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


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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

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