Minamata Disease Research Articles

THE PATHOLOGY OF MINAMATA DISEASE.

The Minamata disaster has certainly been the most outstanding example recorded of the effects of industrial irresponsibility and will remain as a never to be forgotten lesson. In that respect, this review of the outbreak and of the neuropathology of the process, of which much though not by any means all was published in the Japanese literature of the period, is well justified. Several of these papers are printed here in the appendix to this survey of the clinical and pathological features of the illness. It must be admitted that while there are a great deal of data here, especially the detailed mercury analyses of nervous tissues, the book is more remarkable, perhaps, for what it leaves out. The story of the outbreak of poisoning is briefly though incompletely told. There is the account of the shameful behaviour of the physician in charge of the hospital maintained by the factory in question, who realized that the illness of these patients could well be related to chemicals used in the factory, but was restrained by the management from publishing this opinion. Then there were the chemists who for a long while were `economical with the truth' as to …

The Investigations on the Environmental Pollutions in the Actual Spot of the World.

The large-scale mercury contamination has occurred in the Amazon river basin in Brazil. Also, I have visited Tanzania, the Philippines and other countries a number of times, and I convinced that similar problems are spreading worldwide. A numbers of gold-miners already suffer from inorganic mercury poisoning. None of the fishermen living downstream of the gold mine showed symptoms of Minamata disease. However, the mercury content of their hair indicates that the situation is becoming dangerous. Serious arsenic poisoning is occurring on a large scale in various areas of Asia. This is attributable to the use of great quantities of underground water in the large-scale agriculture, particularly in West Bengal (India). In developingcountries, various industrial sectors are developing simultaneously, such as refining, chemical, pulp, petrochemical and high-tech industries, causing complex environmental contamination such as at the Weonsan Industrial Park in Korea. The residents of Weonsan district tended to suffer from combined poisoning that it should be called Weonsan disease instead. The hazardous technologies and industrial plants being transferred from developed countries to developing countries are major cause of industrial poisoning and environmental contamination. Examples of such cases are the Onjin case of Cabon disulfide poisoning in Korea, the gas leak at the agricultural chemical plant in Bhopal, India and radioactive contamination in Ipho city, Malasya.Health damage due to industrial and environmental contaminations is often masked by the effects of unsanitary living condition and health effects of novel chemicals and complex contamination are also frequently invisible.

Differential diagnosis between organic and inorganic mercury poisoning in human cases--the pathologic point of view.

Differences in pathology were found between acute and chronic exposure to methylmercury, mercury vapor, and inorganic mercury. Characteristic pathologic changes produced by organic mercury in the brain have previously been described in patients with Minamata disease. The brains of patients who presented with acute onset of symptoms and died within 2-mo showed loss of neurons with reactive proliferation of glial cells, microcavitation, vascular congestion, petechial hemorrhage, and edema in the cerebral cortices, predominantly in the calcarine, pre- and postcentral, and transverse temporal cortices and in the cerebellar cortex. The neuropathologic changes in the patients with acute onset of symptoms who survived for a long period (>10 yr) were also included neuronal loss with reactive proliferation of glial cells in similar anatomic locations. The neuropathologic changes in patients with inorganic mercury poisoning are quite different. Autopsies performed on 3 individuals with fatal cases of acute inorganic mercury poisoning who were exposed to mercury vapor for about 2 wk revealed diffuse organized pneumonia, renal cortical necrosis, disseminated intravascular coagulopathy, and infarctions in the brain and kidneys. In 2 other patients who worked in mercury mines for about 10 yr and who suffered from chronic inorganic poisoning, no specific lesions were demonstrated in the brain. However, the assay and the histochemistry of mercury revealed that inorganic mercury was present in the brain in all 3 groups irrespective of the brain lesions and the duration of clinical signs.

Methylmercury level in umbilical cords from patients with congenital Minamata disease

A total of 151 umbilical cords during the period from 1950 to 1969 were collected from the residents of the Minamata area (including 25 patients with congenital Minamata disease) for methylmercury (MeHg) analysis. When the MeHg discharge from the Chisso Company’s Minamata factory into the Minamata Bay is compared with the incidence of congenital Minamata disease, the abrupt increase of the former in 1952 [Nishimura H. Chem. Today 1998;323:60–66] was found to precede that of the latter by approximately 2 years, thereby indicating that MeHg is the cause of the disaster. This was confirmed by the elevated levels of MeHg in the umbilical cords from residents of the Minamata area [from 0.35±0.30 (S.D.) ppm in 1952 to 0.96±0.75 ppm in 1955], the MeHg levels (1.60±1.00 ppm) in the cords from patients with congenital Minamata disease showing the highest values [ P<0.01 vs. acquired Minamata disease (0.72±0.65 ppm), mental retardation (0.74±0.64 ppm), other diseases (0.22±0.15 ppm), and no symptoms (0.28±0.20 ppm), respectively]. Thus, in order to fill a gap, which extends over a long period of time, in studies on environmental Hg pollution, umbilical cord samples were considered to be a useful tool.

Representation of the Visual Field in the Striate Cortex

Literature Abstracts: Literature Abstracts-The American Journal of Neuroradiology, 1997: Clinicoanatomic and Pathologic Correlations: PDF Only

Monitoring of mercury pollution in Tanzania: relation between head hair mercury and health

Through 1996 into 1997, a spot investigation on mercury contamination was conducted three times in Tanzania, especially around the Lake Victoria. A total of 150 goldminers, 103 fishermen and their families, and 19 residents of Mwanza City volunteered for the current study. A high total mercury level of 48.3 ppm (near to 50 ppm, a critical level of Minamata disease) and over in the head hair was observed in six goldminers (highest value, 953 ppm), four fishermen and their families (highest value, 416 ppm), and four Mwanza people (highest value, 474 ppm). With the exception of these 14 subjects, however, each mean total mercury level was well within the normal range (below 10 ppm). Out of the goldminers examined, 14 cases were diagnosed as a mild form of inorganic-mercury poisoning according to their clinical symptoms (such as polyneuropathy mercurialis, neuroasthemia, or tremor mercurialis) and the low ratio of methylmercury to total mercury, whereas neither inorganic-mercury poisoning nor methylmercury poisoning (Minamata disease) was noted in the fishermen and their families or in the Mwanza people. In addition, some subjects who showed a high total mercury level made habitual use of toilet soap containing much mercury. The findings obtained suggest that the mercury pollution in Tanzania is not very serious, however, it should be observed continuously.

An appraisal of the judgements of the Kumamoto Minamata Disease Certification Commission from May 1981 to July 1992 for applicants from December 1975 to April 1981

The differences of the diagnosis from December 1975 to April 1981 and from May 1981 to July 1992 of the Committee on Certification of Minamata Disease based on the medical records of 3,870 applicants who had been examined from December 1975 to April 1981 by the Committee were compared and analyzed from a statistical point of view. Three hundred forty inhabitants from December 1975 to April 1981 and two hundred ninety eight inhabitants from May 1981 to July 1992, in total six hundred and thirty eight inhabitants, were certified to have Minamata disease by the Committee on Certification of Minamata Disease. One hundred and eleven inhabitants who were judged likely to have Minamata disease by application of the present criteria presented by the Japanese Environmental Agency in 1977 were certified by the committee from May 1981 to July 1992, and one hundred and thirty three inhabitants who were judged not likely to have Minamata disease by application of the present criteria were certified from May 1981 to July 1992. The author concluded that certification of the patients of Minamata disease by the Committee was inconsistent with the results of applying the present criteria to the data and that the prevalence of the symptoms of the inhabitants certified from December 1975 to April 1981 was inconsistent with that from May 1981 to July 1992.

Lessons from Minamata mercury pollution, Japan - after a continuous 22 years of observation

One of the most visible tragedies by industrial water pollution is Minamata disease, methylmercury poisoning caused by eating contaminated fish, which has killed more than 100 people and paralyzed several thousand people around Minamata Bay, Japan and the adjacent Yatsushiro Sea since 1956. The cause of Minamata disease was confirmed, not by analyzing environmental samples such as sediments (containing more than 600 ppm of Hg) or fish (at least 20 ppm) at the bay, but by symptoms of Minamata disease patients that resembled previous mercury poisoning reported in a European medical journal. Mercury dispersion was traced for 22 years to collect mercury concentration measurements in Yatsushiro Sea surface sediments at 24 fixed stations. The analytical results of mercury revealed four trends of mercury movement from the bay: 1) a rapid increase in Hg concentrations up to 1984; 2) a dramatic decrease in mercury concentrations after an artificial mercury decontamination project began in 1984; 3) a strange drop in mercury contents due to an historical rainfall in the region in 1982 and; 4) natural decontamination, which has been underway since 1985. The tragedy at Minamata has provided many lessons which have shaped the scientific field in environmental research, especially in the area of water quality.

Methylmercury Dose Estimation from Umbilical Cord Concentrations in Patients with Minamata Disease

The methylmercury exposure of patients with congenital or infantile Minamata disease is known only from a small number of analyses of umbilical cords. Four laboratories in Japan have analyzed a total of 176 samples of umbilical cord tissue obtained from Minamata. The highest concentrations were seen in cord tissue from children born during 1950–1965, i.e., the peak period of acetaldehyde production in Minamata before installation of waste water treatment. Twenty-four samples from patients diagnosed with Minamata disease showed a median mercury concentration of 1.63 μg/g and differed significantly from levels seen in cord tissue from control children. However, children diagnosed with mental retardation had mercury concentrations in cord that were intermediate between the two other groups. Using regression coefficients obtained at a study conducted at the Faroe Islands, the median cord mercury concentration from the children with Minamata disease is estimated to correspond to about 216 μg/L cord blood and 41 μg/g in maternal hair. Based on correlations reported in the literature, the median daily mercury intake of the women whose children developed Minamata disease can then be estimated at about 225 μg. Although these children had fully developed Minamata disease, the estimates of median mercury levels are only four to five times higher than current mercury exposure limits.

The Present Mercury Contents of Scalp Hair and Clinical Symptoms in Inhabitants of the Minamata Area

A total of 191 fishermen and their family (32–82 years) living in some mercury-polluted areas along the Shiranui Sea volunteered for the present study. They made a living by fishery and had formerly eaten the methyl mercury-contaminated fish and shellfish caught there. The questionnaire on subjective symptoms, fish eating habits, and past living history was conducted on the subjects. In addition, they were clinically examined in detail by several neurologists and scalp hair was collected. With six exceptions, all the 185 subjects showed a normal total mercury level in hair (<10 ppm). The ratio of methyl mercury to total mercury was 79–94% on the average for each group examined, suggesting indirect contamination (perhaps through the food chain). Despite their low mercury level in scalp hair, however, the subjects showed various neurological symptoms, particularly, sensory disturbance (such as the glove and stocking type), at a very high rate. Thus, it seems fair to state that, in addition to officially recognized Minamata disease patients, there still exist many people with atypical, slight Minamata disease on the coast of the Shiranui Sea. The current hair mercury level is not necessarily useful as a criterion for diagnosing chronic Minamata disease because of the long lapse of time.

MR findings of Minamata disease--organic mercury poisoning.

We describe MR findings in patients with Minamata disease who have been followed for a long time. All patients examined were affected after daily eating of a large quantity of methylmercury-contaminated seafood, from 1955 to 1958, and showed typical neurological findings. On MR images, the visual cortex, the cerebellar vermis and hemispheres, and the postcentral cortex are significantly atrophic in Minamata disease. The visual cortex is slightly hypointense on T1-weighted images and hyperintense on T2-weighted images, probably representing the pathologic changes of status spongiosus. MRI can demonstrate the lesions located in the calcarine area, cerebellum, and postcentral gyri, which are probably related to three of the characteristic manifestations of this disease: the constriction of the visual fields, ataxia, and sensory disturbance, respectively.

Distributional pattern of apoptotic cells in rat cerebellar vermis experimentally induced by methylmercury intoxication

This report deals with the distributional pattern of apoptotic granule cells in rat cerebellar vermis following experimental methylmercury chloride (MMC) toxicosis. The rats administered MMC showed clinical signs of hind leg paralysis around day 19 and this developed to moribund by day 26. Pathologic examination of the moribund animals revealed that cerebellar degeneration characterized by apoptosis of the granule cells was not equally distributed in the cerebellar vermis; apoptotic granule cells were observed in the lingula, central lobule, Lobulus ascendens, pyramis vermis and culmen in the order of decreasing frequency. This selective vulnerability in MMC intoxication is similar to the granule cell loss of Minamata disease in humans and suggests that this rat model is a useful pathobiologic model for studying cerebellar degeneration in Minamata disease.

Widespread neuronal degeneration in rats following oral administration of methylmercury during the postnatal developing phase: a model of fetal-type Minamata disease

The neurotoxicity of methylmercury (MeHg) treatment during the postnatal developing phase in rats was studied. Rats on postnatal day 1 were orally administered 5 mg/kg/day methylmercury chloride (MMC) for more than 30 consecutive days. Body weight loss began 26 days after MMC was administered, and severe paralysis of the hind-limbs and unsteadiness appeared subsequently. Histopathologically, the widespread neuronal degeneration was observed in the cerebral neocortex, neostriatum, red nucleus, brainstem, cerebellum and spinal dorsal root ganglia on day 32. The widespread distribution of the lesions was quite similar to that in fetal cases of MeHg intoxication in Minamata, Japan. These findings suggest that MMC treatment during the postnatal development phase in rats produce a good model of fetal-type Minamata disease.

Minamata Disease from the Viewpoint of Occupational Health

Minamata Disease from the Viewpoint of Occupational Health: Shigeru Nomura, et al. Department of Public Health, Kumamoto University School of Medicine—Minamata disease is a neurological disorder caused by methyl mercury poisoning which occurred as the result of ingestion of large quantities of fish and shellfish polluted by industrial waste water in Minamata and Niigata, Japan. More than 40 years have passed since the epidemic was first reported in 1956 in Minamata. Inorganic mercury used as a catalyst in the acetaldehyde process had methylated inside the factory and had then been discharged into Minamata Bay. The waste from the acetaldehyde process continued to pour into the bay until 1968. In the process of researching possible causal elements, the Minamata Disease Study Group of the Kumamoto University School of Medicine found that the clinical and pathological findings in cases of Minamata disease coincided with certain cases of methyl mercury poisoning in England reported in 1940 by D. Hunter and D. S. Russell and which were published in a monograph on occupational toxicology in 1958. The English cases involved the poisoning of workers in a factory producing methyl mercury pesticide. It is clear that occupational poisoning can provide an important guide for the investigation into the cause of an environmental disease such as Minamata disease but there are differences between the two types of poisoning as they occur under different conditions. Occupational poisoning is a direct poisoning of workers which occurs under certain conditions, whereas Minamata disease involves the poisoning of the entire population of a contaminated area, including embryos, the aged and those who are already suffering from other diseases. When these points are considered, it becomes clear that although Minamata disease and occupational poisoning coincide with each other in some respects, they do not in others.

Lessons from Minamata mercury pollution, Japan — After a continuous 22 years of observation

One of the most visible tragedies by industrial water pollution is Minamata disease, methylmercury poisoning caused by eating contaminated fish, which has killed more than 100 people and paralyzed several thousand people around Minamata Bay, Japan and the adjacent Yatsushiro Sea since 1956. The cause of Minamata disease was confirmed, not by analyzing environmental samples such as sediments (containing more than 600 ppm of Hg) or fish (at least 20 ppm) at the bay, but by symptoms of Minamata disease patients that resembled previous mercury poisoning reported in a European medical journal. Mercury dispersion was traced for 22 years to collect mercury concentration measurements in Yatsushiro Sea surface sediments at 24 fixed stations. The analytical results of mercury revealed four trends of mercury movement from the bay: 1) a rapid increase in Hg concentrations up to 1984; 2) a dramatic decrease in mercury concentrations after an artificial mercury decontamination project began in 1984; 3) a strange drop in mercury contents due to an historical rainfall in the region in 1982 and; 4) natural decontamination, which has been underway since 1985. The tragedy at Minamata has provided many lessons which have shaped the scientific field in environmental research, especially in the area of water quality.

The Logic of Discrimination and Oppression in Areas with Outbreak of Minamata Disease: With Special Reference to the Case of Niigata Minamata Disease

The Logic of Discrimination and Oppression in Areas with Outbreak of Minamata Disease: With Special Reference to the Case of Niigata Minamata Disease

Mercury in the Amazon.

Release and spreading of mercury from gold mining is a widespread problem in the Amazon area. Today we have rather good knowledge of the mercury situation. Tens of investigations have considered mainly concentrations in fish and human hair. Metallic mercury is used for amalgamation of gold, and the mercury is released by evaporation at reburning sites. The first extraction (burning) is performed in the field at the garimpos and the second (reburning) in gold shops in towns. This practice may cause severe exposure to elemental mercury by inhalation for people working with gold purification. Mercury is also released in substantial amounts to rivers and lakes. This mercury may be bioaccumulated as methylmercury in aquatic food chains. Predatory fish often contain mercury in concentrations that far exceed the safety norms in Brazil. As many people eat fish daily, there is a high exposure to methylmercury. Neurological disorders have been found in exposed persons. Methylmercury concentrations in hair are often at levels that may cause clinical symptoms of Minamata disease. The greatest health hazard index values have been estimated for people eating contaminated fish.

Pathology of Minamata disease.

Minamata disease, or methylmercury poisoning, was first discovered in 1956 around Minamata Bay, Kumamoto Prefecture, Japan. A similar epidemic occurred in 1965 along the Agano River, Niigata Prefecture, Japan. The neuropathology of Minamata disease has been well studied; this review focuses on human cases of Minamata disease in Kumamoto Prefecture. Nervous system lesions associated with Minamata disease have a characteristic distribution. In the cerebral cortex, the calcarine cortex was found to be involved in all cases of Minamata disease, particularly along the calcarine fissure. The destruction of nerve tissue was prominent in the anterior portions of the calcarine cortex. Occasionally, the centrifugal route from the visual and visual association areas (internal sagittal stratum) showed secondary degeneration in prolonged cases after acute onset. Postcentral, precentral, and temporal transverse cortices showed similar changes, though they were less severe. Intense lesions in the precentral cortex caused the development of secondary bilateral degeneration of the pyramidal tracts. In the cerebellum, the lesions occurred deeper in the hemisphere. The granule cell population was most affected. In the peripheral nerves, sensory nerves were more affected than motor nerves. Secondary degeneration of Goll's tracts was occasionally seen in prolonged or chronic cases.

Migration of granule neurons in cerebellar organotypic cultures is impaired by methylmercury

To examine whether abnormal migration of granular cells in the external granule layer during cerebellar development is in part of the etiology of fetal Minamata disease, organotypic culture of rat cerebellar slice was established. Migration of external granule cells pulse-labeled with bromodeoxyuridine (BrdU) toward the internal granular layer was inhibited by the presence of methylmercury (0–10 μM) in a dose-dependent manner. Nuclear condensation and DNA fragmentation visualized by the indirect immunofluorescence method with anti-BrdU antibody and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method indicated that a large fraction of cells in the external granular layer underwent apoptotic death in the slices treated with 10 μM methylmercury. Thus, methylmercury inhibits the migration of cerebellar granule cells in a model system for neural development. The impaired migration was a possible cause of the apoptotic death of external granule cells.

An appraisal on the judgements of the Kumamoto Minamata Disease Certification Commission

Medical records of 3,870 applicants living near the Shiranui sea coast who had been examined from August 1975 to April 1981 by the Committee on Certification of Minamata Disease were analyzed from the statistical point of view. The author analyzed the pattern of signs and reevaluated the applicants' records. Three hundred forty applicants (8.8%) were certified to have Minamata disease by the Committee on Certification of Minamata Disease. By application of the present criteria presented by the Japanese Environmental Agency in 1977 to the records, 947 inhabitants (27.9%) were judged likely to have Minamata disease. The author concluded that the certification of the patients of Minamata disease by the Committee was inconsistent with the results of applying the present criteria to the data and that the number of patients certified by the Committee to have Minamata disease was too low.