Environmental exposure of arsenic and fluoride and their combined toxicity: A recent update.

Environmental exposure to arsenic (As) and fluoride (F) in the recent year has been increased because of excessive use of naturally contaminated ground water. Surface water is also regularly contaminated with these elements in various industrial areas. Arsenicosis and fluorosis upon individual exposure of As and F are reported in many studies. A syndrome of endemic As poisoning and fluorosis occurs during concurrent exposure of As and F. Previous reports showed synergistic, antagonistic and independent effects of these two compounds, although few recent reports also revealed antagonistic effects after co-exposure. Interaction during intestinal absorption and influence of F on As metabolism might be the cause of antagonism. The synergism/antagonism is thought to depend on the dose and duration of the co-exposure. However, the detailed mechanism is still not fully understood and needs further studies. Removal technologies of As and F from contaminated water is available but removal of such contaminants from food is yet to be developed. Antioxidants are useful to mitigate the toxic effects of As and F. This review focused on the effect of co-exposure, amelioration as well as removal techniques of As and F.

Coal utilization in China: environmental impacts and human health.

Coal is one of the major energy resources in China, accounting for approximately 70 % of primary energy consumption. Many environmental problems and human health risks arise during coal exploitation, utilization, and waste disposal, especially in the remote mountainous areas of western China (e.g., eastern Yunnan, western Guizhou and Hubei, and southern Shaanxi). In this paper, we report a thorough review of the environmental and human health impacts related to coal utilization in China. The abundance of the toxic trace elements such as F, As, Se, and Hg in Chinese coals is summarized. The environmental problems (i.e., water, soil, and air pollution) that are related to coal utilization are outlined. The provenance, distributions, typical symptoms, sources, and possible pathways of endemic fluorosis, arsenism, and selenosis due to improper coal usage (briquettes mixed with high-F clay, mineralized As-rich coal, and Se-rich stone coal) are discussed in detail. In 2010, 14.8, 1.9 million, and 16,000 Chinese people suffered from dental fluorosis, skeletal fluorosis, and arsenism, respectively. Finally, several suggestions are proposed for the prevention and treatment for endemic problems caused by coal utilization.

Co-exposure of nanoplastics and arsenic causes neurotoxicity in zebrafish (Danio rerio) through disrupting homeostasis of microbiota-intestine-brain axis.

Nanoplastics (NPs) and arsenic (As) are toxic pollutants prevalent on the earth and have gained considerable attention in recent decades. Although numerous studies reported NPs and As can cause neurotoxicity there are still significant knowledge gaps in illustrating their combined toxicity and its mechanism. In this study, the co-exposure of environmentally relevant concentrations of NPs and As caused neurobehavioral toxicity in zebrafish, as evidenced by reduced swimming ability, anxiety and impaired short-term learning memory. Potentially, its toxicity mechanism is through disrupting the homeostasis of microbiota-intestine-brain axis in zebrafish. Specifically, the co-exposure reduced the 5-hydroxytryptamine (5-HT) production in intestine, which led to lower levels of 5-HT transported by the blood circulation to the brain. Ultimately, neurobehavior was adversely affected by the reduced binding of 5-HT to its receptors. Intestine, the primary source of 5-HT, its impaired health (aggravation in oxidative stress, mitochondrial damage and histopathological alterations) induced the dysregulation in the 5-HT system, which may be induced by the increased accumulation of As in the intestine by the co-exposure. Besides, the reduced 5-HT levels were correlated with decreased Firmicutes and Protecbacteria and increased Actinobacteriota and Chloroflexi in intestines. Potentially, intestinal microbiota adversely regulates the intestine-brain axis by reducing SCFAs levels. Thus, the alteration of intestinal microbiota structure may be the other reason for the dysregulation of intestine-brain axis. In summary, co-exposure of NPs and As induced neurobehavior toxicity probably through disrupting the homeostasis of microbiota-intestine-brain axis. This study provides insights into assessing the environmental health risks of the pollution of NPs and As to aquatic organisms.

Co-occurrence of arseniasis and fluorosis due to indoor combustion of high fluorine and arsenic content coal in a rural township in northwest China: epidemiological and toxicological aspects.

A large number of fluorosis and arseniasis cases appeared in a mountainous area in northwest China. The residents relied on local inferior coal ("bone coal") of high fluorine and arsenic content for domestic heating and cooking. For deep-inside information about this rare case of co-endemia of fluorosis and arseniasis in the population in this special exposure scenario, a field investigation in one of the hyperendemic townships was conducted. The resident population registered (n = 27,713) was enrolled in the investigation. All cases were diagnosed and assigned to three symptom severity groups, that is severe, medium, and mild according to Chinese National Standard Criteria GB 16396-96 and to the technical guideline WS/T208-01 or WS/T211-01 issued by the Chinese Ministry of Health. Gender difference was analyzed by standardized incidence ratio. Age trend and severity trend were tested by χ(2) analysis. Fluorosis was diagnosed in 56.7% of the residents. Over 95% of the diagnosed arseniasis cases were simultaneously diagnosed with fluorosis symptoms. Combined fluorosis-arseniasis represented 11.9% of the total fluorosis cases and 6.7% of the local population. No gender-related differences in the prevalence of skeletal, dental, or dermal symptoms inside all severity groups were detected. Symptom severity increased with age. The high frequency of superposition of arseniasis with fluorosis might be due to the fact that the local resident population has been exposed to very high levels of fluorine and arsenic via the same exposure route.

Metabolic profile and assessment of occupational arsenic exposure in copper- and steel-smelting workers in China.

PURPOSE: Analyze the urine arsenic (As) metabolite profiles of workers in copper-and special steel-smelting plants and explore the potential occupationally As exposure as well as the individual arsenicosis risk. METHODS: A total of 95 male workers from two plants, located in northeastern part of China, were recruited. Information about each subject was obtained by questionnaire. Inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) in urine and airborne As concentrations of working sites were determined. RESULTS: Airborne As concentrations in copper smelter sites were significantly higher than steel smelter sites. Workers in copper smelter had significantly higher concentrations of iAs, MMA, DMA in urine with creatinine adjustment but a lower value of primary methylation index (PMI) than that of steel-smelting plants workers. The higher proportion of the inorganic form but the lower proportion of DMA form of copper smelter workers was compared to that of steel smelter workers, and the concentration of DMA in steel smelter workers' urine significantly increased linearly with seafood consumption. Seven workers in copper smelter were found to have hyperkeratosis or/and hyper-pigmentation, and their urine showed higher iAs% but lower DMA% and PMI compared to other workers without As dermatosis at the same level of As exposure. CONCLUSIONS: Release of As dust produced in crude ore extracting and smelting is the main pollution source of As in copper smelter plant. The methylation capacity of As decreases with the increase in As exposure level, and skin damage caused by As is associated with decreasing methylation capacity.

Assessment of arsenic exposure in the population of Sabalpur village of Saran District of Bihar with mitigation approach.

Arsenic poisoning through groundwater is the world's greatest normal groundwater catastrophe which got an immense effect on worldwide general wellbeing. India is confronting the outcomes of arsenic poisoning in the zone of Ganga Brahmaputra alluvial plains. In Bihar, out of 38 districts, 18 districts are exceptionally influenced with groundwater arsenic defilement. In the present study, we have assessed the current situation of arsenic exposure in Sabalpur village of Saran district of Bihar after reporting of breast, renal, skin and thyroid cancer cases from this village along with typical symptoms of arsenicosis. Such cancer patients were identified at our institute and were taken for the study. The present investigation deals with the quantification of arsenic in groundwater, hair and nail samples of subjects as well as the survey of entire village to know the overall health status of the village people. A total of n=128 household handpump water samples as well as n=128 human hair and nail samples were collected from over n=520 households. Using the graphite furnace atomic absorption spectrophotometer (GF-AAS), all the samples were analysed. The investigation resulted that the 61% of the analysed samples particularly the groundwater had the arsenic levels more than the permissible limit of WHO (> 10 µg/L) with 244.20 µg/L as the highest arsenic contamination in one of the handpump water sample. The exposure effect of hair sample was worst as 88% of all the collected samples were having high arsenic levels more than the permissible limit (> 0.2 mg/Kg). In case of nail samples, 92% of the samples were having high arsenic concentration more than the permissible limit (> 0.5 mg/Kg). The health survey study revealed high magnitude of disease burden in the exposed population with symptoms such as asthma, anaemia, hepatomegaly, diabetes, cardiac problem, skin fungal infections, breathlessness and mental disability. Few cancer cases of renal, skin, breast and cervix were also found among the exposed population of this village. The percentage of cancer cases in this village was 0.94% that was low, but it would be an aggravated situation in the near future if people will continue drinking arsenic-contaminated water. Therefore, a mitigation intervention was carried out in March 2020 by installing an arsenic filter plant. The health situation in the village in the present scenario is hope to improve in the coming years. However, motivation and awareness among the village population are still required.

Arsenic inhibits human salivary aldehyde dehydrogenase: Mechanism and a population-based study.

Human salivary aldehyde dehydrogenase (hsALDH) is an important detoxifying enzyme and maintains oral health. Subjects with low hsALDH activity are at a risk of developing oral cancers. Arsenic (As) toxicity causes many health problems in humans. The objective of this population-based study was to correlate As contamination and hence low hsALDH activity with high incidence of cancer cases in Bareilly district of India. Here, it was observed that As inhibited hsALDH (IC50 value: 33.5 ± 2.5 µM), and the mechanism of inhibition was mixed type (in between competitive and non-competitive). Binding of As to hsALDH changed the conformation of the enzyme. A static quenching mechanism was observed between the enzyme and As with a binding constant (Kb) of 9.77 × 104 M-1. There is one binding site for As on hsALDH molecule. Further, the activity of hsALDH in volunteers living in regions of higher As levels in drinking water (Bahroli and Mirganj village of Bareilly district, India), and those living in region having safe levels of As (Aligarh city, India) was determined. The As level in the saliva samples of the volunteers was determined by inductively coupled plasma mass spectroscopy (ICP-MS). Low hsALDH activity was found in volunteers living in the region of higher As levels. The activity of hsALDH and As concentration in the saliva was found to be negatively correlated (r = - 0.427, p < 0.0001). Therefore, we speculate that the high incidence of cancer cases reported in Bareilly district may be due to higher As contamination.

Acute arsenic self-poisoning for suicidal purpose in a dentist: a case report.

Arsenic is a classical poison that has been historically used since ancient times for homicidal purposes. More recently, episodes of deliberate or unintentional arsenic self-poisoning have been increasingly reported. We describe here a case of a 77-year old male patient with a history of major depression, who attempted suicide by ingestion of 4 g of arsenic trioxide. The man, a dentist by profession, used arsenic preparations for pulp devitalization. The patient was admitted to our hospital 5 h after arsenic ingestion with nausea and vomiting. Plain radiograph of the abdomen showed radio-opaque material in the stomach and small intestine. Nasogastric lavage, activated charcoal, and chelators were used to remove arsenic. On day 3, endoscopy disclosed the presence of gastritis and superficial ulcers. The patient developed significant anemia (Hb: 8.7 g/dL on day 7) without significant signs of hemolysis. He gradually recovered from anemia within 5 months. The patient did not suffer any adverse outcome in spite of having ingesting 4 g of arsenic, approximately 20 times the lethal dose.

Successful treatment of potentially fatal heavy metal poisonings.

Pure inorganic heavy metal ingestions for suicidal intent are a rare occurrence. Most case reports on this subject focus on the serious neurological, hepatic, or renal side effects. We describe two cases of significant heavy metal poisonings (arsenic trioxide and mercuric chloride) that were successfully managed with aggressive decontamination and combined chelation therapy. Both chemicals were obtained in pure powder form through the Internet.

A history of arsenic in dentistry.

The history of the use of arsenic in dentistry has been relegated to dental history. Once hailed as a panacea for the relief of pain and the answer to root canal therapy, it soon fell out of use mainly because of its misuse by unskilled and unscrupulous dentists in search of a quick fix to a complex problem. Such is the story of arsenic.

[Two different clinical cases of acute arsenic trioxide intoxication]. / Dwa przypadki ostrego zatrucia arszenikiem o róznym przebiegu klinicznym.

This paper describes two different cases of acute suicidal arsenic trioxide intoxication. Case no 1. A 38-year-old man, alcohol abuser, who ingested 4-5 g dental paste, which corresponds to 2.2-2.7 g of pure arsenic trioxide, developed gastritis with vomiting and abdominal pain, but without diarrhea. No cardiovascular collapse or renal failure were observed. The patient developed also symptoms of central nervous system injury (minor left paresis) and transient hepatic impairment. A head CT revealed no pathological changes in the brain. Hepatic disturbance recovered in a few days and the patient could be discharged on the 12 day. Case no 2. A 57-year-old man, who ingested few grams of pure arsenic developed vomiting, abdominal pain and severe diarrhea. Cardiovascular collapse as a result of intravascular volume depletion, vasodilatation and myocardial dysfunction was observed. The patient died on the first day of hospitalization. In both cases treatment included gastric lavage, BAL therapy, haemodialysis and supportive measures.

Screening high-fluoride and high-arsenic drinking waters and surveying endemic fluorosis and arsenism in Shaanxi province in western China.

The objectives of this study were to screen high-fluoride and high-arsenic drinking waters, to evaluate the effectiveness of fluoride-reducing projects and to assess the present condition of endemic fluorosis and arsenism in Shaanxi province in western China. For screening high-fluoride drinking waters, five water samples were collected from each selected village where dental fluorosis patients were detected in 8-12 year-old children. For evaluating the effectiveness of fluoride-reducing projects, four water samples were collected from each project at end-user level. Fluoride concentrations in water samples were measured by fluoride-selective electrode method or spectrophotometry. Dental fluorosis in children aging 8-12 years was examined according to Horowitz's Tooth Surface Index of Fluorosis. Skeletal fluorosis in adults was detected clinically and radiologically according to Chinese Criteria of Clinical Diagnosis of Skeletal Fluorosis. For screening high-arsenic waters, 20 water samples were collected from each village which was selected from areas characterized by the geographic features to induce high-arsenic underground water, i.e., alluvial plains, ore mining or smelting areas, geothermal artesians, and thermal springs. Arsenic concentrations in water samples were determined by spectrophotometry or arsine generation atomic fluorospectrophotometry. Arsenism in adults aging 40-89 years was examined in villages with arsenic concentrations in drinking water above 0.05 mg/l according to Chinese Criteria for Classification of Endemic Arsenism Areas and Clinical Diagnoses of Endemic Arsenism. The results showed that the fluoride level of 7144 water samples was 1.17 +/- 0.93 mg/l. There were 3396 (47.6%) high-fluoride waters (fluoride level was above 1.0 mg/l) distributing in 786 (45.1%) villages, where about 0.8 million (50.0%) people inhabited. Additionally, the 1315 fluoride-reducing projects were studied. The fluoride level of the projects was 2.79 +/- 1.09 and 0.98 +/- 0.47 mg/l before and after building the projects, which remained at relatively lower level (1.03 +/- 0.47 mg/l). But there were still 58.0% of the projects providing drinking waters with fluoride concentrations beyond 1.0mg/l. The rates of dental fluorosis and skeletal fluorosis were 38.2% and 11.8%, respectively. The arsenic level of 1732 water samples was 0.010 +/- 0.082 mg/l. There were 174 (14.9%) high-arsenic waters (arsenic level was above 0.010 mg/l) being detected, distributing in 41 (38.7%) villages. The arsenic level in 53 (4.5%) water samples was beyond 0.025 mg/l. There were 3 villages with arsenic level in drinking water beyond Chinese National Permissible Limits (0.050 mg/l), and the prevalence rate of arsenism reached 37.0% in these three villages, 3.7%, 22.2%, and 11.1% of subjects suffering from mild, moderate, and severe arsenism, respectively. Conclusively, the wide distribution of high-fluoride drinking waters contributes to the prevalence of dental and skeletal fluorosis in Shaanxi province and the quality of fluoride-reducing projects should be further improved. Ore mining and smelting induces high-arsenic drinking waters, resulting in arsenism prevalence in Shang-luo city. Proper measures should be taken to deal with water pollution in the ore mining and smelting areas in order to solve the high-arsenic water problem in Shaanxi province.

Knowledge of arsenic in drinking-water: risks and avoidance in Matlab, Bangladesh.

Widespread contamination of arsenic in Bangladesh has been jeopardizing the health of millions of people. Residents of Matlab, Bangladesh, are among the millions at risk. Using bivariate models in the analysis of survey data, knowledge of health risks and avoidance of arsenic exposure in response to widespread contamination of arsenic for residents of Matlab were estimated. The models examined individuals' knowledge of an arsenic problem in the household and knowledge of specific illnesses caused by arsenic exposure. The likelihood of avoiding exposure to arsenic contamination was further examined. Results of the estimation showed that individual's knowledge of arsenic problems in the household was gathered through awareness campaigns and by word of mouth and that knowledge of illnesses was predicated on education, health, presence of children, elderly and young women. Adoption of avoidance measures was not affected by exposure to arsenic-information sources, but level of education had a statistically significant positive effect on the decision to avoid arsenic exposure. Lack of convenience of safe drinking-water practices lead people to persist in drinking arsenic-contaminated water.

[Oral multiple carcinomatosis in a patient from an area with endemic regional chronic hydroarsenicism (ERCH)]. / Carcinomatosis múltiple de localización bucal en un paciente de zona de hidroarsenicismo crónico regional endémico (HACRE).

BACKGROUND: Arsenic (As) and its compounds may cause multiple harmful effects on the human organism, interfering with biological processes of vital importance. It is known that the inhabitants of vast areas of the Argentine Republic drink well water contaminated with AS, which results in a disease known as Endemic Regional Chronic Hydroarsenicism (ERCH). It has been observed that these patients present a clinical picture characterized by multiple carcinomatous skin lesions which occur concurrently or successively along long periods of time. PURPOSE: To present the clinical case of a female patient from the arsenical area of Cordoba Province, who had multiple carcinomatous oral lesions. MATERIALS AND METHOD: The patient's history was written and iconographies, surgical excision of the lip lesions, pathological studies of the samples, and evolution observations were done. RESULTS: Based on both the patient's history and follow-up studies, it was possible to prove the presence of multiple successive carcinomatous lesions in the oral mucosa. CONCLUSION: It is concluded that drinking water containing more AS than the quantity accepted by the WHO (0.0 5 ppm) can cause multiple carcinomatous lesions on the oral mucosa as well as on the skin.

The global menace of arsenic and its conventional remediation - A critical review.

Arsenic is a ubiquitous element found in the earth crust with a varying concentration in the earth soil and water. Arsenic has always been under the scanner due to its toxicity in human beings. Contamination of arsenic in drinking water, which generally finds its source from arsenic-containing aquifers; has severely threatened billions of people all over the world. Arsenic poisoning is worse in Bangladesh where As(III) is abundant in waters of tube wells. Natural occurrence of arsenic in groundwater could result from both, oxidative and reductive dissolution. Geothermally heated water has the potential to liberate arsenic from surrounding rocks. Inorganic arsenic has been found to have more toxicity than the organic forms of arsenic. MMA and DMA are now been considered as the organic arsenic compounds having the potential to impair DNA and that is why MMA and DMA are considered as carcinogens. Endless efforts of researchers have elucidated the source, behavior of arsenic in various parts of the environment, mechanism of toxicity and various remediation processes; although, there are lots of areas still to be addressed. In this article, attempts have been made to lay bare an overview of geochemistry, toxicity and current removal techniques of arsenic together.

[Possible health effects associated with Pre-Columbian metallurgy]. / Posibles efectos en la salud asociados con la metalurgia precolombina.

In the Old World, several researchers have indicated that adverse health effects were associated with exposure to arsenic, and that this influenced a change in the use of copper-arsenic alloys to others less toxic. This hypothesis was evaluated for three Pre-Columbian metallurgy traditions: Central Andes, Intermediate Area, and West Mexico. The metal artifacts from the Central Andes showed arsenic concentrations similar to those in the Old World (0.5%-1.0%). In the Intermediate Area the values were smallest; however, in West Mexico the arsenic content was very high (7%-25%). In Central Andes arsenical bronze was used initially, but copper-tin alloys when introduced were preferred and distributed throughout the Inca Empire. Osteological and artistic evidences of foot amputations among Moche individuals from Central Andes support the presence of "black foot disease" (a condition associated with arsenic poisoning) among Pre-Columbian populations. In conclusion, the adverse effects of arsenic have been observed in the New World, and that these effects promoted a change toward the use of less toxic alloys.

Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity.

Heavy metals are, unfortunately, present in the air, water, and food supply. Cases of severe acute lead, mercury, arsenic, and cadmium poisoning are rare; however, when they do occur an effective, non-toxic treatment is essential. In addition, chronic, low-level exposure to lead in the soil and in residues of lead-based paint, to mercury in the atmosphere, in dental amalgams and in seafood, and to cadmium and arsenic in the environment and in cigarette smoke is much more common than acute exposure. Meso-2,3-dimercaptosuccinic acid (DMSA) is a sulfhydryl-containing, water-soluble, non-toxic, orally-administered metal chelator which has been in use as an antidote to heavy metal toxicity since the 1950s. More recent clinical use and research substantiates this compound s efficacy and safety, and establishes it as the premier metal chelation compound, based on oral dosing, urinary excretion, and its safety characteristics compared to other chelating substances.

Case studies--arsenic.

Arsenic is found naturally in the environment. People may be exposed to arsenic by eating food, drinking water, breathing air, or by skin contact with soil or water that contains arsenic. In the U.S., the diet is a predominant source of exposure for the general population with smaller amounts coming from drinking water and air. Children may also be exposed to arsenic because of hand to mouth contact or eating dirt. In addition to the normal levels of arsenic in air, water, soil, and food, people could by exposed to higher levels in several ways such as in areas containing unusually high natural levels of arsenic in rocks which can lead to unusually high levels of arsenic in soil or water. People living in an area like this could take in elevated amounts of arsenic in drinking water. Workers in an occupation that involves arsenic production or use (for example, copper or lead smelting, wood treatment, pesticide application) could be exposed to elevated levels of arsenic at work. People who saw or sand arsenic-treated wood could inhale/ingest some of the sawdust which contains high levels of arsenic. Similarly, when pressure-treated wood is burned, high levels of arsenic could be released in the smoke. In agricultural areas where arsenic pesticides were used on crops the soil could contain high levels of arsenic. Some hazardous waste sites contain large quantities of arsenic. Arsenic ranks #1 on the ATSDR/EPA priority list of hazardous substances. Arsenic has been found in at least 1,014 current or former NPL sites. At the hazardous waster sites evaluated by ATSDR, exposure to arsenic in soil predominated over exposure to water, and no exposure to air had been recorded. However, there is no information on morbidity or mortality from exposure to arsenic in soil at hazardous waste sites. Exposure assessment, community and tribal involvement, and evaluation and surveillance of health effects are among the ATSDR future Superfund research program priority focus areas. Examples of exposures to arsenic in drinking water, diet and pesticide are given.

The use of haemodialysis and 2,3 propanesulphonate (DMPS) to manage acute oral poisoning by lethal dose of arsenic trioxide.

The paper discusses a case of oral acute poisoning by dental paste containing arsenic trioxide. A 33-year-old woman ingested 1/3 of the dental paste package, which corresponds to 1850 mg pure arsenic trioxide. Acute gastroenteritis and oral mucosa burn developed within 3 hours since the poisoning. Considering the amount of the ingested poison, highly exceeding the lethal dose, haemodialysis was undertaken. During the treatment, DMPS (Unithiol) was administered, with the patient's consent. The patient recovered completely, with no complications or side-effects of the therapy.

[Chronic and predominantly sensory polyneuropathy in Toroku Valley where a mining company produced arsenic].

We report 9 patients (5 males, 4 females, ages 63-77) with chronic polyneuropathy. They were exposed to arsenic for about 15-40 years in Toroku Valley, Takachiho-Town, Miyazaki Prefecture, Japan, where a mining company produced arsenic from 1920-1962. Predominantly sensory polyneuropathy was the most significant neurological finding. In 5 of them, superficial and deep sensation was equally affected over the entire body, including head, face, and mucous membranes of the mouth. The corneal reflexes were absent or sluggish. Pin-prick and light-touch perception was absent in their hands and legs. Another sensory disorder such as glove and stocking-type was seen in 4 of them. All 9 patients were comfortable with extremely hot water in their beverages, their baths, and their wash basins compared with controls. But these patients felt that their temperature sensation was normal. Motor involvement was minimal. Although motor-nerve conduction velocities were normal or reduced minimally, sensory-nerve conduction velocities were moderately reduced. Sural-nerve biopsy revealed reduction of both small myelinated and unmyelinated fibers, which occurs with axonal degeneration of peripheral nerves. Other main symptoms and signs were tension-type headaches, non-painful tonic spasms of limbs, and losses or significantly decreased sensations of taste and smell. Dantrolene-sodium was effective for the treatment of their non-painful tonic spasms of limbs. As for the general medical condition of these patients, all of them had suffered from chronic bronchitis and skin eruption during childhood or in their early life or in their young adulthood when the mine was producing arsenic. At the time of this study only four of them suffered from chronic bronchitis and none of them had skin eruptions or discoloration of the skin, 37 years after closure of the mine. These 9 patients were diagnosed as having chronic arsenic poisoning and arsenic polyneuropathy. The multiplicity of symptoms found in these patients--anosmia, ageusia, chronic bronchitis, tension-type headaches, and non-painful tonic spasms of limbs--differs from the symptoms previously reported cases with arsenic poisoning. This may be due to combined overexposure to environmentally hazardous arsenic by effluent gas, dust, and drinking water in Toroku Valley. As concerns the sensory disorders described above, it is necessary to investigate sensory conduction pathways, including cerebral sensory cortex, spinal cord, and skin sensory receptors such as Pacini corpuscles, and Meissner corpuscles. Unfortunately, no information has been obtained about this problem because there were no autopsy cases.