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Itai-itai disease (イタイイタイ病, itai-itai byō, "it hurts-it hurts disease") was the name given to the mass cadmium poisoning of Toyama Prefecture, Japan, starting around 1912. The term "itai-itai disease" was coined by locals for the severe pains (Japanese: 痛い itai) people with the condition felt in the spine and joints. Cadmium (Cd) poisoning can also cause softening of the bones and kidney failure. Effective treatments involve the use of chelators to promote urinary excretion of Cd. The cadmium was released into rivers by mining companies in the mountains, which were successfully sued for the damage. Remediation efforts in the affected region have been ongoing since 1972 and mostly completed as of 2012. Monetary costs of the cleanup have been paid for in part by Japan’s national government, Mitsui Mining, and the Gifu and Toyama prefectural. Itai-itai disease is known as one of the Four Big Pollution Diseases of Japan.

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 equivalent to "ouch".

Causes

Itai-itai disease was caused by cadmium poisoning due to mining in Toyama Prefecture. The earliest records of mining for gold in the area date back to 1710. Regular mining for silver started in 1589, and soon thereafter, mining for lead, copper, and zinc began. Increased demand for raw materials during the Russo-Japanese War and World War I, 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. 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 processes that boosted zinc production. Fine powdered mineral particles formed in the frothing process escaped and were able to drift down river. These particles were subsequently oxidized into ions that were absorbed by surrounding vegetation and humans. Sphalerite, the main zinc containing ore in Komioka, is almost always coupled with Greenockite, 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 due to it being of no industrial value, further exasperating the levels of the element’s release into the waterbody.

Prior to World War II, the mining, controlled by the Mitsui Mining & Smelting Co., Ltd., increased to satisfy the wartime demand. This subsequently increased the pollution of the Jinzū River and its tributaries. The river was used mainly for irrigation of rice fields, but also for drinking water, washing, fishing, and other uses by downstream populations.

After Itai-itai disease had begun to spread in 1912, it took 55 years for the epidemiological investigation to discover that the disease was due to cadmium poisoning. This delay in bureaucratic action was a common thread in the Four Big Pollution Diseases of Japan.

Cadmium Uptake in the Jinzū River

The Jinzū River was used mainly for irrigation of rice fields, but also for drinking water, washing, fishing, and other uses by downstream populations. 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. The fish that prey on the algae then consumed those species, accumulating it within their own systems. The cadmium present in these fish were further increased through passive transport in the gills, as they swam through the cadmium enriched sections of the environment . This had a drastic effect on these organisms, as the cadmium accumulated within the gills, liver and kidneys of the affected population. These resulted in severe complications and sometimes death.

Due to the residents being unaware of the cadmium and its dangers, they used the water from the Jinzu to irrigate their rice fields. Cadmium is extremely water soluble and the rice paddy’s prolonged exposure led to the rice strains quickly becoming contaminated and toxic. The local resident’s consumption of these strains of rice and drinking water then resulted in extremely high levels of cadmium that accumulated within their bodies – leading directly to the exposure of Itai-Itai symptoms. Cadmium is now considered the most dangerous toxic metal due to it's ability to threaten food safety through being easily be absorbed into the rice paddies, then subsequently the rice.

Cadmium Uptake in the 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 afflicted 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 in the blood and traveling to the glomerulus in the kidney. Once the cadmium makes it into the tubular cells in the kidneys, the cadmium is released and accumulates in the renal cortex until it reaches toxic levels. When cadmium reaches dangerous levels in the renal cortex, it can deactivate metal-dependent enzymes or activate calmodulin, which plays a role in smooth muscle contraction by sensing calcium levels.

Once the kidneys have experienced extensive damage, those affected begin experiencing musculoskeletal damage, due to the disruption of calcium homeostasis. This musculoskeletal damage is what causes the bone pain and bone deformities that characterizes Itai-itai disease.

Symptoms

One of the main effects of cadmium poisoning is weak and brittle bones. Spinal and leg pain is common, and a waddling gait often develops due to bone deformities caused by the long-term cadmium exposure. The pain eventually becomes debilitating, with fractures becoming more common as the bone weakens. Permanent deformation in bones can occur. Other complications include coughing, anemia, and kidney failure, leading to death.

A marked prevalence in older, postmenopausal women has been observed, however, the cause of the phenomenon is not fully understood, and is currently under investigation. Cadmium poisoning in postmenopausal women may also result in an increased risk for osteoporosis. Current research has pointed to general malnourishment, as well as poor calcium metabolism relating to the women's age. These studies are pointing to damage of the mitochondria of kidney cells by cadmium as a key factor of the disease.

Society

Legal action

Twenty-nine plaintiffs, consisting of 9 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, 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 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 victims succeeded in instilling almost complete pollution control through legal action.

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.

The cadmium pollution had contaminated many agricultural areas in Japan, and as a result, the Prevention of Soil Contamination in Agricultural Land Law of 1970 was enacted. It ordered planting to be stopped so that restoration of the soil could be implemented to areas with 1ppm of cadmium or more in the soil. Surveying in Toyama Prefecture began in 1971, and by 1977, 1500 hectares 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. As of 1992, only 400 hectares remain contaminated.

Continuous inspections following the lawsuit showcase the vast improvements in terms of greatly reduced pollution levels. Total amounts of cadmium discarded decreased from 35 kg mo−1 in 1972 to 3.8 kg mo−1 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 >5 kg mo−1 in 1972 to 0.17 kg mo−1 in 2010. In 1996, the mean concentration of cadmium in agricultural lands lowered to the background level of 0.1 ppb, signifying trivial cadmium outflow. This is a success in regards to the lawsuit.

The pollution present in the mine is surveyed through specialty checks, and is continually monitored. Water originating from the mine has high levels of cadmium, which requires it to be separated and diverted to the Kamioka Mine slag dump. Here, the water and solids are separated and processed before leaving the mine. These treatment facilities exhaust are also monitored to ensure no cadmium in the airborne byproduct of the zinc refining process.

On March 17th, 2012, officials concluded the cleanup project of the cadmium-polluted areas in the Jinzū River basin. Eight-hundred and sixty-three hectares 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.