Itai-itai Disease
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was the name given to the mass
cadmium poisoning Cadmium is a naturally occurring toxic metal with common exposure in industrial workplaces, plant soils, and from smoking. Due to its low permissible exposure in humans, overexposure may occur even in situations where trace quantities of cadmium ...
of
Toyama Prefecture is a prefecture of Japan located in the Chūbu region of Honshu. Toyama Prefecture has a population of 1,044,588 (1 June 2019) and has a geographic area of 4,247.61 km2 (1,640.01 sq mi). Toyama Prefecture borders Ishikawa Prefecture to the ...
,
Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...
, starting around 1912. The term "''itai-itai'' disease" was coined by localsICETT Itai-itai disease (1998) for the severe
pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
s (Japanese: 痛い ''itai'') people with the condition felt in the spine and joints.
Cadmium Cadmium is a chemical element with the symbol Cd and atomic number 48. This soft, silvery-white metal is chemically similar to the two other stable metals in group 12, zinc and mercury. Like zinc, it demonstrates oxidation state +2 in most of ...
(Cd) poisoning can also cause softening of the bones and
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
. Effective treatments involve the use of chelators to promote urinary excretion of Cd. The cadmium was released into rivers by
mining Mining is the extraction of valuable minerals or other geological materials from the Earth, usually from an ore body, lode, vein, seam, reef, or placer deposit. The exploitation of these deposits for raw material is based on the economic via ...
companies in the mountains, which were successfully sued for the damage. Remediation efforts in the affected region have been ongoing since 1972 and were mostly complete as of 2012. Monetary costs of the cleanup have been paid for in part by Japan's national government, Mitsui Mining, and the
Gifu is a city located in the south-central portion of Gifu Prefecture, Japan, and serves as the prefectural capital. The city has played an important role in Japan's history because of its location in the middle of the country. During the Sengoku ...
and Toyama prefectural governments. Itai-itai disease is known as one of the
Four Big Pollution Diseases of Japan The were a group of man-made diseases all caused by environmental pollution due to improper handling of industrial wastes by Japanese corporations. The first occurred in 1912, and the other three occurred in the 1950s and 1960s. Despite the moni ...
.


Etymology

The term ''itai-itai disease'' (in Japanese イタイイタイ病 ''itai-itai byō'', "it hurts-it hurts disease" or "ouch-ouch disease") was coined by the affected locals for the severe pains that people with itai-itai disease felt in the spine and joints. In Japanese 痛い ''itai'' is used as an adjective meaning "painful" or as an
interjection An interjection is a word or expression that occurs as an utterance on its own and expresses a spontaneous feeling or reaction. It is a diverse category, encompassing many different parts of speech, such as exclamations ''(ouch!'', ''wow!''), curse ...
equivalent to "ouch".


Causes

Itai-itai disease was caused by
cadmium poisoning Cadmium is a naturally occurring toxic metal with common exposure in industrial workplaces, plant soils, and from smoking. Due to its low permissible exposure in humans, overexposure may occur even in situations where trace quantities of cadmium ...
due to mining in Toyama Prefecture. Regular mining for
silver Silver is a chemical element with the Symbol (chemistry), symbol Ag (from the Latin ', derived from the Proto-Indo-European wikt:Reconstruction:Proto-Indo-European/h₂erǵ-, ''h₂erǵ'': "shiny" or "white") and atomic number 47. A soft, whi ...
started in 1589, and soon thereafter, mining for
lead Lead is a chemical element with the symbol Pb (from the Latin ) and atomic number 82. It is a heavy metal that is denser than most common materials. Lead is soft and malleable, and also has a relatively low melting point. When freshly cu ...
,
copper Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
, and
zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
began. The earliest records of mining for
gold Gold is a chemical element with the symbol Au (from la, aurum) and atomic number 79. This makes it one of the higher atomic number elements that occur naturally. It is a bright, slightly orange-yellow, dense, soft, malleable, and ductile met ...
in the area date back to 1710. Cadmium is a metal byproduct of mining that is toxic to most organisms. Recent animal studies have shown that cadmium poisoning alone is not enough to elicit all of the symptoms of itai-itai disease. These studies are pointing to damage of the
mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
of kidney cells by cadmium as a key factor of the disease.


History

Increased demand for raw materials during the
Russo-Japanese War The Russo-Japanese War ( ja, 日露戦争, Nichiro sensō, Japanese-Russian War; russian: Ру́сско-япóнская войнá, Rússko-yapónskaya voyná) was fought between the Empire of Japan and the Russian Empire during 1904 and 1 ...
and
World War I World War I (28 July 1914 11 November 1918), often abbreviated as WWI, was one of the deadliest global conflicts in history. Belligerents included much of Europe, the Russian Empire, the United States, and the Ottoman Empire, with fightin ...
, as well as new mining technologies from Europe, increased the output of the mines, putting the Kamioka Mines in Toyama among the world's top mines. Production increased even more before
World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...
. Starting in 1910 and continuing through 1945, cadmium was released in significant quantities by mining operations, and the disease first appeared around 1912. In the 1920s, levels of contaminated tailing waste increased after the creation of new
froth flotation Froth flotation is a process for selectively separating hydrophobic materials from hydrophilic. This is used in mineral processing, paper recycling and waste-water treatment industries. Historically this was first used in the mining industry, wher ...
processes that boosted zinc production. Fine powdered mineral particles formed in the frothing process escaped and drifted downriver. These particles were subsequently oxidized into ions that were absorbed by aquatic plants, rice crops, fish, and subsequently, humans.
Sphalerite Sphalerite (sometimes spelled sphaelerite) is a sulfide mineral with the chemical formula . It is the most important ore of zinc. Sphalerite is found in a variety of deposit types, but it is primarily in Sedimentary exhalative deposits, sedimen ...
, the main zinc containing ore in Komioka, is almost always coupled with
greenockite Greenockite is a rare cadmium bearing metal sulfide mineral consisting of cadmium sulfide (CdS) in crystalline form. Greenockite crystallizes in the hexagonal system. It occurs as massive encrustations and as hemimorphic six-sided pyramidal cryst ...
, the only major cadmium-containing mineral in the world. Because of this, cadmium is a regular by-product of the zinc ore mining process. Up until 1948, cadmium was discarded as waste into the
Jinzū River The is a river that flows from Gifu Prefecture to Toyama Prefecture in Japan. It is called Miya River (宮川 ''Miya-gawa'') in Gifu. It is in length and has a watershed of . Geography The river flows from Mount Kaore in Gifu and meets the Tak ...
due to it being of no industrial value, exacerbating the levels of the element's release into the waterbody. Prior to World War II, the mining, controlled by the
Mitsui Mining & Smelting is one of the largest ''keiretsu'' in Japan and one of the largest corporate groups in the world. The major companies of the group include Mitsui & Co. (general trading company), Sumitomo Mitsui Banking Corporation, Nippon Paper Industries, ...
Co., Ltd., increased to satisfy wartime demand. This subsequently increased the pollution of the Jinzū River and its tributaries. The river was used mainly for
irrigation Irrigation (also referred to as watering) is the practice of applying controlled amounts of water to land to help grow Crop, crops, Landscape plant, landscape plants, and Lawn, lawns. Irrigation has been a key aspect of agriculture for over 5,00 ...
of rice fields, but also for drinking water, washing, fishing, and other uses by downstream populations. When the population complained to Mitsui Mining & Smelting Co. about this pollution, the company built a basin to store the mining waste water before leading it into the river. This proved ineffective, and many had already been sickened. The causes of the poisoning were not well understood and, up to 1946, it was thought to be simply a regional disease or a type of
bacterial infection Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and are often beneficial but others can cause infectious diseases. The number of ...
. Medical tests started in the 1940s and 1950s, searching for the cause of the disease. Initially, it was expected to be
lead poisoning Lead poisoning, also known as plumbism and saturnism, is a type of metal poisoning caused by lead in the body. The brain is the most sensitive. Symptoms may include abdominal pain, constipation, headaches, irritability, memory problems, inferti ...
due to the lead mining upstream. Only in 1955 did Dr. Hagino and his colleagues suspect cadmium as the cause of the disease. Toyama Prefecture also started an investigation in 1961, determining that the Mitsui Mining and Smelting's Kamioka Mining Station caused the cadmium pollution and that the worst-affected areas were downstream of the mine. In 1968, the Ministry of Health and Welfare issued a statement about the symptoms of ''itai-itai'' disease caused by the cadmium poisoning. The reduction of the levels of cadmium in the water supply reduced the number of new cases; no new case has been recorded since 1946. While the people with the worst symptoms came from Toyama prefecture, the government found patients with itai-itai disease in five other prefectures. After the first reports of Itai-Itai in 1912, it took 55 years for the epidemiological investigation to discover that the disease was due to cadmium poisoning. Delayed bureaucratic response was a common thread in the
Four Big Pollution Diseases of Japan The were a group of man-made diseases all caused by environmental pollution due to improper handling of industrial wastes by Japanese corporations. The first occurred in 1912, and the other three occurred in the 1950s and 1960s. Despite the moni ...
. The mines are still in operation and cadmium pollution levels remain high, although improved nutrition and medical care has reduced the occurrence of itai-itai disease.


Cadmium pollution in Jinzū river

Over time, the cadmium that was released as industrial waste began to accumulate in the soil, algae and river organisms. This resulted in the local phytoplankton and algal species absorbing it in high quantities. Cadmium was subsequently passed through the food web to fish consumers. Fish also bioaccumulated cadmium through passive transport in the gills. Cadmium adversely affected fish, causing
endocrine The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
disruption and inhibited reproduction, and sometimes mortality. Due to the residents being unaware of the cadmium and its dangers, they used the water from the Jinzū to irrigate their rice fields. Cadmium is highly water-soluble and the rice paddies' prolonged exposure led to the rice quickly becoming contaminated and toxic. The local resident's consumption of this rice and drinking water then resulted in elevated cadmium body burdens – leading directly to symptoms characteristic of itai-itai disease. Cadmium is now considered one of the most dangerous toxic metals due to its ability to threaten food safety through being easily be absorbed into the rice paddies, then subsequently the rice.


Cadmium accumulation in a human body

Studies conducted to estimate the amount of cadmium exposure necessary to develop Itai-Itai disease found permissible lifetime cadmium intake (LCD) levels for humans to be 1.7 to 2.1 g. When Itai-Itai disease was first being recognized in just 5% of the affected population, LCD levels are estimated to have already been at 2.6 g. Cadmium accumulates mainly in the liver and the kidneys, but has more of an effect on the kidneys. The severe symptoms seen in Itai-itai disease are a direct result of prolonged exposure to cadmium. Cadmium enters the kidneys by binding to
metallothionein Metallothionein (MT) is a family of cysteine-rich, low molecular weight (MW ranging from 500 to 14000 Da) proteins. They are localized to the membrane of the Golgi apparatus. MTs have the capacity to bind both physiological (such as zinc, copp ...
in the blood and traveling to the
glomerulus ''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to: * the filter ...
in the kidney. Once the cadmium makes it into the
tubular cells The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a Nephron#Renal tubule, renal tubule. The renal corpuscle consists of a tuft of capillary, capillaries called a glomeru ...
in the kidneys, the cadmium is released and accumulates in the
renal cortex The renal cortex is the outer portion of the kidney between the renal capsule and the renal medulla. In the adult, it forms a continuous smooth outer zone with a number of projections ( cortical columns) that extend down between the pyramids. It ...
until it reaches toxic levels. When cadmium reaches dangerous levels in the renal cortex, it can deactivate metal-dependent enzymes or activate
calmodulin Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the bind ...
, which plays a role in smooth muscle contraction by sensing calcium levels. Once the kidneys have experienced extensive damage, those affected begin experiencing
musculoskeletal The human musculoskeletal system (also known as the human locomotor system, and previously the activity system) is an organ system that gives humans the ability to move using their muscular and skeletal systems. The musculoskeletal system prov ...
damage, due to the disruption of
calcium homeostasis Calcium metabolism is the movement and regulation of calcium ions (Ca2+) ''in'' (via the gut) and ''out'' (via the gut and kidneys) of the body, and ''between'' body compartments: the blood plasma, the extracellular and intracellular fluids, and ...
. This musculoskeletal damage is what causes the bone pain and bone deformities that characterize itai-itai disease.


Society


Legal action

29 plaintiffs, consisting of nine people with itai-itai disease and 20 of their family members, sued the Mitsui Mining and Smelting Co. in 1968 in the Toyama Prefectural court. In June 1971, the court found the Mitsui Mining and Smelting Co. guilty. Subsequently, the company appealed to the Nagoya District Court in
Kanazawa is the capital city of Ishikawa Prefecture, Japan. , the city had an estimated population of 466,029 in 203,271 households, and a population density of 990 persons per km2. The total area of the city was . Overview Cityscape File:もてな ...
, but the appeal was rejected in August 1972. The Mitsui Mining and Smelting Co. agreed to pay for the medical care of the people who had been affected, finance the monitoring of the
water quality Water quality refers to the chemical, physical, and biological characteristics of water based on the standards of its usage. It is most frequently used by reference to a set of standards against which compliance, generally achieved through tr ...
performed by the residents, and pay reparations to the people with the disease. Out of the four major pollution events, it was only in the case of itai-itai disease that those affected succeeded in accomplishing almost complete pollution control through legal action. People who believe that they have ''itai-itai'' disease have to contact the Japanese
Ministry of Health, Labor, and Welfare The is a cabinet level ministry of the Japanese government. It is commonly known as in Japan. The ministry provides services on health, labour and welfare. It was formed with the merger of the former Ministry of Health and Welfare or and the ...
to have their claims assessed. Many people with itai-itai disease were not satisfied with government actions and demanded a change in the official procedures. This caused the government to review the criteria for recognizing a patient legally; the government also reassessed the treatment of the disease. A person is considered to have ''itai-itai'' disease if he or she lived in the contaminated areas, has kidney dysfunctions and softening of the bones, but not related heart problems. 184 patients have been legally recognized since 1967, of whom 54 were recognized in the period from 1980 to 2000. An additional 388 people have been identified as potential patients, those who had not been officially examined yet. Fifteen people with itai-itai were still alive .


Remediation process

Following the trial victory of the plaintiffs over the Misui Mining Co in 1972, Mitsui Mining agreed to begin the process of remediation for the mine, as well as the surrounding farmland and river region. This process began with the first on-site inspection conducted by a team of scientists and government officials. These whole site inspections continue to take place yearly, with additional specialty inspections conducted 6–7 times throughout the year. These specialty checks specifically monitor water originating from the mine, as it has high levels of cadmium, which requires it to be separated and diverted to the Kamioka Mine slag dump. The water and solids are separated and processed before leaving the mine to ensure no groundwater contamination to the surrounding area. The treatment facilities' exhaust is also monitored to ensure the absence of cadmium in the airborne byproduct of the zinc refining process. Continuous inspections following the lawsuit have documented considerable decreases in cadmium levels. Total amounts of cadmium discarded decreased from per month in 1972 to per month in 2010; the average concentration of cadmium in the mine's discharge had been reduced to 1.2 ppb in 2010 from 9 ppb in 1972; and in response to improved dust collection methods, the total amount of cadmium discharged in smoke dropped from > per month in 1972 to per month in 2010. In 1996, the mean concentration of cadmium in agricultural lands had returned to the background level of 0.1 ppb, signifying trivial cadmium outflow. This is a success in regards to the lawsuit. The cadmium pollution had also contaminated many of the agricultural areas surrounding the mine. As a response to the metal pollution, the Japanese government enacted the Prevention of Soil Contamination in Agricultural Land Law of 1970. It ordered planting to be stopped so that restoration of the soil could be implemented in areas with 1ppm of cadmium or more in the soil. Surveying in Toyama Prefecture began in 1971, and by 1977, along the Jinzū River were designated for soil restoration. These farmers were compensated for lost crops and for lost production in past years by the Mitsui Mining and Smelting, Toyama Prefecture, and the national government. , only remained contaminated. In 1992, the average annual health expense compensation was ¥743 million. Agricultural damage was compensated with ¥1.75 billion per year, or a total of annually ¥2.518 billion. Another ¥620 million were invested annually to reduce further pollution of the river. On 17 March 2012, officials concluded the cleanup project of the cadmium-polluted areas in the
Jinzū River The is a river that flows from Gifu Prefecture to Toyama Prefecture in Japan. It is called Miya River (宮川 ''Miya-gawa'') in Gifu. It is in length and has a watershed of . Geography The river flows from Mount Kaore in Gifu and meets the Tak ...
basin. of topsoil had been replaced since the cleanup began in 1979 at a total cost of ¥40.7 billion. The project had been financed by the Japanese national government, Mitsui Mining, and the Gifu and Toyama prefectural governments.


See also

*
Heavy metal poisoning A toxic heavy metal is any relatively dense metal or metalloid that is noted for its potential toxicity, especially in environmental contexts. The term has particular application to cadmium, mercury and lead, all of which appear in the World He ...
*
Onsan illness Onsan Illness () is the name for a pollution disease in Korea that occurred in Onsan-eup, Ulju-gun, Ulsan, Korea. It caused a variety of symptoms in the general public and gave rise to an environmental movement in the mid-1980s. Background In ...


References


External links


Additional Information on Itai-Itai Disease

What is Itai-itai disease?

Deletion in proximal tubule cell gene causes symptoms of Itai-Itai
{{DEFAULTSORT:Itai-Itai Disease Political scandals in Japan Water pollution in Japan Cadmium Health disasters in Japan Mining in Japan 1912 health disasters 1912 in Japan Toxic effects of metals Reduplicants