title: A comprehensive evaluation of the toxicology of cigarette ingredients: aliphatic and aromatic carboxylic acids.
abstract: BACKGROUND
  Aromatic and aliphatic carboxylic acids are present in tobacco and tobacco smoke.
  
  
  OBJECTIVE
  A battery of tests was used to compare the toxicity of mainstream smoke from experimental cigarettes containing eight aromatic and aliphatic carboxylic acids and the salt of one acid that were added individually at three different levels (lowest and highest target inclusions were 100 and 90,000 ppm, respectively).
  
  
  METHODS
  Mainstream smoke from cigarettes containing each of the test ingredients was evaluated using analytical chemistry and assays to measure in vitro cytotoxicity (neutral red uptake) and Salmonella (five strains) mutagenicity. For four of the compounds (citric, lactic, benzoic acids, and sodium benzoate), 90-day rodent inhalation studies were also performed.
  
  
  RESULTS
  Although sporadic statistically significant differences in some experimental cigarette smoke constituents occurred, none resulted in significant changes in mutagenicity or cytotoxicity responses, nor in responses measured in the inhalation studies, except for lactic acid (LA). Inclusion of LA resulted in dose-dependent increase in water and caused a dose-dependent decrease in cytotoxicity. Incorporation of LA into cigarettes resulted in several dose-related reductions in histopathology, which were largely restricted to the nasal passages. Incorporation of LA also ameliorated some of the typical decrease in body weight gain seen in cigarette smoke-exposed rats.
  
  
  CONCLUSIONS
  Inclusion of these ingredients at exaggerated use levels resulted in sporadic dose-related and treatment effects for some smoke constituents, but no toxicological response was noted in the in vitro and in vivo tests performed.
authors.affiliation: Carson Watts Consulting, King, NC, USA.
authors.forename: Christopher R E
authors.initials: CR
authors.lastname: Coggins
authors.forename: Jianmin
authors.initials: J
authors.lastname: Liu
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Merski
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; D001835:Body Weight / Q000187:drug effects; D002264:Carboxylic Acids / Q000032:analysis / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D005079:Excipients / Q000032:analysis / Q000633:toxicity; D005260:Female; D005421:Flavoring Agents / Q000032:analysis / Q000633:toxicity; D019344:Lactic Acid / Q000494:pharmacology; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology; 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: D002264:Carboxylic Acids; D005079:Excipients; D005421:Flavoring Agents; D020011:Protective Agents; D012906:Smoke; D015262:Xenobiotics; D019344:Lactic Acid