Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 73
3 Evidence Base and Methods for Studying Health Effects Decades of research on the health effects of tobacco use have generated overwhelming evidence to support the conclusion that tobacco use causes disease. An inference of causality requires evidence along the causal path- way from exposure to disease, including evidence on the effects of tobacco from experimental and observational study designs, and from investiga- tions into the biological mechanisms of disease. A widely cited criteria for making a causal inference in epidemiology and public health are the Hill Criteria (Weed, 2000). The judgment that tobacco use causes diseases such as lung cancer and heart disease has been based on evidence from a wide range of investigations that fulfill the requirements of the Hill Criteria. This has been thoroughly reviewed and documented in reports of the Surgeon General on tobacco, such as the 2004 and 2010 reports (HHS, 2004a, 2010). The evaluation of the health effects and mechanisms of modified risk tobacco products (MRTPs) is a closely related enterprise. Development of many MRTPs will be based on existing evidence and knowledge of the mechanisms of tobacco-related disease. In general, MRTPs are designed to remove or block a step in the causal pathway between tobacco expo- sure and disease. As such, evidence about how an MRTP intervenes on the causal pathways for tobacco-related disease will be critical. However, inferences about the health effects of an MRTP based on prior knowledge of the causal pathways of tobacco disease, while relevant, will not be sufficient to inform regulatory decisions. Independent evidence on the health effects of the MRTP will be necessary. The study of the health effects of tobacco use can provide an illustrative precedent for the evalua- 73
OCR for page 74
74 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS tion of MRTPs. The same range of research methods employed to establish a causal relationship between tobacco and disease will be needed to pro - vide evidence on the health effects of MRTPs on both individual and pub- lic health. This chapter discusses that evidence and provides guidance on how the Food and Drug Administration (FDA) should consider different types of that evidence in its decision-making process. The chapter begins with a discussion of the composition of modified tobacco products. The committee then discusses biomarkers of MRTPs, including biomarkers of exposure and biomarkers of effects. Next, it discusses preclinical and clinical studies, including the advantages and disadvantages of those studies, and what evidence the various study types can provide to inform the FDA’s decisions on MRTPs. PRODUCT COMPOSITION Smokeless tobacco products, such as oral snuff, and combusted tobacco products, such as cigarettes, are the main types of tobacco prod- ucts used in the United States (SAMHSA, 2007). The composition of tobacco and tobacco smoke has been the subject of intense study for at least the past 60 years, and studies have identified more than 8,000 con - stituents of tobacco and tobacco smoke (Rodgman and Perfetti, 2009). Validated methods are available to quantify many constituents of tobacco and tobacco smoke (Borgerding and Klus, 2005; Rodgman and Perfetti, 2009), and the chemical composition can have a large effect on the poten- tial health risks of a given product. Product composition, including how the constituents compare to other products, therefore, is an important aspect of any new product. Although different tobacco products continue to be introduced, this section discusses the types of tobacco products currently available, the methods for analyzing them, and the commonly reported constituents. Smokeless products are discussed first, followed by a discussion of combusted products. Smokeless Tobacco Products Types of Smokeless Products Smokeless tobacco products used in the United States include moist snuff and chewing tobacco (for oral use), and dry snuff (for nasal use). Types of chewing tobacco include plug, twist, and loose leaf varieties. The use of chewing tobacco and dry snuff has declined over time. Oral moist snuff is by far the most popular kind of smokeless tobacco in the United States (Federal Trade Commission, 2007). Oral moist snuff is used by placing the tobacco—either loose or packaged in a tea bag–like sachet—
OCR for page 75
75 METHODS FOR STUDYING HEALTH EFFECTS in the space between the cheek and gum, or lip and gum. Generally, oral moist snuff is not chewed. Brands such as Copenhagen and Skoal, manufactured by Altria Group, Inc., and Grizzly and Kodiak, marketed by Reynolds American, Inc., are common. The use of any form of smokeless tobacco has declined substantially between 1986 and 2003 (Nelson et al., 2006); in this time period, there was an approximately 5 percent decrease in overall smokeless tobacco sales (in pounds) (Federal Trade Commission, 2007). However, the use of moist snuff or dip increased by approximately 87 percent over the same period (Nelson et al., 2006). In 2005, total dollar sales for moist snuff accounted for more than 80 percent of total sales for smokeless tobacco (Federal Trade Commission, 2007). In 2008, 3.5 percent of Americans aged 12 or older (0.4 percent of women aged 12 or older and 6.8 percent of men aged 12 or older) had used a smokeless tobacco product in the previous month (SAMHSA, 2011). Moist snuff for oral use contains both high salt and high moisture content (Stepanov et al., 2010). When placed in the oral cavity, the product generates excess saliva, usually requiring spitting. Recently, the tobacco industry has introduced and promoted spit-free smokeless tobacco prod- ucts. These new products, such as Camel Snus and Marlboro Snus, con- tain low moisture content and are distributed in small pouches of flavored tobacco. The products have been marketed to current cigarette smokers for situations where smoking is prohibited (Hatsukami et al., 2007a). These products have design features in common with snus products that have been used in Sweden for many years. Users of Swedish Snus place the product between the gum and upper lip; it does not usually stimulate salivation. Other new smokeless tobacco products continue to appear. These include dissolvable products such as Camel Orbs (a pellet), Camel Sticks (a twisted toothpick-size stick), and Camel Strips (a film strip placed on the tongue). All of those new products are made from finely ground flavored tobacco (Rainey et al., 2011). Methods of Analysis Methods of analysis of the components of smokeless tobacco are stan- dardized (IARC, 2007; Richter and Spierto, 2003; Richter et al., 2008; Song and Ashley, 1999; Stepanov and Hecht, 2005; Stepanov et al., 2008, 2010). Smokeless tobacco analyses include analyses for moisture content, pH, and components. Moisture content can be determined by the difference in weight before and after drying. For measurement of pH, the tobacco is extracted with water and the pH is determined with a pH meter. Nicotine can be determined by extraction of the tobacco and analysis by combined gas chromatography-mass spectrometry (GC-MS) or high-performance
OCR for page 76
76 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS liquid chromatography-mass spectrometry (LC-MS). Minor tobacco alka- loids such as nornicotine and anatabine are extracted, derivatized by reductive alkylation, and determined by gas chromatography-tandem mass spectrometry (GC-MS/MS). Tobacco-specific N-nitrosamines (TSNAs) are extracted and analyzed by either gas chromatography with nitrosamine selective detection or by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Both conventional and supercritical fluid extractions have been used. Polycyclic aromatic hydrocarbons can be quantified by extraction with cyclohexane followed by solid-phase extraction and GC-MS. Aldehydes are measured by extraction, derivatiza- tion with 2,4-dinitrophenylhydrazine, and GC-MS. Anions such as nitrate, nitrite, and chloride are determined by anion exchange with conductivity detection. Laboratory analysis of constituents in these products would be a standard first step in the initial evaluation of any new product. These analyses are generally quite straightforward involving standard methods of extraction, sample cleanup, analyte identification, and quantitation. Data from diverse laboratories involved in the analysis of various prod- ucts give comparable results for most analytes. There are differences in the literature in the manner in which the analytical data are expressed. Some investigators have expressed their data per dry weight of product, while others use wet weight, or even portion size. Because traditional moist snuff products typically contain about 50 percent water, it is crucial to recognize the manner in which the data are being expressed and to take this into consideration when making judgments on constituent levels. The expression of constituent levels per dry weight of product, with inclu - sion of data on water content is standard (Stepanov et al., 2008). Because portion sizes are fixed in the products encased in tea bag–like sachets, it is also important to report constituent levels per portion size for these products. Laboratory analysis of constituents, however, may not reflect con- stituent uptake under conditions of use. Biomarker of exposure studies, described below, provide a more realistic indication of exposure. Commonly Reported Constituents Thousands of compounds have been identified in unburned tobacco (Rodgman and Perfetti, 2009), but routine analyses of smokeless tobacco have focused on relatively few of these compounds thought to be critical in its biological activities (IARC, 2007; Richter and Spierto, 2003; Richter et al., 2008; Song and Ashley, 1999; Stepanov and Hecht, 2005; Stepanov et al., 2008, 2010). Commonly reported constituents include TSNAs, nicotine and minor tobacco alkaloids, nitrite, nitrate
OCR for page 77
77 METHODS FOR STUDYING HEALTH EFFECTS and other anions, metals, aldehydes, and polycyclic aromatic hydro- carbons. Nicotine is generally reported as protonated and unprotonated (determined by measuring pH of the product). This is important because unprotonated nicotine is absorbed more readily through the oral mucosa than protonated nicotine. Plasma nicotine levels are directly related to pH of the product: higher pH values lead to higher levels of plasma nicotine (IARC, 2007). Minor tobacco alkaloids might, along with nicotine, con- tribute to addiction. Unlike cigarette smoke, the most common strong carcinogens in smokeless tobacco products are TSNAs. Extensive data demonstrating their presence in parts per million quantities, greater than nitrosamine concentrations in any other consumer product intended for oral use, are available (IARC, 2007; Richter et al., 2008; Stepanov et al., 2008). Levels of polycyclic aromatic hydrocarbons and aldehydes have been less frequently reported (Stepanov et al., 2008, 2010). There is solid evidence that nicotine is addictive, but little evidence of addictive potential for other constituents of smokeless tobacco products. With respect to the induction of cancer, it is suspected but not proven that TSNAs play a major role, while other compounds such as polycyclic aromatic hydrocarbons and aldehydes may also contribute. There may be other unidentified or unrecognized compounds in smokeless tobacco that contribute in important ways to its adverse health effects. Among the thousands of identified compounds in smokeless tobacco products, the 28 currently identified carcinogens represent only a small fraction (IARC, 2007; Rodgman and Perfetti, 2009). Furthermore, seemingly innocuous compounds such as sodium chloride, which occurs in amounts more than 5 percent in some smokeless tobacco products (IARC, 2007), could exacerbate the effects of carcinogens by leading to local irritation, among other effects (Stepanov et al., 2008). Combusted Products Types of Products Cigarettes are by far the most used combusted tobacco product. In 2009, there were more than 46 million cigarette smokers in the United States, about 20.6 percent of the adult population (CDC, 2010). Between the mid-1960s and 2004, cigarette smoking among adults decreased from approximately 42 percent to 21 percent; however, prevalence has not changed substantially since then (CDC, 1999, 2011b). Additionally, after substantial declines (66 percent) in cigar consumption from 1964 to 1993, consumption rates for cigars increased by close to 50 percent from 1993 to 1997 (NCI, 1998). In 2010, 5.2 percent of Americans aged 12 or older
OCR for page 78
78 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS had smoked cigars in the past month (SAMHSA, 2011). Other combusted products include pipes and water pipes. Methods of Analysis Because combusted products are burned, their constituents cannot simply be extracted as with smokeless tobacco products. Various machine methods attempt to simulate the smoking of tobacco products, and the smoke is collected and analyzed (IARC, 2004). Different organizations use different methods for generating smoke. For example, the International Organization for Standardization and the U.S. Federal Trade Commission smoking regimen uses a 35 mL puff every 60 seconds, and a puff dura- tion of 2 seconds, with the filter ventilation holes (if present) open. Health Canada uses an intense smoking regimen with a 55 mL puff every 30 sec - onds, and a puff duration of 2 seconds, with the filter ventilation holes completely blocked. The Massachusetts Department of Health method has a 45 mL puff every 30 seconds, and a puff duration of 2 seconds, with the filter ventilation holes 50 percent blocked. It is widely recognized that none of these methods accurately reproduces the many ways smokers actually use cigarettes, but the methods can be used for comparison of one product to another (IARC, 2004). Researchers can collect and analyze both mainstream smoke, which emanates from the filter end of the cigarette, and sidestream smoke, which emanates mainly from the burning tip of the product. For collec - tion, a glass fiber filter separates arbitrarily gas phase constituents from total particulate matter, which collects on the filter (Adam et al., 2006). Once the combusted material is collected, the methods of analysis of the various constituents of cigarette smoke have some similarities to those used for smokeless tobacco. Because the products of combustion are generally more complex than those obtained by extraction of unburned tobacco, multiple extraction or purification steps are often necessary before the analysis can be completed, usually by GC-MS or LC-MS/MS techniques (IARC, 2004). Laboratory analyses by machine smoking would be a standard first step in the initial evaluation of any new product, even though it is widely recognized that this approach has limitations. Machine smoking methods do not replicate human smoking conditions because smokers may vary their way of smoking a cigarette depending on many factors. Important among these is the well-established phenomenon of compensation, in which smokers may alter their method of smoking in order to compensate for lower machine measured amounts of nicotine and other constituents. They accomplish this in a number of different ways including increasing puff number or volume and blocking filter vents (NCI, 2001). Under a
OCR for page 79
79 METHODS FOR STUDYING HEALTH EFFECTS given set of machine smoking conditions, analyses of particular con- stituents are generally well standardized leading to reasonable agreement in constituent levels among different laboratories. However, formalized interlaboratory comparisons have only been carried out for a few con - stituents. When reporting constituent levels for any product, it is crucial to describe the type of smoking regimen that has been used. There is no proven method to replicate the many ways humans smoke cigarettes. The World Health Organization, under the Framework Con- vention on Tobacco Control, has adopted the approach of expressing machine-measured constituents per mg of nicotine for use in regulation, because this would presumably mitigate some of the effects of compensa - tion (Burns et al., 2008). However, this approach is untested in a regula - tory setting. The measurement of smoke constituents can be challenging. Even measurement of parameters seemingly as simple as pH and free nicotine have led to controversy (Chen and Pankow, 2009; Pankow et al., 2003). Commonly Reported Constituents The FDA has developed a list of “harmful and potentially harmful constituents in tobacco products and tobacco smoke” that includes more than 100 constituents from various classes of chemicals (FDA, 2011a, 2011c). These include “tar,” nicotine and minor tobacco alkaloids, car- bon monoxide (CO), nitrogen oxides, polycyclic aromatic hydrocarbons, TSNAs, volatile nitrosamines, aldehydes, aromatic amines, metals, phenols, ketones, volatile hydrocarbons such as benzene and butadi- ene, ethylene and propylene oxide, furan, hydrazine, hydrogen cyanide, heterocyclic aromatic amines, nitrogen compounds, pyridine, vinyl chlo - ride, polonium-210, and others. The majority of these constituents have been routinely analyzed, and extensive data are available on their con - centrations in tobacco smoke (Chen and Moldüveanu, 2003; Counts et al., 2004; Ding et al., 2006, 2007; Gregg et al., 2004; Hammond and O’Connor, 2008; IARC, 2004; Roemer et al., 2004). Furthermore, the same considerations discussed above with respect to smokeless tobacco apply to combusted products. It is not certain that the current list of harmful and potentially harmful constituents is complete. There may be other constituents among the more than 8,000 in tobacco and tobacco smoke (Rodgman and Perfetti, 2009) that are important but currently unrecognized. It is also known that there are interactions between carcinogens and tumor promoters or cocarcinogens that may not be recognized when simply analyzing a list of compounds (HHS, 2010; IARC, 2004).
OCR for page 80
80 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS Summary of Product Composition Analysis of smokeless tobacco products or combusted products can be achieved using standardized and validated methods for a variety of constituents. Although there could be some inter-laboratory differences in results of these analyses, most data are generally comparable for a given product. In the analysis of smokeless tobacco products, the method of extraction and the method of expressing the results need to be taken into account when comparing data. In the analysis of combusted products, the method of machine smoking is critical when comparisons are to be made. None of the standard machine smoking methods replicate human smoking conditions, but these methods can be useful for comparison of different products under comparable conditions. BIOMARKERS Studies of tobacco and tobacco-related diseases use a number of differ- ent biomarkers, and the validity of those biomarkers are key to the validity of the studies; biomarkers will continue to play an important role in the FDA’s regulation of MRTPs. The FDA will be making regulatory decisions about the marketing of MRTPs in the immediate future, but the latency period between tobacco exposure and the development of major clinical adverse health consequences is usually quite long. Validated biomarkers and other surrogates of tobacco-related disease outcomes that can provide information over a shorter time frame, therefore, will play a critical role in the evaluation of MRTPs. The Family Smoking Prevention and Tobacco Control Act of 2009 (FSPTCA) highlights the importance of addressing biomarkers and surrogates when it specifies that regulations or guidance issued by the Agency shall “include validated biomarkers, intermediate clinical endpoints, and other feasible outcome measures, as appropriate.”1 Terminology around biomarkers can be a controversial issue. Over the course of evaluating both the statutory language and the prevailing literature, the committee encountered inconsistencies in the definitions for terms central to this discussion, including the terms “biomarker,” “surrogate,” “intermediate endpoint,” and “endpoint.” The committee also found it important to differentiate between biomarkers of exposure and biomarkers of effect or risk. In this report, the committee broadly categorizes biomarkers as biomarkers of exposure and biomarkers of risk, and further distinguishes among specific types of biomarkers of risk. Spe- cifically, the committee adopts the definitions articulated in the Institute 1 Family Smoking Prevention and Tobacco Control Act of 2009, Public Law 111-31, 123 Stat. 1776 (June 22, 2009).
OCR for page 81
81 METHODS FOR STUDYING HEALTH EFFECTS BOX 3-1 Definitions Related to Biomarkers, Clinical Endpoints, and Surrogate Endpoints Biomarker: A characteristic that is objectively measured and evaluated as an indicator of normal biological responses, pathogenic processes, or pharmacologic responses to an intervention. Biomarker of exposure: The chemical, or its metabolite, or the product of an interaction between a chemical and some target molecule or cell, that is measured in a compartment in an organism. Biomarker of risk: A biomarker that indicates a risk factor for a disease. Clinical endpoint: A characteristic or variable that reflects how a patient or con- sumer feels, functions, or survives. Surrogate endpoint: A biomarker that is intended to substitute for a clinical end- point. A surrogate endpoint is expected to predict clinical benefit (or harm or lack of benefit or harm) based on epidemiologic, therapeutic, pathophysiologic, or other scientific evidence. SOURCE: Adapted from IOM (2010). of Medicine’s (IOM’s) 2010 report, Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease (IOM, 2010). Relevant definitions from that report are presented in Box 3-1. Biomarkers of exposure and biomarkers of risks are discussed below. Biomarkers of Exposure Biomarkers of human exposure to specific constituents of tobacco products may be the constituents themselves; metabolites of the constitu - ents in urine, blood, breath, saliva, nails, or hair; or protein- or DNA- binding products (adducts) of the constituents or their metabolites. These biomarkers have the potential to bypass many of the uncertainties in product analysis and provide a realistic and direct assessment of car- cinogen and toxicant dose in an individual. It should be emphasized however that the biomarkers discussed here are virtually all biomarkers of exposure to specific tobacco or tobacco smoke constituents. In most cases, they have not been validated as biomarkers of risk. Furthermore, these biomarkers are derived from specific constituents of tobacco prod- ucts thought to be harmful to the consumer, but there may be unknown
OCR for page 82
82 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS or unmeasured constituents that are also harmful, or there may be com - bination effects of individual constituents that cannot be recognized by measurement of individual biomarkers of exposure. Presently, there is no single accepted biomarker that predicts the risk of disease in people who use tobacco products. Analytical Validation These biomarkers of exposure to tobacco toxicants and carcinogens are most frequently quantified by LC-MS/MS, GC-MS/MS, and related techniques. The first step in validation is analytical validation. This topic has been previously discussed in detail in a recent IOM report (IOM, 2010). Chapters of this 2010 report are provided in Appendix B. Validation with Respect to Product Use The second step in validation of a biomarker of exposure to tobacco toxicants and carcinogens is demonstrating that the biomarker is actu - ally related to tobacco product exposure. The most reliable method of demonstrating this relationship is to assess levels of the biomarker after a research participant has stopped using the tobacco product. In one representative study, researchers assessed at various times (3, 7, 14, 21, 28, 42, and 56 days) the persistence of eight tobacco smoke carcinogens and toxicant biomarkers in the urine of 17 people who had stopped smoking. The biomarkers were metabolites of 1,3-butadiene, acrolein, crotonaldehyde, benzene, ethylene oxide, pyrene (a representative poly - cyclic aromatic hydrocarbon), and nicotine-derived nitrosamine ketone (NNK), a TSNA. These biomarkers, which are described in more detail below, include some of the major carcinogens and toxicants present in cigarette smoke. Levels of all these biomarkers—except for 1,3-butadiene metabolites (called dihydroxybutyl mercapturic acid)—decreased signifi - cantly after 3 days of smoking cessation (P < .001). The rates of decrease for most of the biomarkers were rapid, reaching nearly their ultimate levels (81–91 percent reduction) after 3 days, while that of the NNK metabolite (called 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol and its glucuronides [total NNAL]) was gradual, reaching a 92 percent reduc- tion after 42 days. The decrease in the pyrene metabolite was variable among research participants, reaching about 50 percent of baseline, con- sistent with other common environmental sources of pyrene, such as diet. These results demonstrated that all biomarkers investigated in this study except dihydroxybutyl mercapturic acid were related to cigarette smoking (Carmella et al., 2009). A similar study carried out in smokeless tobacco users demonstrated the reduction of total NNAL after cessation of product use (Hecht, 2002).
OCR for page 83
83 METHODS FOR STUDYING HEALTH EFFECTS Another method of validating tobacco carcinogen and toxicant bio- markers with respect to tobacco product exposure is to compare their levels in smokers and nonsmokers. Numerous studies of this type have been reported, and individual biomarkers are described in an upcoming section and presented in Table 3-1. Biomarkers of exposure of tobacco- specific compounds such as NNK, N-nitrosonornicotine (NNN), and nico- tine are not found in non-tobacco users unless they have been exposed to secondhand tobacco smoke (see Table 3-1). Other biomarkers, such as those related to combustion products such as pyrene, are detected in both smokers and nonsmokers because they occur not only in tobacco prod- ucts, but also in the diet and polluted air. Therefore, some of the ranges of values overlap between smokers and nonsmokers, as shown in Table 3-1. However, biomarker levels are consistently higher in smokers compared to those in nonsmokers in individual studies (Hecht et al., 2010). Bio- markers of the tobacco-specific compounds are similar in smokers and smokeless tobacco users, while those of some of the volatile organic combustion products are considerably lower in smokeless tobacco users (Hecht, 2002; Hecht et al., 2010). Exposure to secondhand cigarette smoke can contribute to biomarker levels in nonsmokers, but the levels are generally small, about 1–5 per- cent of the levels in smokers (Hecht et al., 2010). Some biomarkers that are consistently elevated in nonsmokers exposed to secondhand tobacco smoke are cotinine, a major metabolite of nicotine, and NNAL and its glucuronides, metabolites of NNK (Hecht, 2002, 2003b; HHS, 2006). Cut points in these biomarkers for distinguishing light smokers from non- smokers exposed to secondhand smoke have been discussed (Goniewicz et al., 2011). Validation with Respect to Disease Risk One approach to determining the relationship of exposure biomarkers to disease risk is to carry out prospective epidemiologic studies, or cohort studies. In these studies, samples from healthy research participants are collected and stored, and demographic and lifestyle data are obtained using questionnaires. The participants are then followed for years, and eventually diseases such as cancers will occur in some of them. The stored samples from these research participants are retrieved, along with samples from appropriately matched controls that remain disease free, to form a nested case-control study. These samples can be analyzed for the biomarkers to determine their relationship to disease. The magnitude of the relationship to disease risk for each biomarker or their combinations can be evaluated using standard statistical analysis methods. Although there are certain limitations of this approach, which have been discussed
OCR for page 138
138 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS Hecht, S. S. 2003b. Carcinogen derived biomarkers: Applications in studies of human expo - sure to secondhand tobacco smoke. Tobacco Control 13(Suppl. 1):i48-i56. Hecht, S. S. 2008. Progress and challenges in selected areas of tobacco carcinogenesis. Chemi- cal Research in Toxicology 21:160-171. Hecht, S. S. 2010. Tobacco smoke carcinogens and lung cancer. In Chemical carcinogenesis, edited by T. M. Penning. New York: Springer. Hecht, S. S., A. Rivenson, J. Braley, J. DiBello, J. D. Adams, and D. Hoffmann. 1986. Induction of oral cavity tumors in F344 rats by tobacco-specific nitrosamines and snuff. Cancer Research 46(8):4162-4166. Hecht, S. S., M. Chen, A. Yoder, J. Jensen, D. Hatsukami, C. Le, and S. G. Carmella. 2005. Longitudinal study of urinary phenanthrene metabolite ratios: Effect of smoking on the diol epoxide pathway. Cancer Epidemiology, Biomarkers & Prevention 14(12):2969-2974. Hecht, S. S., J. M. Yuan, and D. Hatsukami. 2010. Applying tobacco carcinogen and toxicant biomarkers in product regulation and cancer prevention. Chemical Research in Toxicol- ogy 23(6):1001-1008. Herrold, K. M., and L. J. Dunham. 1962. Induction of carcinoma and papilloma of the Syrian hamster by intratracheal instillation of benzo[a]-pyrene. Journal of the National Cancer Institute 28:467-491. HHS (U.S. Department of Health and Human Services). 2004a. The health consequences of smoking: A report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, Center for Health Promotion and Education, Office on Smoking and Health. HHS. 2004b. Report on carcinogens, 11th edition. Research Triangle Park, NC: HHS, National Toxicology Program. HHS. 2006. The health consequences of involuntary exposure to tobacco smoke: A report of the Sur - geon General. Washington, DC: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. HHS. 2010. How tobacco smoke causes disease: The biology and behavioral basis for smoking-attrib - utable disease: A report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. Hirsch, J. M., and S. L. Johansson. 1983. Effect of long-term application of snuff on the oral mucosa: An experimental study in the rat. Journal of Oral Pathology 12(3):187-198. Hirsch, J. M., and H. Thilander. 1981. Snuff-induced lesions of the oral mucosa—an experi - mental model in the rat. Journal of Oral Pathology 10(5):342-353. Hirsch, J. M., S. L. Johansson, and A. Vahlne. 1984. Effect of snuff and herpes simplex virus-1 on rat oral mucosa: Possible associations with the development of squamous cell carci - noma. Journal of Oral Pathology 13(1):52-62. Hoffmann, D., and J. D. Adams. 1981. Carcinogenic tobacco-specific N-nitrosamines in snuff and in the saliva of snuff dippers. Cancer Research 41(11 Pt 1):4305-4308. Hoffmann, D., and E. L. Wynder. 1971. A study of tobacco carcinogenesis. XI. Tumor initia - tors, tumor accelerators, and tumor promoting activity of condensate fractions. Cancer 27(4):848-864. Hoffmann, D., A. Castonguay, A. Rivenson, and S. S. Hecht. 1981. Comparative carcino - genicity and metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N ′- nitrosonornicotine in Syrian golden hamsters. Cancer Research 41(6):2386-2393. Hoffmann, D., A. Rivenson, and S. S. Hecht. 1992. Carcinogenesis of smokeless tobacco. In NCI smoking and tobacco control monograph. Vol. 92-3461. Bethesda, MD: National Cancer Institute, National Institutes of Health.
OCR for page 139
139 METHODS FOR STUDYING HEALTH EFFECTS Hoffmann, K., K. Becker, C. Friedrich, D. Helm, C. Krause, and B. Seifert. 2000. The German environmental survey 1990/1992 (GerES II): Cadmium in blood, urine and hair of adults and children. Journal of Exposure Analysis and Environmental Epidemiology 10:126-135. Homburger, F. 1971. Mechanical irritation, polycyclic hydrocarbons, and snuff. Effects on facial skin, cheek pouch, and oral mucosa in Syrian hamsters. Archives of Pathology 91(5):411-417. Hukkanen, J., P. Jacob, III, and N. L. Benowitz. 2005. Metabolism and disposition kinetics of nicotine. Pharmacological Reviews 57(1):79-115. Hutt, J. A., B. R. Vuillemenot, E. B. Barr, M. J. Grimes, F. F. Hahn, C. H. Hobbs, T. H. March, A. P. Gigliotti, S. K. Seilkop, and G. L. Finch. 2005. Life-span inhalation exposure to mainstream cigarette smoke induces lung cancer in B6C3F1 mice through genetic and epigenetic pathways. Carcinogenesis 26(11):1999. Huvenne, W., E. A. Lanckacker, O. Krysko, K. R. Bracke, T. Demoor, P. W. Hellings, G. G. Brusselle, G. F. Joos, C. Bachert, and T. Maes. 2011. Exacerbation of cigarette smoke- induced pulmonary inflammation by Staphylococcus aureus enterotoxin B in mice. Respiratory Research 12:69. IARC (International Agency for Research on Cancer). 1985. Tobacco habits other than smoking; betel-quid & areca-nut chewing; and some related nitrosamines. In IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 37. Lyon, France: IARC. IARC. 1987. Overall evaluations of carcinogenicity: An updating of IARC monographs vol - umes 1 to 42. In IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans, suppl. 7. Lyon, France: IARC. Pp. 91-122. IARC. 1995. Acrolein. In IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 63. Lyon, France: IARC. Pp. 337-391. IARC. 1999a. Beryllium, cadmium, mercury, and exposures in the glass manufacturing industry. In IARC monographs on the evaluation of carcinogenic risks to humans . Vol. 58. Lyon, France: IARC. Pp. 119-237. IARC. 1999b. Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide (part one). In IARC monographs on the evaluation of carcinogenic risks to humans . Vol. 71. Lyon, France: IARC. Pp. 43-108. IARC. 2004. IARC monographs on the evaluation of carcinogenic risks to humans: Volume 83. Tobacco smoke and involuntary smoking. Lyon, France: IARC. IARC. 2006. Formaldehyde, 2-butoxyethanol and 1- tert -butoxypropan-2-ol. In IARC mono- graphs on the evaluation of carcinogenic risks to humans, vol. 88. Lyon, France: IARC. Pp. 37-325. IARC. 2007. Smokeless tobacco and tobacco-specific nitrosamines. Lyon, France: IARC. IARC. 2008. 1,3-butadiene, ethylene oxide and vinyl halides (vinyl fluoride, vinyl chloride and vinyl bromide). In IARC monographs on the evaluation of carcinogenic risks to humans, vol. 97. Lyon, France: IARC. Pp. 45-309. IOM (Institute of Medicine). 2001. Clearing the smoke: Assessing the science base for tobacco harm reduction. Washington, DC: National Academy Press. IOM. 2009. Initial national priorities for comparative effectiveness research. Washington, DC: The National Academies Press. IOM. 2010. Evaluation of biomarkers and surrogate endpoints in chronic disease . Washington, DC: The National Academies Press. Ismail, A. I., B. A. Burt, and S. A. Eklund. 1983. Epidemiologic patterns of smoking and periodontal disease in the United States. Journal of the American Dental Association 106(5):617-621. Jacob, P., III, M. Wilson, and N. L. Benowitz. 2007. Determination of phenolic metabolites of polycyclic aromatic hydrocarbons in human urine as their pentafluorobenzyl ether derivatives using liquid chromatography-tandem mass spectrometry. Analytical Chem- istry 79(2):587-598.
OCR for page 140
140 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS Jaju, R., R. Patel, S. Bakshi, A. Trivedi, B. Dave, and S. Adhvaryu. 1992. Chromosome damag- ing effects of pan masala. Cancer Letters 65(3):221-226. Jansson, T., L. Romert, J. Magnusson, and D. Jenssen. 1991. Genotoxicity testing of extracts of a Swedish moist oral snuff. Mutation Research/Genetic Toxicology 261(2):101-115. Johansson, S. L., J. M. Hirsch, P. A. Larsson, J. Saidi, and B. G. Österdahl. 1989. Snuff-induced carcinogenesis: Effect of snuff in rats initiated with 4-nitroquinoline N-oxide. Cancer Research 49(11):3063. Johansson, S. L., J. M. Hirsch, P. A. Larsson, J. Saidi, and B. G. Österdahl. 1991a. Lack of pro - moting ability of snuff in rats initiated with 4-nitroquinoline-N-oxide. IARC Scientific Publications (105):507-509. Johansson, S. L., J. Saidi, B. G. Österdahl, and R. A. Smith. 1991b. Promoting effect of snuff in rats initiated by 4-nitroquinoline-N-oxide or 7, 12-dimethylbenz (a) anthracene. Cancer Research 51(16):4388. Johnson, M. D., J. Schilz, M. V. Djordjevic, J. R. Rice, and P. G. Shields. 2009. Evaluation of in vitro assays for assessing the toxicity of cigarette smoke and smokeless tobacco. Cancer Epidemiology, Biomarkers & Prevention 18(12):3263-3304. Jorquera, R., A. Castonguay, and H. M. Schuller. 1992. Placental transfer of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone instilled intratracheally in Syrian golden hamsters. Cancer Research 52(12):3273-3280. Kang, M. J., C. G. Lee, J. Y. Lee, C. S. Dela Cruz, Z. J. Chen, R. Enelow, and J. A. Elias. 2008. Cigarette smoke selectively enhances viral pamp- and virus-induced pulmonary innate immune and remodeling responses in mice. Journal of Clinical Investigation 118(8):2771- 2784. Kavvadias, D., G. Scherer, F. Cheung, G. Errington, J. Shepperd, and M. McEwan. 2009a. Determination of tobacco-specific N-nitrosamines in urine of smokers and non-smokers. Biomarkers 14(8):547-553. Kavvadias, D., G. Scherer, M. Urban, F. Cheung, G. Errington, J. Shepperd, and M. McEwan. 2009b. Simultaneous determination of four tobacco-specific N-nitrosamines (TSNA) in human urine. Journal of Chromatography B 877(11-12):1185-1192. Kim, K. C., J. I. Rearick, P. Nettesheim, and A. M. Jetten. 1985. Biochemical characterization of mucous glycoproteins synthesized and secreted by hamster tracheal epithelial cells in primary culture. Journal of Biological Chemistry 260(7):4021-4027. Klaunig, J. E. 2008. Acrylamide carcinogenicity. Journal of Agricultural and Food Chemistry 56(15):5984-5988. Kotlyar, M., L. A. Hertsgaard, B. R. Lindgren, J. A. Jensen, S. G. Carmella, I. Stepanov, S. E. Murphy, S. S. Hecht, and D. K. Hatsukami. 2011. Effect of oral snus and medicinal nico - tine in smokers on toxicant exposure and withdrawal symptoms: A feasibility study. Cancer Epidemiology, Biomarkers & Prevention 20(1):91-100. Kriebel, D., J. Henry, J. Gold, A. Bronsdon, and B. Commoner. 1985. The mutagenicity of ciga- rette smokers’ urine. Journal of Environmental Pathology, Toxicology and Oncology 6(2):157. Kuenemann-Migeot, C., F. Callais, I. Momas, and B. Festy. 1996. Urinary promutagens of smokers: Comparison of concentration methods and relation to cigarette consumption. Mutation Research/Genetic Toxicology 368(2):141-147. Larsson, P. A., S. L. Johansson, A. Vahlne, and J. M. Hirsch. 1989. Snuff tumorigenesis: Effects of long-term snuff administration after initiation with 4-nitroquinoline-N-oxide and herpes simplex virus type 1. Journal of Oral Pathology and Medicine 18(4):187-192. Leslie, E. M., G. Ghibellini, K. Nezasa, and K. L. Brouwer. 2007. Biotransformation and trans - port of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in bile duct-cannulated wild-type and Mrp2/Abcc2-deficient (TR −) wistar rats. Carcinogenesis 28(12):2650-2656. Levin, M. 1953. The occurrence of lung cancer in man. Acta-Unio Internationalis Contra Cancrum 9(3):531.
OCR for page 141
141 METHODS FOR STUDYING HEALTH EFFECTS Lin, H., D. M. Carlson, J. A. St. George, C. G. Plopper, and R. Wu. 1989. An ELISA method for the quantitation of tracheal mucins from human and nonhuman primates. American Journal of Respiratory Cell and Molecular Biology 1(1):41-48. Lindemann, R. A., and N. H. Park. 1988. Inhibition of human lymphokine-activated killer activity by smokeless tobacco (snuff) extract. Archives of Oral Biology 33(5):317-321. Liu, J., Q. Liang, K. Frost-Pineda, R. Muhammad-Kah, L. Rimmer, H. Roethig, P. Mendes, and M. Sarkar. 2011. Relationship between biomarkers of cigarette smoke exposure and biomarkers of inflammation, oxidative stress, and platelet activation in adult cigarette smokers. Cancer Epidemiology, Biomarkers & Prevention 20(8):1760-1769. Lowe, F. J., E. O. Gregg, and M. McEwan. 2009. Evaluation of biomarkers of exposure and potential harm in smokers, former smokers and never-smokers. Clinical Chemistry and Laboratory Medicine 47(3):311-320. Ma, B., M. J. Kang, C. G. Lee, S. Chapoval, W. Liu, Q. Chen, A. J. Coyle, J. M. Lora, D. Picarella, R. J. Homer, and J. A. Elias. 2005. Role of CCR5 in IFN-γ-induced and cigarette smoke-induced emphysema. Journal of Clinical Investigation 115(12):3460-3472. Malhotra, D., R. Thimmulappa, A. Navas-Acien, A. Sandford, M. Elliott, A. Singh, L. Chen, X. Zhuang, J. Hogg, P. Pare, R. M. Tuder, and S. Biswal. 2008. Decline in NRF2-regulated antioxidants in chronic obstructive pulmonary disease lungs due to loss of its positive regulator, DJ-1. American Journal of Respiratory and Critical Care Medicine 178(6):592-604. Mallia, P., S. D. Message, V. Gielen, M. Contoli, K. Gray, T. Kebadze, J. Aniscenko, V. Laza-Stanca, M. R. Edwards, L. Slater, A. Papi, L. A. Stanciu, O. M. Kon, M. Johnson, and S. L. Johnston. 2011. Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation. American Journal of Respiratory and Critical Care Medicine 183(6):734-742. Mangipudy, R. S., and J. K. Vishwanatha. 1999. Role of nitric oxide in the induction of apoptosis by smokeless tobacco extract. Molecular and Cellular Biochemistry 200(1-2):51-57. Mariner, D. C., M. Ashley, C. J. Shepperd, G. Mullard, and M. Dixon. 2010. Mouth level smoke exposure using analysis of filters from smoked cigarettes: A study of eight countries. Regulatory Toxicology and Pharmacology. Mauderly, J. L., W. E. Bechtold, J. A. Bond, A. L. Brooks, B. T. Chen, R. G. Cuddihy, J. R. Harkema, R. F. Henderson, N. F. Johnson, K. Rithidech, et al. 1989. Comparison of 3 methods of exposing rats to cigarette smoke. Experimental Pathology 37(1-4):194-197. Mauderly, J. L., A. P. Gigliotti, E. B. Barr, W. E. Bechtold, S. A. Belinsky, F. F. Hahn, C. A. Hobbs, T. H. March, S. K. Seilkop, and G. L. Finch. 2004. Chronic inhalation exposure to mainstream cigarette smoke increases lung and nasal tumor incidence in rats. Toxi- cological Sciences 81(2):280. McElroy, J. A., M. M. Shafer, A. Trentham-Dietz, J. M. Hampton, and P. A. Newcomb. 2007. Urinary cadmium levels and tobacco smoke exposure in women age 20-69 years in the United States. Journal of Toxicology and Environmental Health. Part A 70(20):1779-1782. Melikian, A. A., M. V. Djordjevic, S. Chen, J. Richie, and S. D. Stellman. 2007. Effect of deliv - ered dosage of cigarette smoke toxins on the levels of urinary biomarkers of exposure. Cancer Epidemiology, Biomarkers & Prevention 16(7):1408-1415. Mendes, P., S. Kapur, J. Wang, S. Feng, and H. Roethig. 2008. A randomized, controlled expo- sure study in adult smokers of full flavor Marlboro cigarettes switching to Marlboro lights or Marlboro ultra lights cigarettes. Regulatory Toxicology and Pharmacology 51(3):295-305. Merne, M., K. Heikinheimo, I. Saloniemi, and S. Syrjanen. 2004. Effects of snuff extract on epithelial growth and differentiation in vitro. Oral Oncology 40(1):6-12. Morin, A., C. J. Shepperd, A. C. Eldridge, N. Poirier, and R. Voisine. 2011. Estimation and correlation of cigarette smoke exposure in Canadian smokers as determined by fil - ter analysis and biomarkers of exposure. Regulatory Toxicology and Pharmacology 61(3, Supplement):S3-S12.
OCR for page 142
142 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS Mortaz, E., A. D. Kraneveld, J. J. Smit, M. Kool, B. N. Lambrecht, S. L. Kunkel, N. W. Lukacs, F. P. Nijkamp, and G. Folkerts. 2009. Effect of cigarette smoke extract on dendritic cells and their impact on T-cell proliferation. PLoS One 4(3):e4946. Muns, G., J. K. Vishwanatha, and I. Rubinstein. 1994. Effects of smokeless tobacco on chemi - cally transformed hamster oral keratinocytes: Role of angiotensin I-converting enzyme. Carcinogenesis 15(7):1325-1327. Naufal, Z. S., K. M. Marano, S. J. Kathman, and C. L. Wilson. 2011. Differential exposure biomarker levels among cigarette smokers and smokeless tobacco consumers in the National Health and Nutrition Examination Survey 1999-2008. Biomarkers 16(3):222-235. NCI (National Cancer Institute). 1998. Cigars: Health effects and trends, Smoking and tobacco control monograph no. 9. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health. NIH Pub. No. 98-4645. NCI. 2001. Risks associated with smoking cigarettes with low machine-measured yields of tar and nicotine, Smoking and tobacco control monograph no. 13. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. NIH Pub. No. 99-4645. NCI. 2009. Phenotypes and endophenotypes: Foundations for genetic studies of nicotine use and dependence. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Nelson, D. E., P. Mowery, S. Tomar, S. Marcus, G. Giovino, and L. Zhao. 2006. Trends in smokeless tobacco use among adults and adolescents in the United States. American Journal of Public Health 96(5):897-905. Niphadkar, M. P., A. N. Bagwe, and R. A. Bhisey. 1996. Mutagenic potential of Indian tobacco products. Mutagenesis 11(2):151. Pakhale, S., S. Sarkar, K. Jayant, and S. Bhide. 1988. Carcinogenicity of Indian bidi and cigarette smoke condensate in Swiss albino mice. Journal of Cancer Research and Clinical Oncology 114(6):647-649. Palladino, G., J. D. Adams, K. D. Brunnemann, N. J. Haley, and D. Hoffmann. 1986. Snuff- dipping in college students: A clinical profile. Military Medicine 151(6):342-346. Pankow, J. F., A. D. Tavakoli, W. Luo, and L. M. Isabelle. 2003. Percent free base nicotine in the tobacco smoke particulate matter of selected commercial and reference cigarettes. Chemical Research in Toxicology 16(8):1014-1018. Papageorge, M. B., E. Cataldo, and E. G. Jahngen. 1996. The effect of N-nitrosonornicotine on the buccal mucosa of Syrian hamsters. Journal of Oral and Maxillofacial Surgery 54(2):187-190. Park, N. H., J. P. Sapp, and E. G. Herbosa. 1986. Oral cancer induced in hamsters with herpes simplex infection and simulated snuff dipping. Oral Surgery, Oral Medicine, Oral Pathol- ogy 62(2):164-168. Paschal, D. C., V. Burt, S. P. Caudill, E. W. Gunter, J. L. Pirkle, E. J. Sampson, D. T. Miller, and R. J. Jackson. 2000. Exposure of the U.S. population aged 6 years and older to cadmium: 1988-1994. Archives of Environmental Contamination and Toxicology 38:377-383. Patel, R. K., R. J. Jaju, S. R. Bakshi, A. H. Trivedi, B. J. Dave, and S. G. Adhvaryu. 1994. Pan masala—a genotoxic menace. Mutation Research/Genetic Toxicology 320(3):245-249. Pauly, J. L., R. J. O’Connor, G. M. Paszkiewicz, K. M. Cummings, M. V. Djordjevic, and P. G. Shields. 2009. Cigarette filter-based assays as proxies for toxicant exposure and smoking behavior—a literature review. Cancer Epidemiology, Biomarkers & Prevention 18(12):3321- 3333. Peacock, E. E., Jr., and B. W. Brawley. 1959. An evaluation of snuff and tobacco in the produc- tion of mouth cancer. Plastic and Reconstructive Surgery and the Transplantation Bulletin 23(6):628-635.
OCR for page 143
143 METHODS FOR STUDYING HEALTH EFFECTS Peacock, E. E., Jr., B. G. Greenberg, and B. W. Brawley. 1960. The effect of snuff and tobacco on the production of oral carcinoma: An experimental and epidemiological study. Annals of Surgery 151:542-550. Peluffo, G., P. Calcerrada, L. Piacenza, N. Pizzano, and R. Radi. 2009. Superoxide-mediated inactivation of nitric oxide and peroxynitrite formation by tobacco smoke in vascular endothelium: Studies in cultured cells and smokers. American Journal of Physiology— Heart and Circulatory Physiology 296(6):H1781-H1792. Phillips, D. H. 2002. Smoking-related DNA and protein adducts in human tissues. Carcino- genesis 23(12):1979-2004. Prentice, R. L. 1989. Surrogate endpoints in clinical trials: Definition and operational criteria. Statistics in Medicine 8(4):431-440. Putzrath, R. M., D. Langley, and E. Eisenstadt. 1981. Analysis of mutagenic activity in ciga - rette smokers’ urine by high performance liquid chromatography. Mutation Research/ Environmental Mutagenesis and Related Subjects 85(3):97-108. Rainey, C. L., P. A. Conder, and J. V. Goodpaster. 2011. Chemical characterization of dis - solvable tobacco products promoted to reduce harm. Journal of Agricultural and Food Chemistry 59(6):2745-2751. Rangasamy, T., C. Y. Cho, R. K. Thimmulappa, L. Zhen, S. S. Srisuma, T. W. Kensler, M. Yamamoto, I. Petrache, R. M. Tuder, and S. Biswal. 2004. Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice. Journal of Clinical Investigation 114(9):1248-1259. Reilly, K. B., S. Srinivasan, M. E. Hatley, M. K. Patricia, J. Lannigan, D. T. Bolick, G. Vandenhoff, H. Pei, R. Natarajan, J. L. Nadler, and C. C. Hedrick. 2004. 12/15-lipoxygenase activity mediates inflammatory monocyte/endothelial interactions and atherosclerosis in vivo. Journal of Biological Chemistry 279(10):9440-9450. Richter, P., and F. W. Spierto. 2003. Surveillance of smokeless tobacco nicotine, pH, moisture, and unprotonated nicotine content. Nicotine & Tobacco Research 5(6):885-889. Richter, P., K. Hodge, S. Stanfill, L. Zhang, and C. Watson. 2008. Surveillance of moist snuff: Total nicotine, moisture, pH, un-ionized nicotine, and tobacco-specific nitrosamines. Nicotine & Tobacco Research 10(11):1645-1652. Rickert, W. S., P. J. Joza, M. Sharifi, J. Wu, and J. H. Lauterbach. 2008. Reductions in the tobacco specific nitrosamine (TSNA) content of tobaccos taken from commercial Canadian cigarettes and corresponding reductions in TSNA deliveries in mainstream smoke from such cigarettes. Regulatory Toxicology and Pharmacology 51(3):306-310. Rodgman, A., and T. Perfetti. 2009. The chemical components of tobacco and tobacco smoke. Boca Raton, FL: CRC Press. Roemer, E., R. Stabbert, K. Rustemeier, D. J. Veltel, T. J. Meisgen, W. Reininghaus, R. A. Carchman, C. L. Gaworski, and K. F. Podraza. 2004. Chemical composition, cytotoxicity and mutagenicity of smoke from U.S. commercial and reference cigarettes smoked under two sets of machine smoking conditions. Toxicology 195(1):31-52. Roethig, H. J., B. K. Zedler, R. D. Kinser, S. Feng, B. L. Nelson, and Q. Liang. 2007. Short- term clinical exposure evaluation of a second-generation electrically heated cigarette smoking system. Journal of Clinical Pharmacology 47(4):518-530. Roethig, H. J., S. Munjal, S. Feng, Q. Liang, M. Sarkar, R. A. Walk, and P. E. Mendes. 2009. Population estimates for biomarkers of exposure to cigarette smoke in adult U.S. ciga - rette smokers. Nicotine & Tobacco Research 11(10):1216-1225. Rohatgi, N., J. Kaur, A. Srivastava, and R. Ralhan. 2005. Smokeless tobacco (khaini) extracts modulate gene expression in epithelial cell culture from an oral hyperplasia. Oral Oncology 41(8):806-820. Rowland, R., and K. Harding. 1999. Increased sister chromatid exchange in the peripheral blood lymphocytes of young women who smoke cigarettes. Hereditas 131(2):143-146.
OCR for page 144
144 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS Rundle, A., and H. Ahsan. 2008. Molecular epidemiological studies that can be nested within cohorts. In Molecular epidemiology of chronic diseases, edited by C. Wild, P. Vineis, and S. Garte. West Sussex, England: J.W. Wiley. Pp. 23-37. SAMHSA (Substance Abuse and Mental Health Services Administration). 2007. Results from the 2006 national survey on drug use and health: National findings. DHHS Publica- tion No. SMA 07-4293. Rockville, MD: Substance Abuse and Mental Health Services Administration. SAMHSA. 2011. Results from the 2010 national survey on drug use and health: National findings. NSDUH Series H-41, HHS Publication No. (SMA) 11-4658. Rockville, MD: Substance Abuse and Mental Health Services Administration. Sarkar, M., S. Kapur, K. Frost-Pineda, S. Feng, J. Wang, Q. Liang, and H. Roethig. 2008. Evaluation of biomarkers of exposure to selected cigarette smoke constituents in adult smokers switched to carbon-filtered cigarettes in short-term and long-term clinical studies. Nicotine & Tobacco Research 10(12):1761-1772. Sarto, F., M. Faccioli, I. Cominato, and A. Levis. 1985. Aging and smoking increase the frequency of sister-chromatid exchanges (SCE) in man. Mutation Research Letters 144(3):183-187. Scherer, G. 2005. Biomonitoring of inhaled complex mixtures—ambient air, diesel exhaust and cigarette smoke. Experimental and Toxicologic Pathology 57(Suppl. 1):75-110. Scherer, G. 2006. Carboxyhemoglobin and thiocyanate as biomarkers of exposure to carbon monoxide and hydrogen cyanide in tobacco smoke. Experimental and Toxicologic Pathol- ogy 58(2-3):101-124. Scherer, G., M. Urban, J. Engl, H. W. Hagedorn, and K. Riedel. 2006. Influence of smoking charcoal filter tipped cigarettes on various biomarkers of exposure. Inhalation Toxicology 18(10):821-829. Scherer, G., J. Engl, M. Urban, G. Gilch, D. Janket, and K. Riedel. 2007a. Relationship between machine-derived smoke yields and biomarkers in cigarette smokers in Germany. Regu- latory Toxicology and Pharmacology 47(2):171-183. Scherer, G., M. Urban, H. W. Hagedorn, S. Feng, R. D. Kinser, M. Sarkar, Q. Liang, and H. J. Roethig. 2007b. Determination of two mercapturic acids related to crotonaldehyde in human urine: Influence of smoking. Human & Experimental Toxicology 26(1):37-47. Scherer, G., M. Urban, H. W. Hagedorn, R. Serafin, S. Feng, S. Kapur, R. Muhammad, Y. Jin, M. Sarkar, and H. J. Roethig. 2010. Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in ciga - rette smoke. Journal of Chromatography B 878(27):2520-2528. Schuller, H. M., R. Jorquera, A. Reichert, and A. Castonguay. 1993. Transplacental induc - tion of pancreas tumors in hamsters by ethanol and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Research 53(11):2498-2501. Schuller, H. M., R. Jorquera, X. Lu, A. Riechert, and A. Castonguay. 1994. Transplacental carcinogenicity of low doses of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone admin- istered subcutaneously or intratracheally to hamsters. Journal of Cancer Research and Clinical Oncology 120(4):200-203. Schwartz, J., and X. Gu. 2002. Chapter 8: Hamster oral cancer model. In Tumor models in cancer research. Vol. 10, edited by B. A. Teicher. Totowa, NJ: Humana Press, Inc. Schwartz, J. L., K. D. Brunnemann, A. J. Adami, S. Panda, S. C. Gordon, D. Hoffmann, and G. R. Adami. 2010. Brand specific responses to smokeless tobacco in a rat lip canal model. Journal of Oral Pathology and Medicine 39(6):453-459. Secretan, B., K. Straif, R. Baan, Y. Grosse, F. El Ghissassi, V. Bouvard, L. Benbrahim-Tallaa, N. Guha, C. Freeman, L. Galichet, and V. Cogliano. 2009. A review of human carcinogens— Part E: Tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncology 10(11):1033-1034.
OCR for page 145
145 METHODS FOR STUDYING HEALTH EFFECTS Shirname-More, L. 1991. Smokeless tobacco extracts mutate human cells. Carcinogenesis 12(5):927-930. Shklar, G., K. Niukian, M. Hassan, and E. G. Herbosa. 1985. Effects of smokeless tobacco and snuff on oral mucosa of experimental animals. Journal of Oral and Maxillofacial Surgery 43(2):80-86. Singh, R., and H. S. Nalwa. 2011. Medical applications of nanoparticles in biological imag - ing, cell labeling, antimicrobial agents, and anticancer nanodrugs. Journal of Biomedical Nanotechnology 7(4):489-503. Singh, S., Y. K. Loke, J. G. Spangler, and C. D. Furberg. 2011. Risk of serious adverse cardio - vascular events associated with varenicline: A systematic review and meta-analysis. Canadian Medical Association Journal 183(12):1359-1366. Smith, C., S. McKarns, R. Davis, S. Livingston, B. Bombick, J. Avalos, W. Morgan, and D. Doolittle. 1996. Human urine mutagenicity study comparing cigarettes which burn or primarily heat tobacco. Mutation Research/Environmental Mutagenesis and Related Subjects 361(1):1-9. Song, S. Q., and D. L. Ashley. 1999. Supercritical fluid extraction and gas chromatography mass spectrometry for the analysis of tobacco-specific nitrosamines in cigarettes. Analytical Chemistry 71(7):1303-1308. St. George, J. A., D. L. Cranz, S. C. Zicker, J. R. Etchison, D. L. Dungworth, and C. G. Plopper. 1985. An immunohistochemical characterization of rhesus monkey respira - tory secretions using monoclonal antibodies. American Review of Respiratory Disease 132(3):556-563. Stamm, S. C., B. Z. Zhong, W. Z. Whong, and T. Ong. 1994. Mutagenicity of coal-dust and smokeless-tobacco extracts in salmonella typhimurium strains with differing levels of O-acetyltransferase activities. Mutation Research 321(4):253-264. Stanton, M., E. Miller, C. Wrench, and R. Blackwell. 1972. Experimental induction of epi - dermoid carcinoma in the lungs of rats by cigarette smoke condensate. Journal of the National Cancer Institute 49(3):867. Starrett, W., and D. J. Blake. 2011. Sulforaphane inhibits de novo synthesis of IL-8 and MCP- 1 in human epithelial cells generated by cigarette smoke extract. Journal of Immuno- toxicology 8(2):150-158. Stenstrom, B., C. M. Zhao, A. B. Rogers, H. O. Nilsson, E. Sturegard, S. Lundgren, J. G. Fox, T. C. Wang, T. M. Wadstrom, and D. Chen. 2007. Swedish moist snuff accelerates gastric cancer development in Helicobacter pylori-infected wild-type and gastrin transgenic mice. Carcinogenesis 28(9):2041-2046. Stepanov, I., and S. S. Hecht. 2005. Tobacco-specific nitrosamines and their N-glucuronides in the urine of smokers and smokeless tobacco users. Cancer Epidemiology, Biomarkers & Prevention 14:885-891. Stepanov, I., J. Jensen, D. Hatsukami, and S. S. Hecht. 2008. New and traditional smokeless tobacco: Comparison of toxicant and carcinogen levels. Nicotine & Tobacco Research 10:1773-1782. Stepanov, I., S. G. Carmella, A. Briggs, L. Hertsgaard, B. Lindgren, D. K. Hatsukami, and S. S. Hecht. 2009. Presence of the carcinogen N’-nitrosonornicotine in the urine of some users of oral nicotine replacement therapy products. Cancer Research 69:8236-8240. Stepanov, I., P. W. Villalta, A. Knezevich, J. Jensen, D. Hatsukami, and S. S. Hecht. 2010. Analysis of 23 polycyclic aromatic hydrocarbons in smokeless tobacco by gas chromatography-mass spectrometry. Chemical Research in Toxicology 23:66-73. Stinn, W., J. H. E. Arts, A. Buettner, E. Duistermaat, K. Janssens, C. F. Kuper, and H. J. Haussmann. 2010. Murine lung tumor response after exposure to cigarette mainstream smoke or its particulate and gas/vapor phase fractions. Toxicology 275(1-3):10-20. Straif, K., R. Baan, Y. Grosse, B. Secretan, F. El Ghissassi, and V. Cogliano. 2005. Carcino- genicity of polycyclic aromatic hydrocarbons. Lancet Oncology 6(12):931-932.
OCR for page 146
146 STUDIES ON MODIFIED RISK TOBACCO PRODUCTS Sussan, T. E., T. Rangasamy, D. J. Blake, D. Malhotra, H. El-Haddad, D. Bedja, M. S. Yates, P. Kombairaju, M. Yamamoto, K. T. Liby, M. B. Sporn, K. L. Gabrielson, H. C. Champion, R. M. Tuder, T. W. Kensler, and S. Biswal. 2009. Targeting Nrf2 with the triterpenoid CDDO- imidazolide attenuates cigarette smoke-induced emphysema and cardiac dys - function in mice. Proceedings of the National Academy of Sciences 106(1):250-255. Suwan-ampai, P., A. Navas-Acien, P. T. Strickland, and J. Agnew. 2009. Involuntary tobacco smoke exposure and urinary levels of polycyclic aromatic hydrocarbons in the United States, 1999 to 2002. Cancer Epidemiology, Biomarkers & Prevention 18(3):884-893. Thompson, C. A., and P. C. Burcham. 2008. Genome-wide transcriptional responses to acrolein. Chemical Research in Toxicology 21:2245-2256. Trivedi, A. H., B. J. Dave, and S. G. Adhvaryu. 1993. Genotoxic effects of tobacco extract on Chinese hamster ovary cells. Cancer Letters 70(1-2):107-112. Tuomisto, J., S. Kolonen, M. Sorsa, and P. Einistö. 1986. No difference between urinary mutagenicity in smokers of low-tar and medium-tar cigarettes: A double-blind cross- over study. Archives of Toxicology. Supplement 9:115. Wang, Y., E. Rotem, F. Andriani, and J. A. Garlick. 2001. Smokeless tobacco extracts modulate keratinocyte and fibroblast growth in organotypic culture. Journal of Dental Research 80(9):1862-1866. Wang, D., Y. Wang, and Y. N. Liu. 2010. Experimental pulmonary infection and colonization of Haemophilus influenzae in emphysematous hamsters. Pulmonary Pharmacology and Therapeutics 23(4):292-299. Weed, D. L. 2000. Epidemiologic evidence and causal inference. Hematology/Oncology Clinics of North America 14(4):797-807. Weiss, N. S. 1994. Application of the case-control method in the evaluation of screening. Epidemiologic Reviews 16(1):102-108. Whincup, P. H., J. A. Gilg, J. R. Emberson, M. J. Jarvis, C. Feyerabend, A. Bryant, M. Walker, and D. G. Cook. 2004. Passive smoking and risk of coronary heart disease and stroke: Prospective study with cotinine measurement. BMJ 329(7459):200-205. Whitcutt, M. J., K. B. Adler, and R. Wu. 1988. A biphasic chamber system for maintaining polarity of differentiation of cultured respiratory tract epithelial cells. In Vitro Cellular and Developmental Biology 24(5):420-428. Whong, W. Z., R. G. Ames, and T. M. Ong. 1984. Mutagenicity of tobacco snuff: Pos- sible health implications for coal miners. Journal of Toxicology and Environmental Health 14(4):491-496. Whong, W. Z., J. D. Stewart, and T. Ong. 1985. Formation of bacterial mutagens from the reaction of chewing tobacco with nitrite. Mutation Research/Genetic Toxicology 158(3):105- 110. Witschi, H. 2004. A/J mouse as a model for lung tumorigenesis caused by tobacco smoke: Strengths and weaknesses. Experimental Lung Research 31(1):3-18. Worawongvasu, R., S. Ashrafi, A. Das, J. Waterhouse, and H. Medak. 1991. A light and scan - ning electron microscopic study of snuff induced early changes in hamster cheek pouch mucosa. Biomedical Research (India) 2:240-250. Wu, R., E. Nolan, and C. Turner. 1985. Expression of tracheal differentiated functions in se - rum-free hormone-supplemented medium. Journal of Cellular Physiology 125(2):167-181. Wu, R., C. G. Plopper, and P. W. Cheng. 1991. Mucin-like glycoprotein secreted by cultured hamster tracheal epithelial cells. Biochemical and immunological characterization. Biochemical Journal 277(3):713-718. Wu, Z., P. Upadhyaya, S. G. Carmella, S. S. Hecht, and C. L. Zimmerman. 2002. Disposition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanol (NNAL) in bile duct-cannulated rats: Stereoselective metabo - lism and tissue distribution. Carcinogenesis 23(1):171-179.
OCR for page 147
147 METHODS FOR STUDYING HEALTH EFFECTS Wynder, E. L., and D. Hoffmann. 1961. A study of tobacco carcinogenesis. VIII. The role of the acidic fractions as promoters. Cancer 14(6):1306-1315. Wynder, E. L., E. A. Graham, and A. B. Croninger. 1953. Experimental production of carci - noma with cigarette tar. Cancer Research 13(12):855-864. Yamasaki, E., and B. N. Ames. 1977. Concentration of mutagens from urine by absorption with the nonpolar resin XAD-2: Cigarette smokers have mutagenic urine. Proceedings of the National Academy of Sciences 74(8):3555. Yildiz, D., Y. S. Liu, N. Ercal, and D. W. Armstrong. 1999. Comparison of pure nicotine- and smokeless tobacco extract-induced toxicities and oxidative stress. Archives of Environ- mental Contamination and Toxicology 37(4):434-439. Yoshida, T., I. Mett, A. K. Bhunia, J. Bowman, M. Perez, L. Zhang, A. Gandjeva, L. Zhen, U. Chukwueke, T. Mao, A. Richter, E. Brown, H. Ashush, N. Notkin, A. Gelfand, R. K. Thimmulappa, T. Rangasamy, T. Sussan, G. Cosgrove, M. Mouded, S. D. Shapiro, I. Petrache, S. Biswal, E. Feinstein, and R. M. Tuder. 2010. Rtp801, a suppressor of mTOR signaling, is an essential mediator of cigarette smoke-induced pulmonary injury and emphysema. Nature Medicine 16(7):767-773. Yuan, J. M., W. P. Koh, S. E. Murphy, Y. Fan, R. Wang, S. G. Carmella, S. Han, K. Wickham, Y. T. Gao, M. C. Yu, and S. S. Hecht. 2009. Urinary levels of tobacco-specific nitrosa - mine metabolites in relation to lung cancer development in two prospective cohorts of cigarette smokers. Cancer Research 69:2990-2995. Zedler, B. K., R. Kinser, J. Oey, B. Nelson, H. J. Roethig, R. A. Walk, P. Kuhl, K. Rustemeier, G. Schepers, K. Von Holt, and A. R. Tricker. 2006. Biomarkers of exposure and potential harm in adult smokers of 3-7 mg tar yield (Federal Trade Commission) cigarettes and in adult non-smokers. Biomarkers 11(3):201-220. Zhong, Y., S. G. Carmella, J. B. Hochalter, S. Balbo, and S. S. Hecht. 2010. Analysis of r -7, t -8,9, c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene in human urine: A biomarker for directly assessing carcinogenic polycyclic aromatic hydrocarbon exposure plus metabolic activation. Chemical Research in Toxicology 24:73-80. Zhou, J., E. A. Eksioglu, N. R. Fortenbery, X. Chen, H. Wang, P. K. Epling-Burnette, J. Y. Djeu, and S. Wei. 2011. Bone marrow mononuclear cells up-regulate toll-like receptor expression and produce inflammatory mediators in response to cigarette smoke extract. PLoS One 6(6):e21173.
OCR for page 148