title: Toxicological responses in SW mice exposed to inhaled pyrolysates of polymer/tobacco mixtures and blended tobacco.
abstract: Modern cigarette manufacturing is highly automated and produces millions of cigarettes per day. The potential for small inclusions of non-cigarette materials such as wood, cardboard packaging, plastic, and other materials exists as a result of bulk handling and high-speed processing of tobacco. Many non-tobacco inclusions such as wood, paper, and cardboard would be expected to yield similar pyrolysis products as a burning cigarette. The aircraft industry has developed an extensive literature on the pyrolysis products of plastics, however, that have been reported to yield toxic by-products upon burning, by-products that have been lethal in animals and humans upon acute exposure under some exposure conditions. Some of these smoke constituents have also been reported in cigarette smoke. Five synthetic polymers, nylon 6, acrylonitrile-butadiene-styrene (ABS), nylon 12, nylon 6,6, and acrylonitrile-butadiene (AB), and the natural polymer wool were evaluated by adding them to tobacco at a 3, 10, and 30% inclusion level and then pyrolyzing the mixture. The validated smoke generation and exposure system have been described previously. We used the DIN 53-436 tube furnace and nose-only exposure chamber in combination to conduct exposures in Swiss-Webster mice. Potentially useful biological endpoints for predicting hazards in humans included sensory irritation and pulmonary irritation, respiratory function, clinical signs, body weights, bronchoalveolar lavage (BAL) fluid analysis, carboxyhemoglogin, blood cyanide concentrations, and histopathology of the respiratory tract. Chemical analysis of selected smoke constituents in the test atmosphere was also performed in order to compare the toxicological responses with exposure to the test atmospheres. Under the conditions of these studies, biological responses considered relevant and useful for prediction of effects in humans were found for sensory irritation, body weights, BAL fluid analysis, and histopathology of the nose. There was a marked sensory irritation response that recovered slowly for some polymers. Sustained body weight depression, lesions of the respiratory epithelium of the nose, and morphological changes in pulmonary alveolar macrophages (PAM) were observed after exposure to some polymer/tobacco pyrolysates. These responses were increased compared to exposure to tobacco pyrolysate alone. No moribundity or mortality occurred during the study. The data suggest that polymeric inclusions pose a minimal additional toxicologic hazard in humans.
authors.affiliation: Altria Client Services (formerly PM USA), Product Integrity, Richmond, Virginia 23224, USA. michael.s.werley@altria.com
authors.forename: Michael S
authors.initials: MS
authors.lastname: Werley
authors.forename: K Monika
authors.initials: KM
authors.lastname: Lee
authors.forename: Ranulfo
authors.initials: R
authors.lastname: Lemus-Olalde
mesh_terms: D000180:Acrylic Resins / Q000633:toxicity; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002070:Butadienes / Q000633:toxicity; D002209:Caprolactam / Q000031:analogs & derivatives / Q000633:toxicity; D002263:Carboxyhemoglobin / Q000378:metabolism; D003486:Cyanides / Q000097:blood; D004340:Drug Contamination; D019570:Inhalation Exposure; D007509:Irritants / Q000633:toxicity*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000473:pathology; D051379:Mice; D009297:Nasal Mucosa / Q000187:drug effects / Q000473:pathology; D009757:Nylons / Q000633:toxicity; D011108:Polymers / Q000633:toxicity*; D011137:Polystyrenes / Q000633:toxicity; D015656:Respiratory Mechanics / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects / Q000473:pathology; D018570:Risk Assessment; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013990:Tidal Volume / Q000187:drug effects; D013997:Time Factors; D014935:Wool / Q000009:adverse effects; D062789:Tobacco Products
chemical_list: D000180:Acrylic Resins; D002070:Butadienes; D003486:Cyanides; D007509:Irritants; D009757:Nylons; D011108:Polymers; D011137:Polystyrenes; D012906:Smoke; C009916:nylon 6; C036222:nylon 12; D002209:Caprolactam; C024636:ABS resin; D002263:Carboxyhemoglobin