Publications (5)9.83 Total impact
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Article: A comprehensive evaluation of the toxicology of cigarette ingredients: essential oils and resins
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ABSTRACT: Context: A total of 32 essential oils and resins were added individually to experimental cigarettes. Objective: A battery of tests was used to compare the toxicity of mainstream smoke from these experimental cigarettes. The lowest target inclusion level was 100 ppm and the highest was 100,000 ppm. Materials and methods: Smoke from each of the experimental cigarette was evaluated using analytical chemistry and in vitro bacterial (Salmonella, five strains) mutagenicity and cytotoxicity (neutral red uptake) assays. For seven of the ingredients (carob bean, carob bean extract, carrageenan, chamomile flower Hungarian oil, guar gum, peppermint oil, and spearmint oil), 90-day smoke inhalation studies with rats were also performed. Results: In general, inclusion levels resulted in minimal changes in smoke chemistry; the exceptions were PO and SO, where reductions to 40–60% of control values were noted, possibly indicating a tobacco displacement effect. Cytotoxicity and mutagenicity were unaffected by any of the test ingredients, except for a dose-related reduction in cytotoxicity for SO. There were very few statistically significant differences within any of the seven inhalation studies; when present, the differences were sporadic and inconsistent between sexes. The addition of SO appeared to depress body weight gain and increase the atrophy of olfactory epithelia, but only in males. Conclusion: The essential oils and resins tested here as ingredients in experimental cigarettes show minimal toxicological sequelae, even at high inclusion levels. The highest inclusion level for SO showed some equivocal responses.06/2011; 23(S1):41-69. -
Article: A comprehensive evaluation of the toxicology of cigarette ingredients: essential oils and resins.
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ABSTRACT: A total of 32 essential oils and resins were added individually to experimental cigarettes. A battery of tests was used to compare the toxicity of mainstream smoke from these experimental cigarettes. The lowest target inclusion level was 100 ppm and the highest was 100,000 ppm. Smoke from each of the experimental cigarette was evaluated using analytical chemistry and in vitro bacterial (Salmonella, five strains) mutagenicity and cytotoxicity (neutral red uptake) assays. For seven of the ingredients (carob bean, carob bean extract, carrageenan, chamomile flower Hungarian oil, guar gum, peppermint oil, and spearmint oil), 90-day smoke inhalation studies with rats were also performed. Results: In general, inclusion levels resulted in minimal changes in smoke chemistry; the exceptions were PO and SO, where reductions to 40-60% of control values were noted, possibly indicating a tobacco displacement effect. Cytotoxicity and mutagenicity were unaffected by any of the test ingredients, except for a dose-related reduction in cytotoxicity for SO. There were very few statistically significant differences within any of the seven inhalation studies; when present, the differences were sporadic and inconsistent between sexes. The addition of SO appeared to depress body weight gain and increase the atrophy of olfactory epithelia, but only in males. The essential oils and resins tested here as ingredients in experimental cigarettes show minimal toxicological sequelae, even at high inclusion levels. The highest inclusion level for SO showed some equivocal responses.Inhalation Toxicology 06/2011; 23 Suppl 1:41-69. · 1.92 Impact Factor -
Article: A comprehensive evaluation of the toxicology of cigarette ingredients: aromatic carbonyl compounds.
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ABSTRACT: Aromatic carbonyls are typically used in the processing or flavoring of tobacco used in the manufacture of cigarettes. A battery of tests was used to compare the toxicity of mainstream smoke from experimental cigarettes containing different added levels of aromatic carbonyl compounds. Ten aromatic carbonyl compounds, nine of which have been reported in tobacco or in tobacco smoke, were added individually to experimental cigarettes at three different levels. The tenth compound, not found naturally in tobacco, was 2-phenoxyethyl isobutyrate. The lowest target inclusion level was 100 ppm and the highest was 10,000 ppm. Smoke from each of the 10 experimental cigarette types was evaluated using analytical chemistry, in vitro cytotoxicity, and mutagenicity testing. For one of the compounds, ethyl vanillin, a 90-day smoke inhalation study using rats was also performed. Smoke chemistry was effectively unchanged by the addition of any of the compounds. Cytotoxicity, assessed by the neutral red uptake assay and using both gas-vapor and particulate phases of smoke, was unaffected by the addition of any of the test compounds. Mutagenicity, assessed by five strains of Salmonella typhimurium treated with smoke condensate, also was unaffected by any of the test compounds. In the rat inhalation study, there were effectively no differences between cigarettes without added ethyl vanillin and cigarettes containing ~8000 ppm of ethyl vanillin. Even at the exaggerated inclusion levels in cigarette tobacco used in these tests, no adverse toxicological responses occurred for any of aromatic carbonyl compounds tested.Inhalation Toxicology 06/2011; 23 Suppl 1:90-101. · 1.92 Impact Factor -
Article: High-resolution mass spectrometry proteomics for the identification of candidate plasma protein biomarkers for chronic obstructive pulmonary disease.
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ABSTRACT: Although cigarette smoking is recognized as the most important cause of chronic obstructive pulmonary disease (COPD), the pathophysiological mechanisms underlying the lung function decline are not well understood. Using off-line strong cation exchange fractionation with RP-LC-ESI-MS/MS and robust database searching, 1758 tryptic peptides were identified in plasma samples from cigarette smokers. Using two statistical approaches, 30 peptides were identified to be associated with the annualized rate of lung function decline over 5 years among smokers with COPD characterized as having rapid (n = 18) or slow (n = 18) decline and 18 smokers without COPD. The identified peptides belong to proteins that are involved in the complement or coagulation systems or have antiprotease or metabolic functions. This research demonstrates the utility of proteomic profiling to improve the understanding of molecular mechanisms involved in cigarette smoking-related COPD by identifying plasma proteins that correlate with decline in lung function.Biomarkers 06/2010; 15(4):367-77. · 2.21 Impact Factor -
Article: Cigarette smoke extract induced protein phosphorylation changes in human microvascular endothelial cells in vitro.
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ABSTRACT: Phosphorylation is the most widely studied posttranslational modification (PTM) and is an important regulatory mechanism used during cellular responses to external stimuli. The kinases and phosphatases that regulate protein phosphorylation are known to be affected in many human diseases. Cigarette smoking causes cardiovascular disease (CVD). Endothelial cells play a pivotal role in CVD initiation and development; however, there have been limited investigations of the specific signaling cascades and protein phosphorylations activated by cigarette smoke in endothelial cells. The purpose of this research was to better understand the differential protein phosphorylation in endothelial cells stimulated with extracts of cigarette smoke total particulate matter (CS-TPM) in vitro. Human microvascular endothelial cells were exposed in vitro to CS-TPM at concentrations that were shown to cause endothelial cell dysfunction. The phosphorylated proteins were isolated using phosphoprotein-specific chromatography, followed by enzymatic digestion and nano-flow capillary liquid chromatography (ncap-LC) coupled to high resolution mass spectrometry. This study putatively identified 94 proteins in human microvascular endothelial cells that were differentially bound to a phosphoprotein-specific chromatography column following exposure to CS-TPM suggesting differential phosphorylation. Pathway analysis has also been conducted and confirmations of several observations have been made using immunoaffinity-based techniques (e.g., Western blotting).Analytical and Bioanalytical Chemistry 08/2009; 394(6):1609-20. · 3.78 Impact Factor
