TABLE 17.-Lung cancer mortality ratios for cigar and pipe smokers by amount smoked Smoking type Mortality ratio Number of deaths Nonsmoker 1.09 78 Cigar smokers: < 5 cigars per day.. 5 to 8 cigars per day. > 8 cigars per day.. pipe smokers: < 5 pipefuls per day.. 5 to 19 pipefuls per day > 19 pipefuls per day . . . . . . . . . . . . . . . Cigar and pipe: 8 or less cigars, 19 or less pipefuls _. > 8 cigars, > 19 pipefuls 1.14 12 2.64 11 2.07 2 .77 2 2.20 12 247 3 1.62 18 2.19 2 SOURCE: Kahn. HA. (69) Abelin and Gsell(1) is of particular interest. The smoking habits of 118 male patients with cancer of the lung from a rural area of Switzerland were compared with those reported in a survey of all male inhabitants of a town in the same region. About 20 percent of the population of this area were regular cigar smokers, the most popular cigar being the Stuempen, a small Swiss-made machine-manufactured cigar cut at both ends with an average weight of 4.5 g. In this investigation, cigar smokers experienced a risk of developing lung cancer that was similar to the risk of cigarette smokers. A dose-response relationship was demonstrated for inhalation and amount smoked. These data suggest that the heavy smoking of certain cigars may result in a risk of lung cancer that is similar to that experienced by cigarette smokers. Sanderud (106) examined histologic sections from the bronchial tree of 100 male autopsy cases for the presence of squamous epithelial metaplasia. In this study, 39 percent of the population were nonsmok- ers, 20 percent were pipe smokers, and 38 percent smoked cigarettes. A total of 80 percent of the pipe smokers and cigarette smokers demonstrated squamous metaplasia of the bronchial tree, whereas only 13-23 TABLE 18.~Relative risk of lung cancer for men, comparing cigar, pipe, and cigarette smokers with nonsmokers. A summary of retrospective studies Relative risk ratio sod percentage of cases Author. reference NUlllbW and controls by type of smoking Non- Cigar Pipe Total pipe cigarette smoker only only and cigar only Mixed Levin (80): cases. ................. Controls ............... Schrek (110): cases. ................. CQntrols ............... Wynder and Graham W): CW. ................. Controls. .............. Doll and Hill (36): caaea .................. Controls ............... Koulumies (77): caaea .................. Cvntrols ............... Sadowsky (105): CaMS. ................. Controls ............... Wynder and Cornfield (fS9): CaaeS. ................. G3lltilS ............... Ftandig (100): CaseS .................. Controls ............... Milla and Porter (86): casea. ................. Controls. .............. Mills and Porter (87): cases. ................. controls ............... 236 481 82 .52? 605 780 1,357 117 812 3@l 477 615 63 133 415 381 444 430 484 1,= Relative risk 1.0 0.7 0.8 Petvent cases 15 11 14 Percent controls 22 23 25 Relative risk 1.0 .6 .7 1.7 Percent cases 15 4 5 61 Percent controls 22 23 11 59 Relative risk 1.0 5.1 3.6 Percent casea 1 4 4 Percent controls 15 8 12 Relative risk 1.0 5.1 Percent - .5 . . 4 Penxnt controls 5 7 Relative risk Percent cases Percent controls 1.0 . 9.6 .6 . . 2 18 . . . . 6 Relative risk 1.0 2.4 1.4 Percent eases 4 2 3 Percent controls 13 3 7 Relative risk Percent cases Percent controls Relative risk Percent eases Percent controls Relative risk Percent cases Percent controls Relative risk Percent cases Percent controls 1.0 25 4.0 8.5 4 13 6 . 77 21 27 8 45 1.0 5.3 5.0 1 21 11 6 19 11 . . 1.0 . . 6.0 I 37 31 . 26 1.0 8 28 1::: 1::: 2.8 13 16 21 66 44 15.7 91 65 . 9.6 14 69 29.3 77 76 3.7 5.6 57 31 53 19 5.0 67 64 5.4 55 43 4.5 78 57 . . . . 54 percent of the nonsmokers had this abnormality. Knudtson (76) also studied histologic changes. Auerbach, et al. (8) examined 36,340 histologic sections obtained from 1,522 white adults for various epithelial lesions including: 13-B TABLE l&-Relative risk of lung cancer for men, comparing cigar, pipe, and cigarette smokers with nonsmokera A summary of retrosuective studies-continued Author. reference Number kelative risk ratio and percentage of - and controls by type of smoking Non- Cigar Pipe Total pipe Cigarette smoker only only and cigar only Mixed Schwartz and Denoix (111): cases. . . . . . COlltdS.. . . . . stock.9 (Pa): Gases. . . . . controls.. . . . Lombard and Snegireff (81): cases. . . . . . . . Controls.. . . . . Pernu (99): casea. . . controls.. . . . Wicken (1%): cases. . . . . . ColltrolS. . . . Abelin and Gsell (1): CaseS . I . . . . . . . . Gmtrols.. . Wynder (144): cases . controls.. 430 430 2,101 5.960 509 1.839 1,477 713 803 803 118 524 210 420 Relative risk 1.0 . 4.7 . 13.5 . . . Percent cases 1 6 96 . . Percent controls 11 . 14 . . 78 . . Relative risk 1.0 3.1 . . . Percent - 2 . . 9 Percent controls 9 . . . 13 5.0 89 78 . . . . Relative risk 1.0 . . 1.7 Percent - 2 4 Percentcontrols 10 ..:::I 1::: 15 Relative risk 1.0 . . . 4.2 . . . Percent - 7 4 Percent controls 39 . . 5 Relative risk 1.0 . . 2.2 Percent - 4 . 10 Percent controls 14 16 Relative risk 1.0 3.4 4.5 Percent cases 2 23 7 . . . Percent conhIs 35 19 6 . . Relative risk - 1.0 . 20 Percent eases 3 5 Percent controls 21 . 15 8.1 . . . . 95 . 75 . 9.2 77 50 4.3 78 64 5.7 . 12.4 92 47 11.1 13 7 4.2 7 6 24 10 . . presence or absence of ciliated cells, thickness or number of cell rows, atypical nuclei, and the proportion of cells of various types. The pathologic findings in the bronchial epithelium of pipe and cigar smokers were compared to those found in nonsmokers and cigarette smokers. Pipe and cigar smokers had abnormalities that were intermediate between those of nonsmokers and cigarette smokers, although cigar smokers had pathologic changes that in some categories approached the changes seen in cigarette smokers. Tumorigenic Activity Several experimental investigations have been conducted to examine the relative tumorigenic activity of tobacco smoke condensates obtained from cigarettes, cigars, and pipes. Most of these studies were standardized in an attempt to make the results of the cigar and pipe 13-30 experiments more directly comparable with the cigarette data, and most used the shaved skin of mice for the application of tar. Tars from cigars, pipes, and cigarettes were usually applied on an equal weight basis so that qualitative differences in the tars could be determined. In several experiments, the nicotine was extracted from the pipe and cigar condensates in an attempt to reduce the acute toxic effects that resulted in animals from the high concentrations of nicotine frequently found in these products. Wynder and Wright (146) examined the differences in tumorigenic activity of pipe and cigarette condensates. Tars were obtained by the smoking of a popular brand of king-size cigarettes and from the same cigarette tobacco smoked in 12 standard-grade briar bowl pipes. Both the cigarettes and pipes were puffed three times a minute with a 2- second puff and a 35-ml volume. Both the cigarettes and pipes attained similar maximum combustion zone temperatures; however, the use of cigarette tobacco in the pipe resulted in a combustion chamber temperature that averaged about 150" centrigrade higher than temperatures achieved when pipe tobacco was used. Chemical fraction- ation was accomplished and equal concentrations of the neutral fraction were applied in three weekly applications to the shaved skin of CAFl and Swiss mice. The results indicate that neutral tar obtained from cigarette tobacco smoked in pipes is more active than that obtained in the usual manner from cigarettes. About twice as many cancers were obtained in both the CAFi and the Swiss mice, and the latent period was about 2 months shorter. Extending these data, Croninger, et al. (27) examined the biologic activity of tars obtained from cigars, pipes, and cigarettes. Each form of tobacco was smoked as it was manufactured in a manner to simulate human smoking or to maintain tobacco combustion. The whole tar was applied in dilutions of one-to-one and one-to-two with acetone to the shaved backs of female CAFl and female Swiss mice using three applications each week for the life span of the animal. The nicotine was extracted from the pipe and cigar condensates to reduce the acute toxicity of the solutions. In the Swiss mice, pipe, cigar, and cigarette tars produced both benign and malignant tumors. The incidence rates of malignant tumors given as percents were: 44, 41, and 37, respectively. These results suggested a somewhat higher degree of carcinogenic activity for cigar and pipe tars than for cigarette tar. Similar results were reported by Kensler (?2), who applied conden- sates obtained from cigars and cigarettes to the shaved skin of mice. The incidence of papillomas produced by cigar smoke concentrate was no different from that produced by the cigarette smoke condensate. Similarly, there was no difference between cigar and cigarette smoke condensates when carcinoma incidences were compared. Hornburger, et al. (62) prepared tars from cigar, pipe, and cigarette tobaccos that were smoked in the form of cigarettes. In this way, all 13-31 tobaccos were smoked in an identical manner and uniform combustion temperatures were achieved. Because of this standardization, differ- ences in tumor yield could be attributed to tobacco blend and not to the manner in which the tars were prepared. The whole tars were diluted one-to-one with acetone and applied to the shaved skin of CAFl mice three times a week for the life span of the test animal. Skin cancers were produced more quickly with pipe and cigar smoke condensates than with cigarette smoke condensates. This suggests that the smoking of pipe and cigar tobaccos in the form of cigarettes does not alter the condensates to any significant degree. Davies and Day (29) and Roe, et al. (103) conducted other tumorigenic studies. These experimental data suggest that cigar and pipe tobacco condensates have a carcinogenic potential that is comparable to cigarette condensates. This is supported by human epidemiological data for those sites exposed equally to the smoke of cigars, pipes, and cigarettes. The partially alkaline smoke derived from pipes and cigars is generally not inhaled, and as a result there appears to be a lower level of exposure of the lungs and other systems to the harmful properties of pipe and cigar smoke than occurs with cigarette smoking. It is anticipated. that modifications in pipe tobacco or cigars which would result in a product that was more readily inhalable would eventually result in elevated mortality from cancer of the lung, bronchitis and emphysema, arteriosclerotic cardiovascular diseases, and the other conditions which have been clearly associated with cigarette smoking. Cardiovascular Diseases Pipe and cigar smokers experience only a small increase in mortality from coronary heart disease above the rates of nonsmokers. Cigarette smokers have higher death rates from cerebrovascular disease than nonsmokers, whereas pipe and cigar smokers have cerebrovascular death rates that are only slightly above the rates of nonsmokers. Table 19 summarizes the major prospective epidemiological investigations that examined the association of smoking in various forms with total cardiovascular diseases, coronary heart disease, with cerebrovascular disease. Doll and Hill (X?), Best (11), and Kahn (69) examined dose- response relationships for pipe and cigar smokers and reported a slight increase in mortality from coronary heart disease with an increase in the number of cigars or pipefuls smoked. Other prospective epidemiological studies have also examined the relationship of smoking in various forms to coronary heart disease and related risk factors. Jenkins, et al. (66), in the Western Collaborative Group Study of coronary heart disease (CHD), reported an incidence of coronary heart disease in men aged 50 to 59 who were pipe and cigar smokers that was intermediate between the rates seen in cigarette smokers and nonsmokers. No increase in incidence of coronary heart 13-32 TABLE lg.-Mortality ratios for cardiovascular deaths in male cigar and pipe smokers. A summary of prospwtive euidemiolonical studies Trpe of smoking Author, reference CNP-Y Non- Cigar me Total Ciga- smoker only OdY pipe and rette Mixed k?= only Hammond and Horn (BP). Cardiovascular total. Coronary. . . . Cerebrovascular . Doll and Hill (38). Cwdiova.w.ilar total. Cmvnary . Cerebrovascular Best (II). Caniiovaseular total. Coronary . Cerebrovascular . Hammond' (50). Cardiovawular total. Coronary.. Cerebmvascular . Kahn (68). Cardiovascular total. coronary . Cerebmvascular 1.00 1.26 1.07 1.57 1.00 1.28 1.03 1.70 1.00 1.31 1.23 1.39 1.00 .81 1.38 1.00 1.03 1.62 1.00 1.15 1.34 1.00 1.14 .95 .,.. 1.52 1.00 99 1.00 1.60 1.00 1.28 XL5 .88 1.00 1.06 1.90 1.00 1.35 1.19 1.09 1.00 `1.09. 1.41 1.00 1.05 1.06 1.05 1.75 I.00 1.04 1.08 1.05 1.74 1.00 1.08 1.09 1.06 1.52 .81 1.28 1.21 1.41 1.40 . lMwtality ration for agca 55 to 64 only are pm-sent& disease was seen among the pipe and cigar smokers in the younger age groups. Shapiro, et al. (115), in a study of the health insurance plan (HIP) population, reported incidence rates for myocardial infarction (MI), angina pectoris, and possible MI, in pipe and cigar smokers that were similar to the incidence rates seen in cigarette smokers. These rates were considerably higher than those of nonsmokers, Data from the Pooling Project (64) suggested that the incidence of CHD deaths, sudden death, and the first major coronary event in pipe and cigar smokers was intermediate between the incidence experienced by cigarette smokers and nonsmokers. In contrast to these studies, Doyle, et al. (39) reported no increase in CHD deaths, myocardial infarction, or angina pectoris in pipe and cigar smokers over the rates of nonsmokers in the Framingham study. The retrospective studies of Mills and Porter (85), Villiger and Heyden-Stucky (133), Schimmler, et al. (log), and Hood, et al. (63) contained data suggesting that pipe and cigar smokers experience mortality rates from coronary heart disease that are essentially similar 13-33 to those experienced by cigarette smokers. The retrospective study of Spain and Nathan (120) reported lower rates of coronary heart disease for pipe and cigar smokers than were found in nonsmokers. Van Buchem (132) and Dawber, et al. (30, 31) examined serum cholesterol levels in groups of individuals classified according to smoking habits. In these two studies, pipe and cigar smokers had serum cholesterol levels that were nearly identical with the levels found in nonsmokers. Tibblin (125) and Dawber, et al. (30, 31) investigated the effect of smoking on blood pressure. The proportion of smokers decreased in groups with higher blood pressures, although this was not as dramatic for pipe and cigar smokers as it was for cigarette smokers. Kesteloot and Van Houte (75) found that pipe and cigar smokers had slightly lower blood pressures than nonsmokers, in contrast to cigarette smokers who had minimally elevated blood pressures in comparison to nonsmokers. Chronic Obstructive P&rummy Disease Chronic bronchitis and pulmonary emphysema account for most of the morbidity and mortality from chronic respiratory disease in the United States. The relationship between smoking pipes and cigars and these diseases is summarized in this section and in Table 29. In a retrospective study of 1,189 males and matched controls in Northern Ireland, Wicken (135) investigated smoking in various forms and mortality from bronchitis. The relative risk ratios compared to nonsmokers for mortality from chronic bronchitis were 1.98 for all smokers, 1.55 for pipe and cigar smokers, 2.25 for cigarette smokers, and 1.49 for mixed smokers. From a review of these prospective and retrospective studies, it appears that pipe and cigar smokers experience mortality rates from bronchitis and emphysema that are higher than the rates of nonsmokers. Although these mortality rates approach those of cigarette smokers, in most instances they are intermediate between the rates of cigarette smokers and nonsmokers. Pipe and cigar smokers have significantly more respiratory symp- toms and illnesses than nonsmokers. Those studies which contain data on pipe and cigar smoking as related to respiratory symptoms are summarized in Table 21. Haenszel and Hougen (48) showed an increased prevalence of persistent cough and phlegm in pipe and cigar smokers compared to nonsmokers and were able to show that the prevalence increased with increasing amount smoked. Only a few studies have examined pulmonary function in pipe and cigar smokers. There appears to be little difference in pulmonary 13-34 TABLE 20.-Mortality ratios for chronic obstructive pulmonary deaths (COPD) in male cigar and pipe smokera A summary of prospective epidemiological studies Twe of smoking Author, reference CwvY Non- Cigar Pipe Total Ciga- smoker only only pipe and rette Mixed cigar only Hammond and Horn (52). COPD total Exmphsema Bronchitis 1.00 1.29 1.77 2.85 . . . . . . Doll and Hill (SbJW). COPD total Emphysema Bronchitis 1.00 . . 1.00 9.33 4.00 24.67 11.33 ;,oo a67 Best (II). COPD total Emphysema Bronchitis . 1.00 3.33 .75 `iI.& : : : : 1.00 3.57 2.11 11.42 Hammond (50). COPD total Emphysema Bronchitis . . . 1.00 . 1.37 . `$.& :::: . Kahn (69). COPD total 1.00 Emphysema 1.00 Bronchitis 1.00 .79 2.36 99 10.08 . . 1.24 213 1.31 14.17 . . 1.17 1s 1.17 4.49 . . `Only mortality ntiaa for ages 55 to a are presented function values for pipe and cigar smokers as compared to nonsmokers (Table 22). Naeye (88) conducted an autopsy study on 322 Appalachian coal workers who were classified according to the type of coal mined and tobacco usage. Emphysema was slightly greater in cigarette smokers, as were anatomic evidences of chronic bronchitis and bronchiolitis. Those changes found in pipe and cigar smokers were intermediate between those of cigarette-smoking miners and nonsmoking miners. Changes in pulmonary histology in relation to smoking habits and age were examined by Auerbach, et al. (6, IO). Fibrosis, alveolar rupture, thickening of the walls of small arteries, and thickening of the walls of the pulmonary arterioles were found to be highly related to the smoking habits of the 1,340 male subjects examined. The 91 pipe and cigar smokers over the age of 60 were found to have somewhat more alveolar rupture than the men of the same age distribution who never smoked regularly. However, pipe and cigar smokers as a group had far less rupture than cigarette smokers. The same relations as described above were found for fibrosis, thickening of the walls of the arterioles and small arteries, and padlike attachments to the alveolar septums. 13-35 TABLE PI.-Prevalence of respiratory symptoms and illness by type of smoking Percent orevalence Author, reference Number a"d type of population 1ll"esS Total ,~~~~, pipe and Ciga rette Mixed cigar only Boake (22). EdWardS w. AShfOrd (5). Bower (14). Wynder W). Parents of 59 families. 1,737 nude outpatients 4,014 male workers in 3 Scottish collieries. 95 male bank employees. 315 male pa- tients in New York and 315 male patients in California 5237 male postal and 7,213 male transit workers in New York City. 4,379 twin pairs, all U.S. veterans Rimington (202). 41,729 male volunteers. COUgh. Sputum production. Chest illness. Chronic bronchitis. Bronchitis. Pneumoconiosis. Cough. Sputum production. wheeze. Chest illness. Cough (New York). Cough (California). Influenza (New York). Influenza (California). Chest illness (New York). Chest illness (California). Persistent cough. Persistent sputum production. Dyspnea. wheeze. Chest illness. Cough. Prolonged cough. Bronchitis. Chronic bronchitis. 32 32 48 24 15 20 5 4 5 17 19' 31 10 11 35' 34' 21 14 0 8 0 15 29 33 8 15 31 54 33 40 14 33 56 22 30 67 11 21 28 24 9 10 7 6 7 11 11 16 16 19 14 21 13 16 24 31 12 11 25 26 26 32 18 17 11 10 17 . . . . 14 37 2 . . . 51 66 . . . Tobacco smoke has been shown experimentally to have a ciliostatic 13-36 TABLE 21.--Prevalence of respiratory symptoms and illness by type of smoking-continued Percent prevalence Author, reference Number and type of population Ill"t?SS Non- Total Ciga- smoker pipe and ratte Mixed cigar OdY Camstock (24). 670 male telephone employees. Lefcoe and 310 male phy Wonnacott (79). sicians in London, Ontario. Haenszel and Hougen (48). 6,712 Norwegian males and 3,337 siblings who emigrated. Persistent cough. Persistent sputum Dyspnea. Cheat illness in past 3 yrs. Chronic respir- atmy disease. Chronic bronchitis. OMructive lung disease. Asthma. Rhonchi. Persistent cough and phlegm, age=-= Persistent cough and phkm age 5S74. Chronic bmn- chitis, age 35-54. Chronic bmn- chitis, age f&74. 10 13 33 14 9 1 1 7 0 3.0 3.7 0.4 1.3 1.6 16 41 . . . . 20 42 . 39 44 . . . . 18 a0 . 13 12 3 3 3 b7 1.2 1.1 44 . . . . 34 . . . 4 . . 6 . 9 . . 14.3 14.5 15.0 14.3 1.9 1.3 3.7 3.5 Tii for pips only. effect on the respiratory epithelium. The interval between puffs, the amount. of volatile and particulate compounds in the smoke, and the exposure volume have been shown to influence the toxic effect of tobacco smoke. Dalhamn and Rylander (28) exposed the upper trachea of anesthetized cats to the smoke of cigarettes and cigars, observing the effect on ciliary activity through an incident-light microscope. A chemical analysis of the gas and particulate phases revealed that the cigar smoke was more alkaline and, in general, contained higher concentrations of isoprene, acetone, acetonitrile, toluene, and total particulate matter compared to cigarette smoke. The average number of puffs required to arrest ciliary activity was found to be 73 for the cigarette smoke and 114 for the cigar smoke. The difference is statistically significant (P < 0.01). Of the two smokes, the smoke with the highest concentration of volatile compounds was found to be the least ciliostatic. This suggests that the degree of ciliotoxicity of a 1337 ~~_____ TABLE 22.~-Pulmonary function values for cigar and pipe smokers as compared to nonsmokers Author. reference Number a"d type of population Function Type of smoking Non- Total Ciga- smoker pipe and rette Mixed cigar only Ashford (5). 4,014 male workers in 3 Scottish collieries. FEVI~..................... 3.39 2.59' 3.14 262 Goldsmith. et al. (47). 3,311 active Puffmeter _.....,.......... 313.63 299.26 303.44 . or retired FEV,.o . . . . . . . . 2.99 2.36 291 longshoremen. TVC.. 3.87 3.66 3.33 Cornstock (24). 670 male telephone employees. FEVU, . _. . 3.12 3.26 2.82 . Lefcoe and 310 male Wonnacott (79). physicians in London, Ontario. FEV,.,, . . . . MMFR liters per second . . . . 3.39 3.17 3.11 . 4.09 4.17 3.64 ~Figurea for pips only smoke is not necessarily correlated to the level of one or several of the substances found in the smoke. Passey, et al. (95, 96,97) studied smoke effects in rats. Gastrointestinal lXwrdlers Cigar and pipe smokers experience higher death rates from peptic ulcer disease than nonsmokers. These rates are higher for gastric ulcers than for duodenal ulcers but are somewhat less than those rates experienced by cigarette smokers. Retrospective or cross-sectional studies by Trowel1 (129), All&one and Flint (3), Doll, et al. (37), and Edwards, et al. (42) contain data on ulcer disease in pipe smokers as well as cigarette smokers, but no association was found between pipe smoking and ulcer disease in these investigations. Snuff and Chewing Tobacco In the United States most of the tobacco consumed is used in pipes, cigars, or cigarettes, forms that involve combustion. Nicotine and other substances can be absorbed through the oral mucosa, however, and so tobacco can also be chewed, inhaled into the nose, or retained between the cheek and gum. 13-38 A variety of forms of tobacco are designed for noncombustive use (141). Plug tobacco contains Burley, cigar, and Virginia tobaccos sweetened with honey, sugars, molasses, syrups, and licorice, pressed into flattened blocks and then wrapped with natural leaf. Scrap chewing tobacco is made from fermented cigar leaf tobacco. Some brands are only lightly sweetened, whereas others carry large amounts of sugars, syrups, licorice, and other flavoring materials. The treated tobacco is not compressed, but is packaged as loose pieces of cut strips. In some countries, chewing tobacco is made from tar-like material extracted by boiling the green leaves in water. This extract is mixed with slaked lime or wood ashes. When dipped into this mixture, cured leaf absorbs it. These materials are then twisted into strands and allowed to dry. In India, betel nut may be mixed with tobacco leaf to make a chewing tobacco. Dark air-cured and fire-cured tobaccos are powdered, flavored, and variously packaged to make snuff. The consumer places the snuff between the lower lip and gum, inhales a pinch into the nostril, or dips a moistened brush into the snuff and places the brush between the cheek and gum. Prevalence of Snuff Use and Tobacco Chewing Only a small percentage of the United States population chews tobacco (Table 2), and an even smaller percentage uses snuff (91, 92). Use of these products is more frequent in males than in females, and usage is relatively stable. The combination of the low prevalence of snuff use and tobacco chewing and the low incidence of oral cancer in the U.S. makes it difficult to accumulate the large numbers of subjects necessary for an adequate epidemiologic study. Many of those who now use snuff or chew tobacco are either current or former smokers and, therefore, are likely to obscure an independent effect of snuff or chewing tobacco. Finally, such use involves a very small percentage of the population ethnically, geographically, and culturally different from the general population, which makes it difficult to compare incidence rates with the general population. Because of these problems, many of the studies on tobacco chewing have been done in Asia, where the prevalence of both oral cancer and tobacco chewing is higher. The validity of applying those results to the United States is questionable, however, because of differences in the type of tobacco chewed, nutritional status, and social habits. Benign Oral Imions and Oral Cancer A population of 15,000 snuff users, 75 percent female, from a large clinic in the southern U.S., was examined by Smith, et al. (117) for oral lesions. In most patients no mucosal abnormalities were found, even in the areas of the mouth where the tobacco quid was usually held. Only 13-39 1,751 (11.7 percent) demonstrated any mucosal change, and only 157 had lesions suspicious enough to biopsy. The biopsies showed early epithelial changes, such as atrophy, but none of the biopsies showed changes consistent with dyskeratosis or malignancy. Of the 1,751 patients who showed some tissue change by visual examination and had cytologic examinations performed, 1,502 had normal findings, I2 had unsatisfactory smears, and 237 had benign hyperkeratosis. Seventy-five percent of the subjects were followed with repeated cytologic smears at 6month intervals for 5 l/2 years, and none showed any mucosal changes different from the original testing. The conclusion was that snuff is not a risk factor for oral cancer and is not associated with an excess incidence of other oral lesions. F&d-Petersen and Pindborg (10&z), who studied 450 Danish patients with oral leukoplakias, of whom 32 used snuff, were unable to show any difference between snuff-associated leukoplakias and other leukoplakias in degree of dysplasia observed histologically or in malignant development. In contrast to these negative studies, a number of studies from Asia have found an association between tobacco chewing and oral lesions, but, again, questions of application to an American population arise. Mehta, et al. (84, conducted a house-to-house survey of 101,761 villagers in the Poona district of India and found a prevalence of leukoplakia of 1.18 percent in male chewers of tobacco, and 1.34 percent in female chewers. Nonchewers had rates of 0.05 percent for males and 0.04 percent for females. Smokers and those with mixed habits had rates higher than persons who just chewed tobacco. Smith, et al. (118) found an increased prevalence of leukoplakia in tobacco chewers compared to nonchewers among 57,518 industrial workers of Gujarat, but none of the tobacco-chewing subjects had developed oral cancer during a Zyear follow-up (116). Mehta, et al. (84) also found an increased prevalence of leukoplakia in Bombay policemen, but found that the lesions in tobacco chewers tended to regress, whereas lesions in smokers did not. Jussawalla and Deshpande (67) conducted a retrospective study of 2,005 oral cancer patients and matched controls. They found chewing to be associated with an increased risk of cancer of the anterior two- thirds of the tongue, alveolus, buccal mucosa, hard palate, base of the tongue, tonsil, oropharynx, hypopharynx, and esophagus. The risk was greatest for sites where the bolus was retained for a significant length of time, and the locations of greatest risk were considerably different from the sites affected in smokers. They felt that this was due to the different exposures experienced by smokers and chewers. Soda (119) also found an excess risk of oral cancer in chewers with a different distribution of lesion sites between chewers and smokers. Shanta and Krishnamurthi (IQ), Sanghvi, et al. (IOr), and Paymaster (98) have also found an association between oral cancer and tobacco habits, 13-40 especially the use of "pan" consisting of green leaf in which sliced betel nut, tobacco dust, slaked lime, liquified catechu, and other spices are rolled. In summary, there does seem to be an association between tobacco chewing and leukoplakia and oral cancer in Asia, but it is not clear that the same risk holds true in the United States due to a difference in the tobacco being chewed and to differences in the nutritional status and other characteristics of the population. Conclusions Pipe and cigar smokers in the United States as a group experience overall mortality rates that are slightly higher than those of nonsmokers, but at rates substantially lower than those of cigarette smokers. This appears to be due to the fact that the total exposure to smoke that a pipe or cigar smoker receives from these products is relatively low. The typical cigar smoker smokes fewer than 5 cigars a day and the typical pipe smoker consumes less than 20 pipefuls a day. Most pipe and cigar smokers report that they do not inhale the smoke. Those who do, say they inhale infrequently and only slightly. As a result, the harmful effects of cigar and pipe smoking appear to be largely limited to those sites which are exposed to the smoke of these products. Mortality rates from cancer of the oral cavity, intrinsic and extrinsic larynx, pharynx, and esophagus are approximately equal in users of cigars, pipes, and cigarettes. Inhalation is evidently not necessary to expose these sites to tobacco smoke, and these sites account for only about 5 percent of the cancer mortality among men. Coronary heart disease, lung cancer, emphysema, and chronic bronchitis clearly are associated with cigarette smoking; but for cigar and pipe smokers, death rates from these diseases are not greatly elevated above the rates of nonsmokers. These diseases seem to depend on moderate to deep inhalation to bring the smoke into direct contact with the tissue at risk or to allow certain constituents, such as carbon monoxide, to be systematically absorbed through the lungs or to affect the temporal patterns of absorption of other constituents, such as nicotine, that can be absorbed either through the oral mucosa or through the lungs. Evidence from countries where smokers tend to consume more cigars and inhale them to a greater degree than in the United States indicates that rates of lung cancer become elevated to levels approaching those of cigarette smokers. Data on the chemical constituents of cigar, pipe, and cigarette smoke suggest that the composition of these products is similar. Pipe and cigar smoke, however, tends to be more alkaline than cigarette smoke, and fermented tobaccos commonly used in pipes and cigars contain less reducing sugars than the rapidly dried varieties commonly used in cigarettes. 13-41 Experimental evidence suggests little difference between the tumorigenic activities of tars obtained from cigar or cigarette tobaccos. Malignant skin tumors appear somewhat more rapidly and in larger numbers in animals whose skin has been painted with cigar tars than in those animals painted with cigarette tars. It must be concluded that some risk exists from smoking cigars and pipes, as currently used in the United States, but for most diseases the risk is small relative to the enormous risk of smoking cigarettes. Nevertheless, changes in patterns of usage that would bring about increased exposure either through increased use of cigars and pipes or increased inhalation of pipe and cigar smoke have the potential of producing risks similar to those now incurred by cigarette smokers. Tobacco chewing is associated with an increased risk of leukoplakia and oral cancer in Asian populations, but the risk for populations in the United States is not clear. An increased risk of oral leukoplakia associated with snuff use in the U.S. has not been demonstrated. 13-42 Other Forms of Tobacco Use: References (I) ABELIN, T., GSELL, OR. Relative risk of pulmonary cancer in cigar and pipe smokers. Cancer 29(8): 12881296, August 1967. (6) ALLIBONE, A., FLINT, F.J. Bronchitis, aspirin, smoking, and other factors in the aetiology of peptic ulcer. Lancet 2(`7939): 179182, July 23,1958. (4) ARMITAGE, A.K., TURNER, D.M. Absorption of nicotine in cigarette and cigar smoke through the oral mucosa. Nature 226(5252): 1251-1232, June 27, 1970. (5). ASHFGRD, JR, BROWN, S. DUFFIELD, D.P., SMITH, C.S., FAY, J.W.J. The relation between smoking habita and physique, respiratory symptoms, ventilatory function, and radiological pneumoconiosis amongst coal workers at three Scottish collieries. British Journal of Preventive and Social Medicine 15: 106-117,196l. (6) AUERBACH, O., GARFINKEL, L., HAMMOND, EC. Relation of smoking and age to findings in lung parenchyma: A microscopic study. Chest 65(l): 2935, January 1974. (r) AUERBACH, O., HAMMOND, EC., GARFINKEL, L. Histologic changes in the larynx in relation o a smoking habits. Cancer 28(l): 92104, January 1979. (8) AUERBACH, O., STOUT, A.P., HAMMOND, E.C., GARFINKEL, L. Changes in bronchial epithelium in relation to sex, age, residence, smoking and pneumonia New England Journal of Medicine !%7(3): 111-125, July 19, 1962. (9) AUERBACH, O., STOUT, A.P., HAMMOND, E.C., GARFINKEL, L. Histologic changes in esophagus in relation to smoking habits Archives of Environmental Health 11: 4-15, July 1965. (10) AUERBACH, O., STOUT, A.P., HAMMOND, E.C., GARFINKEL, L. Smoking habits and age in relation to pulmonary changes. Rupture of alveolar septums, fibrosis and thickening of walls of small arteries and arterioles. New England Journal of Medicine 269: 1045-1954, November 14,1983. (II) BEST, E.W.R., MCGREGOR, J.T. A Canadian Study of Smoking and Health. Ottawa, Department of National Health and Welfare, 1936,137 pp. (16) BOAKE, WC. A study of illness in a group of Cleveland families. XVIII. Tobacco smoking and respiratory infections. New England Journal of Medicine 259(26): I245-1249, December 25,1958. (14) BOWER, G. Respiratory symptoms and ventilatory function in 172 adults employed in a bank. American Review of Respiratory Disease 83: 684-389, 1981. (15) BRADSHAW, E., SCHONIAND, M. Cksophageal and lung cancers in Natal African males in relation to certain so&-economic factor. An analysis of 484 interviews. British Journal of Cancer 23(2): 275-284, June 1939. (16) BRODERS, A.C. Squamouscell epithelioma of the lip. A study of Five hundred and thirty-seven cases. Journal of the American Medical Association 74(10): 656-664, March 6,1929. (17) BROSS, I., TIDINGS, J. Switching from cigarettes to small cigars-is it likely to reduce the health hazards of smoking? Paper presented at the Sixty-Fourth Annual Meeting of the American Association for Cancer Fkearch, Atlantic City, NJ., April 11-13, 1973. Proceedings of the American Association for Cancer Research 14: 21, March 1973. (Abstract) (18) BRUNNEMANN, K.D., HOFFMANN, D. Chemical studies on tobacco smoke. XXIV. A quantitative method for carbon monoxide and carbon dioxide in cigarette and cigar smoke. Journal of Chromatographic Science 12(2): 7&75, February 1974. (19) BRUNNEMANN, K.D., HOFFMANN, D. The pH of tobacco smoke. Food and Cosmetics Toxicology 12: 115-R&4,1974 (66) BUELL, P., DUNN, J.E., JR, BRESLOW, L. Cancer of the lung and Los Angeles-type air pollution. Prospective study. Cancer 29(l2): 2139-2147, December 1967. 1343 (21) CAMPBELL, J.M., LINDSEY, A.J. Polycyclic hydrocarbons in cigar smoke, British Journal of Cancer 11: 192195,1957. (2.2) CASTLEDEN, C.M., COLE, P.V. Inhalation of tobacco smoke by pipe and cigar smokers. Lancet 2(7819): 21-22, July 7,1973. (25) CEDERLOF, R., FRIBERG, L., HRUBEC, Z. Cardiovascular and respiratory symptoms in relation to tobacco smoking. A study on American twins. Archives of Environmental Health 18(6): 934946, June 1969. (a,$) COMSTOCK, G.W., BROWNLOW, W.J., STONE, R.W., SARTWELL, P.E. Cigarette smoking and changes in respiratory findings. Archives of Environ- mental Health 21(l): 59-57, July 1970. (,%) COWIE, J., BALL, K.P., SILLETT, R.W. Changing to cigar smoking. Postgraduate Medical Journal 49(576): 767-710, October 1973. (96) COWIE, J., SILLETT, R.W., BALL, K.P. Carbon-monoxide absorption by cigarette smokers who change to smoking cigars. Lancet l(7811): 1633-1635, May l2,1973. (27) CRONINGER, A.B., GRAHAM, E.A., WYNDER, E.L. Experimental production of carcinoma with tobacco products. V. Carcinoma induction in mice with cigar, pipe, and all-tobacco cigarette tar. Cancer Research 18(11): X263-1271, December 1958. (28) DALHAMN, T., RYLANDER, R. Ciliotoxicity of cigar and cigarette smoke. Archives of Environmental Health 20(2): 252253, February 1970. (299) DAVIES, RF., DAY, T.D. A study of the comparative carcinogenicity of cigarette and cigar smoke condensate on mouse skin. British Journal of Cancer 23(2): 363-368, June 1969. (SO) DAWBER, T.R. The interrelationship of tobacco smoke components to hyperlipidemia and other risk factors. In: Wynder, E.L., Hoffmann, D., Gori, G.B. (Editotn). Proceedings of the Third World Conference on Smoking and Health, New York, June 2-5, 1975. Volume I. Modifying the Risk for the Smoker. U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, National Cancer Institute, DHEW Publication No. (NIH) 761221, pp. 235292 (31) DAWBER, T.R., KANNEL, W.B., REVOTSKIE, N., STOKES, J., III, KAGAN, A., GORDON, T. Some factors associated with the development of coronary heart disease. Six years' follow-up experience in the Framingham study. American Journal of Public Health and the Nation's Health 49(10): 1349-1356, October 1959. ($2) DENSEN, P.M., JONES, E.W., BASS, H.E., BREUER, J. A survey of respiratory disease among New York City postal and transit workers. I. Prevalence of symptoms. Environmental Research l(3): 262286, November 1967. ($3) DOLL, R., HILL, A.B. Mortality of British doctors in relation to smoking: Observations on coronary thrombosis. In: Haenszel, W. (Editor). Epidemiologi- cal Approaches to the Study of Cancer and Other Chronic Diseases. National Cancer Institute Monograph No. 19. U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, National Cancer Institute, January 1966, pp. 205215. (34) DOLL, R., HILL, A.B. Mortality in relation to smoking: Ten years' observations of British doctors (Part 1). British Medical Journal l(5395): 1399-1410, May 36, 1964. (35) DOLL, R. HILL, A.B. Mortality in relation to smoking: Ten years' observations of British doctors (Concluded). British Medical Journal l(5396): 1460-1467, June 6,1964. (96) DOLL, R., HILL, A.B. A study of the aetiology of carcinoma of the lung. British Medical Journal 2: 1271-1286, December 13,1952. 13-44 (40) (41) (12) (44) (W) (46) WI (48) tw (51) (W (5.9 (54) (58) DOLL, R., JONES, F.A., PYGOTT, F. Effect of smoking on the production and maintenance of gastric and duodenal ulcers. Lancet l(7022): 657662, March 23, 1958. DOLL, R., PETO, R. Mortality in relation to smoking: 29 years' observations on male British doctors. British Medical Journal 2(6051): 1525-1536, December 25, 1976. DOYLE, J.T., DAWBER, T.R., KANNEL, W.B., KINCH, S.H., KAHN, H.A. The relationship of cigarette smoking to coronary heart disease. The second report of the combined experience of the Albany, NY,..., and Framingham, Mass, Studies. Journal of the American Medical Association 190(10): 886-896, December 7,1964. DUNN, J.E., JR, LINDEN, G., BRESLOW, L. Lung cancer mortality experience of men in certain occupations in California American Journal of Public Health and the Nation's Health 59(10): 14751487, October 1969. EBENIUS, B. Cancer of the lip. A clinical study of 778 cases with particular regard to predisposing factors and radium therapy. Acta Radiologiea 24 (Supplement 48): l-232,1943. EDWARDS, F., MCKEOWN, T., WHITFIELD, A.G.W. Association between smoking and disease in men over sixty. Lancet l(7665): 196200, January 24, 1959. FRANKENBURG, W.G. Chemical changes in the harvested tobacco leaf. Part I. Chemical and enzymic conversions during the curing process. Advances in Enzymology 6: 309-38'7,1946. FRANKENBURG, W.G. Chemical changes in the harvested tobacco leaf. Part II. Chemical and enxymic conversions during fermentation and aging. Advances in Enzymology 10: 325-441,1956. GOLDMAN, A.L. Cigar inhaling. American Review of Respiratory Disease 113(l): 87-89, January 1976. GOLDSMITH, JR., HECHTER, H.H., PERKINS, N.M., BORHANI, N.O. Pulmonary function and respiratory findings among longshoremen. American Review of Respiratory Diseases 86(6): 867-8'74, December 1962. HAENSEEL, W., HOUGEN, A. Prevalence of respiratory symptoms in Norway. Journal of Chronic Diseases 25(g): 519-544, September 1972 HAMMOND, E.C. Smoking in relation to the death rates of one million men and women. In: Haenszel, W. (Editor). Epidemiological Approaches to the Study of Cancer and Other Chronic Dii. National Cancer Institute Monograph No. 19. U.S. Department of Health, Education, and Welfare, Public Health Service, National Cancer Institute, January 1966, pp. 121-294. HAMMOND, E.C., GARFINKEL, L. The influence of health on smoking habits. In: Haenszel, W. (Editor). Epidemiological Approaches to the Study of Cancer and Other Chronic D&ases. National Cancer Institute Monograph No. 19. U.S. Department of Health, Education, and Welfare, Public Health Service, National Cancer Institute, January 1966, pp. 269-285. HAMMOND, EC., HORN, D. Smoking and death rates-Report on forty-four months of follow-up of 187,783 men. I. Total mortality. Journal of the American Medical Associition 166(10): 1159-1172, March 8,1953. HAMMOND, EC., HORN, D. Smoking and death rates-Report on forty-four months of follow-up of 18'7,783 men. II. Death rates by cause. Journal of the American Medical Association 166(11): 1294-1308, March 15,1958. HARKE, H.-P. The problem of "passive smoking". Muenchener Medixinisehe Wochenachrift 112(51): 23282334, December 18,197O. HIRAYAMA, T. Smoking in relation to the death rates of 265,118 men and women in Japan. A report on five years of follow-up. Presented at the American Cancer Society's Fourteenth Science Writers' Seminar, Clearwater Beach, Florida, March 27,1972,15 pp. 13-45 (60) HOFFMANN, D., RATHKAMP, G., WYNDER, E.L. Comparison of the yields of several selected components in the smoke from different tobacco products. Journal of the National Cancer Institute 31(3): 627637, September 1963. (62) HOMBURGER, F., TREGER, A., BAKER, J.R. Mouse-skin painting with smoke condensates from cigarettes made of pipe, cigar, and cigarette tobaccos. Journal of the National Cancer Institute 31(6): 14451459, December 1963. (63) HOOD, B., TIBBLIN, G., WELIN, G., ORNDAHL, G., KORSAN-BENGTSEN, K. Myocardial infarction in early age. III. Coronary risk factors and their deficient control. Acta Medica Scandinavica lJ35(4): 241-251, April 1969. (64) INTER-SOCIETY COMMISSION FOR HEART DISEASE RESOURCES. Primary prevention of the Atherosclerotic diseases. Atherosclerosis Study Group and Epidemiology Study Group. Circulation 42(6): A-55A-95, December 1970. (65) ISAAC, P.F., RAND, M.J. Cigarette smoking and plasma levels of nicotine. Nature 236@345): 303310, April 7,1972. (66) JENKINS, C.D., ROSENMAN, R.H., ZYZANSKI, S.J. Cigarette smoking. Its relationship to coronary heart disease and related risk factors in the Western Collaborative Group Study. Circulation 36(6): 1146-1155, December 1966. (67) JUSSAWALLA, D.J., DESHPANDE, V.A. Evaluation of cancer risk in tobacco chewers and smokers: An epidemiologic assessment. Cancer 23(l): 244252, July 1971. (68) KAHN, A., RUTLEDGE, R.B., DAVIS, G.L., ALTES, J.A., GANTNER, G.E, THORNTON, C.A., WALLACE, N.D., FERGUSON, S.S. A Study of Carbon Monoxide Sources in the St. Louis Metropolitan Population and Some Policy Implications. CUERS Report No. 4. Edwardsville, Illinois, Southern Illinois University at Edwardsville, Center for Urban and Environmental Research and Services, September 1975,165 pp. (69) KAHN, H.A. The Dom study of smoking and mortality among U.S. veterans: Report on eight and one-half years of observation. In: Haensrel, W. (Editor). Epidemiological Approaches to the Study of Cancer and Other Chronic Diseases. National Cancer Institute Monograph No. 19. U.S. Department of Health, Education, and Welfare, Public Health Service, National Cancer Institute, January 1966, pp. l-125. (70) KELLER, A.Z. Cellular types, survival, race, nativity, occupations, habita and associated diseases in the pathogenesis of lip cancers. American Journal of Epidemiology 91(5): 436499, May 1970. (71) KELLER, A.Z. Cirrhosis of the liver, alcoholism and heavy smoking associated with cancer of the mouth and pharynx. Cancer 29(6): 10151022, June 1967. (72) KENSLER, C.J. The pharmacology of tobacco smoke effects of chronic exposure. In: James, G., Rosenthal, T. (Editors). Tobacco and Health. Springfield, Illinois, Charles C. Thomas, 1962, pp. 5-20. (75) KESTELOOT, H., VAN HOUTE, 0. An epidemiologic survey of arterial blood pressure in a large male population group. American Journal of Epidemiology 99(l): 14-29, January 1974. (76) KNUDTSON, K.P. The pathologic effects of smoking tobacco on the trachea and bronchial mucosa. American Journal of Clinical Pathology 33(4): 316-317, April 1969. (77) KOULUMIES, M. Smoking and pulmonary carcinoma. Acta Radiologica 39(3): 255269, March 1953. (78) KUHN, H. A comparative study of cigarette and cigar smoke. In: FVocedings of the Fourth International Tobacco Scientific Congress, The National Tobacco Board of Greece, Athens, September 1%%,1966, pp. 967-971. (80) LEVIN, M.L., GOLDSTEIN, H., GERHARDT, P.R. Cancer and tobacco smoking. A preliminary report. Journal of the American Medical Association 143(4): 336333, May 27,195O. 13-46 (81) LOMBARD, H.L., SNEGIREFF, L.S. An epidemiological study of lung cancer. Cancer q2): 466-413, March/April 1959. (82) MARTINEZ, I. Factors associated with cancer of the esophagus, mouth, and pharynx in Puerto Rico. Journal of the National Cancer Institute 42(6): 166% 1094, June 1969. (88) MARTINEZ, I. Retrospective and prospective study of carcinoma of the esophagus, mouth, and pharynx in Puerto Rico. Boletin de la Asociacion Medica de Puerto Rico 62(6): 170-178, June 1970. (84) MEHTA, F.S., SHROFF, B.C., GUPTA, P.C., DAFTARY, D.K. Oral leukoplakia in relation to tobacco habits. A ten-year follow-up study of Bombay policemen. Oral Surgery, Oral Medicine, Oral Pathology 34(3): 426433, September 1972 (85) MILLS, C.A., PORTER, M.M. Tobacco smoking and automobile-driving stress in relation to deaths from cardiac and vascular causes. American Journal of the Medical Sciences 234(l): 35-43, July 1957. (86) MILLS, C.A., PORTER, M.M. Tobacco smoking habits and cancer of the mouth and respiratory system. Cancer Research 10: 539542,195O. (87) MILLS, C.A., PORTER, M.M. Tobacco smoking, motor exhaust fumes., and general air pollution in relation to lung cancer incidence. Cancer Reaeamh 17(6): 981990, July 1957. (88) NAEYE, R.L. Structural features in Appalachian coal workers. In: Key, M.M., Kerr, L.E., Bundy, M. (Editors). Pulmonary Reactions to Coal Dust. A Review of U.S. Experience. New York, Academic Press, 1971, pp. 93-110. (go) NATIONAL CLEARINGHOUSE FOR SMOKING AND HEALTH. Use of Tobacco. Practices, Attitudes, Knowledge, and Beliefs, United States-Fall 1964 and Spring 1966. U.S. Department of Health, Education, and Welfare, Public Health Service, National Clearinghouse for Smoking and Health, July 19% 807 PP. (91) NATIONAL CLEARINGHOUSE FOR SMOKING AND HEALTH. Adult Use of Tobacco, 1970. U.S. Department of Health, Education, and Welfare, Public HeaIth Service, DHEW Publication No. (HSM) 733227, June 1973, 129 pp. (92) NATIONAL CLEARINGHOUSE FOR SMOKING AND HEALTH. Adult Use of Tobacco, 1975. U.S. Department of Health, Education, and Welfare, Public Health Service, June 1976. (9.9) OSMAN, S., BARSON, J. Hydrocarbons of cigar smoke. Tobacco 159(24): 3032, December l&1964. (94) OSMAN, S., SCHMELTZ, I., HIGMAN, H.C., STEDMAN, R.L. Volatile phenols of cigar smoke. Tobacco 157(g): 30-32, August 36,1963. (95) PASSEY, R.D., BLACKMORE, M. Biological effects of cigar and cigarette smoke. British Empire Cancer Campaign for Research, Annual Report 44(Part 2): 6,1966. (96) PASSEY, R.D., BLACKMORE, M. The causation of lung cancer. Some experimental biological effects of cigar and cigarette smoke. Thorax 22(3): 290, May 1967. (Abstract) (gr) PASSJZY, RD., BLACKMORE, M., WARBRICK-SMITH, D.; JONES, R. Smoking risks of different tobacecs. British MedicaI Journal 4(5731): 198201, October 23,197l. (98) PAYMASTER, J.C. Some observations on oral and pharyngeal carcinomaa in the State of Bombay. Cancer X(3): 573533, May/June 1962 (99) PERNU, J. An epidemiological study on cancer of the digestive organs and respiratory system. A study based on 7,973 cases. Annales Medicinae Internae Fenniae 49(Supplement 33): l-117,1969. (100) RANDIG, K. Untersuchungen zur Aetiologie des Bronchialkarzinoms (Inveati- g&ions on the aetiology of bronchial carcinoma). Oeffentliche Gesundheits- dienst X(9): 305-313, December 1954. 1347 (101) REA, J.N., TYRER, P.J., KASAP, H.S., BERESFORD, S.A.A. Expired air carbon monoxide, smoking, and other variables. A community study. British Journal of Preventive and Social Medicine 27(2): 114-120, May 19'78. (102) RIMINGTON, J. Chronic bronchitis, smoking and social class. A study among working people in the towns of Mid and East Cheshire. British Journal of Diseases of the Chest 63(4): 193-205, October 1969. (IO.?) ROE, F.J.C., CLACK, J.C., BISHOP, D., PEI!O, R. Comparative carcinogenicity for mouse-skin of smoke condensates prepared from cigarettes made from the same Uacco cued by two pm. British Journal of Cancer 24(l): 107-121, March 1970. (I&%) ROED-PETERSEN, B., PINDBORG, J.J. A study of Danish snuff-induced ora1 leukoplakias. Journal of Oral pathology 2: 361313,1973 (104) ROGOT, E. Smoking and mortality among U.S. veterans. Journal of Chronic Diseases 27: 139-203,1974. (105) SADOWSKY, D.A., GILLIAM, A.G., CORNFIELD, J. The statistical association between smoking and carcinoma of the lung. Journal of the National Cancer Institute 18(5): 1237-1258, April 1958. (106) SANDERUD, K. Squamous metaplasia of the respiratory tract epithelium: An autopsy study of 214 eases. II. Relation to tobacco smoking, occupation and residence. Acta Pathologica et Microbiologica Scandinavica 43: 47-61, 1953. (107) SANGHVI, L.D., RAO, K.C.M., KHANOLKAR, V.R. Smoking and chewing of tobacco in relation to cancer of the upper alimentary tract. British Medical Journal l(4922): 1111-1114, May 7,1955. (108) SCHIEVELBEIN, H., EBERHARDT, R. Cardiovascular actions of nicotine and smoking. Journal of the National Cancer Institute 43(6): 17351794, June 1972 (109) SCHIMMLER, W., NEFF, C., SCHIMERT, G. Risikofaktoren und Herxinfarkt Eine retrospektive Studie (Risk factors and myocardial infarct. A retrosm tive study). Muenchener Medixinisehe Wochenschrift llO(27): 15851594, July 5,1963. (110) SCHREK, R, BAKER, L.A., BALLARD, G.P., DOLGOFF, S. Tobacco smoking as an etiologic factor in dii. I. Cancer. Cancer Research lo(l): 49-53, January 1956. (111) SCHWARTZ, D., DENOIX, P.-F. L'enquete Fran&se sur I'etiologie du cancer broncho-pulmonaire. Role du tabac (French investigation on the etiology of bronchopulmonary cancer. Role of tobacco). Semaine des Hopitaux de Paris 33(62/7): 36393643, October 39,1957. (113) SCHWARTZ, D., FLAMANT, R., LELLOUCH, J., DENOIX, P.-F. Results of a French survey on the role of tobacco, particularly inhalation, in different cancer sites. Journal of the National Cancer Institute 26(5): 10851103, May 1961. (214) SHANTA, V., KRISHNAMURTHI, S. A study of aetiological factors in oral squamous cell carcinoma. British Journal of Cancer 13(3): 331-333, September 1959. (115) SHAPIRO, S., WEINBLATT, E., FRANK, C.W., SAGER, RV. Incidence of coronary heart disease in a population insured for medical care (HIP). Myocardial infarction, angina pectoris, and possible myocardiai infarction. American Journal of Public Health and the Nation's Health 59 (6, Supplement, Part 2): l-101, June 1969. (f16) SILVERMAN, S., JR, BHARGAvTA, K., MANI, N.J., SMITH, L.W., MA- LAOWALLA, A.M. Malignant transformation and natural history of oral leukoplakia in 57,518 industrial workers of Gujarat, India. Cancer 88(4): 1790- 1795, October 1976. (117) SMITH, J.F., MINCER, H.A., HOPKINS, K.P., BELL, J. Snuff-dipper's lesion. A cytological and pathological study in a large population. Archives of otolaryngology 92(5): 456-456, November 1970. 13--48 (118) SMITH, L.W., MALAOWALLA, A.M., BHARGAVA, K., MANI, N.J. A report on the study of oral cancer and precancerous lesions among 57,518 industrial workers of Gujarat, Phase I. Oral Cancer Research Project, Government Dental College and Hospital, Ahmedabad, Gujarat, India, September 1, 1973. (119) SODA, T. Cancer of oral cavity. Asian Medical Journal l2(10): 228234, October 1969. (1.60) SPAIN, D.M., NATHAN, D.J. Smoking habits and coronary atherosclerotic heart disease. Journal of the American Medical Association 177(10): 683-638, September 9,196l. (1.61) STASZEWSKI, J. Palenie a rak wargi, jamy ustnej, migdalkow i krtani (Tobacco smoking and its relation to cancer of the mouth, tonsils and larynx). Nowotwory lo(2): 121-132,1969. (128) STOCKS, P. Cancer incidence in North Wales and Liverpool region in relation to habits and environment. British Empire Cancer Campaign Thirty-fifth Annual Report Covering the Year 195'7, Supplement to Part II, 1957,156 pp. (125) TIBBLIN, G. High blood pressure in men aged 59-A population study of men born in 1913. Acta Medica Scandinavica (Supplementum 470): l-84,1967. (126) TODD, G.F. (Editor). Statistics of Smoking in the United Kingdom. Research Paper I, 4th Edition. London, Tobacco Research Council, 1966,193 pp. (127) TODD, G.F. (Editor) Statistics of Smoking in the United Kingdom. Research Paper 1,5th Edition. London, Tobacco Research Council, 1969,124 pp. (128) TODD, G.F. (Editor). Statistics of Smoking in the United Kingdom. Research Paper I, 6th Edition. London, Tobacco Resoamh Council, 1972,132 pp. (129) TROWELL, O.A. The relation of tobacco smoking to the incidence of chronic duodenal ulcer. Lancet 1: 84M-809, April 14,1934. (130) UNITED STATES CODE OF FEDERAL REGULATIONS. Title 26 (Internal Revenue Service) Part no-Manufacture of Cigars and Cigarettes. (As adopted at 26 F.R. 8173, effective October 1, 1961). B(270)3-B(270)5, October 31,197o. (181) U.S. DEPARTMENT OF THE TREASURY. Revenue Ruling 69-198. Internal Revenue Cumulative Bulletin: 359,1969-l. (182) VAN BUCHEM, F.S.P. Serum lipids, nutrition and atherosclerotic complications in man. Acta Medica Scandinavica 181(4): 493-416,1967. (188) VILLIGER, U., HEYDEN-STUCKY, S. Das Infarktprofii. Unterschiede zwischen Infarktpatienten und Kontrollpersonen in der Ostschweiz (The infarct profile. Differences between infarct patients and control persons in East Switzerland). Schweizerische Medizinische Wochenschrift 96(23): 748758, 1966. (f84) WEIR, J.M., DUNN, J.E., JR. Smoking and mortality: A prospective study. Cancer 25(l): 195-112, January 1970. (135) WICKEN, A.J. Environmental and Personal Factors in Lung Cancer and Bronchitis Mortality in Northern Ireland, 1969-62. Research Paper 9. London, Tobacco Research Council, 1966,84 pp. (186) WYNDER, EL., BROSS, I.J. A study of etiologiral factors in cancer of the esophagus. Cancer 14(2): 389-413, March/April 1961. (1%") WYNDER, E.L., BROSS, I.J., DAY, E. A study of environmental factors in cancer of the larynx. Cancer 9(l): 86-110, January/February 1956. (188) WYNDER, E.L., BROSS, I.J., FELDMAN, R.M. A study of the etiological factors in cancer of the mouth. Cancer lo(6): X%9&1323, November/December 1957. (189) WYNDER, E.L., CORNFIELD, J. Cancer of the lung in physicians. New England Journal of Medicine 248(11): 441-444, March 12,1953. 1349 (240) WYNDER, E.L., GRAHAM, E.A. Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma: A study of six hundred and eighty-four proved cases. Journal of the American Medical Association 143(4): 329333, May 27, 1950. (141) WYNDER, E.L., HOFFMANN, D. Tobacco and Tobacco Smoke. Studies in Experimental Carcinogenesis. New York, Academic Press, 1957,739 pp. (1&Z) WYNDER, EL., HULTBERG, S., JACOBSSON, F., BROSS, I.J. Environmental factors in cancer of the upper alimentary tract. A Swedish study with special reference. to Plummer-Vinson (Paterson-Kelly) syndrome. Cancer lo(3): 470- 437, May/June 1957. (I&?) WYNDER, E.L., LEMON, F.R., MANTEL, N. Epidemiology of persistent cough. American Review of Respiratory Diseases 91(5): 679-709, May 1965. (141) WYNDER, E.L., MABUCHI, K., BEATTIE, E.J., JR. The epidemiology of lung cancer. Recent trends. Journal of the American Medical Associition 213(X3): ml-2223, September 23,197O. (Z&) WYNDER, E.L., NAVARRETE, A., AROSTEGUI, G.E., LLAMBES, J.L. Study of environmental factors in cancer of the respiratory tract in Cuba Journal of the National Cancer Institute 20(4): 635-373, April 1953. (146) WYNDER, EL., WRIGHT, G. A study of tobacco carcinogenesis. I. The primary fractions. Cancer lO(2): 255-271, March/April 1957. 13-W 14. CONSTITUENTS OF TOBACCO SMOKE. National Cancer Institute CONTENTS Introduction .............................................................. 9 References .......................................................... 10 The Cigarette: Composition and Construction ................. 11 Types and Classes of Tobacco ............................... .13 Physical and Chemical Characteristics ..................... 14 Culture and Harvesting Practices ........................... 17 Curing and Aging .............................................. .18 Other Factors .................................................... .20 Relationships Among Tobacco Leaf, Smoke, and Biological Response ........................................... 22 Modification of Tobacco and Tobacco Products.. ...... .26 Cigarette Engineering .......................................... `2% Other Tobacco Products.. ..................................... .30 Summary .......................................................... .31 References .......................................................... 32 Smoke Formation ...................................................... 35 Physics-Chemical Nature of Cigarette Smpke.. ........ .35 Temperature Profiles ..................................... 35 Material Balance ......................................... .36 Mainstream Smoke Aerosol ........................... .37 Chemical Composition of Tobacco Smoke.. .............. .33 Gas Phase ................................................... 38 Carbon Monoxide and Carbon Dioxide.. ....... .33 Nitrogen Oxides ........................................ 39 Ammonia ................................................. 39 Volatile N-Nitrosamines ............................. 39 Hydrogen Cyanide and Cyanogen ................ .39 Volatile Sulfur Compounds ........................ .46 Volatile Nitriles ....................................... .46 Other N-Containing Volatile Compounds ...... .41 Volatile Hydrocarbons ................................ 41 Volatile Alcohols ...................................... .42 Volatile Aldehydes and Ketones .................. .42 Particulate Phase.. ....................................... .43 Total Particulate Matter ............................ 43 Nicotine and Minor Tobacco Alkaloids.. ....... .44 Nonvolatile N-Nitrosamines ........................ .45 14-3