure monitors, as well as electric appliances such as lighting equipment and dry batteries. Large amounts of metallic mercury are still used in other countries as a catalyst in the production of caustic soda by electrolysis. In addition, mercury compounds have been used in various chemicals such as mercurochrome, agricultural chemicals, and mildew-proofing agents. However, the use of mercury has also caused health problems for people. Minamata disease in Japan is a typical example. Also, since mercury is highly volatile, it is discharged as a product of industrial activities or derived from volcanoes, and it has been concluded on the basis of the findings of the United Nations Environment Program (UNEP) that it is circulating globally. Therefore, with the aim of establishing an internationally legally binding treaty for the regulation of mercury use to reduce risk, an intergovernmental negotiating committee was established in 2009. Japan actively contributed to this negotiation owing to its experience with Minamata disease, which led to the Convention on the regulation of mercury use being discharged as the "Minamata Convention on Mercury" and the treaty came into force on August 16, 2017. In this review, we introduce 1) the Global Mercury Assessment by UNEP; 2) mercury kinetics, exposure assessment and toxicity of different chemical forms; 3) large-scale epidemics of methylmercury poisoning; 4) methylmercury exposure assessment and health survey in whale-eating populations; 5) elemental mercury exposure assessment and health survey of mercury mine workers in China.

The "Madness" of Friedrich Hölderlin: an iatrogenic intoxication.

The German poet Hölderlin, assumed to have suffered from schizophrenia, in fact has been the victim of a combined calomel and cantharidine intoxication administered by his physician Autenrieth. This new theory explains much better his behavioural changes and also his neurological and other concomitant symptoms; it can be tested by analysing a very few of his hairs for the presence of these compounds.

Inorganic mercury intoxication: A case report.

Mercury is a heavy metal with unique physico-chemical properties, and it is well distributed throughout the environment, being present in soil, water and air. This non-essential element is considered by the World Health Organization (WHO) as one of the ten most troublesome chemical to public health. Its toxicity spectrum depends on the chemical form in which it presents: elemental (metallic), organic or inorganic. The known intoxications are mainly occupational (mining, agriculture, incineration) or related to the use of dental amalgams or the consumption of contaminated fish and shellfish. Nowadays, acute exposures to toxic amounts of mercury are increasingly rare, especially those involving inorganic mercury compounds. The rate is even lower if we refer to intentional poisonings. Although there is a growing understanding of the toxicokinetics of mercury, there is still a lack of studies that support the emerging theories about its bioavailability in humans. In this manuscript we describe a rare case of an individual who committed suicide by ingesting mercuric oxide. The aim is to offer a medical contribution to the better understanding of the kinetics of this metal, making a discussion based on published literature and analyzing its distribution, metabolism, internal doses, target and reservoir organs. The whole case - clinical course of the victim and her fatal destiny, the ante- and post-mortem sample concentrations and the necropsy findings - illustrates a situation that meets specific features of acute poisoning by ingestion of inorganic mercury, thus constituting an important support towards a more realistic and a based on evidence understanding of mercury biodistribution in humans.

A forensic hypothesis for the mystery of al-Hasan's death in the 7th century: Mercury(I) chloride intoxication.

The puzzle of a mysterious death in the Middle Ages has been hypothesized in terms of contemporary forensic legal and scientific methods. That al-Hasan ibn-'Ali died in 669 aged just 45 has been forensically analyzed based on written sources that dictate eyewitness accounts of historical events. The report of the contemporaneous poisoning of another individual who resided under the same household as al-Hasan's and experienced similar, yet non-lethal, symptoms has served as the beginning of the analysis. In light of ancient (medieval) documents and through using mineralogical, medical, and chemical facts, it has been hypothesized that mineral calomel (mercury(I) chloride, Hg2Cl2) from a certain region in the Byzantine Empire (present-day western Turkey) was the substance primarily responsible for the murder of al-Hasan.

[Neuropsychologic traits in individuals with chronic exposure to mercury at work].

The article deals with diagnostic peculiarities of neuropsychologic traits in individuals with previous exposure to industrial neurotoxic chemicals. Pilot studies demonstrated brain disorders characteristic for toxic (mercurial) and vascular (discirculatory) encephalopathies, justified necessity of neuropsychologic approach in occupational therapeutic diagnosis. The authors presented results of suggested scheme of neuropsychologic prompt screening aimed to reveal higher psychic functional disorders in individuals with occupational neurointoxications.

Health assessment of artisanal gold miners in Indonesia.

Small scale miners use mercury to extract gold from ore in many countries. An environmental and health assessment was performed in Indonesia in two regions, Galangan in Central Kalimantan and Talawaan in Northern Sulawesi. The environmental assessment showed severe mercury contamination of the sediments, and increased mercury levels in local fish. For the health investigation 281 volunteers were recruited and examined by a standardized questionnaire, a neurological examination and neuro-psychological tests. A medical score was used consisting of significant factors of mercury intoxication. Mercury exposed workers showed typical symptoms of mercury intoxication, such as movement disorders (ataxia, tremor, dysdiadochokinesia, etc.). Blood, urine and hair samples were taken from any participant and analyzed for mercury. The mercury concentration in the biomonitors was high, partly extreme high in the working population, increased in the population living in the same habitat and low in the control group. By a standard protocol which includes a combination of threshold values of mercury in the biomonitors and a medical sum score the diagnosis of chronic mercury intoxication was made for highly burdened workers (amalgam smelters) in 55% in Sulawesi and in 62% in Kalimantan. Less exposed mineral processors and the general population in the mining areas were also intoxicated to a high percentage.

Health assessment of artisanal gold miners in Tanzania.

In 2003 UNIDO (United Nations Industrial Development Organization) conducted an environmental and health assessment in a small-scale mining area in Tanzania. BGS (British Geological Survey) performed the environmental assessment. The Institute of Forensic Medicine - University of Munich performed the health assessment. The results of the medical, neurological and neuro-psychological examination of 180 participants from the affected area of Rwamagasa and 31 controls were analyzed. Urine, blood and hair samples were analyzed to detect the level of mercury body burden. Mercury concentrations in the bio-monitors urine, blood and hair were statistically significantly higher in the exposed population from Rwamagasa compared to the control group from Katoro. Only amalgam burners showed mercury levels above the toxicological threshold limits. A speciation of mercury in hair indicated that mainly elemental mercury vapor contributed to the high body burden of the artisanal miners. 104 amalgam-burners, the most exposed population group, were examined. 25 of these workers were found to be intoxicated. Small-scale mining is a serious health hazard for amalgam burners. Reduction of the exposure is essential to prevent further damage.

Stevens-Johnson syndrome in a child with chronic mercury exposure and 2,3-dimercaptopropane-1-sulfonate (DMPS) therapy.

INTRODUCTION: Stevens-Johnson syndrome (SJS) is an uncommon and potentially serious mucocutaneous disease. The most important step in the management of SJS is early recognition and immediate withdrawal of the causative agent. We present a patient with SJS associated with dimercaptopropane-1-sulfonate (DMPS) therapy. CASE REPORT: An asymptomatic 11-year old boy who had been exposed chronically to mercury vapour had a 24-hour urine mercury concentration of 37 microgram/L (reference value <10 microgram/L). Exposure to the mercury vapour was stopped and treatment with oral DMPS was begun. After two weeks of therapy, he developed a disseminated cutaneous eruption of red pruritic macules on his chest and back, which three days later had spread all over his body with the discrete maculae becoming confluent; erosions and crusts developed on his lips and he had blisters in his mouth. The diagnosis of SJS was made, the DMPS was stopped, and the SJS resolved gradually. DISCUSSION: Chelation agents like DMPS or DMSA are increasingly used and are available over the counter in some countries. These drugs are used in patients with complaints that are attributed to mercury-containing dental amalgams and in children with autism. CONCLUSION: The reported association suggests that SJS may be a potential complication of DMPS therapy, and this should be considered in the risk-benefit analysis of chelation. The reported association suggests that SJS may be a potential complication of DMPS therapy, and this should be considered in the risk-benefit analysis of chelation.

Molecular mechanisms triggered by mercury.

Mercury is an ubiquitous environmental toxin that causes a wide range of adverse health effects in humans. Three forms of mercury exist: elemental, inorganic and organic. Each of them has its own profile of toxicity. Exposure to mercury typically occurs by inhalation or ingestion. Mercury can be an indoor air pollutant, however industry emission remains the most important source of inhaled mercury. Furthermore, fresh water and ocean fish may contain large amounts of mercury and dental amalgam can be another important source of inorganic and mercury vapor. The present review discusses the current information on mercury toxicity and the distinct toxicologic profile of the three forms of mercury. The existing therapeutics, new therapeutics development or agents for treating mercury poisoning will also discussed. Since in general low levels of mercurial are tolerable, herein, we also discuss the defensive mechanisms developed by the cell to protect itself against mercury injury. This aspect may be useful to provide a biological protection against toxic effects exerted by mercury or by specific forms of mercury in view of a medicinal purposes.

Baboon syndrome induced by mercury - first case report in China.

A case of mercury-induced baboon syndrome was reported. A 31-year-old woman presented with itching papules and vesicles in the right axilla, which extended to the left axilla, arms, fossa poplitea, buttocks, and groin. A mercury thermometer was broken 2 days before exanthema. Patch testing to ammoniated mercury, mercury, mercuric chloride, and mercurochrome were positive. Blood and urine mercury level was marginally normal, yet showed a descending trend over time.

The toxicology of mercury and its chemical compounds.

This review covers the toxicology of mercury and its compounds. Special attention is paid to those forms of mercury of current public health concern. Human exposure to the vapor of metallic mercury dates back to antiquity but continues today in occupational settings and from dental amalgam. Health risks from methylmercury in edible tissues of fish have been the subject of several large epidemiological investigations and continue to be the subject of intense debate. Ethylmercury in the form of a preservative, thimerosal, added to certain vaccines, is the most recent form of mercury that has become a public health concern. The review leads to general discussion of evolutionary aspects of mercury, protective and toxic mechanisms, and ends on a note that mercury is still an "element of mystery."

Agentes químicos. Mercurio y compuestos

Guía que tiene como objetivos establecer recomendaciones para efectuar la vigilancia de la salud de los trabajadores expuestos a los compuestos inorgánicos del mercurio en su lugar de trabajo y así poder detectar de forma rápida los trastornos de salud relacionados con esta exposición e identificar al personal especialmente sensible a los efectos de este contaminante químico.

Definición de una cohorte para el estudio de la relación entre el mercurio y el cáncer / Definition of a cohort for studying the relationship between mercury and cancer

Objetivos: describir una cohorte de mineros de mercurio y discutir los problemas metodológicos surgidos en la definición de la misma. Se avanzan también resultados preliminares de la mortalidad de los mineros por algunas causas seleccionadas. Población y métodos: la cohorte se construyó en 1.950 a partir de los registros de personal de Minas de Almadén y Arrayanes S.A., y se incluyeron en la misma a los trabajadores que fueron incorporándose en los años siguientes hasta el final del periodo de seguimiento, en 1.994. El seguimiento se completó con la determinación del estado vital y causa básica de defunción, en caso de muerte. Se calcularon las razones de mortalidad estandarizadas según edad, sexo y periodo de calendario. Las muertes esperadas se obtuvieron a partir de las tasas especificas por edad, sexo y periodo de calendario, de la población española. Resultados: el periodo de seguimiento ha sido de 44 años, lo que permite cubrir los periodos de inducción y latencia de las causas de muerte objetivo del estudio, habiendo sido el seguimiento del 92%. Las observaciones realizadas abarcan el periodo comprendido entre 1880 y 1994, siendo el número total de personas-año a riesgo que aportaron los trabajadores expuestos de 103.728. Las primeras causas de muerte en los trabajadores estudiados son las enfermedades cardiovasculares (RME 1,11 IC 95% 1,02-1,20), los cánceres (RME 0,72 IC 95% 0,63-0,82) y las enfermedades respiratorias (RME 1,67 IC 95% 1,46-1,90). .. Conclusiones: la existencia de un exhaustivo fichero de personal bien cuidado en Almadén ha permitido obtener una cohorte dinámica con entradas y salidas a lo largo del tiempo. Sin embargo, en España resulta muy difícil y caro realizar estudios de cohortes debido a las dificultades para completar el seguimiento y conocer el estado vital final de las personas a estudio utilizando los registros nacionales automatizados

Objectives: to describe a cohort of mercury miners and discuss the methodological problems which appeared in its definition. Preliminary results of a mortality analysis by selected causes are also presented. Population and methods: the cohort was assembled in 1950 from the personnel records of Minas de Almadén y Arrayanes S.A. Workers subsequently hiring into the mining company through the end of the follow-up period in 1994 were also included. The follow-up was completed by determination of vital status and, in the case of decedents, by identification of primary cause of death. Standardised mortality ratios by age, sex and calendar period were calculated. Expected deaths were computed based on age-, sex- and calendar period-specific rates for the general Spanish population. Results: the follow-up period was 44 years, which allows for appropriate induction and latency periods of main causes of death; follow-up was 92% complete. The observations cover the period 1880 to 1994, with a total of 103,728 at-risk-person-years among exposed workers. The leading causes of death among workers are cardiovascular diseases(SMR 1,11 CI95% 1,02-1,20), cancer (SMR 0,72 CI 95% 0,63-0,82) and respiratory diseases (SMR 1,67 CI 95% 1,46-1,90). Conclusions: the existence of detailed and meticulously kept personnel records in Almadén has allowed the establishment of a dynamic cohort with entries and exits ayer the study period. However, in Spain it is very difficult and expensive to conduct cohort studies due to difficulties in completing follow-up and ascertainment of vital status based computerised national records