title: Toxicological assessment of kretek cigarettes Part 3: kretek and American-blended cigarettes, inhalation toxicity.
abstract: A typical Indonesian kretek cigarette brand and an experimental kretek reference cigarette were compared to the reference cigarette 2R4F in two 90-day inhalation studies. Male and female rats were exposed nose-only to mainstream smoke for 6 hours daily, for 90 consecutive days. Biological endpoints were assessed according to OECD guideline 413, with special emphasis on respiratory tract histopathology and on lung inflammation (broncho-alveolar lavage fluid levels of neutrophils, macrophages and lymphocytes). Histopathological alterations included: in the nose, hyperplasia and squamous metaplasia of the respiratory epithelium and squamous metaplasia and atrophy of the olfactory epithelium; in the larynx, epithelial squamous metaplasia and hyperplasia; in the lungs, accumulation of macrophages in alveoli and goblet cell hyperplasia in bronchial epithelium. The findings were qualitatively consistent with observations from previous similar studies on conventional cigarettes. Compared to 2R4F cigarette, however, kretek smoke exposure was associated with a pronounced attenuation of pulmonary inflammation and less severe histopathological changes in the respiratory tract. Neutrophilic inflammation was also significantly lower (>70%). These results are consistent with the observations made on smoke chemistry and in vitro toxicology. They do not support any increased toxicity of the smoke of kretek cigarettes compared to conventional American-blended cigarettes.
authors.affiliation: Philip Morris International, Philip Morris Products SA, Rue des Usines 90, 2000 Neuchâtel, Switzerland.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Piadé
authors.affiliation: Philip Morris International, Philip Morris Products SA, Rue des Usines 90, 2000 Neuchâtel, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Roemer
authors.affiliation: Philip Morris International, Philip Morris Products SA, Rue des Usines 90, 2000 Neuchâtel, Switzerland. Electronic address: Ruth.Dempsey@pmi.com.
authors.forename: R
authors.initials: R
authors.lastname: Dempsey
authors.affiliation: Philip Morris Research Laboratories GmbH, Fuggerstrasse 3, 51149 Cologne, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Weiler
authors.affiliation: Philip Morris Research Laboratories bvba, Grauwmeer 14, 3001 Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Meurrens
authors.affiliation: Philip Morris Research Laboratories bvba, Grauwmeer 14, 3001 Leuven, Belgium; Philip Morris International, Philip Morris Products SA, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Vanscheeuwijck
authors.affiliation: Philip Morris International, Philip Morris Products SA, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland.
authors.forename: M K
authors.initials: MK
authors.lastname: Schorp
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002263:Carboxyhemoglobin / Q000032:analysis; D002452:Cell Count; D005260:Female; D007509:Irritants / Q000633:toxicity; D008297:Male; D009538:Nicotine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012137:Respiratory System / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D012906:Smoke / Q000009:adverse effects*; D027842:Syzygium; D062789:Tobacco Products / Q000633:toxicity*; D059550:Toxicity Tests, Subchronic
chemical_list: D007509:Irritants; D012906:Smoke; D009538:Nicotine; D002263:Carboxyhemoglobin
keywords: Clove; Eugenol; Inhalation; Kretek; Rat; Smoke