There was not any tobacco in Spain until ______.

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问题 There was not any tobacco in Spain until ______.
The use of tobacco originated among the natives inhabitants of the Western Hemisphere in pre-Columbian times. Tobacco was introduced into Spain and Portugal in the mid-16th century, initially for its supposed virtues as a "wonder drug". It spread to other European countries and then to Asia and Africa.
    However, after it spread across the Europe as a panacea, tobacco ironically began to be considered a health hazard because it contains nicotine, a poisonous alkaloid, and other harmful substances such as carbon monoxide, ammonia, and a number of aldehydes and tars; in all, tobacco contains some 4,000 chemicals. In 1964 the United States presented definitive proof that cigarette smoking is a serious health hazard. Tobacco, a large-leaved perennial, usually cultivated as an annual, grown from seed in hotbeds and then transplanted to the field. After being harvested, tobacco leaves are made to develop aroma and reduce the harsh, rank odor and taste of fresh leaves. Most commercial tobaccos are blends of several types, and flavorings are often added. The United States, China, India, Brazil, Turkey, and Zimbabwe are the chief producing countries, and Russia, Japan, and Germany are the major importers.

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答案the mid-16th century

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