title: A comprehensive evaluation of the toxicology of cigarette ingredients: inorganic compounds.
abstract: BACKGROUND
  Two ammonia compounds, diammonium phosphate and ammonium hydroxide, are typically used in the processing or flavoring of tobacco used in the manufacture of cigarettes.
  
  
  OBJECTIVE
  A battery of tests was used to compare the toxicity of mainstream smoke from experimental cigarettes containing different added levels of diammonium phosphate (target maximal inclusion level, 50,000 ppm) or both ammonium hydroxide (target maximal inclusion level 11,160 ppm) and diammonium phosphate.
  
  
  METHODS
  The tests included analytical chemistry, with over 40 constituents in mainstream cigarette smoke; in vitro bacterial (Salmonella) mutagenicity and cytotoxicity (neutral red uptake) assays, and 90-day smoke inhalation studies using rats. Diammonium phosphate acted as a burn retardant, and consequently, the highest planned inclusion level could not be used. Ammonium hydroxide could not be added to cigarettes at meaningfully different levels.
  
  
  RESULTS
  Apart from a substantial reduction in smoke concentrations of formaldehyde seen in the smoke chemistry analysis and animal exposure characterization, there were very few endpoints in any of the analyses that showed significant differences as a result of the addition of either of the two ammonia compounds. These differences, when present, occurred only sporadically, with no evidence of any dose-response relationships.
  
  
  CONCLUSIONS
  The results of these experiments show that the ammonia compounds, diammonium phosphate and ammonium hydroxide, when added to cigarette tobacco, even at high inclusion levels, have minimal toxicological sequelae.
authors.affiliation: Carson Watts Consulting, King, North Carolina, USA.
authors.forename: Christopher R E
authors.initials: CR
authors.lastname: Coggins
authors.forename: Erica J
authors.initials: EJ
authors.lastname: Sena
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Oldham
mesh_terms: D000280:Administration, Inhalation; D064753:Ammonium Hydroxide; 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; D006878:Hydroxides / Q000032:analysis / Q000633:toxicity; D007287:Inorganic Chemicals / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D010710:Phosphates / Q000032:analysis / Q000633:toxicity; 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*; D062789:Tobacco Products
chemical_list: D005079:Excipients; D005421:Flavoring Agents; D006878:Hydroxides; D007287:Inorganic Chemicals; D010710:Phosphates; D012906:Smoke; D015262:Xenobiotics; C024788:ammonium phosphate; D064753:Ammonium Hydroxide