The composition of cigarette smoke: a retrospective, with emphasis on polycyclic components

2000 ◽  
Vol 19 (10) ◽  
pp. 573-595 ◽  
Author(s):  
A Rodgman ◽  
C J Smith ◽  
T A Perfetti
Keyword(s):  
Biological Activity ◽  
Cigarette Smoke ◽  
Tobacco Smoke ◽  
Complex Mixture ◽  
Mouse Skin ◽  
Chemical Indicators ◽  
Polycyclic Aromatic ◽  
Mechanistic Basis ◽  
Cigarette Mainstream Smoke ◽  
Aza Arenes

The difficulties encountered in extrapolating biological activity from cigarette smoke composition provide generally applicable lessons as they are representative of the problems encountered with other complex mixtures. Researchers attempting to assess risk are faced with attempting to interpret data from a number of areas including: tobacco science; smoke/aerosol chemistry specific to tobacco; sophisticated analytical chemistry applications and techniques for trapping, collecting, separating, and quantifying very specific compounds at nanogram to picogram levels; numerous biological testing methodologies; and animal models of tumors and carcinogenesis. Numerous hypotheses have been developed over the past five decades and tested with the technology of the day in attempts to interpret the biological activity of cigarette smoke in relation to the chemistry of this complex mixture. These hypotheses fall into several categories discussed in this review: mechanisms of pyrogenesis of polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke; levels of PAHs in cigarette mainstream smoke (MS) and its tumorigenicity in mouse skin-painting experiments; control of PAH levels in MS; chemical indicators of cigarette smoke condensate (CSC) tumorigenicity; control of levels of MS components partitioned between the vapor phase and particulate phase of MS; tumorigenic threshold limits of CSC and many of its components; tumorigenic aza-arenes in tobacco smoke; MS components reported to be ciliastatic to smokers' respiratory tract cilia; anticarcinogenic tobacco-smoke components. Of 52 hypotheses reviewed in this paper, 15 have excellent data supporting the hypothesis based on today's technology. The remaining 37 hypotheses, although originally plausible, have since become insupportable in light of new and contradictory data generated over the years. Such data were generated sometimes by the original authors of the hypotheses and sometimes by other investigators. The hypotheses presented today are less likely to be supplanted because they are well conceived and have a strong mechanistic basis. The challenge for the future is the generation and interpretation of data relating the chemistry and biological activity associated with the dynamic and complex mixture of tobacco smoke.

scholarly journals The Composition of Cigarette Smoke. An Historical Perspective of Several Polycyclic Aromatic Hydrocarbons

2009 ◽  
Vol 23 (6) ◽  
pp. 384-410 ◽  
Author(s):  
A Rodgman ◽  
LC Cook
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Melting Point ◽  
Cigarette Smoke ◽  
Aromatic Hydrocarbons ◽  
Tobacco Smoke ◽  
Individual Component ◽  
Complex Mixtures ◽  
Polycyclic Aromatic ◽  
The Individual ◽  
Cigarette Mainstream Smoke

AbstractBecause of the significant advancements in fractionation, analytical, and characterization technologies since the early 1960s, hundreds of components of complex mixtures have been accurately characterized without the necessity of actually isolating the individual component. This has been particularly true in the case of the complex mixtures tobacco and tobacco smoke. Herein, an historical account of a mid-1950 situation concerning polycyclic aromatic hydrocarbons (PAHs) in cigarette smoke is presented. While the number of PAHs identified in tobacco smoke has escalated from the initial PAH, azulene, identified in 1947 to almost 100 PAHs identified by late 1963 to more than 500 PAHs identified by the late 1970s, the number of PAHs isolated individually and characterized by several of the so-called classical chemical means (melting point, mixture melting point, derivative preparation and properties) in the mid-1950s and since is relatively few, 14 in all. They were among 44 PAHs identified in cigarette mainstream smoke and included the following PAHs ranging from bicyclic to pentacyclic: Acenaphthylene, 1,2-dihydroacenaphthylene, anthracene, benz[a]anthracene, benzo[a]pyrene, chrysene, dibenz[a, h]anthracene, fluoranthene, 9H-fluorene, naphthalene, 1-methylnaphthalene, 2-methylnaphthalene, phenanthrene, and pyrene. One of them, benzo[a]pyrene, was similarly characterized in another study in 1959 by Hoffmann.

scholarly journals The Composition of Cigarette Smoke: A Chronology of the Studies of Four Polycyclic Aromatic Hydrocarbons

2006 ◽  
Vol 22 (3) ◽  
pp. 208-254
Author(s):  
A Rodgman ◽  
TA Perfetti
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Cigarette Smoke ◽  
Aromatic Hydrocarbons ◽  
Tobacco Smoke ◽  
Mouse Skin ◽  
Laboratory Animals ◽  
Current Evidence ◽  
United States Department ◽  
Polycyclic Aromatic ◽  
Skin Painting

AbstractAmong the polycyclic aromatic hydrocarbons (PAHs), a major class of identified cigarette mainstream smoke (MSS) components, are several shown to be tumorigenic in laboratory animals and suspect as possible tumorigens to humans. To date, nearly 540 PAHs have been completely or partially identified in tobacco smoke [Rodgman and Perfetti (1)]. A detailed chronology is presented of studies on four much discussed PAHs identified in tobacco smoke, namely, benz[a]anthracene (B[a]A), its 7,12-dimethyl derivative (DMB[a]A), dibenz[a, h]anthracene (DB[a, h]A), and benzo[a]pyrene (B[a]P). Of the four, DMB[a]A, DB[a, h]A, and B[a]P are considered to be potently tumorigenic on mouse skin painting and subcutaneous injection. Opinions on the tumorigenicity of B[a]A to mouse skin vary. DMB[a]A is frequently used in tumorigenicity studies as an initiator. Examination of the number of tobacco smoke-related citations listed for these four PAHs reveals the enormous effort devoted since the early 1950s to B[a]P vs. the other three. An annotated chronology from 1886 to date describes the tobacco smoke-related research pertinent to these four PAHs, their discovery, isolation and/or identification, quantitation, and contribution to the observed biological activity of MSS or cigarette smoke condensate (CSC). Much of the major literature on these four PAHs in tobacco smoke is presented in order to permit the reader to decide whether the current evidence is sufficient to classify them as a health risk to smokers. There has certainly been a tremendous effort by researchers to learn about these PAHs over the past several decades. Each of these PAHs when tested individually has been shown to possess the following biological properties: 1) Mutagenicity in certain bacterial situations, 2) tumorigenicity in certain animal species, to varying degrees under various administration modes, and 3) a threshold limit below which no tumorigenesis occurs. For more than five decades, it has been known that some of the PAHs, when co-administered in pairs of a potent tumorigen plus a non-tumorigen or weak tumorigen, show inhibitory effects on the tumorigenicity of the most potent, e.g., B[a]A plus DB[a, h]A; B[a]A plus B[a]P; anthracene plus DB[a, h]A. Over the period studied, some regulatory agencies considered these tobacco smoke PAHs to be serious health concerns, others did not.With respect to cigarette MSS, certainly the ‘danger is in the dose’ for any MSS component tested singularly to be tumorigenic. But is the level of any of these MSS PAHs high enough to be of concern to smokers? The information herein presented indicates that over the last five decades the following has occurred: 1) The per cigarette yields of these four PAHs have decreased substantially, 2) compared to CSC or Federal Trade Commission (FTC) ‘tar’, their per cigarette yields have also decreased to a point that they may be below any significance biologically, and 3) the specific tumorigenicity in mouse skin-painting studies of the CSC has decreased. These are the three criteria originally proposed to define the ‘less hazardous’ cigarette. Actually, criterion 1) was first directed only at B[a]P. Previous studies highlighted the concern that some regulatory bodies had in attempting to understand why lung cancer and other forms of cancer seemed more prevalent in smokers. But cigarette smoking alone could not reconcile the evidence. Social, ethnic, environmental, and economic factors are also very important in understanding the entire biological effect. In fact, the level of B[a]P in CSC could only explain about 2% of its specific tumorigenicity observed in skin-painted mice and the combination of the levels of all the known tumorigenic PAHs in CSC could only explain about 3% of its tumorigenicity. Despite an 18-month study in the late 1950s, the search for a ‘supercarcinogen’ in MSS and CSC to explain the observed biological effects was unsuccessful. In addition, the exceptional study on MSS PAHs by United States Department of Agriculture (USDA) personnel in the 1970s indicated no ‘supercarcinogen’ was present. Only recently has the concept of complex mixtures in relation to the understanding of the complexity of carcinogenesis taken hold. Perhaps the reason why MSS is less tumorigenic than expected in humans is because of the presence of other MSS components that inhibit or prevent tumorigenesis. For example, it is well known that MSS contains numerous anticarcinogens present in quantities significantly greater than those of the PAHs of concern. When one reviews the history of these four PAHs in MSS or CSC it is clear that many unanswered questions remain.

scholarly journals Studies of Polycyclic Aromatic Hydrocarbons in Cigarette Mainstream Smoke: Identification, Tobacco Precursors, Control of Levels: A Review

2001 ◽  
Vol 19 (7) ◽  
pp. 361-379 ◽  
Author(s):  
A Rodgman
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Aromatic Hydrocarbons ◽  
Tobacco Smoke ◽  
Laboratory Animals ◽  
Mainstream Smoke ◽  
Recent Letter ◽  
Tract Cancer ◽  
Polycyclic Aromatic ◽  
Cigarette Mainstream Smoke ◽  
Aza Arenes

AbstractDuring the period of tobacco smoke research from the early 1950s to the mid-1960s it was repeatedly asserted that a) tobacco and many tobacco components were involved in the pyrogenesis of polycyclic aromatic hydrocarbons (PAHs), several of which were reported to initiate tumors on the skin of laboratory animals and b) tobacco additives (flavorants, casing materials, humectants) were highly likely to be similarly involved in PAH pyrogenesis. Extensive knowledge on PAHs was deemed highly necessary because of their claimed importance in the smoking-health issue. The numerous assertions about the generation of PAHs in cigarette mainstream smoke (MSS) triggered extensive and intensive research both within and outside the Tobacco Industry to define the nature of the PAHs, their per cigarette MSS delivery amounts, their precursors, etc. It was not until 1960 that VAN DUUREN et al. (1) reported three specific aza-arenes in cigarette MSS that were asserted to be involved in smokers’ respiratory tract cancer. As noted in a recent Letter to the Editors (2), the presence of these three aza-arenes in tobacco smoke has never been confirmed. Between 1960 and 1965, other MSS components (phenols as promoters, polonium-210, N-nitrosamines, ciliastatic compounds) were asserted to be responsible for smoking related diseases. However, no major assertions were made that phenols, polonium-210, or the N-nitrosamines were derived from flavorants, casing materials, or humectants. Some investigators did report that several ciliastats were derived from added sugars and glycerol. The ciliastat proposal was drastically diminished in importance by the findings in the 1960s that only a relatively small proportion of the ciliastats reached the smoker's cilia. During that time, pertinent skills and competencies in research on tobacco smoke composition, particularly the PAH fraction, have been developed. Such skills permitted the isolation in crystalline form of 14 PAHs and the quantitation of these and many other PAHs. They were also used to put in perspective the pyrogenesis of PAHs from a) specific tobacco components, b) additives, and c) processed tobaccos (reconstituted tobacco sheet [RTS], expanded tobacco). R.J. Reynolds Tobacco Company (RJRT) pioneered the use of RTS (1953) and expanded tobaccos (1969) in cigarette blends and generated much previously unpublished data on the effect of such processed tobaccos on MSS composition.

scholarly journals The Complexity of Tobacco and Tobacco Smoke

2011 ◽  
Vol 24 (5) ◽  
pp. 215-232 ◽  
Author(s):  
TA Perfetti ◽  
A Rodgman
Keyword(s):  
Tobacco Smoke ◽  
Complex Mixture ◽  
Operational Definition ◽  
Biological Properties ◽  
Complex Mixtures ◽  
Chemical Components ◽  
Detailed Knowledge ◽  
Polycyclic Aromatic ◽  
Definition Of ◽  
Risk Potential

AbstractTobacco and tobacco smoke are both complex mixtures. We previously reported 8430 unique chemical components identified in these complex mixtures but two years later our updated number was 8889. Addition of unlisted isomers raised these numbers to 8622 and 9081, respectively. Our previous number of 4994 identified tobacco components is now 5229; our previous number of 5315 identified tobacco smoke components is now 5685. An operational definition of a complex mixture is as follows: A complex mixture is a characterizable substance containing many chemical components (perhaps thousands) in inexact proportions.Detailed knowledge of the amount and type of each component within the substance is uncertain even with today's analytical technology. Although it has been estimated that as many as 100000 components are present in these complex mixtures, their analyses indicate that the vast majority of the mass of each of these complex mixtures accounts for the 8430 compounds reported previously. Over 98.7% of the mass of tobacco has been accounted for in terms of identified components in tobacco. Greater than 99% of the mass of whole smoke has been accounted for based on identified chemical components. Certainly, many more tobacco and tobacco smoke components are present in these complex mixtures but the total mass of these components obviously is quite small.One of the significant challenges we face as a scientific community is addressing the problems of determining the risk potential of complex mixtures. Many issues are associated with toxicological testing of the complex mixture of tobacco smoke. Conducting valid experiments and interpreting the results of those experiments can be quite difficult. Not only is the test agent a complex mixture but also the tests are performed on species that have complicated life-processes. Interpretations of test results are often paradoxical. Significant progress has been made in the toxicological evaluations of complex mixtures in the last 80 years. The challenges we face in terms of testing the biological properties of tobacco smoke are substantial. The statement by DIPPLE et al. in their summary of the research on polycyclic aromatic hydrocarbons from the 1930s through 1980 is equally true today for the cigarette smoke situation:…many important questions remain unanswered…many questions persist despite the considerable progress that has been made.

scholarly journals Changes in Water Sorption and Solubility of Dental Adhesive Systems after Cigarette Smoke

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Lívia Andrade Vitória ◽  
Thaiane Rodrigues Aguiar ◽  
Poliana Ramos Braga Santos ◽  
Andrea Nóbrega Cavalcanti ◽  
Paula Mathias
Keyword(s):  
Cigarette Smoke ◽  
Tobacco Smoke ◽  
Water Sorption ◽  
Complex Mixture ◽  
Adhesive System ◽  
Deionized Water ◽  
Constant Mass ◽  
Single Bond ◽  
Adhesive Systems ◽  
Dental Adhesive

Aim. To evaluate the effect of cigarette smoke on water sorption and solubility of four adhesive systems. Materials and Methods. Sixteen disks of each adhesive system were prepared (Adper Scotchbond Multipurpose Adhesive (SA); Adper Scotchbond Multipurpose Adhesive System (Adhesive + Primer) (SAP); Adper Single Bond Plus (SB); Adper Easy One (EO)). Specimens were desiccated until a constant mass was obtained and divided into two groups (n=8). One-half of the specimens were immersed in deionized water, while the other half were also immersed, but with daily exposure to tobacco smoke. After 21 days, disks were measured again and stored in desiccators until constant mass was achieved. Data were calculated according to ISO specifications and statistically analyzed. Results. The tobacco smoke only significantly affected the water sorption and solubility of EO. There were significant differences in both analyses among materials tested. The SB exhibited the highest water sorption, followed by EO, which demonstrated significantly higher solubility values than SB. The SA and SAP showed low water sorption and solubility, and there were no significant differences between the two. Conclusion. Regardless of smoke exposure, both simplified adhesive systems presented an inferior performance that could be related to the complex mixture of components in such versions.

scholarly journals The Composition of Cigarette Smoke: A Catalogue of the Polycyclic Aromatic Hydrocarbons

2006 ◽  
Vol 22 (1) ◽  
pp. 13-69 ◽  
Author(s):  
A Rodgman ◽  
TA Perfetti
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Cigarette Smoke ◽  
Aromatic Hydrocarbons ◽  
Tobacco Smoke ◽  
Air Pollutants ◽  
Consumer Product ◽  
Laboratory Animals ◽  
Polycyclic Aromatic ◽  
The Relationship

AbstractClassified as toxicants in many of the substances to which humans are exposed are the polycyclic aromatic hydrocarbons (PAHs). Such exposures include air pollutants from a variety of sources, foodstuffs and beverages, and tobacco smoke. Since the early 1950s, the composition of the latter has been more completely defined than that of any other consumer product. Nearly 4800 components have been identified in tobacco smoke and among these are over 500 PAHs either completely or partially identified. Because of the tumorigenicity of many PAHs, much research has been conducted in attempts to define the relationship between the PAH structures and their specific tumorigenicities in laboratory animals. None of the theories to date completely answers all the questions.As a prelude to an attempt to develop a more reasonable PAH structure-tumorigenicity relationship, the PAHs completely or partially identified in cigarette smoke have been catalogued. In the catalogue, they are categorized as bicyclic, tricyclic, tetracyclic, etc. with each group subdivided into all-benzenoid PAHs and cyclopentanoid-benzenoid PAHs. Another tabulation includes the PAHs considered in several previous studies on structure-tumorigenicity relationships, studies that dealt primarily with all-benzenoid PAHs.

scholarly journals An Analysis of the Role of Tobacco-Specific Nitrosamines in the Carcinogenicity of Tobacco Smoke

2003 ◽  
Vol 1 (2) ◽  
pp. 154014203914343 ◽  
Author(s):  
Buddy G. Brown ◽  
August J. Borschke ◽  
David J. Doolittle
Keyword(s):  
Cigarette Smoke ◽  
Dna Adducts ◽  
Tobacco Smoke ◽  
Complex Mixture ◽  
Tobacco Smoke Exposure ◽  
In Vivo Studies ◽  
Laboratory Animals ◽  
Causative Role ◽  
Mainstream Smoke ◽  
Tobacco Specific Nitrosamines

Cigarette smoke is a complex mixture consisting of more than 4500 chemicals, including several tobacco-specific nitrosamines (TSNA). TSNA typically form in tobacco during the post-harvest period, with some fraction being transferred into mainstream smoke when a cigarette is burned during use. The most studied of the TSNA is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK has been shown to be carcinogenic in laboratory animals. Studies examining the carcinogenicity of NNK frequently are conducted by injecting rodents with a single dose of 2.5 to 10 μmol of pure NNK; the amount of NNK contained in all of the mainstream smoke from about 3700 to 14,800 typical U.S. cigarettes. Extrapolated to a 70-kg smoker, the carcinogenic dose of pure NNK administered to rodents would be equivalent to the amount of NNK in all of the mainstream smoke of 22 to 87 million typical U.S. cigarettes. Furthermore, extrapolating results from rodent studies based on a single injection of pure NNK to establish a causative role for NNK in the carcinogenicity of chronic tobacco smoke exposure in humans is not consistent with basic pharmacological and toxicological principles. For example, such an approach fails to consider the effect of other smoke constituents upon the toxicity of NNK. In vitro studies demonstrate that nicotine, cotinine, and aqueous cigarette “tar” extract (ACTE) all inhibit the mutagenic activity of NNK. In vivo studies reveal that the formation of pulmonary DNA adducts in mice injected with NNK is inhibited by the administration of cotinine and mainstream cigarette smoke. Cigarette smoke has been shown to modulate the metabolism of NNK, providing a mechanism for the inhibitory effects of cigarette smoke and cigarette smoke constituents on NNK-induced tumorigenesis. NNK-related pulmonary DNA adducts have not been detected in rodents exposed to cigarette smoke, nor has the toxicity of tobacco smoke or tobacco smoke condensate containing marked reductions in TSNA concentrations been shown to be reduced in any biological assay. In summary, there is no experimental evidence to suggest that reduction of TSNA will reduce the mutagenic, cytotoxic, or carcinogenic potential of tobacco smoke.

scholarly journals High-Risk Human Papillomavirus and Tobacco Smoke Interactions in Epithelial Carcinogenesis

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2201 ◽  
Author(s):  
Francisco Aguayo ◽  
Juan P. Muñoz ◽  
Francisco Perez-Dominguez ◽  
Diego Carrillo-Beltrán ◽  
Carolina Oliva ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Tobacco Smoke ◽  
Molecular Mechanisms ◽  
Complex Mixture ◽  
Epidemiological Studies ◽  
Hpv Infection ◽  
Oncogenic Viruses ◽  
Cancer Initiation ◽  
Physical Environmental Factors

Cervical, anogenital, and some head and neck cancers (HNC) are etiologically associated with high-risk human papillomavirus (HR-HPV) infection, even though additional cofactors are necessary. Epidemiological studies have established that tobacco smoke (TS) is a cofactor for cervical carcinogenesis because women who smoke are more susceptible to cervical cancer when compared to non-smokers. Even though such a relationship has not been established in HPV-related HNC, a group of HPV positive patients with this malignancy are smokers. TS is a complex mixture of more than 4500 chemical compounds and approximately 60 of them show oncogenic properties such as benzo[α]pyrene (BaP) and nitrosamines, among others. Some of these compounds have been evaluated for carcinogenesis through experimental settings in collaboration with HR-HPV. Here, we conducted a comprehensive review of the suggested molecular mechanisms involved in cooperation with both HR-HPV and TS for epithelial carcinogenesis. Furthermore, we propose interaction models in which TS collaborates with HR-HPV to promote epithelial cancer initiation, promotion, and progression. More studies are warranted to clarify interactions between oncogenic viruses and chemical or physical environmental factors for epithelial carcinogenesis.

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