title: Toxicological assessment of kretek cigarettes. Part 7: the impact of ingredients added to kretek cigarettes on inhalation toxicity.
abstract: The biological activity of mainstream smoke from experimental kretek cigarettes with and without three mixes of ingredients was assessed in a 90-day rat inhalation study and in a 4-day in vivo micronucleus assay. 350 ingredients, commonly used in various combinations and in a limited number in a given brand in the manufacture of marketed kretek cigarettes, were applied at a low and a high target level to test cigarettes with a typical Indonesian blend of tobaccos and cloves. In the 90-day inhalation study, effects commonly seen in rat inhalation studies with mainstream smoke were observed. In general, no ingredients-related histopathological changes were found in the respiratory tract. In the 4-day micronucleus assay exposure of male rats to mainstream smoke from the test cigarettes containing any of the three mixes did not increase the proportions of micronucleated cells in peripheral blood and bone marrow over the proportion of micronucleated cells in the control group. Based on the results of these studies, it can be concluded that the addition of ingredients commonly used in the manufacture of kretek cigarettes did not change the overall in vivo toxicity profile of the mainstream smoke.
authors.affiliation: Philip Morris International, Philip Morris Products SA, Rue des Usines 90, 2000 Neuchâtel, Switzerland. Electronic address: Heike.Schramke@pmi.com.
authors.forename: H
authors.initials: H
authors.lastname: Schramke
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.
authors.forename: R
authors.initials: R
authors.lastname: Dempsey
authors.affiliation: Philip Morris International, Philip Morris Products SA, Rue des Usines 90, 2000 Neuchâtel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Hirter
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.
authors.forename: A
authors.initials: A
authors.lastname: Berges
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; 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; D002263:Carboxyhemoglobin / Q000032:analysis; D005260:Female; D008297:Male; D015162:Micronucleus Tests; D009538:Nicotine / Q000378:metabolism; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects* / Q000473:pathology; D012906:Smoke / Q000009:adverse effects*; D027842:Syzygium; D062789:Tobacco Products / Q000633:toxicity*; D059550:Toxicity Tests, Subchronic
chemical_list: D012906:Smoke; D009538:Nicotine; D002263:Carboxyhemoglobin
keywords: Clove cigarette; Flavor; In vivo; Ingredient; Inhalation; Kretek; Micronucleus