Minamata Disease Research Articles

歯牙発生過程の口腔領域における塩化メチル水銀-^<203>Hg の組織細胞内分布とその推移

Distribution of methylmercury in tissue cells in dental fields of adult and fetal rats during the process of dental development and its time course change were compared and the following results were obtained. 1. Many tissues and cells in the oral cavity could be exposed to methylmercury in various degrees. 2. Intongue, relatively intense deposition of methylmercury was noted in the mucous membrane of the tip and body of the tongue and in the lingual muscles. Especially in the former, the mechanism of excretion of methylmercury along with epithelial desquamation was suggested. 3. Among the perioral tissues, the deposition was not as intense in the epidermis as in lingual mucous membrane, but deposition and accumulation of methylmercury was noted in the hair. In the muscle tissues of the same portion, the deposition was almost as intense as in the lingual muscle. 4. In the parotid gland, marked deposition was noted in the glandular cells and ducts in the initial period of administration. This was followed by a rapid decrease as time progressed. An excretory mechanism via the saliva is suggested indicating recontamination in the oral cavity. 5. The dental tissues of mature rats showed the lowest mercury uptake among the tissues studied. 6. Tissues and cells in the process of dental development, on the other hand, readily take up methylmercury. The main findings included the following : 1) Intense deposition is generally seen in the epidermal tissues of ectodermal origin in the lamina-shaped stage and bud-shaped stage. Along with the formation of the enamel organ, intense deposition is seen in the inner enamel epithelial cells. 2) In tissues of mesodermal origin, marked deposition of methylmercury was noted in the tissue cells of mesenchymal nature along with formation of the dental papilla, and a considerable uptake was noted in the odontoblasts. 7. Through each period of dental development, such findings of deposition of methylmercury gives a suggestion on the pathogenesis of dental developmental anomaly in patients with fetal Minamata disease.

A closer look at minamata disease

A closer look at minamata disease

The effect of organic mercury on intrauterine life.

The Minamata disease originates from the consumption of great amounts of fish and shellfish caught in the Minamata Bay, the Kumamoto Prefecture of Kyushu, Japan (Figure 1). The water system of the Minamata Bay has been polluted by methyl mercuric sulfide (CH3HgSCH3) and methyl mercuric chloride (CH3HgCl) through waste water discharged into the Minamata River by a vinylchloride and acetaldehyde plant (Figure 2).

Alkylmercury Contamination of Foods

No cases of human poisoning by alkylmercury compounds in intended foodstuffs have been reported in North America to date. 1 However, its symptoms are well known, from accidental poisonings and the tragic episodes at Minamata and Niigata, Japan. The chief culprit has been methylmercury. Summarized, these symptoms include, more or less in order of ascending severity, ( a ) excessive weakness, fatigue, apathy, lack of interest; ( b ) paresthesias of perioral area and extremities; ( c ) tunnel vision, hearing difficulties, fits of rage, depression; ( d ) dysarthria, dysdiadochokinesia, ataxia, alexia, agraphia, clumsiness in handling familiar objects, intention tremor; ( e ) gross motor incoordination, spasticity, paralysis, coma, death. Minamata disease, first reported in Japan in 1953, affected 121 persons, causing 46 deaths. Its origin was methylmercury chloride, discharged into the Minamata Bay and River by a plastics plant; fish containing 20

大気汚染公害について

Before the second War, the state of emitting a clouds of smoke from a number of chimney in towns and cities is cordially received as a sufficient evidence of energetic activities of industries.Since about 1955, Japanese economy showed a sign of reconstruction, and from about 1962 the Japanese industries have vigorously developed and the gross national production is ranked second or third in the world. With the advance of industries, the social deformation has been caused in traffic and public nuisance problems.Around 1962, peoples were not concerned about the public nuisances, and the “Minamata disease” is considered as a special accident in a partial area.Thereafter, in various places in the country the analogous diseases have been outbroken. For inrtance, these are the “Yokohama asthma”, the “Yokkaichi asthma”, the “Minamata disease” on the River Agano, and the “Itai-itai disease” etc.Recently peoples, the government and the enterprises have been concerned with these public nuisance problems and the improvements in the social deformation are being expected.The author will describe in this paper follows:1. Determination methods of air pollutant suspending dust, falling dust, sulfur oxides, automotive exhaust, poisonous substances.2. The present situation of air pollution in Japan suspending and falling dust, sulfur dioxide, automotive exhaust, poisonous substances.3. Desirable environment of air, environment standards of SO2, other gases and dusts, standards of labour environment.4. The prevention policy for air pollution, law and ordinances. effluents tandards of stack gases and dusts, standard of automotive exhaust for CO, ordinance regulation for air pollutant emission.

A study of the motor pattern in crebral palsied children with “Minamata disease. ”

A study of the motor pattern in crebral palsied children with “Minamata disease. ”

Congenital Minamata Disease : Environmental disruption and congenital anomalies

Congenital Minamata Disease : Environmental disruption and congenital anomalies

水銀の尿中排泄におよぼすD-Penicillamineの効果 : メチル水銀中毒の2症例における

There is a considerable amount of literatures on the therapeutic use of BAL or CaNa2EDTA in inorganic mercury poisoning, but little has been studied on the effect of D-penicillamine, especially in organic mercury poisoning. The present authors experienced some cases of methyl mercury thioacetamide (CH3HgSCH2CONH2) poisoning caused by dermal application of the compound for the treatment of a fungus disease of the skin. Signs and symptoms of these intoxicated cases has been found to be similar to those in cases reported by Hunter and Russel and those in so-called "Minamata disease". The present paper deals with results of administration of D-penicillamine in two patients who showed prominent nervous disorders.

3) Organic Mercury Poisoning

It has been proved that the Minamata disease is the poisoning by alkyl compound (AM), and recently phenyl mercury compounds (PM) which are used as agricultural drugs have been brought on public discussion. This report deals with clinical and experimental studies on these poisonings.

Studies on the toxicity of low alkyl mercury compounds.

Since late 1953, with its peak in 1956, Minamata disease appeared among those who lived by fishing at Minamata Bay in southern parts of Kumamoto Prefecture. The number of patients reached 111, and 42 of them died. Some of the patients are still suffering from severe sequels with poor prognostic expectation.In 1964, 10 years after the onset of the disease, “second” Minamata disease broke out at near the mouth of the Agano River in Niigata Prefecture. Since that time, this disease began to attract the various fields of medicine and fundamental investigations started.Several years after the first occurrence in Kumamoto Prefecture, the causative agents were suspected to be methyl mercury compounds, because the symptoms were discovered among those who ate at each meal mainly fishes and shellfishes polluted with methyl mercury compounds in waste water. Therefore, it was necessary to investigate the toxicity of low alkyl mercury compounds both from the possibility of poisoning potential and metabolism in the animal body.After oral administrations of foods mixed with various mercury compounds to rats, Sebe et al. followed its Minamata disease-like symptoms and measured the contents of mercury in several organs and hair. However, these were not measured as the form of organic mercury.Miller's method has been used for quantitative measurement of organic mercury, as being employed by Sadakane. For the measurement by this method, some extent of organic mercury was generally thought to be needed.In our laboratory, quantitative analysis of organic mercury using gas chromatography was recently developed and ultra-microanalysis of tissue specimen became possible. Employing this method, the author investigated toxicities of various low alkyl mercury compounds by comparing organic with total inorganized mercuries of the same sample. Some of the results obtained by the author's method are as follows.

Mercury Content of Some British Soils

During the past three years considerable attention has been paid to hazards presented by mercury entering food supplies. Kurland, Faro, and Siedler (1960) have demonstrated that Minamata disease is caused by mercury entering sea food. Hurtig (pers. comm.) has drawn our attention to health problems arising because of the use of mercury compounds in pesticides. In January, 1966, a Symposium concerning Mercury in the Environment was held in Stockholm, and was attended by scientists not only from Sweden but also from the U.S.A., and the United Kingdom (Oikos Supplementum 9, 1967). Later, in 1966, the Food and Agriculture Organization of the United Nations(1967: 73) gave recommended tolerances for organo-mercurials as none. Routine investigations in our biogeochemical laboratories at the University of British Columbia revealed the fact that some soils in Great Britain contain highly anomalous amounts of mercury, a few, at least, carrying not less than between 5 and 15 p.p.m. We do not know, nor have we been able to discover, the background mercury values for the particular areas on which we are reporting. However, on the basis of available data (Hawkes and Webb 1962, Vinogradov 1959) we would normally expect agricultural soils to run from 0.01 to 0.06 p.p.m. of mercury. Thus these British soils are anomalous by an amount in the order of one hundred, a matter which should not be viewed with equanimity.

Synthesis of methyl-mercury compounds by extracts of a methanogenic bacterium.

THERE have been incidences of extensive alkyl-mercury poisoning in Japan and Sweden. In Japan a large number of people belonging to the fishing population around Minamata Bay were seriously affected by what is now called Minamata disease. This incident was traced back to pollution of the bay with the mercury containing effluent of a large chemical plant. When methyl thiomethyl-mercury was isolated from shellfish in the area of the bay it was suggested that mercury could be alkylated by “plankton and other marine life”2. It was discovered later that the spent catalyst of an acetaldehyde reactor, which caused the pollution, contained approximately 1 per cent methyl mercury; and the biological methylation of mercury was thought to be insignificant.

Studies on the brain and bladder. 1. Clinical and experimental studies on minamata disease

Minamata disease which broke out on the coast of Minamata, a southern city in Japan, from 1955 to 1959, was a disorder of the central nervous system. It was proved that the cause of this disease was methyl mercuric compound which was taken from fishes or shellfishes contaminated by an effluent from a chemical plant. There have been many clinical and pathological reports on this disease. However, up to today, there have been no observations on the function of the urinary tract in this disease. The purpose of the present report is to research into the renal and vesical functions in Minamata disease.Examinations were made in 33 cases of Minamata disease, including neurological examination, electroencephalography, renal clearance test, PSP test, Fishberg's concentration test, blood chemistry, urine examination, IVP, cystography and cystometry. As controls, renal function and cystometrogram in 15 rabbits of ethyl mercuric phosphate poisoning and cystometrogram in 21 cases of brain diseases were studied.The following results were obtained.1) Neurological examination and electroencephalography revealed that, the chiefly disturbed portions in Minamata disease were the cerebral cortex and cerebellum. In the cerebral cortex, the chief lesions involved covered Sulcus calcalinus and Gyrus centralis in adult cases. In children, especially in congenital cases, involvement is extended wider to the frontal lobe.2) A majority of cases of Minamata disease showed normal renal function, while some showed moderate disturbance of RPF and proximal tubular function.3) Hypertonic small bladder was observed in 4 of 14 adult cases of Minamata disease, in 5 of 7 child cases and in 11 of 12 congenital cases. On the other hand, 3 of 14 adult cases showed a normotonic or hypotonic large bladder. Efficiency of micturition was generally good. Urinary incontinence was observed in only 3 congenital cases.4) Six rabbits which were given 2mg per kg of body weight of ethyl mercuric phosphate every other day developed moderate disturbance of renal function; and 9 rabbits, which were given 4mg per kg of body weight every day showed severe disturbance of that at the time of development of Minamata-disease-like symptoms. Some of these rabbits showed hypertonic small bladder, while some others showed large bladder.5) A large number of cases of either cerebral arteriosclerosis or frontal lobe tumor showed a hypertonic bladder, on the other hand, almost all cases of traumatic epidural hematoma showed a hypotonic bladder.The above results show that organic mercuric compounds have direct poisoning effect on the kidney, but in Mimanata disease, the disturbance of renal function was very rare. The results also suggest that there may be two centers which control the urinary bladder. One is the suppression certer which might be situated in the frontal part of the frontal lobe and the other is the promotion center situated behind the former.

3) ORGANIC MERCURY POISONING

It has been proved that the Minamata disease is the poisoning by alkyl compound (AM), and recently phenyl mercury compounds (PM) which are used as agricultural drugs have been brought on public discussion. This report deals with clinical and experimental studies on these poisonings.

Studies on the origin of the causative agent of Minamata disease. IX. Transition of the pollution of Minamata Bay and its neighbourhood

1) No new cases of Minamata disease have been found since 1961. However it was considered that a slight amount of the organomercury compound as the causative agent of the disease had been discharged from Minamata Factory until May, 1966, notwithstanding the completion of the waste treatment of the factory in January, 1961. In June, 1966, the system of waste treatment wsa revised. Then, the mercury content in the fish from the bay abruptly decreased.2) Methylmercury chloride was extracted as crystalline solids from the waste water discharged from the rectifying column of acetaldehyde plant, and a considerable amount of chloride appeared in in the same waste water.

Studies on the Origin of the Causative Agent of Minamata Disease Report VIII On the Formation of Methyl Mercury Compounds in an Acetaldehyde Plant

1) An organomercury compound with the same Rf value on the thin-layer chromatogram as methylmercuric hydroxide was detected in the mixtures of acetaldehyde and mercuric oxide or basic mercuric sulfate. When chloride was added to the above mixtures, an organomercury compound having the same Rf value as methylmercuric chloride was formed.2) The reaction of acetaldehyde and mercuric oxide yielded two mercury compounds as crystals. One of them was identified as mercuric acetate by IR spectrum, elementary analyses, melting point determination and chemical properties. Methylmercuric chloride was extracted from the mixture of mercuric acetate and sodium chloride into chloroform and recrystallized from ethanol.

正誤表

正誤表

Difference of Mercury Contents of Divided Hair Fragments by Eating Food Contaminated with Organic Mercury Compounds

The Minamata disease is known since 1953 as an organic mercury intoxication, mainly among fishermen along the Minamata Bay, Kumamoto Prefecture, by eating seafoods contaminated with organic mercury compounds. In connection with the disease the mercury content in hair of the coastal residents of the Shiranui Sea was determined. By using the samples in which high contents were noted, the critical determinations were made by cutting the hair in 3 cm portions from the base and consequently remarkably uneven distributions of the mercury along the length were observed. The portions of hair with unusually high contents of mercury were presumed to grow during the uptake of the contaminated food. The application of this method to the residents of the contaminated area will be useful for better speculation of the period of contamination.

Some Considerations on the Pathogenesis of Cerebral Palsy, with Special Reference to Prenatal Factors (comparative study of own cases of cerebral palsy and of the Minamata disease in literature)

Some Considerations on the Pathogenesis of Cerebral Palsy, with Special Reference to Prenatal Factors (comparative study of own cases of cerebral palsy and of the Minamata disease in literature)

Toxicity and metabolism of methyl mercury compounds in animals -especially in relation to Minamata disease

In order to explain the significance as the causative agent of Minamata disease of methyl mercury chloride which was extracted from the sludge in the reaction tube in the acetaldehyde plant of Minamata Factory and from the shellfish in the Minamata Bay, methyl mercury chloride and other methyl mercury compounds which are able to be derived from methyl mercury chloride were synthesized, and the toxicity and the chemical properties of mercury compounds accumulated in organs of animals administered with those methyl mercury compounds were observed.