title: Insights from a multi-year program designed to test the impact of ingredients on mainstream cigarette smoke toxicity.
abstract: BACKGROUND
  Cigarette tobacco ingredients may alter the distribution of chemical constituents present in smoke. When considering the toxicological relevance of potential ingredient-related effects on chemical and biological measurements assessing cigarette smoke toxicity, it is critical to understand the intrinsic variability of tobacco and cigarette smoke that is influenced by the environmental conditions during growing, agricultural practices during preparation, cigarette manufacturing tolerances, and stability of the assay methods.
  
  
  OBJECTIVE
  To understand possible effects of ingredients on cigarette smoke toxicity, various chemical and biological endpoints were measured in smoke from experimental cigarettes (added ingredient) to the intrinsic variability of control cigarettes (no added ingredient).
  
  
  METHODS
  Data were collected during a multi-year program testing a variety of cigarette ingredients from several chemical classes. Chemical analysis of mainstream cigarette smoke,and biological procedures (Salmonella mutagenicity, cytotoxicity, and smoke inhalation) were performed using validated and controlled laboratory methods. The within-study and temporal variation of control cigarettes manufactured in parallel with experimental cigarettes was calculated and used to measure intrinsic variability.
  
  
  RESULTS
  The overwhelming majority of data generated from experimental cigarettes fell within the experiment variability represented by the pooled standard error of the entire multi-year dataset for the control cigarettes.
  
  
  CONCLUSIONS
  The results of this evaluation add to a growing body of the literature regarding a weight of evidence assessment of cigarette ingredient toxicity. When assessed against the variability of assay methodology, natural agricultural change, and manufacturing control, the ingredients studied here demonstrated little relevant influence on the mainstream cigarette smoke toxicity endpoints measured.
authors.affiliation: Altria Client Services, Richmond, Virginia, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Gaworski
authors.forename: Karl A
authors.initials: KA
authors.lastname: Wagner
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morton
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Oldham
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005079:Excipients / Q000032:analysis / Q000633:toxicity; D005260:Female; D005421:Flavoring Agents / Q000032:analysis / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D012906:Smoke / Q000009:adverse effects / Q000032:analysis; D012907:Smoking / Q000009:adverse effects*; D018675:Toxicity Tests; D015262:Xenobiotics / Q000633:toxicity*
chemical_list: D005079:Excipients; D005421:Flavoring Agents; D012906:Smoke; D015262:Xenobiotics