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Some sources believe early wild species may have arisen around 6,000 BCE, especially in South America, and there may be several sites of origin for each species throughout North and South America

Encyclopedia of smoking and tobacco (1999) online James I of England, A Counterblaste to Tobacco Lloyd, J & Mitchinson, J: "The Book of General Ignorance"

Kuiper, N., Coats, E

DNA adduct formation from metabolic 5-hydroxylation of the tobacco-specific carcinogen N -nitrosonornicotine in human enzyme systems and in rats

However, patients still need to consider the dose, adhesive ingredients, skin reactions, sleep effects, cardiovascular response, and dependence potential