title: Industry research on the use and effects of levulinic acid: a case study in cigarette additives.
abstract: Public health officials and tobacco researchers have raised concerns about the possible contributions of additives to the toxicity of cigarettes. However, little attention has been given to the process whereby additives promote initiation and addiction. Levulinic acid is a known cigarette additive. Review of internal tobacco industry documents indicates that levulinic acid was used to increase nicotine yields while enhancing perceptions of smoothness and mildness. Levulinic acid reduces the pH of cigarette smoke and desensitizes the upper respiratory tract, increasing the potential for cigarette smoke to be inhaled deeper into the lungs. Levulinic acid also may enhance the binding of nicotine to neurons that ordinarily would be unresponsive to nicotine. These findings held particular interest in the internal development of ultralight and so-called reduced-exposure cigarette prototypes. Industry studies found significantly increased peak plasma nicotine levels in smokers of ultralight cigarettes following addition of levulinic acid. Further, internal studies observed changes in mainstream and sidestream smoke composition that may present increased health risks. The use of levulinic acid illustrates the need for regulatory authority over tobacco products as well as better understanding of the role of additives in cigarettes and other tobacco products.
authors.affiliation: Massachusetts Department of Public Health Tobacco Control Program, Boston, MA 02108, USA. lois.keithly@state.ma.us
authors.forename: Lois
authors.initials: L
authors.lastname: Keithly
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Ferris Wayne
authors.forename: Doris M
authors.initials: DM
authors.lastname: Cullen
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Connolly
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D005731:Ganglionic Stimulants / Q000493:pharmacokinetics; D049673:History, 20th Century; D006801:Humans; D007982:Levulinic Acids / Q000737:chemistry* / Q000494:pharmacology*; D009538:Nicotine / Q000493:pharmacokinetics; D012106:Research / Q000266:history; D019460:Tobacco Industry / Q000266:history; D014029:Tobacco Use Disorder / Q000503:physiopathology*
chemical_list: D004791:Enzyme Inhibitors; D005731:Ganglionic Stimulants; D007982:Levulinic Acids; D009538:Nicotine; C032246:levulinic acid