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The cause of itai-itai disease was determined to be cadmium poisoning in the drinking water from the Jinzugawa River basin. The source of cadmium was discovered to be from Mitsui Mining and Smelting Company. Mitsui Mining began to discharge cadmium into the Jinzugawa River in 1910.
One of the most extreme forms of disease related to cadmium exposure by the oral route is itai-itai disease, described in Japan in the 1960s. Itai-itai disease is characterized by osteomalacia, osteoporosis, renal tubular dysfunction, malabsorption, and anemia. The bone effects are prominent features in humans suffering from itai-itai disease.