Minamata Disease Research Articles

Environmental Contamination and Human Rights — Case of Minamata Disease

Minamata disease is methylmercury poisoning that occurred in humans who ingested fish and shellfish contaminated by methylmercury discharged in waste water from a chemical plant. A total of 2,255 persons have been diagnosed with the Minamata disease, as of January 1993, 1,096 have already died. In addition, about 10,000 per sons are suspected of Minamata disease. What is the reason for this disaster that is unprecedented and unparalleled in the history of mankind? World War II ended in August 1945 with Japan's defeat. Japan was faced with the urgent need to restore its devastated land and rebuild its economy. Under these conditions, priority was given to industrialization at all costs. The rights of individuals were slighted because the government subsidized industry, and collaborated with it. Productivity and efficiency were valued above anything else. Safety and post-treatment technologies were ignored. Japan rapidly achieved economic development, but experienced many inci dences of occupational hazards and environmental contamination. The most typical example is Minamata disease. People who suffer first from the damages of environmental contamina tion are always those who maintain close contact with nature, particularly children and the elderly. Minamata disease brought about tragic results because the patient's cen tral nervous system was primarily damaged. People became acutely aware of environmental contamination when they learned that the fetus of a contami nated mother may suffer more serious damages. This paper discusses the outline of Minamata disease and its etiologi cal changes.

Health effects associated with wastewater treatment, disposal, and reuse

and transfer of fecal indicator organisms (coliforms, enterococci, sulphite-reducing clostridia, and coliphages) downstream of a wastewater treatment plant were investigated at Lake Kallavesi, Finland (R?jala and Heinonen-Tanski, 1998). The observation of indicator organisms up to 18 km from the discharge point and good survival in the summer suggested that direct use of lake water could constitute a health risk. The effect of combined sewer overflows (CSOs) on the occur rence of Giardia and Cryptosporidium was investigated (Gibson et al., 1998). The results suggested that CSOs significantly contribute to the load of Giardia and Cryptosporidium in ambient waters and source waters for drinking and recreational uses. An outbreak of waterborne giardiasis in Temagami, Ontario, in 1994 was assessed (Wallis et al., 1998). The outbreak was traced to leakage from the municipal wastewater system into the lake and exacerbated by spring snow-melt runoff. The influence of rainwater on the con centration of helminth eggs in wastewater was investigated (Capizzi and Schwartzbrod, 1998). Concentrations of parasite eggs vary according to water flow rates and sedimentation; heavy rain following rainless days yielded higher concentrations in raw wastewater at the treatment plant, whereas continuous moderate rain resulted in low variation of parasite eggs. The prevalence of respiratory symptoms, skin disorders, status of spirometric lung functions, and amino acid profiles among wastewater workers were reported (Bener et al., 1998). Wastewa ter workers had a higher prevalence of respiratory symptoms than controls, significant for chronic cough (p < 0.02), chronic phlegm (p < 0.03), chronic bronchitis (p < 0.02), asthma (p < 0.02), dyspneoa (p < 0.001), and nasal catarrh (p < 0.001) and acute symptoms of pruritus (p < 0.003), tinea (p < 0.004), dermatitis (p < 0.001), and nose irritation (p < 0.005). Spirometry tests scored lower in wastewater workers, and most of the plasma amino acids concentrations were elevated among wastewater workers. An investigation examining whether inadequate septic system construction may cause contamination of wells with coliform bacteria or nitrates was reported (Tuthill et al., 1998). The authors found that coliform bacteria and nitrate contamination were neg atively correlated with lot size, and coliform bacteria levels were negatively correlated with casing length, which suggested that septic systems may be a source of coliform bacteria and nitrate contamination in wells. CONTAMINATION OF WATER SUPPLIES

The Use of Photosynthetic Microorganisms in Bioremediation.

The microorganisms play an important role in selfpurification of water and soil environment as decomposers in the ecosystem. Microbial technologies, such as a activated sludge or oxidation pond processes, have been extensively applied to the treatment of industrial and domestic sewages to break down organic wastes. Another type of treatment is based on their ability to remove specific substances such as phosphorus, nitrates and heavy metals. The environmental pollution by toxic metals, especially Pb, Hg, Cd, is a potential hazard to the health and welfare of mankind. Many people in Japan suffered from diseases caused by pollution of heavy metals, such as ache-ache disease and Minamata disease. We feel misgivings about the similar environmental pollution in the developing countries, for the rapidly growing industrial operations would release heavy metals and those metals even at very low concentrations would be concentrated biologically through natural food chains. Microalgae can concentrate metals and transform them into less hazardous forms, and the use of microalgal biomass would offer a potential alternative to conventional methods for detoxification and for recovery of toxic or valuable metals. This review summarizes an information on physiological relations between heavy metals and microorganisms, especially microalgae, and presents some applications of algal biotechnology that has been developed to use microalgal biomass for bioremediation of heavy metals.

Mercury in the Umbilical Cord: Implications for Risk Assessment for Minamata Disease.

Umbilical cord tissue was obtained from 50 births in the Faroe Islands, where high mercury intake is due to ingestion of pilot whale meat. The mercury concentration correlated significantly with the frequency of maternal whale meat dinners during pregnancy and with mercury concentrations in umbilical cord blood and in maternal hair. The results were compared with published values for mercury in umbilical cord tissue from 12 infants diagnosed with congenital methylmercury poisoning in Minamata, Japan. From the regression coefficients obtained in the Faroese samples, the median umbilical cord mercury concentration of 4.95 nmol/g dry weight in Minamata would correspond to 668 nmol/l cord blood and 114 nmol/g maternal hair. These levels agree well with other evidence of susceptibility of the fetus to increased exposure to methylmercury.

新潟水俣病における地域の社会的被害

We will consider the social damage, especially discrimination, which Niigata Minamata Disease decisively reinforced. There are many causes of discrimination, but this paper focuses on how institutions and standards regulate the conditions of discrimination in the community.Here, we will deal with the case of the town of Yasuda, along side the Agano River, and discussing the serious problems which institutions and standards cause to the people of the town.

Profile of Subjective Complaints and Activities of Daily Living among Current Patients with Minamata Disease after 3 Decades

We surveyed 1144 current patients with Minamata disease (MD) aged 40 or over in the Minamata area and the same number of neighbor controls matched with age and sex by questionnaire interview with regard to subjective complaints and activities of daily living (ADL). From analysis of subjective complaints, it was found that MD patients had significantly higher rates of all complaints than controls (P < 0.05). Multivariate analysis showed that subjective complaints in controls were clearly separated into the following two categories: sensory disturbances and movement nerve disturbances, but all complaints in MD patients formed one cluster. Such variation seemed to be due to methylmercury exposure to the central nervous system. ADL analysis revealed that the difference in the ADL disability between MD patients and controls significantly increased with age (P < 0.05) and that ADL disability in MD patients was aggravated by aging.

Epidemiologic and Clinical Features of Minamata Disease

Minamata disease is methyl mercury intoxication from fish contaminated by a chemical factory in Minamata city. Based on the results of our regional survey, cardinal clinical features of the disease were clarified by a multivariant analysis of all symptoms in inhabitants in the polluted area. The clinical features were found to be essentially the same as those of Hunter Russell syndrome; however, some additional symptoms were also found. Those symptoms are influenced by many factors, such as degree of exposure and duration of pollution. The disposition of each inhabitant also plays a role in clinical manifestation. This analysis contributes to a correct individual diagnosis and to the correct estimation of patients in polluted areas. Long-term studies also uncovered a few inhabitants who claimed to have begun to experience some neurological symptoms after pollution ceased. These symptoms were attributed mainly to aging. As many inhabitants with mild neurological complaints were not easily diagnosed, a questionable borderline group should be postulated for social settlement of Minamata disease. The characteristics of Minamata disease are discussed and compared to cases of methyl mercury poisoning in other parts of the world.

Field studies using the oyster Crassostrea virginica to determine mercury accumulation and depuration rates

Mercury as an environmental hazard, especially with regard to human health, has been of concern since the Minamata disaster. From 1966 to 1970 a chlor-alkali plant in Point Comfort, Texas released mercury-enriched wastewater (up to 29.9 kgHg/day) into Lavaca Bay (TWQB 1977). Since 1970 the Texas Department of Health (TDH) has periodically closed and then re-opened portions of Lavaca Bay to the harvesting of crabs and finfish based on their levels ( 0.5 ppm Hg wet weight) of mercury. A 1988 closure remains in effect as of this writing. Mercury contamination in Lavaca Bay organisms thus continues to be a problem 22 years after the chlor-alkali plant ceased releasing mercury into the bay. The goal of the following research was to better understand the behavior of mercury in Lavaca Bay. Oysters have been widely used as indicator species in metal pollution studies. Most such programs have focused on the concentrations of metals in oysters from different geographic areas. This study, however, investigated the rate and amount of mercury a [open quotes]clean[close quotes] oyster would accumulate when transplanted to a contaminated estuary and the rate of mercury depuration by contaminated oysters placed in a clean environment. The oysters were additionally analyzed formore » Ba, Cu, Fe, P, and Zn to test for the possible involvement of these metals in mercury accumulation and depuration. 17 refs., 3 figs., 2 tabs.« less

Environmental release of chemicals and reproductive ecology.

Reproductive ecology is defined as "the study of causes and mechanisms of the effects of environmental risk factors on reproductive health and the methods of their prevention and management." Major areas of concern, within the purview of this paper, relate to adverse pregnancy outcomes, effects on target tissues in the male and the female, and alterations in the control and regulatory mechanisms of reproductive processes. Teratogenic potential of chemicals, released as a result of accidents and catastrophes, is of critical significance. Congenital Minamata disease is due to transplacental fetal toxicity caused by accidental ingestion of methyl mercury. Generalized disorders of ectodermal tissue following prenatal exposure to polychlorinated biphenyls have been reported in Taiwan and Japan. The Bhopal gas disaster, a catastrophic industrial accident, was due to a leak of toxic gas, methyl isocyanate (MIC), in the pesticide manufacturing process. The outcome of pregnancy was studied in female survivors of MIC exposure. The spontaneous abortion rate was nearly four times more common in the affected areas as compared to the control area (24.2% versus 5.6%; p < 0.0001). Furthermore, while stillbirth rate was found to be similar in the affected and control areas, the perinatal and neonatal mortality rates were observed to be higher in the affected area. The rate of congenital malformations in the affected and control areas did not show any significant difference. Chromosomal aberrations and sister chromatid exchange (SCE) frequencies were investigated in human survivors of exposure. The observed SCE frequencies in control and exposed groups indicated that mutagenesis has been induced. Strategies for the management, prediction, and preventability of such disasters are outlined.

Disturbances of accommodation in Minamata disease: A neuropathological study of methylmercury toxicity in common marmoset monkeys

Disturbances of accommodation are part of the spectrum of neuro-ophthalmological findings in patients with Minamata disease. The authors conducted a study in an animal model of mercury toxicity to identify the anatomical lesions underlying these defects. Three common marmosets received 1.0 mg/kg of methylmercury chloride (MMC) twice weekly for seven to ten weeks until signs of mercury toxicity evolved. Histopathological analysis revealed severe neuronal loss and proliferation of astroglia in the Edinger-Westphal (EW) and anteromedian (AM) nuclei of the midbrain. Less severe neuronal degeneration was observed in the cerebral cortex surrounding the lateral sulcus. In addition, a single animal showed gliosis in the region of the fastigial nucleus of the cerebellum. Among cortical and subcortical structures involved in accommodation the EW and AM nuclei were the most severely affected.The authors' results suggest that impaired accommodation in patients with methylmercury intoxication arises mainly from lesion...

Difference in susceptibility to experimental thiophene poisoning between spontaneously hypertensive and wistar-kyoto rats.

Many of the patients with Minamata disease, caused by methylmercury have developed hypertension. In experimental methylmercury poisoning, the level of mercury and the mortality are higher in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto rats (WKY). Thiophene induces cerebellar degeneration, which is also found in rats with methylmercury poisoning and hepatic necrosis. To clarify the pathophysiology of the thiophene-induced lesions female SHR and WKY aged 150 days were studied and a comparison was made between the two strains. Up to an age of 150 days, the body weight of SHR was less than that of WKY, but food consumption by SHR was higher than that of WKY. SHR were more susceptible to thiophene poisoning than WKY in terms of symptoms, changes in auditory brainstem response (ABR), and histopathological findings. Administration of pentobarbital was more effective in producing hepatic lesions in SHR than in WKY. Ultrastructurally, nuclear chromatin segregation and irregular distribution of rough endoplasmic reticulum (rER) were prominent in the hepatic cells of non-treated SHR. An osmiophilic homogeneous substance appeared to play an important role in the formation of cerebellar lesions in both SHR and WKY. The hepatic injury and disturbance of cerebellar blood vessels seem to cause the cerebellar lesions. It is suggested that a reduced ability for drug metabolism in SHR, which might be inherited or acquired, is one of the causes of the higher susceptibility of this strain to thiphene poisoning, compared with WKY.

The Pollution of Minamata Bay by Mercury

Minamata Disease, methylmercury poisoning, was recognized late in 1953 among the inhabitants living around Minamata Bay. In a chemical factory situated near Minamata Bay, acetaldehyde had been synthesized by the hydration of acetylene till 1968; in the reaction mercury oxide dissolved in sulfuric acid had been used as a catalyst. Inorganic mercury in waste water from the acetaldehyde plant had been discharged into the bay and it had accumulated into bottom sediment. It was proved that a part of inorganic mercury used as the catalyst had changed into methylmercury by a sidereaction in the plant and waste water containing methylmercury from the plant had discharged into the bay and methylmercury had accumulated into the fishes. The mercury concentrations in the muds were very high: in 1963, 29~713 ppm (dry weight); in 1969, 19~908 ppm (dry weight); in 1970, 8~253 ppm (dry weight) and in 1971, 14~586 ppm (dry weight). Since 1977, dredging work had been carried out to remove mercury-contaminated mud and all of the work had finished at March 1990. The concentration of mercury in fishes from the bay was very high in 1959: shellfishes 108~178 ppm (dry weight) and fish 15 ppm (wet weight). Mercury concentration in fishes has decreased markedly since 1966. Total mercury concentration in fishes (87 species) were 0.01~1.74 ppm (wet weight) and fishes containing over 0.4 ppm of total mercury were 16 species in 1989. The hair of patients contained a high concentration of mercury, the highest being 705 ppm. In 1968, the average mercury concentration in patients was 10.6 ppm, for fishermen, the average was 9.2 ppm, and for general inhabitants, the average was 8.1 ppm. In 1982, the average methylmercury concentration in fishermen was 6.15 ppm and for general inhabitants, the averge was 3.78 ppm. Thus, the mercury content in hair decreased gradually with time. After treatment of mercury in waste water was initiated, the mercury content in fishes from Minamta Bay was gradually reduced. It is necessary to supervise strictly to avoid mercury pollution of the environment.

Predicted Restoration of the Surrounding Marine Environment after an Artificial Mercury Decontamination at Minamata Bay, Japan - Economic Values for Natural and Artificial Processes

More than 35 years ago, an accident surfaced because of human misery at Minamata Bay, Japan. By 1960, more than 100 people suffered (mortality rate was over 20%) by eating fish containing methylmercury. By 1987, 1742 people were identified with this Minamata disease. The methylmercury along with inorganic mercury was released from a nearby chemical factory into the Bay, contaminating not only fish but the entire ecosystem including the bottom sediments. The amount of mercury deposited in the sediments was considered to be 150 tons. The Japanese Government initiated, in 1984, a decontamination project vacuuming the contaminated sediments into a sealed area creating a reclaimed land mass of 582,000 m2. The movement of the mercury deposited in the Bay outward to Yatsushiro Sea, was observed during the last 16 years by sampling and analyzing the surface sediments of Yatsushiro Sea. Since 1975, the deposited mercury moved continuously outside from the Bay at an annual rate of 3.7 tons. The initiation of the artificial decontamination (over $500 million in US funds), however, changed the pattern of mercury movement and drastically reduced its contents with a half-life of 1.83 years. Since 1985, the amounts of mercury in the surface sediments of Yatsushiro Sea have been decreasing dramatically with a half-life of 9.5 years. If this present trend of decrease continues, it becomes possible to predict that the Sea would be completely restored by 2011 AD. Another interesting observation was a historical storm in 1982, which cleaned-up the surface sediments of Yatsushiro Sea with a half-life of 2.76 years. If the clean-up effect of the natural processes in Yatsushiro Sea was compared to the artificial one, its economic value was calculated to be $96 million (US funds). Any decontamination attempt for polluted sites should consider a combination of the natural and artificial decontamination processes for economic reasons.

A fetal type of Minamata disease. An autopsy case report with special reference to the nervous system.

Our knowledge concerning the pathology of fetal cases of human Minamata disease (methylmercury poisoning) is relatively limited. We report here a case with description of the distribution of mercury in the systemic organs, and the ultrastructural changes of the nervous system after a survival of 29 yr. The patient was a female born in 1957, with a body wt of 3000 g, who died in 1987. She carried a diagnosis of cerebral palsy, and had a convulsion at age 3 yr. Mercury levels in her mother's hair were 101 micrograms/g at the time of examination in 1959. At autopsy, the body measured 43 cm and weighed 23 kg. The brain weighed 920 g and showed marked cerebral atrophy, mild neuronal loss in the calcarine, postcentral and precentral cortices, cerebellar atrophy, and segmental demyelination of peripheral nerves. Mercury granules were present in the brain, kidney, and liver. Ultrastructural examination of the calcarine, post- and precentral cortices, and cerebellar cortices, showed severe atrophy of nerve cells, with a decrease in rough ER and an increase in nuclear chromatin and preservation of mitochondria. Autophagosomes were increased in number. In addition, high electron density, globular and dense bodies, measuring 0.3-1.8 microns in diameter, were found, surrounded by limited membrane, within both cerebral and cerebellar neurons. In the cellebellum, synapses were well-preserved.

Truncal hypesthesia in patients with Minamata disease.

Patients with Minamata disease (methylmercury intoxication) usually suffer from the glove and stocking type hypesthesia in the extremities. Recently it is believed that the sensory disturbance of the disease may be a manifestation of the cerebral involvement. The aim of this study was to determine the pain threshold of their extremities and body by algesimeter. The results showed that a majority of the patients had elevated pain thresholds in the body and the extremities, and suggest that the pain impairment is not responsible for the peripheral nerve involvement.

Future of Rural Medicine.

The Japanese Association of Rural Medicine (JARM) was established in 1952. In those years, the living standards of rural communities were poor, contagious diseases were prevalent and rural people fell with malnutrition. As the Japanese economy began to grow at a high pace in or around 1960, rural communities have drastically changed, enabling farmers to enjoy a better life. With farmers having access to jobs other than agriculture, their cash incomes increased, rural manpower drifted to cities, and the number of farming families has since been on the downswing. It is inconceivable that agriculture, which forms part of the primary industry, will die out, and authoritative sources agree that there will appear an international food crisis toward the 21st century.When it comes to “agricultural medicine” in Japan, I must point out, more than anything else, that deaths in labor accidents become increasingly frequent. The safety measures are inadequate, so are the measures to compensate for labor accidents. In the ongoing development of agricultural technology, meanwhile, it is noted that there appear new types of health disorders and diseases. They include pesticide poisoning, greenhouse diseases, abortions caused by vibrating cultivators and pollinosis. The future question is to compensate for them as “agricultural diseases.” As regards “rural health, ” it must be pointed out that there are cases of family disruption and many cases with stress diseases in the midst of the ongoing trend in which farmers try to have access to better side jobs. The most crucial issue is the rapid pace at which aging is in progress in rural communities. How do we deliver care to bedridden old people and those with dementia? How to organize such community care? Those are questions we have yet to find solutions.In the past, there were struggles against diseases caused by pollutants (such as Minamata Disease and Itai-Itai Disease). There will be the need for a positive campaign for the protection of water and green in the rural environment. Environmental issues have to be taken up in an international perspective. On the question developing countries is a major causative factor. We are no longer able to discuss about agricultural medicine and rural health without relevance to the developing world.

TRACE ELEMENTS IN MEDICINE

1) ZINC: In 1963, Prasad found that dwarfism in Egypt was caused by zinc deficiency. Since then, many clinical pictures involving zinc deficiency have been reported on, such as alopecia (baldness), intestinal acrodermatitis (dermatitis of the extremities), alcohol-induced anencephalic children, and depressed immune response. 2) COPPER: Wilson’s disease is characterized by hepato-cerebral degeneration, which is caused by the deposition of copper in the liver and the cerebrum. Chelete therapy has been applied to remove the copper from the organs in order to treat Wilson’s disease. However, during the last several years zinc or manganese has also been applied to remove copper. The therapy mechanism is based on the interaction of copper to zinc and manganese. Zinc and copper deficiency is also an important topic in medical elementology. 3) MERCURY: Sir Isaac Newton was well known to be distrustful of others in his last years. The clinical picture was characterized by severe neuropathy, which was caused by heavy exposure to mercury during his long scholarly life. Children sometimes break thermometer in their mouth. Does metallic mercury in the thermometer induce mercury intoxication ? The answer is no. Intestinal absorption of metallic mercury is quite low, and thus ingested mercury rarely induces intoxication. The mercury is simply excreted through the feces within a day or two. One should attempt to wash the mercury out from the stomach with water. However, do not treat the child with laxatives, as they can increase the intestinal absorption of mercury, resulting in intoxication. 4) METHYLMERCURY: Severe neuropathy was endemic among fishermen and their families in a particular area of Kyushu Island, Japan. They were found to have eaten a great amount of fish, which were contaminated with organic mercury emitted from a fertilizer producing plant. The disease was later named as Minamata disease. The total number of recognized patients has amounted to 3,000 people, to date. 5) CADMIUM: Cadmium deficiency was recently found to depress the development of baby animals by Anke. This finding suggests that cadmium is not only a harmful element but also an essential element. Itai-Itai disease is characterized as osteomalacia, which is followed by severe renal tubular damage. Patients were comprised largely of elderly women who lived in the Jintsu river basin over a long period, and ingested excess cadmium emitted from a mine, which contaminated the local rice and drinking water. Long-term monkey experiments could not demonstrate osteomalacia by cadmium, however, epidemiological and experimental studies showed that an age-related increase in blood pressure is accelerated by cadmium at low doses, but depressed by cadmium at high doses. 6) LEAD: Lead is a very useful element, but a very harmful element as well. Lead has a potent hematopoietic effect on adults, and also negative psycho-neurological effects on babies. Soil pollution from lead has been discussed in relation to depressed intelligence among children living in U. S. slums. Sometimes residents in rural areas are shot with lead slugs by mistake. Do does lead slugs cause lead intoxication? Usually not. Medication is necessary only when lead slugs injure blood vessels or neurons. Most lead slugs do not induce lead intoxication because the lead slugs are soon covered with granular tissues. 7) CHROMIUM: Chromium is one of the essential trace elements, and is related to glucose tolerance and transmission velocity of peripheral nerves. Adverse effects of excessive chromium are chromium ulcers, perforation of the nasal septum, and lung cancer. 8) ARSENIC: Neutron activation analysis revealed excess amounts of arsenic in the hair of Napoleon. It was then suspected that he was killed with arsenic. Concerning the cause of his death, it was shown that grapes were disinfected with arsenic in those days, and that Napoleon might have consumed excess arsenic from drinking wine. However, the cause of his death remains unsolved. On the other hand, arsenic was used to promote health in Austria. Huge doses of arsenic, lethal for ordinary people, were administered to Austrian youths to assist them in Alpinc hiking. Japanese, especially residents in seashore areas, eat sizable amounts of sea weeds, which contain a huge amount of arsenic. Do they suffer from arsenic intoxication? The answer is no. The chemical form of arsenic in sea weeds is methyl-arsenic, the detoxicated chemical form, which does not revert to the active chemical form of arsenic.

Responsibility of Chisso Subsidiaries on the Minamata Disease : On the Theories of Disregarding the Corporate Fiction, Responsibility of Sole Shareholder of One-man Company, and Responsibility of Subsidiary Corporations

Responsibility of Chisso Subsidiaries on the Minamata Disease : On the Theories of Disregarding the Corporate Fiction, Responsibility of Sole Shareholder of One-man Company, and Responsibility of Subsidiary Corporations

Abnormal Auditory Brainstem Response(ABR) And PAS-Positive Substance in Inferior Colliculus at Acute Stage of Thiophene Poisoning in Rat.

Many cases of hearing loss have been reported in victims of Minamata disease, caused by methylmercury poisoning. Thiophene, like methylmercury, induces cerebellar granule cell degeneration in rats. To investigate the pathophysiology of the central auditory system in thiophene-poisoned rats, spontaneously hypertensive rats stroke resistance (SHR·SR) were given 0.15ml of thiophene daily for 5 or 6 days. After the rats had undergone brainstem recording and analysis of the auditory brainstem response (ABR), they were necropsied for histopathological examination. In the thiophene-poisoned animals, an abnormal ABR pattern like that in methylmercury poisoning appeared. In the acute stage, by 5 days after administration (DAA), the IV wave amplitude was reduced and the interpeak latency (IPL) was prolonged to various degrees. At 5 DAA, the IPL returned to the pretreatment level, earlier than the amplitude. In rats with severe cerebellar injury, a PAS-positive substance was localized in the inferior colliculus, comprising the central nucleus, and especially its ventrolateral portion. The lesions included neuronal necrosis, edema of the neuropil, and axonal degeneration. Proliferated GFAP-positive cells were located close to areas of neuronal loss. Our results suggest that demonstration of ABR is useful for evaluating disturbance of the central auditory system induced by chemicals.

The discovery of the causal agent of Minamata disease.

After the outbreak of an epidemic of a strange disease characterized by severe neurological signs in the small Japanese town of Minamata, a number of scientists in different disciplines were required to identify the causal agent. An account is given of the three-year program, with its disappointments and frustrations as a result of the limitations of knowledge of ecological principles and the absence of adequate techniques for detection and measurement. The lessons that have been learned on how toxic compounds can accumulate and concentrate in food chains are described as are the ecological contributions of environmentally safe waste disposal techniques. This article is based on the recollections of Dr. Shoji Kitamura, who contributed greatly to the discovery of the causative agent of Minamata disease.