title: Significance of ammonium compounds on nicotine exposure to cigarette smokers.
abstract: The tobacco industry publicly contends that ammonia compounds are solely used as tobacco additive for purposes of tobacco flavoring, process conditioning and reduction of its subjective harshness and irritation. However, neither objective scientific reports, nor the contents of a large number of internal tobacco company documents support this contention. The present review focuses on the hypothesis that addition of ammonium compounds to tobacco enhances global tobacco use due to smoke alkalization and enhanced free-nicotine nicotine exposure. Obviously, ammonia enhances the alkalinity of tobacco smoke. Consequently, the equilibrium shifts from non-volatile nicotine salts to the volatile free base that is more readily absorbed from the airways. The observed change in the kinetics of nicotine (i.e., shorter t(1/2) and higher c(max)) after ammoniation is, however, predominantly due to the higher concentration of nicotine in the smoke, rather than to an increase in the absorption rate of free-base nicotine in the respiratory tract. Although several findings support the hypothesis, additional studies are required and suggested to provide a proper, objective and independent scientific judgment about the effect of tobacco ammoniation on nicotine bioavailability. Scientific and public awareness of the effects of tobacco-specific ammonia compounds may stimulate global control, legislation and restriction of their use in cigarette manufacture.
authors.affiliation: Laboratory for Toxicology, Pathology and Genetics, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands. edwin.willems@rivm.nl
authors.forename: E W
authors.initials: EW
authors.lastname: Willems
authors.forename: B
authors.initials: B
authors.lastname: Rambali
authors.forename: W
authors.initials: W
authors.lastname: Vleeming
authors.forename: A
authors.initials: A
authors.lastname: Opperhuizen
authors.forename: J G C
authors.initials: JG
authors.lastname: van Amsterdam
mesh_terms: D000042:Absorption / Q000187:drug effects; D001682:Biological Availability; D005421:Flavoring Agents / Q000032:analysis / Q000494:pharmacology*; D006801:Humans; D009538:Nicotine / Q000032:analysis / Q000493:pharmacokinetics*; D018722:Nicotinic Agonists / Q000032:analysis / Q000493:pharmacokinetics*; D000644:Quaternary Ammonium Compounds / Q000032:analysis / Q000494:pharmacology* / Q000633:toxicity; D012907:Smoking / Q000009:adverse effects / Q000331:legislation & jurisprudence; D019460:Tobacco Industry / Q000331:legislation & jurisprudence / Q000592:standards; D014481:United States
chemical_list: D005421:Flavoring Agents; D018722:Nicotinic Agonists; D000644:Quaternary Ammonium Compounds; D009538:Nicotine