title: A comprehensive evaluation of the toxicology of cigarette ingredients: cocoa-derived ingredients.
abstract: BACKGROUND
  Cocoa-derived ingredients are used in cigarette tobacco.
  
  
  OBJECTIVE
  A battery of tests was used to compare toxicity of mainstream smoke from experimental cigarettes containing different added levels of cocoa-derived ingredients.
  
  
  METHODS
  Five cocoa-derived ingredients chocolate (CH), cocoa (COC), cocoa-grand prix black (CGPB), cocoa nibs tincture (CNT) and cocoa shells extract (CSE) were added individually to experimental cigarettes at three different levels. Smoke from each of the experimental cigarette types was evaluated using analytical chemistry; in vitro cytotoxicity and mutagenicity testing were performed for four of the five compounds. For CH, COC and CNT, 90-day smoke inhalation studies were performed with 6-week recovery periods.
  
  
  RESULTS
  No consistent changes were found in the analytical chemistry results. Results of the cytotoxicity and mutagenicity were unaffected by any of the ingredients. Two of the three inhalation studies showed very few differences between the groups. The inhalation study with COC showed several increases in mean histopathology severity scores in groups exposed to different levels of COC, compared with the controls. These apparent effects of COC on histopathology lesion severity scores were only present in a single sex and none were dose-related, which is not consistent with a true increase in biological activity. Also there were effectively no differences in the patterns of recovery for any of the compounds.
  
  
  CONCLUSIONS
  Even at high inclusion levels there was a lack of toxicological response in these COC derived ingredients.
authors.affiliation: Carson Watts Consulting, King, North Carolina, USA.
authors.forename: Christopher R E
authors.initials: CR
authors.lastname: Coggins
authors.forename: Michael T
authors.initials: MT
authors.lastname: Fisher
authors.forename: Donna C
authors.initials: DC
authors.lastname: Smith
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Oldham
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002099:Cacao / Q000737:chemistry / 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; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000473:pathology; 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