title: A comprehensive evaluation of the toxicology of cigarette ingredients: carbohydrates and natural products.
abstract: BACKGROUND
  Eleven carbohydrates and natural product ingredients were added individually to experimental cigarettes.
  
  
  OBJECTIVE
  A battery of tests was used to compare toxicity of mainstream smoke from these experimental cigarettes to matched control cigarettes without test ingredients.
  
  
  METHODS
  Smoke fractions from each cigarette type were evaluated using analytical chemistry; in vitro cytotoxicity (neutral red uptake) and in vitro bacterial (Salmonella) mutagenicity (five strains) testing. For 10 ingredients (β-cyclodextrin, cleargum, D-sorbitol, high fructose corn syrup, honey, invert sugar, maltodextrin, molasses, raisin juice concentrate, and sucrose), 90-day nose-only smoke inhalation studies using rats were also performed.
  
  
  RESULTS
  In general, addition of each ingredient in experimental cigarettes resulted in minimal changes in smoke chemistry; the exceptions were D-sorbitol and sucrose, where reductions in amount of 60% to 80% of control values for some smoke constituents were noted. Additionally, each ingredient resulted in small increases in smoke formaldehyde concentrations. Except for a reduction in cytotoxicity by inclusion of maltodextrin and an increase by inclusion of plum juice concentrate, the cytotoxicity and mutagenicity results were unaffected by addition of the other ingredients in experimental cigarettes. There were also very few statistically significant differences within any of the 10 inhalation studies, and when present, the differences were largely sporadic and inconsistent between sexes.
  
  
  CONCLUSIONS
  The carbohydrates and natural products tested here as ingredients in experimental cigarettes as a class increased formaldehyde, but resulted in minimal toxicological responses, even at high inclusion levels compared with the levels used in commercial cigarette products.
authors.affiliation: Carson Watts Consulting, King, North Carolina, USA.
authors.forename: Christopher R E
authors.initials: CR
authors.lastname: Coggins
authors.forename: Karl A
authors.initials: KA
authors.lastname: Wagner
authors.forename: Michael S
authors.initials: MS
authors.lastname: Werley
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Oldham
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001688:Biological Products / Q000032:analysis / Q000633:toxicity*; D002241:Carbohydrates / Q000032:analysis / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005079:Excipients / Q000032:analysis / Q000633:toxicity; D005260:Female; D005421:Flavoring Agents / Q000032:analysis / Q000633:toxicity; D005557:Formaldehyde / Q000032:analysis / Q000378:metabolism; 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*; D014026:Nicotiana / Q000737:chemistry / Q000633:toxicity*; D018675:Toxicity Tests; D015262:Xenobiotics / Q000032:analysis / Q000633:toxicity*
chemical_list: D001688:Biological Products; D002241:Carbohydrates; D005079:Excipients; D005421:Flavoring Agents; D012906:Smoke; D015262:Xenobiotics; D005557:Formaldehyde