Residual Risk of Nicotine

Abstract Smokers are exposed to the harmful and potentially harmful constituents generated by cigarette combustion. Discriminating the independent effects of nicotine from those of other chemicals present in cigarette smoke is difficult. Nevertheless, investigating circumstances in which individuals are exposed to nicotine without combustion—as with the use of smokeless tobacco products, nicotine replacement therapies, and, to some extent, e-vapor products—provides evidence on the possible health effects of nicotine. Where epidemiological data are lacking, nonclinical studies may provide mechanistic insights into nicotine's ability to modulate molecular and cellular processes. This chapter summarizes the current knowledge about the effects of nicotine exposure on the circulatory system, lungs, female and male reproductive organs, and developing fetus and critically reviews nicotine's potential involvement in cardiovascular diseases, lung cancer, and developmental defects. This chapter also highlights key gaps in our current understanding of the biological effects of nicotine.