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In cigarettes, nicotine has been identified as the component primarily responsible for the vascular consequences resulting from persistent smoking [145]

For a drug administered orally, bioavailability may be less than 100% for two main reasonsincomplete extent of absorption across the gut wall and first-pass elimination by the liver (see below)

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Even in the case of synthetic chemicals, an increased risk of disease has been associated with increasing doses within the sub-hormetic zone, but the risk flattens out as doses approach the hormetic zone