The asbestos minerals are classified according to structural
features into two groups, serpentine and amphibole. Chrysotile, a
serpentine (white asbestos), comprises pliable, curl: fibers that are
formed individually from fibrillar subunits. Layers of linked silica
tetrahedra alternate with layers of magnesium hydroxide octahedra
to form long, hollow, scroll-like structures. Chrysotile accounts for
approximately 95 percent of the world usage of asbestos today. The
major producers are the Soviet Union and Canada.

The amphibole types of asbestos (crocidolite, amosite, tremolite,
actinolite, and anthophyllite) are generally made up of straight,
needle-like fibers consisting of strips of silica tetrahedra linked by
one or more cations (calcium, sodium, magnesium, and iron). The
mineral names are often distinguished by adding the modifier
asbestos after the name for those minerals that may occur both as a
fiber and not as a fiber. In this text, crocidolite refers to asbestiform
richterite and amosite refers to asbestiform grunerite. In the United
States, amosite and, to a lesser extent, crocidul'te were widely used
in the past, but their commercial importance has aecreased dramati-
cally in the last two decades (Craighead and Mossman 1982). The
amphiboles tremolite, actinolite, and anthophy!lite are minor con-
taminants of some chrysotile and industrial tale products, are
present in both asbestiform and nonabestiform types, and are not
produced for commercial use.

The occupations and industries in which the major mortality
studies of asbestos-exposed workers have been conducted are pre-
sented in Table 1. Groups not described in this table, but for whom
there is considerable concern about substantial asbestos exposure,
include workers in the building and demolition trades and mainte-
nance workers.

The number of workers exposed to asbestos in the United States
has been variously calculated, but a detailed review by Nicholson
and colleagues (1982) estimated that 18.8 million workers have had
more than 2 months of exposure in occupations where significant
asbestos exposure may have occurred.

An earlier chapter of this Report documents that ave and
occupation are associated with substantial differences in s ing
behavior. These differences would be expected to substantia. « « ter
lung cancer and chronic lung disease mortality; therefore, a careful
examination of the smoking habits of asbestos-exposed popula... 1s is
needed in order to interpret the data on mortality and disecs~
incidence and prevalence reported in the literature. Table 2 ore 3:
the smoking habits of asbestos workers from a number of «°: -¢s of
asbestos-exposed populations. In most of the studies o: ashestos-
exposed populations, approximately ;0 to 80 percent of male asbestcs
workers smoked. In some subsets of workers, well over 9C percent ot
the individuals were current smokers or had smoked in the past. Li

201
157-964 0 - 86 - 8
GUS

TABLE 1.—Mortality from asbestos-related dis:

—

eases in various cohort studies

 

 

 

 

Asbestosis Lung cancer
Type of Percent § Number in Total Meso- (pneumo-
activity Study Place Fiber type smoking cohort deaths thelioma coniosis) Observed Expected SMR
Mining McDonald et al. Quebec Chrysotile 10,939 3,291 10 42 230 184 125
(1980)
Nicholson et al. Quebec Chrysotile 544 178 1 26 28 111 252
(1979)
Rubino et al. Italy Chrysotile 952 332 0 9 i! 10.4 106
(1979)
Hobbe et al. Western Crocidolite 6,200 526 17* 14 60 38.2 157
(1980) Australia
Meurman et al. Finland Anthophyllite 66.7 1,092 248 0 13 21 12.6 167
(1974)
Friction Berry and England Chrysotile M 9,113 1,640 8 NS 143° 139.5 103
materials Newhouse Crocidolite * W 4,347 346 2 NS 6? 11.3 53
(1983)
McDonald et al. Connecticut Chrysotile 3,641 1,267 0 125 73 49.1 148.7
(1984) Crocidolite *
Anthophyllite*
General Henderson and United States Chrysotile 81 1,075 781 5 31 63° 23.3 270.4
manufacturing Enterline Crocidolite
(1979) Amosite
Newhouse and England Chrysotile M 2,887 545 46 NS 103° 43.2 238
Berry (1979) Crocidolite Ww 693 200 21 NS 27° 3.2 844

Amosite
€0¢

TABLE 1.—Continued

 

 

 

 

 

Asbestosis Lung cancer
Type of Percent Number in Total Meso- (pneumo-
activity Study Place Fiber type smoking cohort deaths thelioma coniosis) Observed Expected SMR
Textiles Peto et al. England Chrysotile 1,106 317 10 NS 514 23.8 214
(1977) Crocidolite (?)
Peto (1980) England Chrysotile 679 239 7 10 40 23.3 172
Crocidolite (?)
Dement et al. South Chrysotile 62.4 768 191 1 15 26 75 348
(1982) Carolina Crocidolite ‘
McDonald et al. South Chrysotile 89° 2,543 | 857 1 21 59 29.6 199.5
(1983a) Carolina Crocidolite‘
McDonald et al. Pennsylvania Chrysotile 75° 4,137 1,392 14 74 53 50.5 105
(1983b) Amosite
Crocidolite *
Robinson et al. Pennsylvania Chrysotile M 2,722 912 13 NS 49 36.1 136
(1979) Amosite W554 128 4 NS 14 17 824
Crocidolite ¢
Cement Weill et al. New Orleans Chrysotile 5,645 601 0” NS 51 49.2 104
products (1979) Crocidolite
Amosite*
Finkelstein Scarborough Chrysotile 535 138 19 NS 26 5.4 480
(1983) Crocidolite
Thomas et al. Cardiff Chrysotile 1,592 351 2 NS 28 33.0 85
(1982) Crocidolite *
Gas mask Jones et al. England Crocidolite 578 166 17 NS 12 6.3 190
manufacturing (1980)
Insulation Seidman et al. New Jersey Amosite 820 528 14 30 93 22.8 408
products (1979)

 
OS

TABLE 1.—Continued

 

 

Asbestosis Lung cancer
Type of Percent Number in Total Meso-— (pneumo-
activity Study Place Fiber type smoking cohort deaths thelioma coniosis) Observed Expected SMR
Insulators Newhouse and England Chrysotile 1,368 83 10 NS 21° 5.6 375
Berry (1979) Amosite
Selikoff et al. United States Chrysotile 82.3 17,800 2,271 175 168 486 105.6 480
(1979) and Canada Amosite
Selikoff, New York and Chrysotile 632 478 38 4) 93 13.3 699
Seidman et al. New Jersey  Amosite
(1980)
Shipyard Rossiter and England Chrysotile 66.8 6,076 1,043 31 9 84 119.7 70
workers Coles (1980) Crocidolite
Amosite

 

NOTE: NS, not stated; M, men; W, women.
‘Includes one suspected case of mesothelioma.

? According to the mortality study, which was restricted to deaths before January 1, 1978. The text o
3 Pleural mesotheliomas included in lung cancer total given by the

‘Minimal usage.

® Authors stated that none of the cases were clearly attributable to asbestos exposure.
® Male eversmokers, 1910-1919 birth cohort.
"Two cases did not meet criteria for entry into the cohort.

* Includes mesotheliomas.

f this study also noted 26 cases of mesothelioma diagnosed to January 1, 1979.
authors but taken out of the lung cancer total for the purpose of this Table.
and colleagues (1983) showed lower rates of smoking among shipyard
workers in South Carolina. Only 42.9 percent reported that they
were current smokers, and 24.8 percent had ceased smoking. This
decline in smoking found in the United States is not evident in
studies of asbestos workers in Great Britain.

Lung Cancer

Cigarette smoking is the major cause of lung cancer in the U.S.
population considered as a whole (US DHHS 1982). Among U.S. men
aged 50 to 70 (the group most commonly examined in occupational
mortality studies), over 10 percent of the deaths were due to lung
cancer in 1977 (McKay et al. 1982). The prevalence of smoking and
the percentage of deaths due to lung cancer vary substantially in the
studies of asbestos-exposed populations reported in the literature,
but in the largest study (Hammond et al. 1979) of heavily exposed
workers with a high smoking prevalence (82.3 percent), 21.4 percent
of the deaths were due to lung cancer.

The high incidence of lung cancer in both asbestos-exposed
workers and the U.S. population, together with the potency of
cigarette smoking in determining lung cancer risk, makes the
determination of the smoking habits of asbestos-exposed populations
essential to any evaluation of lung cancer. The prevalence of
smoking varies markedly among men born in different years of this
century, between blue-collar and white-collar workers (see the
chapter on smoking patterns), and among the populations of asbestos
workers studied in the literature. In particular, men born between
1910 and 1930 have a higher prevalence of smoking than men born
earlier; men born after 1930 have had lower prevalences of smoking
at any given age than the men born between 1910 and 1930. Levels
of asbestos exposure have also not been constant with time. Since the
recognition of the hazards of asbestos exposure, improved control of
asbestos dust has reduce the levels of asbestos in mines and
manufacturing plants and. more recently, in other areas where
asbestos exposure may also occur. These temporal trends of smoking
prevalence and asbestos dust levels result in complex relationships
between cumulative asbestos dust exposure and cumulative smoking
exposure. The oldest workers (those born before 1910) may have
higher cumulative asbestos dust exposure at any given age than
younger workers, but will have a lower smoking prevalence.
Workers born between 1910 and 1930 are likely to have both a
higher smoking prevalence and a higher cumulative asbestos
exposure at any given age than workers born after 1930. Therefore,
in many studies of currently employed asbestos workers, cumulative
asbestos exposure will be somewhat correlated with smoking preva-
lence, and biased estimates of dose-response relationships with

205
906

TABLE 2.—Smoking characteristics of asbestos-exposed workers

 

Number and type

 

Study of population Smoking characteristics (percent) Comments
Selikoff et al. 370 union local members, SM/EX NR’ Pipe/cigar *Never smoked
(1968) aged 45-74, New Jersey 76.5 13 10.5 regularly
Hammond et al. 17,800 union local SM* EX NS Pipe/cigar *82.9% smoked
(1979) members, New Jersey 54.2 22.2 10.8 59 >20 cigs/day
Langlands et al. 252 insulation workers, Age <40 years 69° “19% smoked
(1971) Belfast >40 years 74 >25 cigs/day
Ferris et al. 183 shipyard workers SM NS/EX
(1971) 54.6 45.4
Murphy et al. 101 shipyard pipecoverers, SM EX NS
(1971) New England 66.4 26.8 6.9
Harries et al. 2,443 male dockyard 64.7 2.2 33.1
(1972) workers, Great Britain
Harries and Lumley 945 royal naval dockyard 67.2 16.2 16.6
(1977) workers, Great Britain
McMillan et al. 719 royal naval shipyard 48.7 28.7 22.7

(1979)

workers, Great Britain
L026

TABLE 2.—Continued

 

Number and type
Study of population

Smoking characteristics (percent)

Comments

 

Kolonel et al. Male shipyard workers,

(1980) Hawaii

Pearle 131 male shipyard workers
(1982)

Li et al. 3,991 shipyard workers,
(1983) South Carolina

Becklake et al. Asbestos workers, Canada

(1972)

Meurman et al. Anthophyllite mine workers,

(1973, 1974) 1936-1967

Liddell et al. 515 asbestos workers,
(1982) Quebec

Berry et al. 1,203 male asbestos
(1972) workers

Meurman et al.
(1979)

Asbestos workers, Finland

Asbestos-exposed workers
Nonexposed workers
General population

Cohort survivors
Deceased workers

63.8
62.5
58.8

75.6
SM
42.9

SM*
85.3

SM*
66.7

SM
74.5

66.7
79.8

EX

NS
14.7

NS
33.8

19.5

NS
32.3

* Smokers = ever
smoked 1 cig/day
for >1 yr;
includes pipe
and cigar

*28.1% smoked
>15 cigs/day

 
806

TABLE 2.—Continued

 

Number and type

 

 

Study of population Smoking characteristics (percent) Comments
Weill et al. 859 asbestos cement mfg. SM EX NS

(1975) workers, New Orleans 51 26 23

and

Selikoff et al.

(1979)
Greenberg et al. 890 asbestos workers, 84

(1976) Texas
Weiss and Theodos 40 asbestos workers 55.7° 22.7 216 *22.7% smoked

(1978) >1 pack/day
Berry et al. Asbestos textile factory SM EX NS

(1979) workers, Great Britain 69.2 13.8 W
Selikoff, Seidman, 933 amosite asbestos SM EX NS Other

et al. (1980) workers, examined 20 yrs. 617 12.1 13.4 12.6

from employment start date

Skerfving et al. 241 asbestos workers, 64.3

(1980) Sweden
Weiss et al. 45 asbestos workers, aged SM EX NS

(1981) > 40, reexamined 42.2 31.1 26.7

 

 
606

TABLE 2.—Continued

Study

McDermott et al.
(1982)

Acheson et al.
(1984)

Berry et al.
(1985)

Number and type
of population

Two groups of asbestos
workers, Swaziland

Amosite asbestos workers,
Great Britain

1,253 male and 423 female
asbestos factory workers

NOTE: SM =Smoker; EX = Ex-smoker; NS = Nonsmoker.

Group

Group

Men
Women

Smoking characteristics (percent)

SM
38

3d

7

74.5
49.4

EX
10

4

19.6
22.7

NS

19

5.9
279

Comments
asbestos may result. These associations between asbestos exposure
and smoking must be considered when examining the literature and
are particularly important when drawing conclusions from studies
that either do not control for smoking or control for smoking
inadequately. For these reasons, this discussion is limited largely to
those studies that have provided data on the smoking habits of their
populations.

Examination of the relationships among smoking, asbestos expo-
sure, and lung cancer includes consideration of a series of separate
questions. Does asbestos exposure exert an effect in the absence of
active smoking exposure? What are the effects of combined expo-
sure? Is there a threshold of exposure below which no effect occurs?
What happens to the risk following smoking cessation and after
cessation of new asbestos exposure?

Lung Cancer in Nonsmoking Asbestos Workers

The most direct way to demonstrate that asbestos exposure results
in an increased lung cancer risk independent of cigarette smoking is
to monitor disease occurrence in asbestos-exposed individuals who
have never smoked cigarettes regularly. However, because lung
cancer is a relatively rare phenomenon in people who have never
smoked cigarettes, even among asbestos-exposed populations, a large
population of nonsmokers is required before a statistically signifi-
cant number of cases would be expected. The relatively high
prevalence of smoking in asbestos-exposed populations decreases
even further the number of nonsmoking asbestos-exposed workers
available for study, making the evaluation of risks for the nonsmok-
ers difficult. For example, no lung cancer deaths were identified
among the nonsmokers in the original cohort of asbestos insulation
workers reported by Selikoff and colleagues (1968).

Some authors have attempted to increase subject numbers in the
nonsmoker category by combining ex-smokers or light smokers with
never smokers (Blot et al. 1980). However, the risk of developing lung
cancer remains elevated in ex-smokers compared with nonsmokers
for at least 10 to 15 years after cessation, and the excess risk is
proportionate to the amount smoked (US DHHS 1982). Smokers of
less than 10 cigarettes per day have less risk than heavy smokers,
but the relative risk for lung cancer in these light smokers compared
with individuals who have never smoked regularly still varied from
2.3 to 9.5 in the major prospective studies on smoking mortality (US
DHHS 1982). Thus, combining people who have never smoked with
ex-smokers and light smokers is inappropriate and may introduce
bias when the effects of asbestos exposure alone are being assessed.

Several studies have examined populations large enough to
address the question of the risk of asbestos exposure in individuals
who have never smoked regularly. Hammond and colleagues (1979)

210
examined the mortality experience of the 17,800 members of the
International Association of Heat and Frost Insulators and Asbestos
Workers who were alive on January 1, 1967. This group was followed
to December 1976, and the mortality of the 12,051 workers more
than 20 years after onset of exposure was analyzed. Of this group,
smoking histories were available for 8,220, of whom 6,841 (83.2
percent) had been regular smokers at some point and 891 (10.8
percent) had never smoked regularly. Of the 891 workers who had
never smoked regularly, death certificates indicated that 4 died of
lung cancer. The expected number of deaths was calculated from the
mortality experience of a population of blue-collar workers who had
never smoked regularly, drawn from the American Cancer Society
(ACS) prospective mortality study of 1 million men and women. The
resulting expected number of lung cancer deaths of 0.7 and the
observed number of 4 yielded a relative risk for asbestos exposure of
5.33. When the deaths were classified according to the best estimate
of the cause of death from all available data, rather than from the
death certificate alone, one additional case of lung cancer was
identified in a worker who had never smoked regularly.

Selikoff, Seidman, and Hammond (1980) reported the mortality of
933 men who began working in an amosite asbestos factory between
June 1941 and December 1945. Of these men, 78 (8.4 percent) were
known to have never smoked regularly; the death certificates of 5 of
this group listed lung cancer as the cause of death. When the best
estimate of cause of death was used, only three men were believed to
have died of lung cancer. The expected number of deaths was 0.2,
based on the ACS mortality study. This led to a relative risk of 25
(5/0.2) for workers who had never smoked regularly.

McDonald and colleagues (1980) examined the mortality experi-
ence of Quebec asbestos miners and millers and reported a dose—
response relationship between cumulative asbestos exposure and
lung cancer in nonsmokers. They compared the standardized mortal-
ity ratio (SMR) for lung cancer in miners who had never smoked,
using the mortality rates for the Province of Quebec, which are based
on both smokers and nonsmokers. The SMR increased from 0.18
among nonsmoking miners with less than 30 million particles per
cubic foot times years (mppcfey) of exposure to 0.36 in miners with 30
to 299 mppcfey of exposure and 1.24 in nonsmoking miners with
more than 300 mppcfey of exposure. There were 19 lung cancer
deaths among nonsmoking asbestos miners. These authors (McDon-
ald et al. 1980) also performed a case-control study of the 245 miners
who had died of lung cancer. The distribution of cumulative asbestos
exposure among the 20 nonsmoking miners with lung cancer and 20
nonsmoking control miners matched for year of birth and smoking
status was examined, and the relative risk for lung cancer was found

211
to have increased from 1 in nonsmoking miners with less than 30
mppcfey to 10 in nonsmoking miners with more than 1,000 mppcfey.

Liddell and colleagues (1984) reexamined the same por ‘lation of
Quebec asbestos miners after recording their smoking history by
pack-years of exposure. They identified 223 cases of lung cancer in
men who worked in the asbestos mines and mills of Quebec for a
month or more before January 1967 and who were followed to the
end of 1975. The controls were selected from men in the same cohort,
born in the same years as the lung cancer cases, but still living.
Never smokers represented 23 of the 223 lung cancer cases and 201
of the 715 controls. The relative risks (RR) were calculated on the
basis of the mortality experience of the entire asbestos-exposed
population (whole population RR, 1.0), and the risk in even the most
heavily exposed nonsmokers was still lower than the risk in the
entire population, which included both smokers and nonsmokers.
The RR for lung cancer increased from 0.19 in the nonsmoking
miners who had experienced a cumulative exposure of less than 100
fibers per milliliter times years ((f/mL)y) to 0.37 for those with 101 to
1,000 (f/mL)y and 0.87 for those nonsmoking miners with over 1,000
(f/mL)y, thus demonstrating a dose-response relationship with
cumulative asbestos exposure for lung cancer in the workers who
had never smoked regularly.

Berry and colleagues (1972) conducted a retrospective study of the
lung cancer mortality in more than 1,300 male and 480 female
asbestos factory workers over a 10-year period and compared their
mortality with the national lung cancer rates (Table 3). The national
lung cancer rates were converted to smoking-specific rates by
multiplying them by factors from the study of mortality of British
physicians by smoking status (Doll and Hill 1964) in order to develop
smoking-specific expected numbers of deaths. No lung cancer deaths
were recorded among the men who had never smoked, and only one
lung cancer death was recorded among the women who had never
smoked. The expected number of deaths was also very low, and so
even a single death was greater than expected, and it occurred in the
group of women with heavy asbestos exposure. The women in the
highest asbestos exposure category who had never smoked had 3.5
times the number of subject years at risk when compared with men
in the same exposure category (1,404 to 399) owing to the higher
prevalence of never-smoker status among women in the study. This
difference in number of individuals at risk may have contributed to
the demonstration of a lung cancer death among nonsmoking women
but not among men. Subsequently, Berry and colleagues (1985)
followed prospectively 1,253 male and 423 female asbestos factory
workers from the same plants. Smoking habits were determined in
1971 at the start of the study, and the population was followed
through 1980. The expected number of lung cancer deaths was

212
calculated from the death rates for England and Wales multiplied by
the lung cancer SMR for greater London, and an adjustment for
smoking status was made using the data from the mortality study of
British physicians. Observed and expected numbers of lung cancer
deaths by smoking status and level of asbestos exposure are
presented in Table 4. One lung cancer death occurred among the
men who had never smoked (0.1 expected) and three lung cancer
deaths occurred among the nonsmoking women (0.2 expected).

Meurman and colleagues (1979) reported 1 lung cancer death (of 23
total lung cancer deaths), a nonsmoking male anthophyllite miner.
Acheson and colleagues (1984) also reported 1 death from lung
cancer among the nonsmokers employed in an amosite manufactur-
ing factory, with an expected number of 1.1. However, the expected
number was calculated from age-specific population rates that
included both smokers and nonsmokers rather than from the rates
for a population of nonsmokers. Each of these studies supports an
increased risk for lung cancer in nonsmoking asbestos workers, but
the conclusions are based on a single death in a population.

In summary, the evidence that asbestos exposure results in an
increased lung cancer risk in the absence of cigarette smoking is
based on a small number of cases, but has been confirmed in several
different populations of asbestos workers. The high smoking preva-
lence in asbestos workers introduces the possibility that environmen-
tal tobacco smoke may increase the risk of lung cancer among the
nonsmokers, particularly if the synergism demonstrated between
active smoking and asbestos exposure pertains to environmental
tobacco smoke as well. In spite of these concerns, the available
evidence supports the conclusion that nonsmokers with substantial
occupational asbestos exposure are at increased risk of developing
lung cancer and that the risk increases with increasing cumulative
asbestos exposure.

Lung Cancer in Cigarette-Smoking Asbestos Workers

The risk of lung cancer in cigarette smokers has been examined in
a number of asbestos-exposed populations, and the increased risk of
lung cancer in smokers, coupled with the high prevalence of smoking
in many of these populations, has generated substantial numbers of
lung cancer deaths for analysis. These populations differ in smoking
habits, type of asbestos and duration and intensity of exposure, type
of activity that resulted in exposure, and duration of the followup of
the population.

A number of authors have compared the lung cancer rates in
asbestos-exposed populations with the rates in control populations
(Table 1). This approach can establish an excess mortality in a
population, but may not identify the causes of that excess. To
establish a causal link between an exposure and lung cancer, specific

213
FIG

TABLE 3.—Comparison of number of observed and expected deaths from

cancers of the lung

 

 

Number Subject-years Observed lung Adjusted observed
Smoking habits on of at risk Observed deaths cancer deaths lung cancer Expected lung
January 1, 1960 subjects (adjusted) (all causes) (ICD 162, 163) deaths cancer deaths
Men
Low/moderate asbestos exposure
Never smoked 44 376 2 0 0 0.0
Ex-smokers 38 335 1 0 0 0.1
Smokers 509 4,423 32 8(2)' 46 6.2
Not known 219 2,122 20 0 3.4 2.0
Severe asbestos exposure
Never smoked 41 399 11 0 0 0.0
Ex-smokers 39 415 3 2 16 0.2
Smokers 663 6,920 82 32(5) 25.5 9.9
Not known 281 2,722 29 4 10.9 24
Women
Low/moderate asbestos exposure
Never smoked 25 271 8 0 0 0.0
Smokers 45 577 6 1 1 03
Not known 19 195 0 0 0 0.1
Severe asbestos exposure
Never smoked 120 1,404 23 21) 17 0.2
Smokers 292 3,474 52 18(4) 15.5 14
Not known 157 1,547 9 0 28 0.4

 

1 Figures in parentheses indicate number of pleuralmesotheliomas.

SOURCE: Berry et al. (1972).
GTé

TABLE 4.—Observed and expected deaths from cancer of the lung during 1971-1980

 

Lung cancer deaths

Smoking habits in 1971 Number of subjects Subject-years at risk Total deaths Observed Expected!

 

Men
Low/moderate asbestos exposure

Never smoked 45 396 6 1 0.10
Ex-smokers 123 1,092 18 3 1.07
Smokers 441 3,557 84 17 11.29

Severe asbestos exposure

Never smoked 29 273 2 0 0.06

Ex-smokers 123 1,003 38 8 1.25

Smokers 522 4,394 135 35 14.63
Women

Low/moderate asbestos exposure

Never smoked 7 128 5 0 0.04
Ex-smokers 12 93 3 0 0.09
Smokers 27 220 4 0 0.32

Severe asbestos exposure

Never smoked 101 799 26 3 0.20
Ex-smokers 84 659 24 2 0.50
Smokers 182 1,413 52 10 2.02

 

‘Calculated after allowing for the effect of smoking, sex, age, period, and region.
SOURCE: Berry et al. (1985).
criteria must be applied to the entire body of information available
on the exposure. This approach has been carefully and comprehen-
sively followed for both cigarette smoking (US DHHS 1982) and
asbestos exposure (Selikoff and Lee 1978), and the evidence is
sufficient to establish a causal role for both of these agents in
producing lung cancer. This section confines itself to an examination
of their interaction.

Selikoff and colleagues (1968) were the first to demonstrate
increased lung cancer risk among asbestos workers in an investiga-
tion that assessed smoking habits. In a group of 370 asbestac
insulation workers, none of the 48 workers who had never sr“ }¢a
regularly or of the 39 workers who smoked only pipes or cig: :s
developed lung cancer. Of the 283 cigarette-smoking workers, 24 died
of lung cancer during the 4 years and 4 months of the followup
period, although only 2.98 lung cancer deaths were expected on the
basis of smoking-specific death rates.

A more extensive evaluation of the risk of cigarette smoxing for
asbestos insulation. workers was provided (Hammond et al. 1979) by 4
prospective evaluation of the 17,800 members of the International
Association of Heat and Frost Insulators and Asbestos Workers
discussed earlier. Of this population, 8,220 workers were more than
20 years beyond their onset of asbestos exposure and had a known
smoking status. Fifty-four percent of this group were cigarette
smokers at the start of the study. The comparison group was drawn
from the ACS study of 1 million men and women, and consisted of
73,763 white men with no more than a high school education and not
employed as farmers, but with a history of occupational exposure to
dust, fumes, vapors, gases, chemicals, or radiation, who were living
on January 1, 1967, and were traced thereafter. The control group
was followed only until September 30, 1972, and the asbestos
workers were followed through 1976; therefore, the lung cancer
death rates in the control group were adjusted upward to reflect
changes in the U-S. national mortality experience for lung cancer
during the time period of differential followup.

There were 1,332 deaths among workers more ihan 20 years after
onset of exposure whose smoking habits were known; 314 (23.6
percent) deaths were due to lung cancer, using the best estimate of
cause of death. Death certificate data indicated 272 lung cancer
Ceai us. Figure 2 portrays the n vitality ratios for smokers and
nonsmokers in the conrol and t.ic asbestos-exposed populations,
with the mortality ravio of nonsmokers in the control group set at 1.
The lung cancer death rates increased from 11.3 per 100,000 among
nonsmokers in the control group to 58.4 in the nonsmoking asbestos
workers, 122.6 for smokers in the contro! group, and 601.6 for
smoking asbestos workers. The lung cancer relative risk with
combined exposure (53.24) is far larger than the sum of the

216
individual risks for cigarette smoking and asbestos exposure sepa-
rately, and is quite close to the product of the separate mortality
ratios (5.17 and 10.85) together.

Accurate data on the intensity of asbestos exposure for individual
workers (dose} were not available for this group of insulation
workers, ad so an asbestos dose-response relationship was not
examinea. Dosage data were available for cigarette smokers in this
population, however, and the ratio of observed to expected lung
cancer deaths (with the expected deaths calculated from the rates in
nonsmoking non-asbestos-exposed controls) increased from 5.33 in
asbestos workers who never smoked regularly to 7.02 in pipe and
cigar smokers, 36.56 in ex-smokers, 50.82 in smokers of fewer than
20 cigarettes per day, and 87.36 in asbestos workers who smoked one
pack or more per day.

Interaction between smoking and asbestos exposure in the devel-
opment of lung cancer has also been explored in other populations.
In some studies the numbers have been too small to clearly
differentiate between an additive and a multiplicative effect with
combined exposure; however, the data have been consistent with an
effect that is at least more than additive. This interaction of
cigarette smoking and asbestos exposure has been demonstrated in
asbestos factory workers (Berry et al. 1972, 1985), Quebec miners and
millers (McDonald et al. 1980; Liddell et al. 1984), amosite asbestos
factory workers (Sc:ikoff, Seidman, and Hammond 1980) and Finn-
ish anthophyllite miners and millers (Meurman et al. 1979).

A dose-response relationship between cigarette smoking and lung
cancer in the general population has been readily demonstrated in a
number of prospective mortality studies (US DHHS 1982); however,
dose-response relationships for asbestos exposure and lung cancer
have been more difficult to establish. The carcinogenicity of asbestos
may vary with the type of asbestos, and possibly with the length or
diameter of the fiber. There are also potential differences in the
carcinogenic risk associated with the different stages and processes
of converting asbestos from the raw mineral in the mine into a
finished manufactured product. As a result, it is difficult to classify
the asbestos exposure of different study populations with a single
measurement that quantifies the carcinogenic dose. Even if such a
scale were agreed upon, actual measurements of asbestos dust levels
in the work environment are often not available. Measures of dust
exposures for individual workers are even less frequently available.
The quantification of asbestos dust exposure has frequently used
estimates of likely exposures based on work conditions and job
classification, rather than actual measurements of asbestos dust in
the air, because of the absence of these measurements for most
workers. This lack of information has been particularly problematic
for workers employed more than 20 years ago, a group now at high

217
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L 87.36

 

 

 

 

 

 

 

 

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e YY
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workers

FIGURE 2.—Relative risk of dying of lung cancer for
smoking and nousmoking asbestos workers
and smoking and nonsmoking control group

members
SOURCE: Hammond et al. (1979).

risk of developing lung cancer. Finally, cumulative asbestos expo-
sure, age, and cumulative cigarette smoking exposure are generally

218
correlated. Older employees worked under conditions of much higher
asbestos exposure than their younger counterparts, and these same
older cohorts probably also had higher prevalences of cigarette
smoking, as described in the chapter on smoking patterns by
occupation. Confounding between cumulative asbestos exposure and
cumulative cigarette smoke exposure may result when dose-re-
sponse relationships between cumulative asbestos exposure and lung
cancer are examined without a control for differences in smoking
habits among the different asbestos exposure groups.

Berry and colleagues (1972) examined dose-response relationships
in a population of 1,300 male and 480 female asbestos factory
workers in Great Britain. Workers were categorized as having low to
moderate asbestos exposure or severe asbestos exposure, and the
expected number of lung cancer deaths was calculated from stand-
ardized mortality rates for lung cancer for the greater London area.
An adjustment for cigarette smoking status, derived from the
mortality study of British physicians by Doll and Hill (1964), was
used to estimate rates for smokers and nonsmokers. The results are
presented in Table 3. The small number of lung cancer deaths makes
interpretation somewhat difficult, but it appears that the increased
lung cancer death rate is limited to smokers with severe asbestos
exposure.

McDonald and colleagues (1980) examined Quebec miners and
presented evidence for a dose-response relationship between cumu-
lative asbestos exposure and lung cancer risk in the smoking miners.
They compared the lung cancer mortality rates in the Quebec miners
with the mortality rates for the Province of Quebec. Table 5 shows
the SMRs for lung cancer in miners by level of cumulative asbestos
exposure and smoking habits. Heavy smokers consistently had
higher SMRs than moderate smokers at the same level of cumulative
asbestos exposure, and the SMRs increased with increasing cumula-
tive exposure to asbestos in each of the smoking categories. Using
the same population of miners, these authors conducted a case—
control study of 245 lung cancer victims and a similar number of
control miners matched for smoking habits and year of birth. The
distribution of cumulative asbestos dust exposure was examined, and
the results in cigarette smoking miners showed an increase in
relative risk with increasing cumulative exposure. The relative risk
of cigarette smokers in the lowest exposure category (< 30 mppcfey)
was set at 1.0, and the relative risk increased to 1.12 at 30 to 300
mppcfey of exposure, 1.58 at 300 to 1,000 mppcfey, and 1.99 at
> 1,000 mppcfey of exposure.

A more quantitative description of the smoking habits of the same
Quebec miners was provided by Liddell and colleagues (1984). Their
data are presented in Table 6. The dust exposure measurements
were made as particles per cubic foot with midget impingers, and

219
TABLE 5.—Deaths from lung cancer in relation to dust
exposure and smoking habit

 

Dust exposure (mppefey! accumulated to age 45

 

 

«30 30-299 > 300 All
Smoking habit 0 SMR 0 SMR 0 SMR 0 SMR
Nonsmokers 5 0.18 6 0.36 8 1.24 19 0.38
Moderate smokers 73 1.14 64 1.35 52 2.31 189 141
Heavy smokers 13 2.12 11 2.39 10 4.50 34 2.63
All smoking habits 91 0.93 81 1.18 70 2.25 242 1.23

 

SOURCE: Liddell et al. 1984)

individual exposures were calculated on the basis of the work
histories and the measurements of impinger dust counts in the work
environment between 1949 and 1966. These counts were then
converted to fibers per mL. Two hundred and twenty-three cases of
lung cancer were identified and matched to 715 controls born in the
same year, and a case-control analysis was conducted. As is shown in
Table 6, the relative risk of developing lung cancer increases with
increasing asbestos exposure category for each of the cumulative
pack-year categories. The analysis also suggests that the interaction
between cigarette smoking and asbestos exposure is greater than
additive.

Thus the studies that have examined the question of a dose-
response relationship for asbestos exposure and lung cancer in the
face of an adequate control for cigarette smoking have shown an
increasing risk of lung cancer as asbestos exposure increases. This
suggests that a dose-response relationship for asbestos exposure and
lung cancer does exist, and that it is not explained by differences in
smoking habits.

Threshold

The question whether a level of asbestos exposure exists below
which an exposure does not result in an increased risk of lung cancer
is one that is both technically extremely difficult to answer and
extremely important to those required to make policy with regard to
asbestos exposure. Current understanding of carcinogenesis and host
defenses against cancer are not advanced sufficiently to allow either
the acceptance or the rejection of a threshold. It is common practice
to assume a linear relationship between the dose of a carcinogen and
the development of carcinoma, and to assume that the dose-response
relationship does not have a threshold. The linear nonthreshold
model allows the extrapolation of data obtained for higher exposures

220
TABLE 6.—Risks of lung cancer, by cigarette smoking and
asbestos exposure, relative to all 223 cases and
715 referents for whom smoking histories were
reliable; unmatched analysis

 

Exposure accumulated up to 9 years before death of case

 

 

fimby

High and

Low Medium very high
Pack-years ' »< 100) {+ 1.000) (> 1,000: All
0 Number of cases 6 7 10 23
Number of referents 103 61 37 201
Relative risk 0.19 0.37 0.87 0.37
1. « 40 Number of cases 29 27 34 90
Number of referents 123 93 63 279
Relative risk 0.76 0.93 173 1.03
>40 Number of cases 40 35 35 110
Number of referents 117 79 39 235
Relative risk 1.10 1.42 2.88 1.50
All Number of cases 75 69 79 223
Number of referents 343 233 139 715
Relative risk 0.70 0.95 1.82 1.00

 

' Number of cigarettes a day. 20 x duration in years.
SOURCE: Liddell et al. (1984).

to the very low exposures. This extrapolation is substituted for the
examination of the very large populations that would have to be
examined in order to demonstrate the small expected excess risk
with low dose exposure. Such models are particularly attractive for
exposures for which human epidemiologic data are limited or absent.
As discussed earlier, however, minimal exposure to cigarette smoke
and asbestos is probably a nearly universal experience in urbanized
society. Because of the large population exposed, more careful
examination of the available evidence on the risks of these exposures
is necessary.

The number of cigarettes smoked per day by an individual is a
readily available measure of the dose of smoke exposure in the active
cigarette smoker; therefore, it has been possible to examine relative-
ly completely the dose-response relationship for cigarette smoking
and lung cancer. There is a consistent increased risk for lung cancer
among smokers in the lowest category of number of cigarettes
smoked per day in the major prospective mortality studies on
smoking (US DHHS 1982). In the study of U.S. veterans (Kahn 1966),
a relative risk for lung cancer of 3.77 was demonstrated in those who
smoked only occasionally compared with those who had never
smoked regularly (the relative risk for those who smoked 1 to 9
cigarettes per day was 4.07 compared with those who never smoked

221
regularly). It seems clear that for the active cigarette smoker there is
no safe cigarette and no safe level of cigarette smoking (US DHHS
1982). Furthermore, recent data (IARC, in press) suggest that
repetitive exposure to environmental tobacco smoke may be accom-
panied by an increased risk of lung cancer, thereby suggesting that
the dose-response relationship may extend even to those individuals
who do not actively smoke cigarettes.

The quantification of asbestos exposure is far more difficult. One
method is to quantitatively estimate the number of asbestos fibers in
digested lung tissue. Asbestos fibers are demonstrable in the lungs of
the majority of urban dwellers (Churg and Warnock 1977); however,
the number of fibers per gram of lung tissue in urban dwellers
without known asbestos exposure is usually several orders of
magnitude below that found in occupationally exposed workers, and
the type of asbestos varies as well. Churg and Warnock (1979)
assessed this urban asbestos exposure as a risk factor for lung cancer
by comparing the number of asbestos bodies in 103 patients with
lung cancer compared with the number in control patients matched
for age, sex, smoking habits, and in some cases, occupation. No
differences in the number of asbestos bodies per gram of lung tissue
were found between the lung cancer patients and the control
population, suggesting that, at this level of exposure, asbestos did not
increase the risk of lung cancer in these patients. However, the small
number of patients in this study limits the power of the study to find
a small effect of asbestos lung burden on lung cancer risk.

Confounding by cigarette smoking is another potential source of
bias in evaluating the effects of low levels of asbestos exposure.
Several of the studies presented in Table 1 do not show excess lung
cancer risks at low levels of asbestos exposure, a pattern consistent
with the existence of a threshold. However, lung cancer rates in the
general population are determined largely by smoking habits, and if
the asbestos-exposed populations have even modestly lower lifetime
smoking rates, the effect of asbestos exposure may be masked. This
bias is of particular importance at the relatively low levels of
asbestos exposure at which the effect of cigarette smoking would be
expected to predominate. Thus, in interpreting standardized mortali-
ty ratios at or below 1, careful consideration must be given to
confounding by the smoking habits of the workforce before conclud-
ing that the levels of asbestos exposure experienced by these
populations do not result in an increased lung cancer risk. In
addition, modest differences in the number of cigarettes smoked per
day or the age of initiation of regular smoking between the exposed
population and the population from which the SMR is derived could
counterbalance a modest risk due to asbestos exposure even in
populations with similar smoking prevalences.

222
For lung cancer, the measurement of a threshold in epidemiologic
studies is further constrained by the certainty with which the
absence of an effect can be established. The precision and the
accuracy of an estimation of the expected number of deaths in a
workforce is heavily influenced by the detail with which the smoking
behaviors are determined and the accuracy with which the lung
cancer risk of a given smoking history can be estimated.

In the U.S. population during 1977, 10 percent of the men who died
between the ages of 50 and 70 died of lung cancer (McKay et al.
1982). Therefore, a workforce with smoking patterns similar to the
U.S. population would be expected to have a similar mortality
experience, in the absence of any asbestos exposure. A 10 percent
increase in the risk of lung cancer in a workforce (SMR 110, RR 1.1)
due to asbestos exposure would mean that 1 percent of the deaths
among workers aged 50 to 70 would be excess lung cancers due to
asbestos, a level of risk unacceptable as the basis for an industrial
hygiene standard. However, even with carefully determined smoking
histories for a worksite, no data are currently available that would
allow the calculation of expected death rates in smokers and
nonsmokers with precision sufficient to establish that an increase of
10 percent was not simply an error in the estimates. In addition,
estimates of the smoking habits of the U.S. population are not known
with enough precision to adjust national or regional death rates for
the smoking patterns of a given workforce so that a 10 percent
difference could be considered significant. The result is a dilemma
for those who would try to measure a threshold level, or an
“acceptable” exposure level, for occupational exposure to asbestos:
an effect too small to measure in statistical terms is still too large to
be acceptable in human terms.

A final caution in the determination of a threshold for lung cancer
risk secondary to asbestos exposure, and in the use of such a
threshold to establish environmental dust standards, is the potential
differences between a threshold for lung cancer and one for
mesothelioma or other asbestos-related disease. Mesothelioma,
which is not associated with cigarette smoking, may occur following
exposure to low levels of asbestos, and a level of dust exposure
defined as a “safe” level for lung cancer risk may possibly continue
to produce an increased risk of mesothelioma.

A pragmatic approach to the problems of defining a threshold or
establishing safe levels has been to define asbestos exposure stan-
dards on the basis of the lowest level of asbestos dust exposure that
can be produced with existing technology. This approach reduces the
risk, but does not answer the question whether the exposure of a
worker is “safe.”

An alternate approach has been to use the existing exposure—
response data. In the face of uncertainty about the shape of the

223
exposure-response curve for asbestos exposure and lung cancer and
whether a threshold exists, an assumption that asbestos has a linear
exposure-response relationship with lung cancer and no threshold
for effect has been suggested as both reasonable and a way to set
standards (Peto 1979; NRC 1984). By definition, in this approach
there can be no “safe” level of exposure (i.e., no threshold), only an
“acceptable” degree of risk. However, using this method, once an
“acceptable” level of lung cancer in a working population has been
defined, the level of asbestos exposure that would result in that level
of risk can be estimated. A corollary of this approach is that asbestos
is assumed to contribute to the lung cancer that develops in
populations of workers who have been exposed to asbestos regardless
of their level of exposure; by extension, the asbestos found in the
lungs of urban dwellers with no known occupational asbestos
exposure is assumed to make a small (but finite and definable)
contribution to all lung cancers. The evidence that does exist (Churg
and Warnock 1977) suggests that asbestos exposure makes no
“measurable” contribution to lung cancer in individuals without a
definable exposure, but it is impossible to establish the absence of
“any” effect.

If the issues of liability can be separated from the issue of
threshold, then the problem of reducing and eliminating asbestos-
related disease and disability could be approached with a broader
focus. The focus could be expanded beyond improving technology for
reducing exposure to asbestos to include other methods of reducing
the cancer risk associated with asbestos exposure. If the goal is to
reduce the lung cancer deaths associated with asbestos rather than
simply reducing the levels of asbestos dust in the worksite, then the
deaths due to the interaction between smoking and asbestos must be
dealt with, and the elimination of smoking will be a potent adjunct to
environmental asbestos dust control in this task, particularly for
those workers who have already received substantial asbestos
exposure. A public health “feasibility” threshold could then be
defined, not in terms of what dust levels were achievable, but rather
in terms of what lung cancer death rates were achievable. This
threshold would be the lowest cancer risk achievable, given our
current technology, and would include minimizing asbestos expo-
sure, maximizing smoking cessation, and applying techniques for
early diagnosis and treatment.

In summary, although the level of asbestos exposure that occurs in
the general population does not appear to be accompanied by an
increased risk of lung cancer, the demonstration of a clear threshold
below which there is no effect in occupationally exposed populations
is not possible.

224
TABLE 7.—Lung cancer mortality ratios with cessation of
cigarette smoking in male smokers who smoked
more than 20 cigarettes per day compared with
those who never smoked regularly

 

 

Years since Not exposed Asbestos insulation
cessation to ashestos ' workers?
Current smokers 11.69 10.4

Under 1 year Wi

1-4 years 101 11.5

5-9 years 65 4.2

>10 years 18 3.4

Never smoked
regularly i i

 

‘Data from Hammond (1972)
? Data from Hammond /1979).

Cessation of Exposure

A decline in the relative risk of developing lung cancer following
cessation of cigarette smoking was demonstrated in cigarette-smok-
ing asbestos workers by Hammond and colleagues (1979). Table 7
shows the lung cancer mortality ratios in asbestos workers who are
current smokers and who have quit for varying periods of time,
compared with those workers who have never smoked regularly. A
companion set of numbers is provided of the relative risks for lung
cancer in men not exposed to asbestos, but who are current smokers
or have quit for varying periods of time, derived from the American
Cancer Society study of 1 million men and women (Hammond 1972).

Several authors have attempted to approach the question of the
risk of lung cancer following cessation of asbestos exposure by
examining the relative risks of asbestos exposure in workers
following retirement (Walker 1984; Selikoff, Hammond et al. 1980).
The data in Figure 3 and Table 8 reveal that the relative risk for
lung cancer in asbestos workers increases and then declines with the
increasing number of years from initial exposure. The workers with
the longest interval from onset of exposure are also of the greatest
age within the populations examined. Because of this link with age,
the interpretation of this decline in relative risk as indicating that
cessation of asbestos exposure results in a decline in lung cancer risk
must be made with great caution. Examination of national age-
specific mortality rates for lung cancer (Figure 4) also shows a
decline in male lung cancer death rates with increasing age. This
decline with age is an artifact of the cross-sectional nature of data

225