Kyeonghee M. Lee

Effects of Flavoring and Casing Ingredients on the Toxicity of Mainstream Cigarette Smoke in Rats

A series of in vitro and in vivo studies evaluated the potential effects of tobacco flavoring and casing ingredients. Study 1 utilized as a reference control cigarette a typical commercial tobacco blend without flavoring ingredients, and a test cigarette containing a mixture of 165 low-use flavoring ingredients. Study 2 utilized the same reference control cigarette as used in study 1 and a test cigarette containing eight high-use ingredients. The in vitro Ames Salmonella typhimurium assay did not show any increase in mutagenicity of smoke condensate from test cigarettes designed for studies 1 and 2 as compared to the reference. Sprague-Dawley rats were exposed by nose-only inhalation for 1 h/day, 5 days/wk for 13 wk to smoke from the test or reference cigarettes already described, or to air only, and necropsied after 13 wk of exposure or following 13 wk of recovery from smoke exposure. Exposure to smoke from reference or test cigarettes in both studies induced increases in blood carboxyhemoglobin ((COHb)) and plasma nicotine, decreases in minute volume, differences in body or organ weights compared to air controls, and a concentration-related hyperplasia, squamous metaplasia, and inflammation in the respiratory tract. All these effects were greatly decreased or absent following the recovery period. Comparison of rats exposed to similar concentrations of test and reference cigarette smoke indicated no difference at any concentration. In summary, the results did not indicate any consistent differences in toxicologic effects between smoke from cigarettes containing the flavoring or casing ingredients and reference cigarettes.

Characterization of biochemical, functional and structural changes in mice respiratory organs chronically exposed to cigarette smoke

Abstract Female C57BL/6 mice were exposed to mainstream cigarette smoke at 600 μg WTPM/L, 4 h/day and 5 days/week for up to 52 weeks. At 26, 52 and 65 weeks (52 weeks of exposure plus 13 weeks of no exposure), lungs were assessed for inflammation, function, histopathology and morphometry. Structural changes were observed and accompanied by altered lung function at 26 and 52 weeks (e.g. increase of static compliance and hysteresis, and decrease of elastance). Lung morphometry quantified significant increase in airspace enlargement at 52 weeks. Chronic smoke exposure induced inflammation in respiratory organs, e.g. mixed inflammatory cell infiltrates, perivascular lymphocyte infiltrates and pigmented alveolar macrophages in the lungs. Minimal or mild alveolar emphysema was diagnosed in 70% by 26 weeks or 80% by 52 weeks. After 13 weeks of recovery, most biochemical, histopathological and morphometrical alterations were restored, while emphysema was observed to persist at 18% incidence by 65 weeks. In conclusion, the employed exposure conditions induced emphysematous changes in the lungs, accompanied by altered lung function and morphological/histopathological changes. Following the 13 weeks of no exposure, morphological changes persisted, although some functional/biochemical alterations regressed.

Toxicokinetics of Propylene Glycol Mono-t-Butyl Ether Following Intravenous or Inhalation Exposure in Rats and Mice

Propylene glycol mono-t-butyl ether (PGMBE) is a widely used solvent in industry and in consumer products, posing a potential for human exposure via inhalation or dermal routes. Toxicokinetic studies were conducted on F344/N rats and B6C3F1 mice of both sexes to evaluate single or repeated dose, species, and/or sex differences in PGMBE elimination kinetics following intravenous or inhalation exposure. In the first study, rats and mice received a single intravenous dose of 15 or 200 mg PGMBE/kg and serial blood samples were collected and analyzed for PGMBE. In the second study, rats and mice received a single 6-h whole-body inhalation exposure to 75, 300, or 1200 ppm PGMBE and serial blood samples were collected and analyzed for PGMBE. In the third study, rats and mice received whole-body inhalation exposures to 75, 300, or 1200 ppm PGMBE for 6 h/day, 5 days/wk for 14 (rats) or 16 (mice) wk. Serial blood samples were analyzed for PGMBE after 2, 6, 14 (rats), and 16 (mice) wk on study. Urine samples were also collected for 16 h postexposure and analyzed for creatinine and PGMBE sulfate and PGMBE glucuronide conjugates. These studies revealed that: (1) PGMBE was eliminated from blood following concentration-dependent nonlinear kinetics in both species; (2) saturable Michaelis–Menten kinetics were clearly exhibited following a single inhalation exposure at 1200 ppm, but were less obvious following repeated exposures; (3) mice were more efficient in eliminating PGMBE from blood at lower exposure concentrations (i.e., ≤300 ppm), but at exposure concentrations potentially exceeding their elimination capacity, mice had a greater concentration-dependent decrease in PGMBE elimination than rats; (4) there were minimal but consistent sex differences in PGMBE elimination profiles for rats, with females having higher blood concentrations at all exposure concentrations and sampling times; and (5) sex differences in PGMBE elimination were in part associated with differences in urinary excretion of PGMBE metabolites.