Philip Morris
Environmental Tobacco Smoke: A Compendium of Technical Information
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ENVIRONMENTAL TOBACCO SMOKE:
A COMPENDIUM OF TECHNICAL INFORMATION
May 1991 DRAFT
DISCLAIMER
This document is a preliminary draft. Do not cite or quote.
The contents represent only those views of the individual
chapter authors. It should not be construed as representing
the views or policies of the participating organizations.
Draft - Do not cite or quote
PREF'ACE
This compendium of technical perspectives on Environmental
Tobacco Smoke (ETS) is intended to be a useful resource document
for a diverse audience, including: decision-makers such as labor
and management officials concerned with workplace exposures, public
health officials and corporate medical directors who are concerned
with making health policy recommendations, educators, industrial
hygienists and safety officers, ETS researchers, indoor air
pollution investigators, and legislators who are considering
legislation to restrict smoking in workplaces, restaurants, and
public access buildings. Although the technical level varies, even
the more technical treatments do not require a specialist's
knowledge for understanding. There are eleven chapters in this
compilation, including health effects of active smoking in adults
and passive smoking in children and adults, ETS exposure and
dosimetry, comfort aspects, ventilation and ETS, public beliefs
about the harm of ETS and attitudes toward controls, and effective
workplace smoking policies, each of which is aimed at a somewhat
different aud?.ence. Although not all chapters will appeal equally
to such a varied group, it is hoped that the technical information
in this document, written by experts in the field, will provide
information necessary to allow the public, corporations, government
agencies, and legislators to make well-informed choices regarding
exposure to ETS.
This perspective on ETS reflects the viewpoints and expertise
of authors who were selected based upon their publications and
recognition as experts on various aspects of ETS. Accordingly, the
opinions expressed do not necessarily represent the official
policies of the sponsoring agencies.
This document is the result of a coordinated effort jointly
sponsored and produced by the Environmental Protection Agency (EPA)
(chapters 2,3,4,6,7, and 8), the National Cancer Institute (NCI)
(chapters 1,5), the Office on Smoking and Health (Centers for
Disease Control) (chapter 9), the National Heart, Lung, and Blood
Institute (chapter 10), and the Office of Disease Prevention and
Health Promotion (Department of Health and Human Services) (chapter
11).
The editors acknowledge with gratitude the following distinguished
scientists, physicians, and others who lent their support to the
development of this document by contributing critical reviews of
the various manuscripts, by coordinating manuscript preparation,
or assisting in other ways.
Mr. Robert Axelrad, U.S. Environmental Protection Agency,
2
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Washington, DC (Sponsor)
Dr. Lois Biener, Miriam Hospital, Brown University, Providence, RI
Ronald Davis, M.D. Office on Smoking & Health, Centers for Disease
Control, Rockville, MD (Sponsor)
James W. Davis, M.D., Veterans' Administration Hospital, Kansas
City, MO
Ms. Hildy Dillon, American Lung Association, New York, NY
Dr. Cedric Garland, Dept. of Community Medicine, University of
California, San Diego, CA
Dr. Stanton A. Glantz, Department of Cardiology, University of
California Medical School, San Franscisco, CA
Dr. Lawrence Garfinkel, American Cancer Society, New York, NY
Dr. Katherine Hammond, Dept. of Family & Community Medicine
University of Massachusetts Medical Center, Worcester, MA
Dr. Marvin Kristein, State University of New York, Stony Brook, NY
State Univ. of New York, Stony Brook
Dr. Joellen Lewtas, Office of Research & Development, U.S.
Environmental Protection Agency, Research Triangle Park, NC
Dr. Alfred H. Lowrey, Laboratory for the Structure of Matter,
Naval Research Laboratory, Washington, DC
Henry McIntosh, M.D., American College of Cardiology, Washington,
DC
Dr. Michael McGinnis, Office of Disease Prevention and Health
Promotion, Public Health Service, Washington, DC (Sponsor)
Matthew Meyer, Esq., Coalition on Smoking or Health, Washington,
DC
Dr. Gregory Morosco, Health Education Branch, National Heart, Lung,
and Blood Institute,.Bethesda, MD (Sponsor)
Dr. Demetrios Moschandreas,
Research Institute, Chicago, Illinois Institute of Technology
IL
Dr. David Mudarri, , U.S.
Washington, DC
Dr. Terry Pechacek, Smoking, Environmental Protection
Tobacco, and Cancer Program, Agency,
National
~
Cancer Institute, Bethesda, MD (Sponsor) ~
~
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Draft - Do not cite or quote
Mr. James Repace, U.S. Environmental Protection Agency, Washington,
DC (Editor)
Mr. Donald Shopland, National Cancer Institute, Bethesda, MD
(Editor)
John Slade, M.D., Dept. of Medicine, St. Peter's Medical Center,
Rutgers University, New Brunswick, NJ
Dimitri Trichopoulos, M.D., DrPH, Harvard School of Public Health,
Boston, MA
The editors also acknowledge the comments of the tobacco industry.
Mr. Samuel D. Chilcote, Jr., President, The Tobacco Institute,
Washington, DC
Dr. Thomas Borelli, Phillip Morris USA, Richmond, VA
4
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TABLE OF CONTENTS
Chapter 1. Effects of Smoking on Smokers.
Donald Shopland ..............................................9
Chapter 2. Environmental Concentrations of ETS.
John McCarthy, Elizabeth Miesner, and John D.
Spengler ..................................................... 16
Chapter 3.
Smoke.
Measuring Exposure to Environmental Tobacco
Brian P. Leaderer ...................................... ..... 31
Chapter 4. Absorption of Smoke Constituents by
Nonsmokers. Dietrich Hoffmann, Klaus D. Brunnemann,
and Nancy J. Haley ...........................................43
Chapter 5. Environmental Tobacco Smoke and Cancer.
Jonathan M. Samet ........................................... 67
Chapter 6. Passive Smoking and Heart Disease.
Stanton A. Glantz and William W. Parmley ..................... 81
Chapter 7. Exposure Assessment in Passive Smoking.
James L. Repace ...........................................112
Chapter 8. The Odor and Irritation of Environmental
Tobacco Smoke.
William S. Cain ............................................137
Chapter -9. Passive Smoking -- Beliefs, Attitudes,
and Exposures in the United States.
Thomas E. Novotny ...........................................152
Chapter 10. Passive Smoking and Daycare.
Glen L. Bennett .............:..............................180
Chapter 11. No Smoking Policies at the Worksite: A look at
what companies are doing today.
Ruth Behrens ............................................... 197
Chapter 11 Appendix: Economic Justification for
Worksite Smoking Policies.
Ruth Behrens ...............................................219
5
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INTRODUCTION
In 1986, the Surgeon General and the National Research
Council, the latter under contract to EPA, examined the health
effects of the breathing of Environmental Tobacco Smoke (ETS) by
nonsmokers (also known as involuntary or passive smoking). They
agreed that passive smoking caused lung cancer in nonsmoking
adults, caused increased rates of respiratory infections in
children, caused acute noxious effects in many nonsmokers, and was
a major contributor to indoor air pollution. Subsequent to the
publication of these documents, smoking restrictions began to
proliferate. However, a number of diverse technical questions
arose concerning public attitudes toward smoking restrictions,
health and comfort effects, factors affecting exposure, measuring
environmental concentrations of ETS, effects of ventilation on ETS
and'indoor air quality, nonsmokers' uptake of tobacco combustion
products, and corporate experience in effective smoking policy, all
comprise chapters in this compendium. In the interest of providing
answers to this complex of questions, this technical compendium was
commissioned. A brief summary of each chapter followsc
Chapter 1 demonstrates that high dose exposures to tobacco'
smoke, i.e., the effects of smoking on smokers, are very toxic,
causing cancers, cardiovascular diseases, and respiratory diseases.
it is graphically illustrated why cigarette smoking is now
recognized as the Nation's single largest cause of premature death
and disability.
Chapter 2 reviews studies of the concentrations of certain
ETS constituents observed in homes, offices, and other locations
by personal exposure monitors. It is concluded that ETS is the
primary contaminant contributing to respirable particulate air
pollution, and contributes substantially to other indoor
contamininants such as benzene, carbon monoxide, and others. Even
in low doses, tobacco smoke contains a wide variety of toxins,
including many carcinogenso
Chapter 3 treats the methods of assessing nonsmoker's exposure
to environmental tobacco smoke by atmospheric markers, and the
measurement of these marker substances in indoor air. It is
concluded that atmospheric monitoring for respirable particles or
nicotine from ETS is critical for assessing exposures and control
efforts, and that a number of reliable methods are available for
such monitoring.
Chapter 4 provides a detailed treatment of the absorption and
metabolism of tobacco combustion products by nonsmokers. It shows
that absorption has been conclusively demonstrated by studies of
nicotine and its metabolite, cotinine, in the body fuids of
nonsmokers, and that such biomarkers represent a reliable specific
method for assaying the level of uptake of ETS. This exemplifies
6
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that low dose exposure to tobacco smoke leads to the absorption of
toxins from the smoke in amounts sufficient to potentially cause
disease.
Chapter 5 discusses the evidence that low dose exposure to
tobacco smoke has been observed to increase the risk of lung cancer
in nonsmokers, and discusses conclusions of the World Health
Organization, the National Research Council, and the U.S. Surgeon
General that ETS exposure increases lung cancer incidence in
nonsmokers.
Chapter 6 discusses the evidence that low dose exposure to
tobacco smoke has been observed to increase the risk of heart
diseases in nonsmokers, and discusses the epidemiological,
biochemical, and biological bases for this inference. It is
concluded that the combined epidemiological and physiological
evidence suggests that ETS exposure is a cause of heart disease in
nonsmokers.
Chapter 7 investigates the assessment of nonsmokers' exposures
to ETS by mathematical modeling, atmospheric indicators, and
biomarkers in body fluids. Exposures assessed by these various
methods produce consistent results. Because of the large source
strength of tobacco-burning products, exposure to environmental
tobacco smoke is inadequately controlled by measures short of
physical separation of smokers and nonsmokers on different
ventilation systems, making ETS a significant indoor pollutant of
buildings.
Chapter 8 explores the effects of ventilation on the
perception of odor and irritation from ETS in both nonsmokers and
smokers, and shows that attempts to control the odor and irritation
of ETS through ventilation and air cleaning have significant
limitations.
Chapter 9 shows through national surveys of trends in public
attitudes, that the general public, including both smokers and
nonsmokers, believe that tobacco smoke polluted air is harmful and
a large majority find it irritating. There is widespread support
for restrictions against smoking, particularly in the workplace.
Chapter.10 discusses the evidence that smoking both at home
and in daycare centers harms children and infants from tobacco-
smoke polluted air. This has direct -implications for public
education of both parents and daycare providers, as well as for
state policies and regulations affecting facilities which offer
daycare.
Chapter 11 points out the common solution to the problem of
ETS is source control, and examines features of corporate smoking
policies in the workplace, with attention to benefits, incentives,
employee and union involvement, and education. Case histories are
7
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discussed involving several major corporations, detailing problems
encountered and successes. It is concluded that smoke free
workplaces have been achieved in a variety of settings. if
thoughtfully implemented, they enjoy widespread support.
8
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CHAPTER 1
EFFECTS OF SMOKING ON SMOKERS
Donald Shopland
Coordinator
Smoking and Tobacco Control Program
National Cancer Institute, Bethesda, MD
Cigarette smoking is the nation's leading cause of premature
death and disabilityo In 1985, smoking caused approximately
390,000 deaths in the tJnited States (Figure 1). By 1991, this
number had increased to 440,000. In addition, tens of millions of
people suffer from chronic disabling diseases and conditions caused
or aggrevated by smoking. Every medical authority and organization
who has objectively examined the evidence linking smoking to early
death and disability has reached a similar conclusion. The
,evidence that smoking is a major health threat is staggering: over
50,000 citations from dozens of cultures are in the scientific
literature. Smoking causes or is associated with cancers of the
lung and bronchus, larynx, lip and oral cavity, bladder, pancreas,
kidney, stomach and cervix, coronary artery disease,
cerebrovascular disease (stroke), atherosclerotic aortic aneurysm,
atherosclerotic peripheral vascular disease, chronic bronchitis,
emphysema, low birth weight babies, and unsuccessful pregnancy.
This chapter concentrates on the relationship between active
smoking and three diseases caused by ETS -- lung cancer, heart
disease, and nonmalignant lung disease. While there are
qualitative differences between the mainstream smoke inhaied by the
smoker and the ETS nonsmokers inhale, both forms of tobacco smoke
contain the same carcinogens, irritants, and other toxins. The
effects of high doses of smoke on smokers thus provide an
indication of what effects low dose exposures of ETS would be
expected to have on nonsmokers. This connection is particularly
important because the diseases active smoking causes exhibit dose-
response relationships, with higher doses producing greater
effects. Because no threshold has, been demonstrated for the
carcinogenic and other effects of tobacco smoke on tne body, the
existence of a dose-response relationship suugests that ETS would
provide similar, but smaller, dangers than active smoking.
Cancer
Most estimates in the scientific literature indicate that
nearly one-third of all U.S. cancer deaths result from cigarette
smoking. Of the approximately 136,000 cancer deaths which occurred
in 1985 because of smoking, 106,000 are of the lung (Figure 1).
Lung cancer alone is responsible for fully one-quarter of all
9
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cancer mortality; were it not for the increasing number of deaths
from lung cancer produced by smoking, we would be experiencing a
substantial decline in the cancer death rate in the United States.
Approximately 85 to 90 percent of all lung cancer deaths are
smoking related. The evidence linking smoking and excess cancer
mortality is so strong that only the tobacco lobby continues to
claim that no causative role has been established. An examination
of the association between cigarette smoking and lung cancer
graphically illustrates smoking's role in the causation of
neoplastic diseases.
Tobacco smoke contains at least 43 known or suspected human
carcinogens (Table 1), several of which are regulated by the
federal government as environmental toxins. There is no known
threshold for the carcinogenic effects of these agents.
A host of epidemiological studies published during the last
two decades provides an abundance of data which demonstrate that
exposure to these carcinogens because of smoking leads to an
increase in cancer deaths. In particular are the major prospective
studies on smoking and health. These studies, conducted in the
United States, Canada, England, Japan and Sweden represent some of
the largest population based studies ever undertaken by medical
science (Table 2). They involved enrolling healthy men and women
into a study design and then followed these individual over time.
Numerous factor about them were recorded including where they
lived, their occupations, dietary habits, whether they used
tobacco, access to health care, and many other factors. As a
group, these eight studies in the United States, the U.S. Veteran's
Study and the American Cancer Society (ACS) 25-state Study
contained cohorts of 290,000 and 1 million persons respectively.
The Veteran's Study continues to this day and this cohort has been
followed prospectively for 26 years. These studies convincingly
demonstrate that smoking causes cancer.
Lung Cancer
Lung cancer mortality rates are strongly influenced by the
total dose of cigarette smoke received. If one smokes more
cigarettes per day, inhales deeply, if they started smoking at an
early age had has smoked for many years, the risk for lung cancer
.is increased dramatically.
The most often used measure to gauge lung cancer mortality is
the number of cigarettes consumed daily. In the ACS 25-state
study, for example, among males smoking less than 1/2 pack per day
their lung cancer rate was nearly 5 times greater than that of a
nonsmoker. With each increase in the number of cigarettes consumed
daily, a corresponding increase in lung cancer mortality is
observed (Figure 2). For those smokers consuming two or more packs
daily, their lung cancer mortality is about 24 times greater than
10
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that of the nonsmoker. At the other extreme, even light smokers,
who consume only 1-9 cigarettes per day, see a quadrupling of the
risk of lung cancer.
An inverse dose-response relationship exists between an early
age of regular smoking and lung cancer mortality. In the U.S.
Veterans Study, those smokers who started smoking in their early
teens had substantially higher lung cancer death rates than those
who started in their late teens or twenties (Figure 3). Those who
began smoking before age 15 experienced a 19-fold greater lung
cancer mortality, compared to a slightly greater than 5-fold excess
risk for those who initiated their behavior after age 25.
These results demonstrate that a dose-response relationship
exists for exposure to the carcinogens in cigarette smoke and the
risk of death from lung cancer: the greater the lifetime exposure
to tobacco smoke, the greater the risk.
Further evidence for the existence of a dose-response
relationship comes from follow-up of people who stop smoking and
so remove the exposure from the carcinogenic agents in mainstream
smoke. When an individual stops smoking, his or her lung cancer
risk declines relative to the continuing smoker. After about 15
years off cigarettes the former smoker's lung cancer risk
approaches that of the life-long nonsmoker. However, it appears
that some excess risk may be carried throughout life. This
residual risk is strongly influenced by the individual's total
lifetime exposure to the agent and the total number of years of
smoking cessation.
The presence of a dose-response relationship between smoking
and lung cancer, combined with the fact that there are significant
elevations in risk associated with even the lowest levels of
smoking, demonstrates that there is no threshold for the
carcinogenic effects of cigarette smoke. This result from active
smokers is consistent with the observed elevations of lung cancer
risk among nonsmokers exposed to ETS.
Coronary Heart Disease
In contrast to cancer, in which.smoking produces the disease
through the cumulative effects of long term exposure to the
carcinogens and co-carcinogens in the smoke, smoking effects the
cardiovascular system immediately as well as over the long term.
The carbon monoxide in the smoke reduces the oxygen carrying
capacity of the blood by binding to hemoglobin competitively with
oxygen. Nicotine is a vasoconstrictor, which increases blood
pressure and narrows coronary arteries. Smoking causes release of
catecholamine, which increase blood pressure and heart rate.
Smoking also increases platelet aggregation and adhesion, which
contributes to the development of atherosclerosis. All these
11
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effects occur immediately upon smoking and resolve relatively
quickly after stopping smoking. As a result, one year after
stopping smoking, the excess risk of death from heart disease falls
by half; the same drop in risk for lung cancer takes 10 years. As
with cancer, these effects exhibit a dose-response relationship,
with greater more smoking and smoking in combination with other
heart disease risk factors, increasing the risk of death from
coronary heart disease. As with cancer, there is no threshold for
these effects, so the effects of active smoking on the heart and
cardiovascular system support the biological plausibility of the
observed effects of ETS on the heart.
Coronary heart disease (CHD) continues to be this nation's
leading cause of death, and for nearly 20 years, medical research
has shown that smoking is one of the major independent risk factors
or causes of CHD (along with high blood pressure and high
cholesterol levels). In the final report of the Pooling Project,
an interaction between smoking and other risk factors was observed
(Figure 4). Each independent risk factor contributed about the
same increased level of risk, however, when two or more factors
were present, the risk of a major CHD event was increased beyond
the sum of the independent risk -- thus, synergistic effect was
created when two or more risk factors were present. Overall,
smokers have a 70% greater CHD death rate, a two- to fourfold
greater incidence of CHD, and a two- to fourfold greater risk for
sudden death than nonsmokers.
Dose-response relationships between cigarette smoking and CHD
mortality have been demonstrated for several measures of exposure
to cigarettes, including the number of cigarettes smoked per day,
the depth of inhalation, age at which smoking began, and the number
of years of smoking. Smoking cigarettes with reduced yields of tar
and nicotine does not reduce CHD risk, probably because these
cigarettes do not have reduced yields of carbon monoxide and other
combustion products which affect the cardiovascular system.
The independent risk of CHD for smoking is greater at the
younger age groups although the greatest number of excess CHD
deaths due to smoking actually occurs in the older age groups
(Figure 5). Smoking has also been shown to increase the risk for
other cardiovascular diseases, including peripheral vascular
disease, cerebrovascular disease (at younger age groups), and
aortic aneurysms. For women, smoking can interact with oral
contraceptives to greatly increase the risk factor for fatal and
nonfatal myocardial infarction and subarachnoid hemorrhage.
Smokers exhibit more atherosclerosis, both in the aorta and
coronary arteriese Cigarette smokers who continue to smoke
following transluminal coronary angioplasty appear more likely to
require repeat angioplasty than nonsmokers, suggesting that the
effects of smoking on atherosclerosis occur quickly. The
polycyclic aromatic hydrocarbons which result from the combustion
12
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of the smoking materials contribute to these effects. The
increase in platelet adhesion observed in smokers also contributes
to the development of atherosclerotic plaque.
Cigarette smoking aggravates the conditions of people with
CHD. Smokers have a more difficult course following coronary
artery bypass surgery. Smokers who experience angina pectoris have
a higher risk of death than nonsmokers, a poorer prognosis
following non-fatal myocardial infarction, and a greater risk of
sudden death. Smoking increases the risk of silent ischemia in
patients with stable angina.
Many public health estimates place the total number of excess
cardiovascular disease (including stroke) deaths due to smoking to
be.greater than those due to cancer (Figure 1). Up to 30 percent
of all CHD deaths may be due to cigarette smoking and its
interaction with other risk factors.
These effects all exhibit a dose-response relationship with
no threshold in active smokers, with detectable damage even among
light smokers. These facts support the biological plausability of
the evidence linking ETS with heart disease in nonsmokers.
" Nonmalignant Respiratory Diseases
In addition to causing lung cancer, smoking causes or
aggravates several related nonmalignant respiratory diseases,
including emphysema, asthma, chronic bronchitis, and chronic
obstructive pulmonary disease (COPD). While the number of
sZnoking-induced deaths classified due to chronic obstructive
pulmonary disease (COPD) is smaller than for cancer or
cardiovascular disease (Figure 1), COPD afflicts about 12 million
Americans. Even if not fatal, COPD and related disorders such as
emphysema severely debilitate the victim and represent a
substantial number of people who become disabled due to their
condition, unable to work or even seek employment.
~
For many years cigarette smoking has been known to increase
the risk of developing and dying from COPD. Even the first Surgeon
General's Report issued in 1964 identified a causative role between
smoking and chronic bronchitis. As with lung cancer, the risk of
contracting and dying from COPD is substantially elevated among
smokers (Figure 6) and this risk increases with an increased dose
of cigarette smoke received; as with the other smoking-induced
diseases discussed in this chapter, there is :a positive dose-
response relationship. Mortality rations for COPD in smokers
versus nonsmokers are very high, exceeding 30 to 1 for heavy
smokers (Figure 7).
Smoking also has a dramatic effect on lung function. The
normal rate of lung function decline with increasing age is
accelerated in cigarette smokers (Figure 8). These effects
13
Draft - Do not cite or quote
probably reflect damage to the small airways of the lungs as well
as a thickening and increased reactivityof the airways in response
to chronic exposure to the irritants in cigarette smoke. The
volume an individual and exhale in one second of forced expiration
(FEVj) is a measure of small airway function. Figure 9 shows that
FEV9 falls in a dose-dependent manner as the amount of smoking
increases. There is no safe level of exposure: there is a
measurable decrement in pulmonary function even among light
smokers.
Stopping smoking partially reverses the nonmalignant effects
of the respiratory system (Figure 8). When one stops smoking, the
decline in lung function with age resembles that of a nonsmoker,
but a permanent decrement in lung function remains, indicating some
permanent damage. The amount of this permanent deficit depends on
the duration and intensity of smoking.
ETS exposure produces similar, but more modest nonmalignant
pulmonary effects. FEV1 is reduced in passive smokers among both
children and adults to levels similar to that observed in light
smokers. Children of parents who smoke develop more asthma,
bronchitis and other respiratory problems. The rate of lung
development in children exposed to ETS is smaller than that of
unexposed children. These effects of ETS are what one would expect
based on the effects of active smoking.
conclusions
This chapter has reviewed the effects of active smoking in on
those cancers, heart disease, and nonmalignant pulmonary diseases
which have also been identified with passive smoking. In each
case, cigarette smoking significantly increased the risk of disease
in smokers in a dose-dependent manner. There is no evidence of a
threshold level for adverse effects. Because ETS is similar to
(but more toxic than) mainstream smoke, these effects on the smoker
help provide evidence for the biological plausibility for the
epidemiological evidence linking ETS with lung cancer, heart
disease, and nonmalignant respiratory disorders, after accounting
for the lower dose the involuntary smoker receives.
1. There is a dose-response relationship between exposure to
tobacco smoke and the diseases of smoking.
2. There are no discernable thresholds of exposure for the diseases
of smoking.
3. Adverse health effects observed in smokers provide biological
plausibility for the occurrence of those diseases in nonsmokers.
14
Draft - Do not cite or quote
TABLES AND FIGURES, CHAPTER 1
N
Q
~
~
2- Q
N
- W
US Deaths Attributed to Srnoking in 1985
Source: US Surgeon General, 1989
CVD
28000
Cancer, lung
106000
30000
Vzoszz9'Pfl~
Draft - Do not cite or quote
~-~ Zy, ----
I
0s
Men
6005 1000% 16005 2000% 26005
' Cwrent Smoker --~ Former Smoker
3000%
0%
600%
1000%
16005
= Ourrent Smokrtr ''GFormer Smoicer
2000s
EZGURE 2 c Percent increased cancer morality risk, by site and qender, in current and former smoke,a
as deri ed fron: the
American Car.cer Socir.ty 50-State Study.
Draft - Do not cite or quote
Ndrle
At1 SM
410 14-19 20
Nos at c1garettes daJly
,
FIGURE 3.
(1989 SURGEON GENERAL'S REPORT, p. 49)
21-30
310
FIGURE 4.
Lung cancer' mortality ratios for males, by age
began smoking - U.S. Veterans' Study
20
<
18.7
0
Q
0
Ct
(D
4Z aSZZa~ ~?; ,
FIGiUR4 5.
Major risk factor combirrations,10-year
incidence of first major coronary events,
men age 30-59 at entry, Pooling project
w
200
SM
Only
C or ti
Only
SM&C C&H
or (No SM)
SM&H
189
None
of 3
AII 3
to
0
rt
0
~.
rt
Risk Factor Status at Entry ~
SM =smokerB C = cholesterol, H = hypertension
®
~
~
szoszZoV02-01
Coronary heart disease
deaths, smokers vstaEt - Do
nonsmokers
Deaths per 100,000 men
not cite
or quote
500 1000 996
2500
- ~ 422 ~ 2025
400 -I _ 600 ~ 2000 ~
300 -~ ~ 600 542 ~ 1500 1400 ~
~
..._ ~
400 ` ~ 1000 ~
200 ~
~
100 -~ - = 200 ~ 500 ~
t ~
ln~
~ ~ ~ .~ '
0 ---
- 0 ° _ -
~ 0
'Ages 45-54 Ag es 5 5-64 Ages 65-74
=Nonsmokers = Smokers
FIGURE 6.
COL® deathSDraft - Do not cite or quotei
smokers vs. nonsmokers
Deaths per
100,000 persons
500
400
300
200
100
0
35-44 45-54 55-64 65-74 75-84
Age group
FIGURE 8.
~
O
~ COLD mortality ratios for men and women,
° by number of cigarettes smoked per day,
W
~ British Physicians' Study
~
O
r-
O
A
10
©
11111W Male
Female
38.0
2040225031 '
Cigarettes per day
Draft - Do riot cite or quote
0 PR-TRs
M3303
I1s 10R.512
f'1_
-3.0 -2.0 -1.0 0.0 1.0 2.0 3.0
30.
~ 20
10
0
0
-3.0 -2.0 -1.0 0.0 1.0 2.0 3.0
10
30
x 20
2H-q0 PK-TRS
M.I539
IOR..638
-2.0 -1.0 0.0 1.0 2.0 3.0
.14
N*
30,
~
1-20 PK-TRS
M.2477
41-60 PK-TRS
Ne575
IOR®
699
.
I.1-LL_
-3.0 -2.0 -1.0 0.0 1.0 2.0 3.0
I0
0
30
20.
10
0
~3.0 -2.0 =1.0
30
20 ~
30
0
riEIGHT AOJuSTEO
61-®Q PK-TRS
M.189
10Rn.8ei
a
0.0 1.0 2.0 3.0
e14 PK-TRS
wel0®
lOR.966
0.0 1.0 2.0 3.0
fEv( RESIOuAL (LITERS)
,
FIGURE 10 e-Percent distribution of predicted values of forced expiratory
volume in fl-sectFEY1) in subjects with varying pack-years of smok-
ing. '
NOTE: Tnar+gl indicates mean, IQR is intesquaatile raasge.
SOUREE: Burtows ta si. (1977): Cuc@erq et sl. (19gg).
10Re.560
Draft - Do not cite or quote
TABLE 1 Expected Cancer Deaths Caused by
Smoking-United States 1989
1989
Cancer Smdcing
Dsaths Attributable
Site Expsctsd Risk (%)
Estimatad
D.aths Dua
to Smoking
Men
Buccal cavity
and pharynx 5,775 92
5,313
Larynx 3,000 81 2,430
Lung 93,000 90 83.700
Esophagus 6,900 78 5,382
Bladder 6,900 47 3,243
Kidney 6,000 48 2,880
Pancreas 12,500 29 3,625
Total 106,573
Women
Buccal cavity
and pharynx 2,875 61
1,754
Larynx 700 87 609
Lung 49,000 79 38,710
Esophagus 2,500 75 1,875
Bladder 3,300 37 1,221
Kidney 4,000 12 480
Pancreas 12,500 34 4,250
Total 48,899
Total men and women expected to die
of cancer in 1989
502,000
Percent attributed to smoking .31
Total excess cancer deaths due to
smoking expected in 1989
155,472
y;e
TABLE 2. (SG, 1989: p. 86-87)
-Tumorigenic agents in tobacco and tobacco smoke
.
Evidence for IARC evaluation
Mainstream of carcinogenicity
Processed tobacco smoke
Compounds (per gram) (per cigarette) In lab animals In humans
Aromatic amines
2-1-oluidine 30-200 ng
2-Naphthylamine 1-22 ng
4-Aminohiphenyl 2-5 ng
Aldehydes
Sufficient Inadequate
Sufficient Sufficient
Sufficient Sufficient
Formaldchyder 1.6-7.4 pg 7(1-100 pg' Sufficient NA
Acetaldehydc' 1.4-7.4mg )8-1,400mg° Sufficient NA
Crotmtaldchyde 0.2-2.4 pg I(1-20 pg NA NA
Miscellaneous organic
compounds
nenzcne 12-48 pg Sufficient
Acrylonilrile 3.2-15 pg Sufficient
1. I-Dirnclhylhydrazinc 6/f-147 pg Sufficient
Sufficient
Limited
NA
2-Nitropropane 0.73-1.21 pg Sufficient NA
Ethylcarhamate 310-375 ng 20-3B ng Sufficient NA
ilinyl chloride 1-16 ng Sufficient Sufficient
Inorganic compounds
Ilydra.ine 14-SI ng 24-43ng Sufficient
Arsenic 500-9(N) ng 40-120 ng Inadequate
Nickel 2.fMX)-6.fX)Ong 0-60f)ng Sufficient
Chromium 1,000-2.OIX)ng 4-70ng Sufficient
Cadmium 1.3(NI-I,6tI0ng 4)-Cr2ng Sufficient
Lead 8-10 )tg Sufficient
Inadequate
Sufficient
Limited
Sufficient
Limited
Inadequate
I'oluniwn-210 0.2-I.2 pCi 0.03-1.0 pCi NA NA
NI ) I li: NI). no data; NA, evaluatiun has not hcen done by IARC.
'7 hc Founh Rcluon of the hrdcpendem Scientific Ceimmittce on "Smoking and Ilcahh" (19gR1 puhlished
valucs for the
14 Ieading 1/ K- cigareues in 1986 t4514 pereent of the market) of 20-In5 pg/cigarene Imean. 59 pg)
for /onnaWeh) de
and 5511 1.15111rg/agarcue 1 mcan. 9111 Pg / for ac ctaldch)de
ti/11921 I- lhdlm.mn and IIr, hl. In pi,-
Mainstream Evidence for IARC evaluation
of carcinogenicity
Compounds Processed tobacco
(per gram) smoke
(per cigarate)
In lab animals
In humans
PAII
f)enzla)anthracene
20-70 ng
Sufficient
NA
®enzo(b)/luoranthcne 4-22 ng Sufficient NA
Benzo(j)Ouoranthene 6-21 ng Sufficient NA
Benzo(k)Ouoranthene 6-12 ng Sufficient NA
I)enzo(a)pyrenc 0.1-90ng 20-40 ng Sufficient Probable
Chrysene 40-60ng Sufficient NA
Dibenz(a.h)anthracene 4 ng Sufficient NA
Dibenzo(a.i)pyrene 1.7-3.2 nR Sufficient NA
Dibenzo(a,l)pyrene Present Sufficient NA
Indeno(1.2a3-c,d)pyrene 4-20 ng Sufficient NA
5-Atethylchrysene 0.6 ng Sufficient NA
Aza-arenes
Quinohne
1-2 pg
NA
NA
Dibenz(a.h)acradine 0.1 ng Sufficient NA
Dibcnz(aj)acridine 3-10ng Sufficient NA
71#-Dibcnzo(c.g)carbazole 0.7 ng Sufficient NA
N-Nhrosamines
N-Nitrosodimethy)amine
ND-215 ng
0.1-180 ng
Sufficienl
NA
N-Nitrosoethyl 3-13 ng Sufficient NA
methylamine
N-Niuosodiethylaminc
ND-25 ng
Suffrcient
NA
N-Niuosopyrrolidine ND-360ng 1.5-110ng Sufficient NA
N-Niuosodicthanolamine ND-6.900 ng ND-36 ng Sufficient NA
N'-Nilrosonomicotine 03-89 pg 0.12-3.7 pg Sufficient NA
4-IMcghylnitrosamino)-I- 0.2-7 pg 0.08-O.77 pg Sufficient NA
(3-pyridyl)-I-butanone
N'-Nitrosoanabasine
0 01-1.91tg
0.14-4 6 pg
Limited
NA
nl.. mw.il I,. Imr N1) c!NI im -IIr n ni tiN
v pCOSZ7,®VOOZ,
i,
TABLE 3.
Outline of Eight Major Prospective Studies
Doll Welr Cedorbl
Authors HIW Hsmmond [>brn Hksyema 8ost Hammond Dunn Friborp
Ptto Kahn Joal* Horn Linden Hruboo
Plk RoQo1 Walker Brwsbxl Uxkh
lulalw and Total poputstlon ProboWWty
isrnalas of California sample of
SubJects British In U.S. 29 hsalth Canadian Whlie rnalss malssln th-CI
doctors 25 vrtwu-s dlstrlcts in prnslonerr In varlous 8v,radlsh
Statss Japan nlre, statN oocupallona population
Population slts 40.000 1.000.000 290.000 265.000 02,000 187.000 60.000 66.000
Fema1Ns 0,000 502,e71 < 1% 142,857 14.000 27.700
Aps Ranp 20-85t 35-64 35-04 40 30-00 6040 33-04 16-tlO
and up
Year of 1051 1960 1054 1060 1956 1962 1964 1943
enrollmsnt 10.ri7
Years of 20-22 6a
lollowup years 12 yews 16 yosrs 13 yews 0 yews 4 y+ars yews 10 yews
reportsd
Numt»r
of 11.196 150.000 107,500 39.100 11.000 12.000 4.700 4.600
deaths
Person yesrs
of 800.000 8.000.000 3.600.000 3.000.000 500.000 670.000 400.000 660,000
xperlsnc,~
~~~SIZIz0toz
Draft - Do not cite or quote
TABLE 4 Mortaiity Ratios for N1en and Women 36 Years
and Older According to Smoking Status at Tim* of
Enrotlment
2:-Strta Study 50-Stuo Study
Current
9mdcer Former
Smoker Curesnt
Smoker Farm.r
Smo`~to°
Men
Lung
11.35
4.96
22.36
9.36
Oral 6.33 2.73 27.48 8.80
Esophagus 3.62 1.28 7.60 5.83
Larynx 10.00 8.60 10.48 5.24
Bladder 2.90 1.75 2.86 1.90
Pancreas 2.34 1.30 2.14 1.12
Kidney . 1.84 1.79 2.95 1.95
Women
Lun9
2.69
2.59
11.94
4.96
Oral 1.96 1.89 5.59 2.88
Esophagus 1.94 2.15 10.25 3.16
Larynx 3.81 3.10 17.78 11.88
Bladder 2.87 2.31 2.58 1.85
Pancreas 1.39 1.38 2.33 1.78
Kidney 1.43 1.47 1.41 1.16
Uterus 1.18 - - -
Data from the Surgeon General's Report, 1989.5
Draft - Do not cite or quote
CHAPTER 2
EXPOSURES TO INDOOR PARTICULATE AIR POLLUTANTS
John McCarthy PhD, Elizabeth Miesner PhD, John Spengler PhD
Department of Environmental Science and Physiology
Harvard School of Public Health
Boston, Massachusetts 02115
Throughout our lives, we are exposed to gaseous and
particulate contaminants in the air. For some airborne
contaminants, our exposure is dominated by their occurrence in
outdoor air and the time we spend outdoors. However, even for the
pollutants that have only outdoor sources, the air that ventilates
our homes, offices, and vehicles originate outdoors. Considering
chronic exposure or protection from acute episodic outdoor
tollution events, the time we spend indoors and the protection
these indoor environments provide are important considerations.
In the presence of indoor sources of contaminants such as
unvented combustion, evaporation of solvents, and dispersion of
microbiological organisms among others, the time-activity patterns
of people in their use of these indoor environments become
important considerations in determining exposures. People can have
very different exposures to indoor contaminants depending on
social,- demographic and economic differences in the population, as
well as the physical differences that exist across indoor
environments. These differences are characterized by the use of
the structure, its volume air flow and air exchange, the efficiency
of contaminant removal and, most importantly, the generation rate
of the source itself.
Thus, concentrations of air pollutants can and do vary
depending on location. Outdoor pollutant levels may differ from
indoor levels. Different indoor locations like homes, schools or
workplace can also register varying pollutant levels. An
individual's total exposure to air pollutants therefore depends on
the time spent in each of these microenvironments and the various
concentrations of air pollutants.
Time-Activity Patterns
The activity patterns of people determine the duration of
exposure and, at times, the intensity of exposure to airborne
16
Draft - Do not cite or quote
contaminants. The amount of time a person spends in different
microenvironments is influenced by age, sex, occupation, social
class, and season. Letz et al. (1984) studied the time-activity
patterns of 332 residents of Roane County, Tennessee. The results
of study showed that these individuals spent 75% of their time in
the home. This figure was higher (84.9%) for housewives,
unemployed and retired persons. Overall 10.8% of the participants
time was spent at "work". Full-time employed individuals worked
between 21-24% of the time. Of the remaining time, 8.5% was spent
in public places, 9% in travel, and 2.8% in various other
locations.
Quakenboss et al. (1982) studied the time allocation for 66
family members from 19 homes in Portage, WI. Individuals were put
into one of five general subgroups which are shown in Table 1.
Despite wide variations, each group spent most of the time at home.
'For all participants, total time spent indoors was 85%.
More recently, Quakenboss and his colleagues analyzed time-
activity data for over 300 individuals in the Portage, WI area.
Participants were categorized into three groups: workers,
nonworkers, and students. Activity data was collected from both
summer and winter seasons and is summarized in Table 2. Again all
groups spent the largest percentage of their time in the home.
Time spent outdoors decreased from summer to winter.
Infants, because they are essentially immobile, spend most of
their time in the bedroom according to a recent study by Harlos et
al. (1987). The rest of their time is usually spent in the living
room, kitchen, or in travel as illustrated in Figure 1.
I
Knowing an individual's or a population's activity patterns
is not sufficient in itself to determine exposure to contaminants.
Outdoor pollutants do penetrate indoors and can undergo reactions.
Indoor contaminant concentrations vary according to the source
rate, air exchange and air flow, and reactions. Characterizing
sources indoors will not always lead to accurate estimates of
concentrations or exposures. Therefore, depending on the
distribution of sources indoors and the degree of mixing, there may
be considerable differences in pollutant concentrations across
indoor environments.
Lebret (1985) examined the respirable suspended particulate
(RSP) levels in rooms while participants were smoking or within
one-half hour of smoking. He found significant variation between
the living room kitchen and bedroom. Ju and Spengler (1981), who
studied 24-hour average concentrations of respirable particulates,
also found statistically significant variation between some rooms
although the absolute differences were relatively small.
Monitoring
17
Draft - Do not cite or quote
There are a number of different instruments available to
monitor air pollutants. Often the type of instrument used depends
on the exposure of interest. Immediate exposures are most
important when studying irritant and acute allergic responses. For
this type of exposure, instruments which take short-term or
instantaneous readings are often used: the piezobalance or
nephelometer are both used to measure particulates, the ecolyzer
is used to measure carbon monoxide. One advantage to these types
of instruments is their ability to detect peak pollutant levels.
For acute effects such as upper or lower respiratory
infections, the exposures of interest range from hours to days.
For increased prevalence of even a lifetime.(?) To measure these
exposures, integrated or time-averaging methods are used. These
methods include filters which are used to collect particles over
long time periods.
EXPOSURE TO AIRBORNE PARTICLES
,Size Distribution and Composition of Particulates
The distribution of particulates is essentially trimodal with
peak diameters at approximately '0. 02 µm, 0.5 µm and 10 µm as shown
in Figure 2. These size modes reflect the origins of the particles
and the physical chemical processes affecting them. The ultrafine
fractions are typically fresh combustion emissions of aiken nuclei
and condensing vapors. The submicron size (0.1-1 µm) has been
called the accumulation mode. Again, incomplete combustion adds
particles to this size range; however, the oxidation of gases such
as SOZ and NOZ to form sulfates and nitrates are predominantly found
in this range.
Particles larger than 1 µm can be of biological origin--fiber
fraFgments, spores, pollens, and bacteria. Bursting bubbles and sea
spray can generate condensation nuclei. But it is mostly abrasion
and/or erosion that generate larger particles.
The fine particle fraction, or <2.5 µm, is produced by
combustion or condensation of vapors. At least 75% of the sulfur,
zinc, bromide and lead are found in this size range (Dzubay and
Stevens, 1975). Particles <2.5 µm are very important for health
reasons since these particles can reach the alveolar regions of the
lungs.
Particles greater than 2.5 µm in diameter, or coarse
particles, are usually formed by mechanical processes like
grinding, crushing, and abrasion. At least 75% of the silicon,
calcium and iron, elements commonly found in soil, appear in this
size fraction (Dzubay and Stevens, 1975). Particles from 2.5-10
µm can be inhaled and can become deposited in the tracheobronchial
18
Draft - Do not cite or quote
regions.
Environmental Tobacco Smoke
Environmental tobacco smoke (ETS) is a mixture of exhaled
mainstream smoke and sidestream smoke. Sidestream smoke is the
smoke that is formed by smoldering between puffs of a tobacco
product and is the major source of ETS. Approximately half the
tobacco in a cigarette is burned in the sidestream mode. The
complex mixture that the smoker inhales with each puff of a
cigarette, cigar, or pipe is called mainstream smoke. The portion
of mainstream smoke that the smoker exhales and the small amount
of vapor diffusing through the wrapping of the cigar or cigarette
add little to ETS.
ETS consists of fresh and_aged sidestream and mainstream
smokeo The particle sizes which make up ETS vary due to
coagulation (the process where two or more particles collide and
combine to form a larger particle), evaporation, and the adhesion
of particles to surfaces. The size distribution of particles is
also affected by air dilution, relative humidity and temperature.
- Under controlled conditions, several researchers have measured
the particle size distribution of sidestream smoke (Keith and
Derrick, 1960; Porstendorfer and Schraub, 1972; Hiller et al.,
1982; Leaderer et al.$*1984; Ingebrethsen and Sears, 1986). Based'
on these studies, the mass median diameter of sidestream smoke can
be estimated to be between 0.2 µm and 0.4 µm. The mass median
diameter is the diameter which divides the mass distribution in
half, i.e. one half of the mass is contributed by particles larger
than this diameter and one half by particles smaller. Because much
of the time the tobacco is burning at substoichiometric conditions,
particles are produced in the accumulation size mode. As ETS ages,
the processes of coagulation cause particles to grow. This offsets
mass loss due to evaporation.
Composition of ETS
Environmental tobacco smoke is made up of several thousand
different chemical compounds. These compounds may be in the
gaseous or solid phase or both. The chemical composition of
sidestream smoke differs from that of mainstream smoke. Over 2,000
compounds have been.measured in sidestre;am and mainstream smoke.
Some of the constituents in the mainstream smoke of nonfilter
cigarettes are listed in Table 3. Also given are ratios of these
substances in sidestream smoke compared to mainstream smoke. A
ratio of greater than 1.0 means the constituent is found in higher
concentrations in sidestream smoke than mainstream smoke.
Nicotine, a substantial component of tobacco combustion, is
produced mainly in the particulate phase. However, as the ETS
mixture dilutes and ages, the nicotine rapidly shifts to vapor
phase. Chamber studies by McCarthy (1987) and others have
19
Draft - Do not cite or quote
demonstrated that the half-life decay of nicotine is more than
twice that of the particulate phase. A number of the constituents
listed are carcinogens or suspected carcinogens according to the
International Agency for Research on Cancer (IARC).
Measurement of ETS
The large number of constituents in ETS make it impossible to
assess overall exposure based on measurement of each one. Instead
most researchers have measured one or more compounds and have used
those to estimate the total exposure to ETS. Changes in ETS
composition over time and exposure conditions limit the accuracy
of this method.
This chapter will discuss in detail only a few of the possible
measures of ETS: particles, nicotine, cadmium and nitrosamine.
Most of the data presented will be from studies involving cigarette
smoke since this is a major source of indoor ETS. Little work has
been done on pipe or cigar smoke.
Exposures to Environmental Tobacco Smoke
- According to the U.S. Department of Commerce (1985) about 30%
of adults in the U.S. are smokers. 40% of homes nationwide have
at least one smoker. In a survey of over 10,000 children in six
U.S. cities, the percentage of children living with one or more
smoking adults varied from a low of 60% to a high of 75% (Ferris
et al., 1979). Lebowitz and Burrows (1976) reported 54% of
children in a study in Tucson had at least one smoxer in the home.
These data indicate that the potential for exposure to ETS in the
home is greater than that inferred from national statistics. In
part, this reflects the demographics of smoking where it is adults
in their child-raising years that are more likely to be smokers
than the overall average. Surveying a new cohort of elementary-
age children in six U.S. cities reveals that on average, parental
smoking has decreased between 10% to 15% over a decade (mid 1970's
to mid 1980's).
Smoking between different demographic~groups can vary widely
and this will modify the exposure of nonsmokers to ETS. Overall,
ETS exposure will depend on the proximity of an individual to the
source of smoke. Patterns of smoking will be influenced by time,
location, and type of activity.
MICROENVIRONMENTAL MEASUREMENTS OF CONCENTRATIONS
Concentrations of Particles and ETS
Numerous studies have been conducted using respirable ~~
suspended particulates (RSP) as markers for ETS. Both continuous p
and integrated measurements methods have been used. Although RSP O
20 N
N
~
O
!'~:
Draft - Do not cite or quote
is not specific for the presence of smokers in the home and other
indoor locations, the number of cigarettes smoked have shown to
correlate well with RSP.
Particulate Concentrations in Homes
Spengler et al. (1981) measured 24-hour respirable particulate
levels in 55 homes in six U.S. Cities. The mean monthly
concentration across cities is presented in Figure 3, with indoor
particulate levels similar to the outdoor levels. Table 4 shows
the respirable particulate levels in the homes as a function of the
number of smokers. The actual amount of smoking in the home was
not reported. The researchers concluded that the major source of
indoor particulates in smoking homes was cigarette smoke. Each
smoker in the home raised the mean respirable particulate level by
2 0 Ag/m3 .
Further analysis of the data by Dockery and Spengler (1981)
showed that each cigarette smoked in the home increased the mean
respirable particulate levels by 0.88 Ag/m3 . In air conditioned
homes, the respirable particulate levels increased by 2.11 µg/m3
per cigarette per day. This increase was probably caused by
recirculation of indoor air which reduced the cigarette smoke
dilution.
More recently Spengler and colleagues (1986) analyzed RSP data
from over 200 homes in Watertown, MA. Homes with smokers had RSP
concentrations of 30 to 35 µg/m3 higher than nonsmoking homes. RSP
concentration and the number of cigarettes smoked per week were
highly correlated. Models based on this data predict a
contribution of 0.77 µg/m3 per cigarette per day. This would mean
a pack of cigarettes would increase the indoor RSP concentration
by 15.5 ~cg/m3.
Particulate Concentration in Offices
Using a piezobalance, Weber and Fischer (1980) monitored 44
workrooms at seven different companies in Switzerland. The
workrooms had varying levels of smoking. A number of samples were
taken in each room over a two-day period. After subtracting the
particulate levels found in an unoccupied room, t3e mean
particulate level for the 492 sam3ples taken was 133 ~cg/m with a
standard deviation of 130 µg/m . The maximum concentration
measured was 962 ug/m3
.
Quant et al. (1982) used a piezobalance to monitor three
offices. The offices were divided into cubicles with half-wall
partitions and contained both smoking and nonsmoking areas.
Offices were monitored continuously for one work week. Figure 4
shows the results of continuous monitoring in one of the offices.
For the three offices, the ten-hour day averages ranged from
37µg/m3 to 89 µg/m3.
21
Draft - Do not cite or quote
Miesner et al. (1988) used both continuous and integrated
methods to monitor in five office buildings in metropolitan Boston.
Both filters and nephelometer were used to measure in 12 offices,
one conference room, and a designated smoking room of a large
nonsmoking office. In offices without smoking, concentrations
typically ranged from 15 to 10 µg/m3. In offices with smoking,
concentrations were higher, ranging from 20 to 80 µg/m3. In
designated smoking areas, concentrations were 100 to 500 µg/m .
Short-term concentrations measured with the portable MINIRAM
exceeded 1000 µg/m3 in one of the designated smoking areas.
Particulate Concentration in Offices
Repace and Lowry (1980) measured particulate levels in various
indoor public facilities both in the absence and presence of
smoking. For nonsmoking locations such as restaurants, libraries,
a church, and a bakery, the mean indoor RSP level was less than 60
Ag/m3. Measurements taken in public facilities in the presence of
smoking are shown on Table 5. Measurements range from 86µg/m3 to
187 µg/m3 for restaurants and cafes that permit smoking. Other
areas where there are likely to be more smokers per area than in
restaurants had much higher concentrations of particulate matter,
zanging from 200 to 700 µg/m3.
Besides monitoring in offices, Miesner et al. (1988) also took
continuous and integrated RSP measurements in numerous public
facilities including a library, museum, school, subway, bars, and
restaurants. They found that for most public buildings where no
smoking was p~resent the particulate levels were low usually less
than 30 µg/m . Levels in transportation facilities such as the
subway and bus stations were slightly higher with a mean integrated
measurement of 63 µg/m3. Higher concentrations were found in
smoking areas such as bars, restaurants and a public smoking room
with a mean integrated measurement of 79 µg/m3 and a standard
deviation of 44 µg/m3.
Concentration of Other Components of ETS
Numerous researchers have looked at other tracers for ETS.
Because of its high specificity for tobacco smoke and its presence
in high concentration, nicotine is a promising choice. McCarthy
et al. (1987) measured indoor nicotine levels in smoking and
nonsmoking homes. The home nicotine values ranged from an average
of 0.1 µg/m3 in the nonsmoking households to 4.2 µg/m3 in the
smoking households. The presence of low nicotine values in some
of the nonsmoking households can be accounted for by visitors to
the home who were smokers.
A number of studies have used integrated readings to determine
nicotine levels in offices and public buildings. A selection of
these studies are presented in Table 6.
22
. ..
Draft - Do not cite or quote
Cigarettes are also known to be a source of cadmium. Lebret
et al. (1987) considered cadmium as a useful tracer for ETS. They
monitored twenty homes and one outdoor site for fine particulates
in Watertown, MA. Particles were analyzed for elemental
composition using x-ray fluorescence. At the outdoor site and in
homes without smokers, cadmium levels were below the detectable
limit. In homes with smokers, indoor cadmium levels were highly
correlated with indoor fine particulate measurements.
Nitrosamines, some of which have been listed as animal
carcinogens by the IARC, have been studied in public facilities and
homes (Brunnemann et al., 1978). Using continuous measurements
they found mean levels of nitrosamines in public facilities which
ranged from 0.01 to 0.24 ng/L. Both homes monitored had levels of
less than 0.005 ng/L.
Wallace et al. (1987) measured the personal exposure and
breath levels of benzene and other aromatics in 200 smokers and
322 nonsmokers in New Jersey and California. Benzene is listed as
a human carcinogen by the IARC (1986). They found a significant
increase in breath concentration with the number of cigarettes
smoked. Smokers were found to have up to 10 times the breath
concentration of benzene compared to nonsmokers. Nonsmokers who
reported smoke exposure at work showed elevated levels for fall and
winter but not for spring and summer. The authors concluded that
cigarettes were the major source of benzene for about 50 million
U.S. smokers.
No single constituent of ETS is sufficient to completely
characterize an individual's exposure to ETS., Research on ways to
relate these measurements to specific health effects continues to
be done. The most prudent course is to measure several of these
components in exposure studies. Markers specific to the class of
ETS components, or health outcome of interest, could be utilized
in epidemiologic studies to enhance precision of the exposure.
Personal Exposures
Personal monitoring studies have many of the same problems
that area monitoring has, such as trying to measure ETS exposure
based on one or more markers. However, personal exposure
monitoring has the advantage of including spatial and temporal
dimensions to the measurements. It is also possible to use time-
activity diaries to link exposure with location and activity.
The results of a personal monitoring study by McCarthy et al.
(1987) show that the exposure of children to RSP was much higher
than that of children from nonsmoking households. The average
personal RSP value increased from 29 µg/m3 for children from
nonsmoking families to 56 µg/m3 for children from smoking families.
The average personal nicotine concentration increased from 0.3 ,
2 3
~
Q
~
, Draft - Do not cite or quote
µg/m3 to 2.5µg/m3 for children from nonsmoking and smoking families
respectively. A child's personal nicotine is highly correlated
with the consumption of cigarettes in the home while the personal
RSP was not. This implies that although there are multiple sources
of RSP, the majority of ETS exposure is from the child's home.
Spengler et al. (1985) had 101 nonsmoking volunteers from
Kingston/Harriman, Tennessee wear personal respirable suspended
particulate monitors for 3 days. Nonsmokers were divided in two
groups: those who lived with a smoker and those who did not.
Outdoor and indoor particulate levels were taken for comparison.
Results showed that personal exposure was not correlated with
outdoor concentrations but that ETS significantly increased an
individual's personal concentration profile.
In Spengler and Tosteson (1981), 45 nonsmoking adults were
monitored for RSP for 18 days. They were also divided into two
groups: those exposed to ETS and those who were not. Area monitors
were also placed inside and outside. Personal exposure was higher
than both indoor and outdoor measurements. On average, the
individual exposure was increased by 20 µg/m3 among those who
reported exposure to ETS.
Cotinine is a major metabolite of nicotine. McCarthy et al.
(1987) measured cotinine levels in the urine and saliva of 81
nonsmoking children. Nicotine levels in the air were also
monitored as was RSP. They found a high correlation between
personal nicotine levels and cotinine indicating a quantitative
relationship may exist. They did however find high variability.
Coultas et al. (1987) measured cotinine in the saliva of 1360
nonsmoking children and adults. They found an increase with the
number of smokers in the home at all ages. However, household
variability was wide and even 30% of the nonsmokers living in a
nonsmoking home had detectable cotinine levels.
..4
Summary
1. Environmental tobacco smoke is the primary contaminant causing
elevated RSP levels in enclosed spaces.
2. Environmental tobacco smoke can be a substantial contributor
to the level of indoor air pollution concentration of benzene,
acrolein, N-nitrosamine, pyrene and carbon monoxide.
3. Measured exposures to respirable suspended particulates are
higher for nonsmokers who report exposure to ETS.
N
Q
~
a
~
24 ~
~
~
~
CA
~
Draft - Do not cite or quote
REFERENCES
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CJ
0
N
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A
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400, 1982.
Draft - Do not cite or quote
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26
Draft - Do not cite or quote
MCcARTHY, J. Physical and Biological Markers to Assess Exposure
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27
i
Draft - Do not cite or quote
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B.C. JR. Long-term measurements of respirable sulfates and
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15(1):23-30, 1981.
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M.L. Personal exposures to respirable particulates and
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R. Exposures to benzene and other volatile compounds from active
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WHITBY, K.T. The physical characteristics of sulfur aerosols.
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U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. The Health
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General. DHHS Publication No. (CDC) 87-8398, 1986.
28
Draft - Do not cite or quote
U.S. DEPARTMENT OF TRANSPORTATION AND U.S. DEPARTMENT OF HEALTH,
EDUCATION, AND WELFARE. Health Aspects of Smokinct in
Transportation Aircraft. U.S. Department of Health, Education, and
Welfare, National Institute for Occupational Safety and Health,
December 1971. '
29
Draft - Do not cite or quote
FIGURES AND TABLES, CHAPTER 2
~
~
~
3 0 '~
~
~
©
Oat
Draft oDo flot cite or quote
40
30
20
10
2
4
f
0
10 12 14
hlour oa g+w daY
1{
F-IGI7RE 1. -Time Location Patterns for 46 Infants
m
20
22
24
Source: Harlos et al. (1987)
Draft - Do not cite or quote
I
YIMO {lOYM DUST
EMISSIOMS
SEA SPRAT
roEUJ1oS
e
PLAMT PARTICLES
10 100
TRAMSfEMT MUCLEI OR ACCVWUTIOM ~ MECHAMICAIIr GEMERATED _
A1TCEM huCLEi RAMGE ~~ MAMGE AEROSOI RA)IBE
FIME PARTICLES
C6ARSE PARTICLES "
FIGURE 2. Schematic of an atmospheric aerosol surface area distribution
showing the three modes, main source of mass for each mode, the
princeipal process involved inserting mass into each mode, and the
principal removal mechanisms.
Source: Whitby (1978)
Draft E Do not cite or quote
92Q 196
~
~ 90®
~ 9®
~ b6
70
~
~
~ 6050
a®
30-
2
t®
®
T-~
tr~v. B.e. J.r~ ~.D'. ua~. l~y.. ilay Arri Jua: Auq. 5.~. oa wov O.e ~ a.b. Wr. Ap.
9176 19i77 997{
FIGURE 3. Monthly Mean Mass Respirable Particulate Concentrations (,c&/M')
Across Six Cities
Source: Spengler et al. (1981)
Draft - Do not cite or quote
FIGURE 4. Aerosol Mass Concentration in R & D Office
Source: Quant et al. (1982)
Draft - Do not cite or quote
TABLE 1. Mean Percent and Standard Deviation of Time Allocation in Various
Locations by Work or School Classification Subgroup
Locatiac
Homemd.r
Shadeat Outdaoe
worts Q(lSoe/
S.rvia 1ndu.tcial/
Coossal+dion Total, al)
p.rtidpant..
Hom 84.34 6991 49.99 68.74 6725 64.21
(2.02)' (13.92) (12.24) (8.72) (J.06) (13.99)
Oufii& 5.52 &62 19.31 247 10.60 iAd
(3.27) (6.63) . (5.86) (2.49) (10.74) (7.07)
3lotor .ehicl. 4.23 6.11 8.67 4.69 7.64 5.51
(3.19) (3.74) . (6.16) (2.33) (7.62) (429)
Other indoom 6.01 29.61 21.66 24.99 24.80 21.68
(2.27) (10.61) (6.32) (10.24) (12.86) (11.37)
Cookia6 4.69 0.34 0.00 132 0.52 1.24
(1.88) (0.79) (0.00) (2.30) (0.!!6) (1.96)
Near emokere 2.84 6.20 2.75 11.73 12.03 6.89
(4.32) (7.E8) (3.38) (16.19) (10.06) (9.71)
Numbu 8 32 4 12 6 66'
' Numb.rs in pwntA.re..r. tb. stan&d ds.i.tiaa.
'Trre anempiayi psrticip.nte rere ix)ud.d la tho total, but na4 gi..a ..Kwata nt.eor'.
9pUROL Data hsm Quaa.nDra .fl 61. (1lRZL
Draft - Do not cite or quote
TABLE 2. Mean Percent Time Spent in Various Locations for Three Population
Groups
phase location
summer home (SD)
outside (SD)
motor vehicle (SD)
work/school (SD)
other indoors (SD)
N
winter home (SD)
outside (SD)
motor vehicle (SD)
work/school (SD)
other indoors (SD)
N
population group
workers nonworkers students combined totals
59.3 (11.9) 75.2 (12.1) 68.3 (12.5) 65.4 (13.3)
12.3 (9.1) 12.9 (9.9) 15.0 (9.3) 13.7 (9.4)
5.8 (4.2) 4.4 (2.7) 3.3 (4.3) 4.4 (4.3)
15.5 (10.9) 0.2 (0.8) 4.4 (7.8) 8.4 (10.6)
7.0 (6.4) 7.2 (6.4) 9.0 (9.6) 8.1 (8.2)
137 32 177 346
66.1 (11.4) 83.3 (8.4) 66.1 (10.1) 67.5 (11.5)
3.3 (5.35) 1.9 (2.0) 3.9 (3.3) 3.5 (4.2)
5.6 (5.6) 4.3 (2.5) 3.3 (2.6) 4.2 (4.1)
18.6 (10.4) 3.0 (7.1) 19.5 (7.5) 17.9 (9.7)
6.4 (6.0) 7.6 (5.3) 7.3 (6.2) 7.0 (6.1)
127 26 176 329
!~ource: Quackenboss.,et al. (1986)
Draft - Do not cite or quote
TABLE 3.
Distribution of Constituents in Mainstream Smoke (MS) and the
Ratio of Sidestream Smoke (SS) to MS of Nonfilter Cigarettes
Vapor phax constituente' MS
range SS/MS
ratio
Particulate phase constituenta' Ms
range S5/MS
ratio
Carbon monoxide 10-23 mg 2.5-4.7 Particulate mattere 15-40 mg 1.3-1.9
Carbon dioxide 20-40 mg 8-11 Nicotine 1-2.5 mg 2.6-3.3
C`arbonyl sulfide 18-42 µg 0.03-0.13 Anatabine 2-20 µg <0.1-0.5
Benzene' 12-48 µg 10 Phenol 60-140 µg 1.6-3.0
Toluene 1604 6 Catechol 100-60 µg 0.6-0.9
Formaldehyde 70-100 µg 0.1-a50 Hydroquinone 110-300 µg 0.7-0.9
Acrolein 60-100 µg 8-15 Aniline 360 ng 30
Acetone 100-250 µg 2-5 2-Toluidine 160 ng 19
Pyridine 16-40 µg 6.5-20 2-I3aphthylamine' 1.7 ng 30
3-ifethy4pyridine 12-36 pg 3-13 4-Aminobiphenyl' 4.6 ng 31
3-Vinylpyridine 1I-30 µg 20-40 Oenrjajanthracene° 20-70 ng 2-4
Hydrogen cyanide 400 S00 µg 0.1-0.25 Senzo(alpyrene° 20-40 ng 2.5-3.5
Hydrazine' 32 ng 3 Cholesterol 22 µg 0.9
Ammonia ~ 50-130 pg 40-170 y-Sutyrolactone' 10-22 µg 3.6-6.0
bSethylamine 11.5-28.7 µg 4.2-6.4 Quinoline . 0.5-2 µg 8-11
Dimethylamine 7.8-10 lag 3.7 5.1 Harman 1.7-3.1 µg 0.7-1.7
Nitrogen oxide 100=600 µg 4-10 N'Nitrosonornicotine® 200-3,000 ng 0.54
N-Nitroaodimethylamine' 10-40 ng 20-100 NNK' 100=1,000 eg 1-4
N-Nitroeopyrroiidine' 6-30 ng 6-30 N-Nitrosodienthanolamine' 20-70 ng 1.2
Formic acid 210-490 µg 1.4-1.6 Cadmium 100 ng 7.2
Acetic acid 330-810 µg 1.94.6 Nickel' 20-E0 ng 13-30
Zinc 60 ng 6.7
Polonium-2I0r 0.04-0.1 pCi 1.0-4.0
Benzoie acid 14-28 µg 0.67-0.95
Lactic acid 63-174 µg 0.5-0.7
Glyoolic acid 37-126 µg 0.6-0.95
Succinie acid 110-140 ~&C 0.43-0.62
' Values are given for frrsh and undilutaK! MS and SS.
' Human arc(naqen (IARC 1986).
'Suspected human eareinosen (IARC 19861.
'Animal carcinogen (IARC 19861 , -
SOURCE: Elliott and Rowe (1975); HoRmann et aL (1983F, Klu and Kuhn (19d2): Sakuma et al. (1953k
Sakuma, Kusams. YamaNchi, Matsuki et al. (1994r, Sakuma. Kuaama, Yaanatsesh6 "
SuRawara (1984j; Schme(tz et a1./19751. . '
Draft - Do not cite or quote
TABLE 4. Respirable Particulate Levels as a Function of Number of Smokers
Smokx .4tu. Numba Hean (4/m') Stacdard de.iatioa
No &moken Ed bomea/1,186 sample. 21.f 11.A
1 cnwkn 15 bomeJ4S1 ampla 36.3 IlZ
2 smokers
2+ amokea 5 bomei/1bJ .ampia
4 6omerR umpL 10,{
b1.S l2A
1iJ
90URCP- qaen4l.r.t a1. Q9d11
Draft - Do not cite or quote
TABLE 5. Particulates Measured under Realistic Conditions
Nonsluxltint
oaupancy Moaitoriasg Levek. (Pt/m') ooeerole (p4l®')
$tudY 'lYpe.of
premiade Ustive .maksrs
per 100 m')
V.atiLtio® modi tioms
(mia)
Mean SD
itleaa SD
Rep.ee a,ed Cock4oil part' 0.73 Natural 1b 351 t 38 24
GosrM l4dq+e haA 1.26 M.eeuikal 50 997 t 28 So'
(1990Y Bar and frill 1.78 xWAaaieal 16 BW s 26 63'
I'Sre}wu.e Din`o 2.77
Mech
a
a
i
a
l 16 417 t 61 $1,
PSzaria
194 y,
~
'
~
~
~
MI1C..~o;
32
414 t
36
40'
Baa/ooektatl loung. 3.24 Meehanieal 36 J34 t 120 60'
Chumb bin6o pm. 0.47 Mer)Iasical 42 279 t 16 30
laa 0.74 Mxhania1 12 239 ~ 9 YZ'
Bowling aAey 1.b3 M.e6aniad 20 902 ~ 19 49'
Hapital waiting room 2.16 9Ke-nioll 12 187 ~ 62 581
ShoppiM ptara eesuuraat
S.mp1F 1
0.18
l4eehaaid
16
153 *
t
b
oe
3.mp!a 2 0.16 Meehaaiasi 19 lp t 4 ~
36 '
Barbequ" reatanraat 0.139 l!®ehanial 10 1J6 :t 17 40'
S.adw+th rmtaurant A
Smok3n6 sectio®
029
Mer}uakal
20
110 t
J6
40s
Nosan~okiag .ection 0 Mee6anial 2D 56 t ` 30
F"Vood reetaurast 0.42 Idsehaaieal 40 10® t Jd 34'
BportP aaeaa 0.0®' Meehaaieal 12 6/ t 13 86e
NeiYhborbood restaura.etJbat 0.40 MWIaaial 12 93 t 17 66'
Hotel bar 0.b9 Mabaaical 12 93 t 2 3D
Saadwieb reKtaaraat B
Smokiag ..etioe
0.13
Mechaeiea!
6
a6 :t
7
Nosamokint aectio® 0 Mshaaicw 21 61
R.odsido rsdaurast 112 &llxha+aaeal (9A .eh 7 16 107' 30
CWerenoe rao® U4 MeclasairaJ (4.3 ash ') 6 1947° bd
Rspeet md Man®e tb.ataf 0.14 3Bes8sniorl 44 146 t 43 47 :t 10
Lr.rs~ p4aeptiec m.ll 1.19 machaniclal ~ 301 * 30 =B
t29~R21 Baap ball OA3' Natural ! 1140 40'
0.93' Mecbaa" l (1.39 aeh') 6 4434 40'
n+eesrem.at (fi elnefa ~.ac.~.l
' SKuantial attrlow
l.eim.uL
'Ais thancee p.r l+mtt,
- fiQtiilLYvrtiim {tnI Y EoCaPmiNd fECO OOOOnGLrf.Li06 R ti= Qatm
SOURCE: U,S. Department of Health and Human Services (1Q86)
Draft - Do not cite or quote
TABLE 6. Nicotine Measured Under Realistic Conditions
i.vela (u[/m') Noocmoting
mamoir
Study Typp Q(
p+tmi.e.
4ccvpaacl
Veatilatioa Monitoring
ooodition6
lla.a Ra$8.
1le.a Raa6.
Badre at al.
(1978)
- 6 aras
Raom
Hoapital lobby
2 train compattmtata
Car Varied
18 amoketf
12 to 30 arookera
2 to 3 amoktta
3 anokers Not pwa
Not riv.a
Not gives
Not =i.en
Natunl, open
Natural, dord 50 min .ampla
50 mia amph
50 min rmpW
50 mia aamp{a
50 aun sample
50 min aampla 25.a2
600
37
~~
66
1010
Caw et al. Submarinea 157 apr+tt®i Y.s 32 yd/a.'
(1970) 66 m' pW day
94-103 ci8aretter
per day
Ya
163b µi/m'
Harmren aad
F21'caberger
(1967) '1Tain Not tiwn Natural, clard J4-id min
.amplM 0.7-1.1
Hinda and flrst
(1475)'
- Train
Bua
Bu waiting room
Airline waiting room
Rataurant
CockLil lounge
Student lounge Not gives
Not gives
Not Sivan
Not jiren
Not pvea
Not ewa
Not 6irea Not pv.e
Not iSwn
Not given
Not fiwa
Not praa
Not gives
Not 8iv.a 2'/, hr aamples
2'/, hr aamplas
2'1. hr umple.
2'/, hr sample.
2'1, hr aumpl.s
2'/, hr eamplr
2'/, hr .ampi.. 19
6.3
1.0
3.1
6.2
10.3
2.3 Vvuws aa pna
Va)uet oot gives
Values not given
Valua not sivwn
Value. not p..c
Valuss not Si..a
Va]uei Dot gives
Weber and p4acher
(19w)' 44 oAkr Vari.d Varied 140 x 3 hr
aamplw 0.9 2 1! 13.E (peak) Values not p..o
FiM
(1984) I public bwldia8
8 publie buildinis Noosmoksr+
1 to 6 amakfir. Lf.cbaaSd
Natural and
mAch.nic,.i Not p..n
Not p.+.
13.2 i7a0.0 ~
Muramatsu at al.
(1964) 0(Tico
QlSfn
l.botory
5 oxfearsa room.
3 bww
Hapital lobby
4 hotal lobbiw
6 restauraats
3 e,tet,e,;a.
3 bw aad railway
.aiting room.
4 nn
a a,;a.
7 ai.rplana Not 0m,
Not 8i..a
Not p.+a
Not ri..a
Not gives
Not p..c
Not pm
Not gives
Not p+.n
Not gives
Not p.+a
Not pen
Not pm Not p..o
Not gives
Not p..e
Not p..o
Not fina
Not p..n
Not pw.a
Not a..n
Not p..n
Nd gives
Not p..n
Not p.~
Not gives Not pr.a
Not eine
Not p+.n
Not pwaa
Not p.ae
Not Q..s
Not gives
Not given
Noc p..e
Not p..e
Not p.en
Not gives
Na p..a 10.4 f.3-31.i
!21 1~.6-3i.1
6.8
36.7 165-U0
11.1 7.8-11.t
3A 13-&0
11= 6b18.1
1t.i 7.1-27A
36.1 11,d-t2.2
19.1 10.1-JS1
47.7 7.7-at.1
1t6 II.F-!il
16.2 i.S-38,6
' D.cksroasd 1.*aPs ha.% baa wubewK.L
'Qxtrd va1w. (aeooeupiad ram) Ba.e b..o.ub+i.eui,
SOURCE: U.S. Department of Health and Human Services (1986)
Draft - Do not cite or quote
CHAPTER 4
ABSORPTION OF SMOKE CONSTITUENTS BY NONSMOKERS
Dietrich Hoffmann PhD, Klaus D. Brunnemann MSc,
Nancy J. Haley PhD
American Health Foundation
Valhalla, New York 10595
INTRODUCTION
Exposure to environmental tobacco smoke (ETS) occurs at the
worksite, in public places, and in private homes. ETS is a
composite of effluents generated in various ways during the burning
of tobacco products. The major source for ETS is sidestream smoke
(SS) which is formed during smouldering of cigarettes, cigars and
pipes between the taking of puffs. Minor contributions to ETS are
made by those pollutants of the mainstream smoke (MS) that are
exhaled after inhalation of each puff by the active smoker. The
smoke escaping into the air from the burning cone and from the
mouthpiece of a tobacco product during and after puff-drawing is
another minor contributor, in addition there is some diffusion of
MS gas phase components through the cigarette paper into the
environment. More information is needed on the relative sources°
of smoke in the complex mixture of ETS generated from different
cigarettes under varying conditions.
In the laboratory, MS and SS are generated under standardized
conditions by machine smoking (1,2). While these conditions enable
us to compare the yields of individual smoke constituents from
various brands of cigarettes, cigars and pipe tobacco, they do not
fully reflect the patterns of smoking by humans (3,4). The
consumer's intensity of puff-drawing and inhaling of the smoke is
profoundly influenced by the nicotine content of the MS (4,5), and
smoking intensity is highest when cigarettes with perforated filter
tips are being smoked (6).
The SS release is governed by the velocity of air currents
-around the burning cone; thus, higher air flow generates higher
yields of most SS components. Even though a major reduction of
mainstream smoke yields of the sales-weighted average cigarettes
has occurred during the last three decades, (U.S. cigarettes
declined from 35.5 mg tar in 1954 to 12 mg tar in 1983; (7)), the
SS emissions of smoke constituents were not significantly reduced
(8,9). The data in Table 1 emphasize this with a comparison of
the yields of a select group of toxic compounds in the MS and SS
of four types of U.S. cigarettes. These cigarettes were machine-
smoked under identical conditions. Since the consumer of the low-
yield filter cigarettes is likely to smoke more intensely, a
43
Draft - Do not cite or quote
larger portion of the tobacco column is burned during smoking of
this type of cigarette than is burned during smoking of nonfilter
cigarettes. Therefore, a somewhat lower yield of SS is expected
from the low-yield cigarette smoked by the consumer than is
obtained by its standardized machine smoking.
The exposure of nonsmokers to the effluents of burning tobacco
products usually occurs after considerable dilution of these air
pollutants. This is well substantiated by analyses of the air in
enclosed spaces polluted by tobacco smoke (10,11).
A. Biological Markers in Physiological Fluids
The exposure of nonsmokers to ETS can be assessed with the
help of questionnaires, by estimating the dose from the chemical
analysis of smoke-polluted air, by personal monitoring of ETS
components and/or by measuring the uptake of individual smoke
components in physiological fluids of individuals during or after
exposure. The last and most promising method will be discussed in
this chapter.
The degree of exposure to ETS depends on several factors,
including length of time spent in a smoke-polluted area, the number
of smokers within this area, the size and nature of the space, the
degree of ventilation and the respiratory rate of the exposed
individual. Thus, optimal assessment of ETS exposure is achieved
by analysis of physiological fluids of exposed individuals as well
as by analysis of the respiratory environment. New biochemical
methods enable us to quantify exposure to ETS by determining the
uptake of certain smoke contstituents (or their metabolites) in
biological fluids. An primary requirement for such biochemical
measurements is the availability of highly sensitive and specific
methods.
1. Nicotine and Cotinine.
Disregarding accidental or occupational exposure to tobacco
(12,13), or the use of nicotine-containing chewing gum or nicotine
aerosol rods as aids for smoking cessation (14), the presence of
nicotine and of its major metabolites in physiological fluids is
entirely due to the exposure to tobacco, tobacco smoke, or ETS. Low
levels of nicotine have been found in other members of the
solanaceous variety of plants (14A) but could not be expected to
make an impact on the body burden of nicotine which is obtained
from tobacco sources. Nicotine and its major metabolite, cotinine,
in saliva, blood or urine of active smokers and of passively
exposed nonsmokers are primarily determined by gas chromatography
(GC) with a nitrogen-sensitive detector, and by radioimmunoassay
(RIA) (15-17). An HPLC method which has been developed for
quantitation of cotinine in plasma or saliva of smokers (18) has
not been applied to urine analysis even though the analysis of this
biological fluid appears to have the greatest potential for
44
Draft - Do not cite or quote
evaluation of nicotine uptake by nonsmokers. A problem with this
HPLC method seems to be an unusually high background of cotinine
in persons reporting no exposure to ETS. The possibile co-
migration of caffeine with cotinine in this system needs to be
excluded. (18A) A recently published, highly sensitive method for
determining nicotine in plasma by HPLC with dual electrochemical
detection (2 ng/ml), has not as yet been applied to physiological
samples of involuntary smokers (19). Another emerging analytical
method for the determination of nicotine or cotinine is the enzyme-
linked immunosorbent assay (ELISA; 20).
Trans-3'-hydroxycotinine has been found to be the most
abundant nicotine metabolite in the urine of active smokers
(21), however, it is difficult to quantitate. Since the compound
is not readily soluble it has to be transformed into a heptafluoro
derivative prior to GC detection (22). The levels of 3'-
hydroxycotinine in plasma have been found to be much lower than
those of cotinine in the same smokers although the renal excretion
of 3'-hydroxycotinine has been reported to be greater (23).
Despite its abundance in urine of smokers, this compound has not
yet been applied to the analysis of ETS uptake by nonsmokers.
The GC and RIA methods are most widely used for assaying
nicotine and cotinine in active as well as in passive smokers,
primarily because of their specificity and sensitivity, and because
the needed instrumentation is available in most modern
laboratories. Chromatographic methods, especially those using GC
with nitrogen-phosphorus detectors (detection limit 0.1 ng/ ml
fluid; 16), or a mass-spectral detection system, offer greatest
specificity and high sensitivity; however, they require expensive
instrumentation and technical expertise and they are rather labor
intensive. Since the air as well as glassware in laboratories may
contain traces of nicotine, the chromatographic methods require the
utmost precautions to avoid contamination of samples.
The RIA techniques are operationally simpler, less expensive
and require smaller samples (detection limit 0.35 ng/sample; 17).
More than 50 nicotine metabolites and structurally-related
molecules have been tested as inhibitors of nicotine and cotinine
antigen-antibody reactions; few of them interfere with the RIA
(24). Nevertheless, the potential for cross-reactivity with
unknown endogenous components exists. , The fact that, upon
analysis, thousands of samples obtained from nonsmokers in the US
and UK have been found to be negative, indicates that diets and
drugs commonly used in these two countries do not pose problems of
interference. There is good correlation between results obtained
by GC and RIA analysis for plasma cotinine concentrations (r=0.99;
25). A potential problem in RIA analysis can come from
extrapolation to values below the linear range of the standard
curve. Care must always be taken to insure proportionality of
response.
45
Draft - Do not cite or quote
An interlaboratory comparison of data from 11 laboratories in
6 countries has demonstrated that GC and RIA techniques can
reliably quantitate nicotine and cotinine in urine and plasma
samples. A good correlation of laboratory methods was observed in
plasma samples and in urine samples to which cotinine had been
added as a tracer. However, in urine samples without tracer,
several RIA values for cotinine were found to be slightly higher
than those observed by GC. This could be due to a cross reaction
of the antibody with another compound present in urine, or the
discrepancy could arise from a loss of urinary cotinine during GC
extraction. The former explanation is more likely to apply here
although conventional GC extraction techniques have been reported
to result in the loss of conjugated metabolites of nicotine. The
quantitation of these conjugated compounds by GC methods has
recently been reported by Curvall et al. (25a). In addition cross
reactivity of various cotinine antibodies with trans-
3'hydroxycotinine has been reported to range from 2% (J.J. Langone,
pers. comm.) to 30%; (25b)) All immunoassay methods have led,
however, to perfect distinction between nonsmokers and active
smokers (26).
Table 2 presents data from model studies on the uptake of ETS
by nonsmokers under acute exposure conditions (27-30). The main
purpose of these assays was to develop the methodology for field
studies and to compare the uptake of nicotine from environments
with various degrees of pollution and different types of pollutants
under controlled conditionso It' has been shown that the
equilibrium of nicotine between vapor phase and particulate phase
of ETS depends greatly on the concentration and pH of the emitted
smokestream (31) and, thus, influences the uptake of nicotine by
inhalation.
After repeated exposure to ETS under controlled conditions,
such as twice daily 80-minute exposure on 3 consecutive days to the
diluted pollutants of 4 concurrently smoked cigarettes (32), the
mea`surements in 4 nonsmokers have shown that except for nicotine
in the saliva, the physiological fluids do not reflect maximal
concentrations of nicotine and cotinine until at least 24 hours
later. This observation has led to comparisons of the elimination
of cotinine in smokers and nonsmokers exposed to ETS (33). The
.elimination half-life (tl/2) of cotinine from the urine of smokers
took 21.9 hours and 32.7 hours for nonsmokers. In a second
assay, five cigarette smokers were asked to abstain from tobacco
use for 5 days and were then given nicotine gum for three days.
After another 8 days of abstinence from nicotine, the volunteers
were exposed to sidestream smoke (SS). At this point, the cotinine
elimination (t9/2) from urine (ng/ml) by smokers took 15.4 hours,
by nicotine gum users 18.2 hours, by 8-day exsmokers 27.5 hours,
and by the never-smokers 25.6 hours (33). These findings suggest
that the residence times of nicotine, cotinine and other tobacco
alkaloids, are likely related to the route of nicotine uptake as
well as to possible differences in metabolism between smokers and
46
Draft - Do not cite or quote
nonsmokers. The longer elimination time for cotinine in nonsmokers
has been confirmed by other study groups (35-37), however, the
observation has also been challenged (38,39). A longer residence
time of nicotine metabolites in nonsmokers could conceivably
increase the possibility of endogenous formation of carcinogenic
N-nitrosamines (40).
Most importantly, differences in the elimination times of
cotinine from urine preclude a direct extrapolation to "cigarette
equivalents of smoke uptake" by comparing the levels of cotinine
excreted by active and passive smokers. This has been discussed
by some investigators (10).
Table 3 includes comparisons of nicotine and cotinine in
physiological fluids of nonsmokers with or without ETS exposure,
and of active cigarette smokers in England (41). Data on the
uptake of nicotine by involuntary smokers from additional studies
are summarized in Table 4 (29,42-54). Most of these studies
demonstrate that nicotine and cotinine levels in physiological
fluids of involuntary smokers generally amount to 1 percent and
rsach maximally a few percent of the amounts determined in active
cigarette smokers. Data by Matsukura et al. from Japan on the
other hand, show exceptionally high levels of cotinine in the urine
of passive smokers. This may be due to several factors including
differences in the design of studies and measurement methods (26).
Aside from differences in methodology one cannot rule out that
differences in the uptake and 'metabolism of nicotine which have
been observed in various population groups, and diet may be
partially responsible for the exceptional data reported in the
Japanese study (47). A recent finding indicates that the urinary
excretion rates of Japanese smokers were significantly different
from those determined in adult cigarette smokers in Europe and
North America (55). Additionally, a large epidemiological study
in the U.S. has demonstrated significant differences in serum
cotinine levels between Black and White smokers after adjustment
for cigarettes smoked per day and daily nicotine availability
(55a).These differences in nicotine metabolism require further
thorough investigation.
Survey data on exposure at home, in the workplace and on
social occasions were.collected from 319 employed subjects and were
correlated with levels of cotinine in a random urine sample. Mean
urine/cotinine/creatinine levels were higher for women than for men
possibly due to differences in creatinine excretion between the
sexes. It is also noteworthy that 94% of the women were employed
indoors. Higher levels of urinary cotinine were noted in both men
and women who lived with a smoker than in those subjects who did
not report living with a smoker (13.3±2.4 vs 5.1±0.4 in men and
13.9±1.9 vs. 5.6±0.6 in women). Differences in the prevalence of
exposure at home existed between sexes (males_13.5% vs. females
29.2%). Levels of cotinine found across different exposures
indicate that home exposure has a more pronounced effect on urine
47
Draft - Do not cite or quote
cotinine than does workplace exposure (Table 5; 55b).
The nicotine uptake by infants due to ETS exposure, caused by
smoking mothers or caretakers, appears to be higher than that
observed in adult passive smokers. The amount of cotinine excreted
in the urine of the infants was correlated with the number of
cigarettes smoked by the mother, or caretaker or other persons,
during the 24 hours preceding the measurement (33). The primary
determinant of urinary cotinine levels has been found to be the
smoking behavior of the mother. The finding of relatively high
uptake of ETS, as determined by nicotine/cotinine concentrations
in the urine of infants, is in line with the observation that
infants of smokers have higher rates of respiratory infections than
infants in nonsmokers' homes (56).
Analytical data on nicotine and cotinine in physiological
fluids of nonsmokers can be misleading in a few cases. These
pertain to the very light smokers and those nonsmokers who either
chew tobacco or use oral snuff. It is possible, though rare, that
the very light smoker shows nicotine/cotinine levels approaching
those of passive smokers with extremely high ETS exposure. When
used in combination with cotinine measurements, COHb analyses can
help to differentiate between the two groups. In regular consumers
of snuff or chewing tobacco, cotinine levels are comparable to
those found in cigarette smokers while thiocyanate levels and COHb
values remain low (57).
The determination of nicotine and cotinine in hair has been
tried in an attempt to differentiate between active and passive
smokers. (58). This determination revealed higher nicotine
concentrations in the hair of smokers than in the hair of ETS-
exposed nonsmokers and documented the absence of cotinine, the
major metabolite of nicotine, within the hairshaft of nonsmokers.
Hair sampling for determining ETS-exposure of nonsmokers deserves
more thorough investigation.
In summary, in the hands of experienced biochemists, the
determination of nicotine and, especially, of cotinine in saliva,
serum and/or urine in involuntary smokers represents a reliable,
specific method for assaying the level of uptake of ETS by
nonsmokers. The choice of biological fluid for the quantitation
of cotinine depends upon the question asked. For the evaluation
of changes in smoking behavior, serum or urine are preferred while
saliva is sufficient to determine whether or not a subject is a
smoker (59). For studies of ETS exposure, it is often impractical
to collect serum by venipuncture, and since nicotine concentration
in saliva can be extremely high immediately following ETS exposure,
several hours must pass before the concentration of cotinine in
saliva is stabilized (30). Also, when large numbers of subjects
are to be evaluated, it is preferable to avoid invasive procedures
which might discourage participation and possibly bias the results.
48
Draft - Do not cite or quote
Measurements of cotinine in urine and saliva have been
successfully used to quantitate ETS exposure in large populations.
Cotinine excretion in urine is independent of pH, while nicotine
excretion is greatly influenced by it. At values above pH 6.0,
resorption of nicotine from the urine occurs especially during
longer residence time in the bladder. Cotinine is not subject to
resorption and, as far as it has been investigated, 3'-
hydroxycotinine, a second major nicotine metabolite, is also not
affected (60).
Quantitation of cotinine in random urine samples can have
methodological problems relative to the volume of urine excreted
in any given time period as well as dilution effects. The ideal
standard for evaluation of cotinine excretion in urine would be
the analysis of a 24-hour urine sample. Since this is impractical
in epidemiological studies, random urine samples are usually
collected at the time a questionnaire is administered. In this
case, the ratio of cotinine to creatinine in a given sample is
often used to allow for differences in urine dilution. Urinary
creatinine excretion is usually constant from day to day for a
given individual, but it does vary among individuals. As a
reflection of muscle mass it is generally excreted at about 1 g
per day (men, 1.1 to 3.2 g/day; women, 0.9 to 2.5 g/day). In older
persons, the excretion of creatinine may decrease to 0.5 g/day.
Low levels of creatinine may also be found in dehydrated infants;
this necessitates caution in the expression of ng cotinine/mg
creatinine in a random sample (35). However, a recent study with
pre-school children has shown that cotinine/creatinine ratios in
passively exposed children 'track' over several weeks and reflect
questionnaire data on exposure (61). Epidemiological studies in
adults have also shown good correlations between self-reported
indices of exposure and cotinine/creatinine ratios when data for
men and women are analyzed separately.(55b)
2. Carbon Monoxide. Carbon monoxide (CO) is formed during
the combustion of organic matter including the burning of a tobacco
product. It is also produced in vivo during metabolic processes.
Endogenous CO results primarily from the breakdown of heme-
containing proteins such as hemoglobin. In nonsmokers who are not
exposed to industrial pyrolysis products or vehicle emissions, the
baseline levels of CO, present in the bloodstream as
carboxyhemoglobin (COHb), are generally below 1.5% of the total
hemoglobin.
Persons exposed to heavy vehicle emissions can have COHb
levels up to about 2.5%. In cigarette smokers, COHb levels were
found to average 5.7% in a study of 450 smokers (62) with little
difference being noted between smokers of high- or low-yield
products. This value is similar to that of 4.7% found in middle
aged men in a study by Wald et al. (63).
Carboxyhemoglobin levels are not good indicators of ETS
49
Draft - Do not cite or quote
uptake, due to the fact that CO exposure is not limited to tobacco
smoke; in addition, the measurement of COHb is relatively
insensitive. A study in England did not find significant
differences in COHb levels in subjects reporting no exposure, some
exposure, or a lot of exposure (64). This was confirmed by others
(65) and also by a controlled chamber assay (61). One study in
which significant elevations of COHb were found used controlled
exposure to tobacco smoke at a level of 25 ppm CO for 8 hours.
This intense exposure resulted in an average increase of COHb
levels by 2.5% (85). However, such results are not applicable to
free-living situations in field studies (67).
3. Thiocyanate. Hydrogen cyanide, absorbed from tobacco smoke
is detoxified in the liver to thiocyanate (SCN-). Measurement of
SCN- has been used to differentiate smokers from nonsmokers or, as
mentioned earlier, in combination with nicotine-cotinine assays to
distinguish smokers from chewers of tobacco. Thiocyanate can also
be derived from the diet, cruciferous vegetables being an excellent
source (68). The specificity of SCN as a marker of tobacco smoke
ihhalation is poor and it is generally difficult to distinguish
1-ight smokers from nonsmokers. This lack of specificity makes SCN-
unsuitable for the evaluation of ETS uptake by nonsmoking subjects.
4. H d~oxyproline. Japanese investigators have studied the
excretion of hydroxyproline in persons exposed to ETS as well as
in active smokers and in persons exposed to high levels of air
pollutants (69)a The rationale for these studies is that the
inhalation of nitrogen dioxide causes degradation of lung collagen
and elastin which results in urinary excretion of hydroxyproline.
The investigations of the Japanese group suggested an elevated
excretion of hydroxyproline by children of smoking parents as well
as by wives of smoking husbands, active smokers, and individuals
exposed to vehicle emissions. Since NOx levels in ETS are
relatively low by comparison to mainstream smoke or vehicle
emissions (56,70,71), such increased elimination of hydroxyproline
in passively exposed persons seemed surprising. In fact, another
group of investigators has been unable to confirm this finding
(72).
5. N-Nitroso-Amino Acids.. The occurrence of endogenous
nitrosation reactions in cigarette smokers has been demonstrated
in several studies. This phenomenon entails the risk of endogenous
formation of carcinogenic N-nitrosamines. Endogenous formation of
N-nitrosamines has been proven by urinary excretion of the
noncarcinogenic N-nitrosoproline (NPRO), N-nitrosothioproline
(NTPRO), and N-nitrosomethylthioproline (NMTPRO). Whereas the
average excretion of NPRO in nonsmokers amounted to 2.0±1.5 ug/24
hrs, cigarette smokers excreted an average of 7.0±4.0 ug/24 hrs
(73-77). In the case of NTPRO, the average urinary excretion by
nonsmokers (ug/24 hrs) was 5.9, that by cigarette smokers 8.7 and
that of NMTPRO was 5.6 and 8.5, respectively (75). Only two
studies have explored the possibility that endogenous formation of
50
Draft - Do not cite or quote
N-nitrosamino acids may also be increased in involuntary smokers
(77,78).
The data for NPRO in the urine of a limited number of
involuntary smokers were not different from NPRO data for
nonsmokers without ETS-exposure. A carefully designed study with
a larger number of passive smokers may prove that the average value
for NPRO or, more likely, for NTPRO is higher in ETS- exposed
nonsmokers than in those without ETS-exposure. Controlled long-term
exposures at high levels of ETS have not measured NPRO or NTRO and
such studies might show a value for NPRO or, more likely, for NTPRO
that is higher in ETS-exposed nonsmokers than in those without ETS
exposure. However, it is unlikely that the determination of N-
nitrosamino acids in urine would ever lead to an assay for personal
dosimetry of ETS-exposure in free-living subjects.
6. Aromatic Amines. The sidestream smoke of cigarettes
contains significantly larger quantities of aromatic amines than
the mainstream smoke. For example, the MS of a nonfilter cigarette
contains 0.36 ug aniline and 0.16 ug of 2-toluidine, whereas the
SS of the same cigarette releases 10.8 ug of aniline and 4.1±3.2
ug of 2-toluidine (79). The urine of cigarette smokers contains
somewhat higher amounts of aromatic amines than the urine of
nonsmokers. The 24-hour urine void of cigarette smokers contains
3.1±2.6 ug aniline and 6.3+3.7 ug 2-toluidine, while the urine of
nonsmokers contains 2.8±2.5 ug aniline and 4.1±3.2 ug 2-toluidine
(80). The levels of metabolites of these aromatic amines are
expected to be markedly higher in the urine of smokers than of
nonsmokers. Confirmation of the significance of this difference
would encourage the development of analytical dosimetry for
evaluation of the impact of ETS-exposure on urinary excretion of
the metabolites of aromatic amines.
7. Thioethers in Urine. Cigarette smokers excrete higher
amounts of thioethers than do nonsmokers (81). A study of 26
cigarette smokers showed mean urinary thioether values of 4.3±0.4
mmol/mol creatinine compared to an equivalent mean value for 10
nonsmokers of 2.8±0.2 mmol/mol creatinine (82).
In another study nonsmokers were placed on a controlled diet
and were subjected to 8-hr ETS-exposure at two levels of
.concentration. Prior to ETS exposure 10 nonsmokers excreted
40.0±15.4 umol thioethers/24 hrs. The levels rose to 53.9+22.8
umol after exposure to ETS dose 1 (10 ppm CO). At a higher dose
level (20-22 ppm CO), pre-exposure values were 69.3±36.3 and post-
exposure levels 90.7±44.8. The 10 cigarette smokers who smoked 20
cigarettes each during 8 hrs in order to provide the ETS pollution
in the chamber showed an increase of thioether excretion from
89.1±24.8 to 136.1±38.9 umol/24 hrs (67). In other words, the
urinary thioether excretion of the passive smokers in this study
increased up to 45% and, in the case of the active smokers with the
same ETS exposure it increased about 50- 65%. These findings
51
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require confirmation but they appear to indicate that the thioether
analysis of the urine will most likely not be suitable for the
determination of the ETS uptake by involuntary smokers due to
varying background levels across subjects.
B. Genotoxicity of Physiological Fluids
Several studies have explored the possibility that
physiological fluids of cigarette smokers contain significantly
higher amounts of genotoxic agents than those of nonsmokers (81).
The most extensive data base in this field has shown significantly
higher mutagenicity in the Salmonella thyphimurium assay of urine
of cigarette smokers compared to those of nonsmokers. Since the
original study by Yamasaki and Ames in 1977 (83) at least 20
investigations have shown that the urine of cigarette smokers is
significantly more mutagenic than the urine of nonsmokers who are
not exposed to genotoxic agents in occupational environments. But
it has also been shown that the mutagenicity of the urine of
smokers can be effected by diet (84). It has further been surmised
that exposure of nonsmokers to ETS may lead to increased urinary
excretion of mutagens. Of the 6 published studies in which the
urine of passive smokers was tested for mutagenicity with the Ames
test, 3 showed increased activity and 3 showed no increase or, at
the most an insignificant increase in mutagenic activity (81,85-
87)a
C. Adduct Formation of Carcinogens in Passive Smokers.
a Measurements in physiological fluids of nicotine and its
major metabolite, cotinine, have been shown to be objective
indicators of the uptake of ETS. However, these assays will not
reflect an individual's response to specific ETS carcinogens. That
information is best obtained by assessing levels of macromolecular
adducts with carcinogens or their metabolites. Development of such
assays is based on examining the mechanisms of metabolic activation
and detoxification of tobacco smoke carcinogens.
1. Benzo (a)pyrene. In the case of active smokers, adducts
of at least 4 types of tobacco carcinogens or procarcinogens have
been studied. These adducts are formed by reaction of specific
metabolites of tobacco smoke constituents with DNA and/or
hemoglobin. Benzo(a)pyrene (BaP), a carcinogenic representative
of the polynuclear aromatic hydrocarbons in tobacco smoke is known
to be metabolized to bay region diol epoxides (e.g. 7,8-
dihydroxy-9,10-epoxy-7,8,9,10-tetrahydroBaP). Such diol epoxides
can bind to DNA in human tissues and lymphocytes. Antibodies
developed against the major BPDE-DNA adduct have been used to
assess its presence in surgical specimens of lung tissue, in human
placenta, and in peripheral blood lymphocytes (89-91). Evidence
for the presence of such adducts in samples from smokers has been ~
ascertained but significant differences between smokers and O
I nonsmokers have not been observed. O
~
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2. Aromatic Amines. 4-Aminobiphenyl and 2-naphthylamine are
the known tobacco smoke constituents which are most likely to
contribute to the increased risk of bladder cancer of cigarette
smokers. The mechanisms by which these compounds are metabolically
activated and produce DNA adducts in the bladder epithelium have
been extensively studied (92). These studies have shown that the
corresponding hydroxylamines are key intermediates in DNA and
protein modification. The hydroxylamines also react with
hemoglobin, in the case of 4-aminobiphenyl, a sulfinic acid amide
of the beta-cysteine (93-95). This adduct readily releases 4-
aminobiphenyl upon treatment with dilute acid. A method was
developed to analyze the released 4-aminobiphenyl by gas
chromatography with detection by negative ion chemical ionization
mass spectrometry (95). Application of this method to smokers
showed that adduct levels were higher than in nonsmokers, and
decreased upon smoking cessation. The method may be further
refined for assessing the uptake of carcinogenic aromatic amines
from ETS by nonsmokers.
3. Ethylene. This volatile unsaturated hydrocarbon is
present in both mainstream smoke (200-400 ug/cigarette) and
sidestream smoke of cigarettes (96). Cigarette smoke contains also
traces of the carcinogenic ethylene oxide (7.0 ug/cigarette;
97,98). Upon absorption, ethylene is metabolized to the reactive
ethylene oxide. The latter binds to cellular macromolecules and
to hemoglobin. The alkylated valine is cleaved off of the isolated
hemoglobin and the derivatized hydroxyethylvaline is analyzed by
GC-MS. - Cigarette smokers showed significantly higher
hydroxyethylvaline levels (389±138 pg/g hemoglobin) than nonsmokers
(58+25 pg/g; 99). So far the method has not been applied to
estimates of exposure of involuntary smokers to the procarcinogen
ethylene.
4. Tobacco-Specific N-Nitrosamines. During' tobacco
processing and during smoking tobacco alkaloids give rise to
tobacco-specific N-nitrosamines (TSNA). The nicotine-derived N-
nitrosamines N°-nitrosonornicotine (NNN) and4-(methylnitrosamino)-
1-(3-pyridyl)-1-butanone (NNK) are powerful carcinogens. They
occur in relatively high concentrations in cigarette mainstream
smoke (NNN, 0.12-3.7 ug/cigarette; NNK, 0.08-0.77 ug/cigarette) and
sidestream smoke (NNN, 0.15-1.7 ug/cigarette; NNK, 0.2-1.4
ug/cigarette; 40). These agents are metabolically activated by
alpha-hydroxylation, leading to a highly reactive intermediate
which forms DNA adducts and protein adducts (Fig. I). Metabolic
activation of NNN and NNK also leads to the formation of hemoglobin
adducts. Acid or base hydrolysis of these releases a keto alcohol
(compound 5; Fig. I; 100). A highly sensitive GC-MS method has
been developed to facilitate the detection of a derivative of
compound 5. Refinement towards further increased sensitivity of
the method should lead to a dosimetry assay allowing determination
of the uptake of the carcinogenic TSNA by passive smokers.
53
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FUTURE NEEDS
The absorption of tobacco-specific smoke constituents from
ETS has been demonstrated through analyses of nicotine and its
major metabolite, cotinine in the body fluids of exposed
nonsmokers. Less tobacco-specific markers have also been measured
in exposed populations; however, the results were ambiguous in
regard to the quantitative uptake of ETS. There is a need to
provide information about the uptake and disposition of
carcinogenic constituents by individuals exposed to ETS in acute
and chronic situations. Analyses to be fully developed and applied
to passive smokers will include measurements of adducts of
genotoxic smoke constituents covalently bound to DNA or hemoglobin.
These techniques have been developed for benzo(a)pyrene, 4-
aminobiphenyl, ethylene, and tobacco-specific N- nitrosamines. It
is not known whether or not all of these methods can be made
sufficiently sensitive to monitor the uptake of tobacco-specific
components from ETS.
' Nicotine in ETS is predominantly present in the vapor phase
of the smoke rather than bound to the aerosol particles. In order
to measure the uptake of carcinogens and toxins residing in the
particulate phase of ETS, deposition studies must be developed with
specific markers. Particulate phase constituents which could be
quantitated include tobacco-specific N- nitrosamines, polyphenols,
such as the immunoactive compound rutin, or the tobacco-specific
solanesol.(101) However, the levels of these compounds are
expected to be low so that development of suitable methodology
calls for highly sensitive detection methods.
SUMMARY
1. The absorbtion of tobacco-specific smoke constituents from ETS
has been demonstrated through analyses of nicotine and its major
metabolite, cotinine in the body fluids of exposed nonsmokers.
2. The determination of nicotine or cotinine, in the saliva,
serum, or urine of involuntary smokers represents a reliable,
specific method for assaying the level of uptake of ETS by
nonsmokers.
3. Although cotinine levels in physiological fluids of involuntary
smokers generally are of the order of few percent of those of
active smokers, differences in the elimination times of these
compounds in active and involuntary smokers preclude a direct
extrapolation to "cigarette equivalents of smoke uptake."
4. There is a further need to quantitate uptake and fate of
carcinogenic constitutents of ETS-exposed nonsmokers, particularly
the measurements of adducts of genotoxic smoke components attached
to DNA or hemoglobin.
54
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ACKNOWLEDGEMENTS
We thank Ilse Hoffmann and Bertha Stadler for editorial assistance.
Our studies are supported by Grants No. CA-29580, CA-44377 and CA-
32617 from the National Cancer Institute.
N
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smokers and nonsmokers. J. Natl. Cancer Inst. 73: 83-87, 1984,
75. Tsuda, M., Nutsume, J., Sato, S., Hirayama, F, Kakizoe, T. and
Sugimura, T. Increase in the levels of N-nitrosoproline, N-
nitrosothioproline, and N-nitroso-2-methylthioproline in human
urine by cigarette smoking. Cancer Lett. 30: 117.-124, 1986.
76. Lu, S.H., Ohshima, H., Fu, H.M., Tian, Li, F.M., Blettner, M.,
Wahrendorf, J., and Bartsch, H. Urinary excretion of N-
nitrosamino acids and nitrate by inhabitants of high- and low-risk
areas for esophageal cancer in Northern China: endogenous formation
of nitrosoproline and its inhibition by vitamin C. Cancer Res. 46:
1485-1491, 1986.
77. Scherer , G. and Adlkofer, F. Endogenous formation of N-
62
Draft - Do not cite or quote
nitrosoproline in smokers and nonsmokers. Banbury Rpt. 23: 137-
147, 1986.
78. Brunnemann, K.D., Scott, J.C., Haley, N.J., and Hoffmann, D.
Endogenous formation of N-nitrosoproline upon cigarette smoke
inhalation. IARC Sci. Publ. 57: 819-828, 1984.
79. Patrianakos, C. and Hoffmann, D. Chemical studies on tobacco
smoke LXIV. On the analysis of aromatic amines in cigarette smoke.
J. Anal. Toxicol. 3: 150-154, 1979.
80. El-Bayoumy, K., Donahue, J.M., Hecht, S.S., and Hoffmann, D.
Identification and quantitative determination of aniline and
toluidine in human urine. Cancer Res. 46: 60646067, 1986.
81. International Agency for Research on Cancer. "Tobacco
Smoking, IARC Monogr. 38: 1986, 421 p.
82. Heinonen, T., Kytoniemi, V., Sorsa, M., and Vainio, H.
urinary excretion of thioethers among low-tar and medium-tar
cigarette smokers. Internatl. Arch. Occup. Environ. Health 52:
11-16, 1983. ~
83. Yamasaki, E. and Ames, B.N. Concentration of mutagens
from urine by adsorption with the nonpolar resin CAD-2: cigarette
smokers have mutagenic urine. Proc. Natl. Acad. Sci. U.S.A. 74:
3555-3559, 1977.
84. Sasson, I.M., Coleman, D.T., LaVoie, E.J., Hoffmann, D., and
Wynder E.L. Mutagens in human urine. Effects of cigarette smoking
and diet. Mutat. Res. 158: 149-159, 1985.
85. Scherer, G., Westphal, K., Biber, A., Hoepfner, I., and
Adlkofer, F. Urinary mutagenicity after controlled exposure to
environmental tobacco smoke (ETS). Toxical. Lett. 35: 135-140,
1987.
86. Mohtashamipur, E., Mueller, G., Norpoth, K., Endrikat, M., and
Stuecker, W. Urinary excretion of mutagens in passive smokers.
Toxicol. Letters 35: 141-146, 1987.
87. Husgafvel-Pursiainen, K., Sorsa, M., Engstrom,, K., and
Einistoe, P. Passive smoking at work: biochemical and biological
measures of exposure to environmental tobacco smoke. Int. Arch.
Occup. Environ. Health 59: 337-345, 1987.
88. Ling, P.I., Lofroth, G., and Lewtas, J. Mutagenic
determination of passive smoking. Toxicol. Lett. 35: 147-151,
1987.
89. Harris, C.C., Vahakangas, K., Newman, M.J., Trivers, G.E.,
Shamsuddin, A., Sinapoli, N., Mann, D., and Wright, W.E. Detection
63
Draft - Do not cite or quote
of benzo (a) pyrene diol epoxide-DNA adducts in peripheral blood
lymphocytes and antibodies to the adducts in serum from coke oven
workers. Proc. Natl. Acad. Sci. U.S.A. 82: 6672-6676, 1985.
90. Everson, R.B., Randerath, E., Santella, S.A., Cefalo, R.C.,
Avitts, T.A., and Randerath, K. Detection of smoking-related
covalent DNA adducts in human placentao Science 231: 54-57, 1986.
91. Perera, F.P., Poirier, M.C., Yuspa, S.H., Nakayama, J.,
Jaretzki, A., Curnen, M.M., Knowles, D.M., and Weinstein, I.B. A
pilot project in molecular cancer epidemiology: determination of
benzo(a)pyrene-DNA adducts in animal and human tissues by
immunoassays. Carcinogenesis 3: 1405-1410, 1982.
92. Beland, F.A. and Kadlubar, F.F. Factors involved in the
induction of urinary bladder cancer by aromatic amines. Banbury
Rpt. 23: 315-326, 1986.
93. Neumann, H.G. Analysis of hemoglobin as a dose monitor for
alkylating and arylating agents. Arch. Toxicol. 56: 1-6, 1.984.
94. Green, L.Cr.; Skipper, P.L., Juresky, R.J., Bryant, M.S., and
Tannenbaum, S.R. In vivo dosimetry of 4-aminobiphenyl in rats via
a cysteine adduct in hemoglobin. Cancer Res. 44: 4254-4259, 1984.
95. Bryant, M.So, Skipper, P.L., Tannenbaum, S.R., and Maclure,
M. Hemoglobin adducts of 4-aminobiphenyl in smokers and
nonsmokers. Cancer Res. 47: 602-608, 1987.
96. Wynder, E.L. and Hoffmann, D. "Tobacco and Tobacco
Smoke. Studies in Experimental Tobacco Carcinogenesis." Academic
Press, New York, NY, 1967, 730 p.
97. Binder, H. and Lindner, W. Bestimmung von Aethylenoxyd im
Rau,ch garantiert unbegaster Zigaretten. Fachliche Mitt.
Oesterr. Tabakregie 13: 215-220, 1972.
98. International Agency for Research on Cancer. "Overall
Evaluations of Carcinogenicity: An Updating of IARC Monographs,
Volume 1-42.°' IARC Monogr. Suppl. 7: 1987, 440 p.
99. Tornqvist, M., Osterman-Golkars, S., Kautiainen, A.,
Jensen, S., Farmer, P.B., and Ehrenberg, L. Tissue doses of
ethylene oxide in cigarette smokers determined from adduct levels
in hemoglobin. Carcinogenesis 7: 1519-1521, 1986.
100. Hecht, S.S., Carmella, S.G., Trushin, N., Spratt, T.E.,
Foiles, P.G., and Hoffmann, D. Approaches to the development of
assays for interaction of tobacco-specific nitrosamines with
hemoglobin and DNA. IARC Sci. Publ. 89: 121- 128, 1988.
101. Benner, C.L., Bayona, J.M., Caka, F.M., Tang, H., Lewis, L.,
64
Draft - Do not cite or quote
Crawford, J., Lamb, J. D. , Lee, M. L. , Lewis, E.A., Hansen, L. D. , and
Eatough, D.J. Chemical Composition of Tobacco Smoke. 2. Particulate
Phase Compounds. Environ. Sci. Technol. 23: 688-699, 1989.
65
Draft - Do not cite or quote
Figures and Tables for Chapter 4
66
Draft - Do not cite or quote
N=0
~
N~CHg NNK
0 Nu0
OQ N -. CHZ0H
N \ 1
NO0
i
N '*'CO2Et
9lobin adduct
4
' H*or-OH
0 +
~ ON
5
Figure 1. Metabolic activation of 4-(methylnitrosamino)-1-(3-
pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine
(NNN) to intermediates which bind to DNA 'and
protein.
Table 4 continued ... f ,
Number of
Nonsmoker Group Nonsmokers
Resialts
Reference
Children and adults 529 males Cotinine/Saliva (ng/ml) Coultas
768 females smokers in family et al.
(53)
none one > two
a) <5 years old 0.0 (0~0-2.5) 3.8 (0.0-6.1) 5.4 (3.2-7.7)
b) 6-12 years old 0.0 (0.0-2.1) 2.0 (0.0-3.8) 5.2 (1.5-7.0)
c) 3-17 years old 000 (0.0-2.0) 2.9 (0.0-4.9) 4.1 (2.7-7.6)
d) 18-29 years old 0.0 (0.0-2.6) 0.0 (0.0-5.8) 0.0 (0.0-4.4)
e) 30-64 years old 0.0 (0.0-2®7) 1.9 (0.0-4.5) 4.4 (1.8-11.0)
f) > 65 years old 0.0 (0.0-2.6) 3.6 (0.0-6.5) 0.0
*Numbers in parenthesis median values.
zsaszzo~oz
Table 4 continued ...
Number of
Nonsmoker Group Nonsmokers Results Reference
Municipal workers Cotiine/Urine (ng/mg creatinine) Sepkovic
et al.,
I. ETS exposure in the (52)
wo r kpl ace
a) no exposure
b) light expsoure
c) moderate exposure
d) heavy exposure
II. ETS exposure in the
home
a) no exposure
b) light exposure
c) moderate exposure
d) heavy exposure
School girls (11-16 yrs)
ETS exposure in the home
a) neither parent smokes
b) father smokes only
c) mother smokes only
d) both parents smoke
25 4.510.6
126 6.610.6
84 7.210.8
32 8.411.3
77 6.110.8
83 6.710.6
71 7.811.1
34 7.6f1.3
Jarvis et
104 -
1
1*0
5 al., (53T O
K
76 .
.
2.010.6 w
40 3.210.8 rt
110 5.011.0 I
d
Continued ...
8SOSzzO-Wz
Table 4 continued ...
I
f #tl I I
Nonsmoker Group Number of
Nonsmokers
Results
Reference
Cotinine/Urine (ng/mg creatinine)
Neonates and infants No. .. No. Schwartz-
exp'd I exp'd II Bicken-
a) Mother smokes, bach et.
breastfeeds 20 12 (1756) 0 -3520 8 (935) 488-2440 al., -F51)
b) Mother smokes, !
feeds bottle 16 4 (47) 0 - 160 12 (107) 0- 341
c) Father smokes 18 10 (0) 8 (0) 0- 308
d) No exposure in
the home
15
9
(0)
6 (0)
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
GROsZ90fraZ
Table 4 continued ...
Nonsmoker Group
Neonates and infants
a) No exposure
(4-8 days old)
b) Exposure via
breast feeding
(3-8 days old)
c) Passive smoking
(2.5-6 months old)
d ) Exposure via
breast feeding and
passive smoking
(1-12 months old)
Infants (age 3-15 months)
exposure in the
home
Black infants
a) no exposure
b) passive smoking
White infants
a no exposure
b) passive smoking
1
Number of
Nonsmokers
Results
Reference
Nicotine (n /m creatinine) Cotinine Luck and
10 (0 0 - 14 (0 0- 56 Nau, (49)
19 (14) 5 -110 (100) 10-555
10 (35) 4.7-218 (327) 117-780
9 (12) 3.0- 42 (550) 225-870
Cotinine/ Serum (ng/ml) Pattishall
et al.,
(50T-
9 1.0 (1.8712.38) Pattishall et al., 1985
15 4.0 (5.27+3.50) (51) ty
9
.0
0.22f0.44) H
W
M
Ct
5
0.4
(0.90t1.30) I
0
0
:3
0
Ct
~
Ct
m
0
h
OGoszzataz
1
Table 4 continued ...
Number of
Nonsmoker Group Nonsmokers
Husbands of
a) nonsmokers 101
b) smokers 20
Nonsmokers
a) nonsmokers at home 200
b) smokers at home 272
Cigarettes smoked
day in home of nonsmokers;
1- 9 25
10-19 57
20-29 99
30-39 38
> 40 28
unknown 25
Infants (<10 months,
not breastfed)
a) not exposed to ETS
b ) exposed to ETS
18
28
Results ,
Cotinine,'Urine (ng/ml)
8.51 1.3
25®2±14.8
Cotinine/Urine (ng/mg creatinine)
0.5 10.09
0®79f0.1
Cotinine/Urine (ug/mg) creatinine)
0031=L0008
0.42±0e1
0 . A710 0 1 9
1.0310.25
1.56±0.57
0.56+0.16
Nicotine/Urine Cotinine/Urine
(n~ mg creatinine) (ng/mg)
0 (0-59 4 (0-125)
53 (0-370) 351 (41-1,885)
Reference
Wald and
Ritchie,
(46)
Matsukura
et al.,
(47)
Greenberg ~
et al.; ~
T33T- M,
rt
~
b
0
School children (11-16 yrs) Cotinine/Saliva (ng/ml)
a) Neither parent smoked
b) Only father smoked
c) Only mother smoked
d) Both parents smoked
269 0.4410.68
96 1.31t1.21
76 1.9511.71
128 3.3812.45
Jarvis et
al., (48j
:3
0
rt
N-
rt
m
0
Continued ...
Q
0
cr
~
T6OS`LZUVOZ
Table 4.
Uptake of nicotine by nonsmokers exposed to ETS under daily life conditions
Number of
Nonsmoker Group Nonsmokers Results Reference
Nicotine/Urine (ng/ml)
Hospital personnel 14 12.4116.9 Russell and
Feyerabend
(78 min in smoke- 13 8.9+9.1 (29)
filled room)
Hospital personnel
and outpatients Nicotine/Saliva (ng/ml)
a) no exposure to ETS 26 5.9 7.5 Feyerabend
b) exposed to ETS 30 10.1 21.6 et al. (42)
Flight attendants Nicotine/Serum (ng/ml)
6 pre flight: 1.610.8 Foliart et al.
post flight: 3.211.0 (43) ~ ~
Office workers 7 Content/ml Nicotine (ng) Cotinine (ng) Jarvis et al.
a) 11:30 a.m. sample saliva a 1.90 b 43.63 a 1.50 b 8.04 (44) ~~
b) 7:45 p.m. sample serum 0.76 2.49 1.07 7.33
after 2 hr stay urine 10.57 92.63 4.80 12.94
in pub
:3
0
t
Hospital staff and
Cotinine/Urine (ng/ml)
Wald et al. r
(l
N-
outpations (45) V ~ rt
m
a) no exposure to ETS 22 2.0 (0.0 - 9.3 0
b) exposed to ETS 190 6.0 (1.4 -22.0)
112
0
Continued ...
rt
(D
ZsaszZoW
f
Table 3.
Approximate Relations of Nicotine as a Parameter Between Nonsmokers,
Passive Smokers, and Active Smokersa (41)
Nonsmokers without
ETS Exposure Nonsmokers with
ETS Exposure
Active Smokers
No. = 46 No. = 54 No. = 94
Nicotine/Cotinine %o
Mean
Value Actgve
Smokers°
Value % o
Mean
Value A
Smokersm
Value ~
Mean Value
Nicotine (ng/ml)
in plasma 1.0 7 0.8 5.5 14.8
in saliva 3.8 0.6 5®5 0.8 673
in ur ine 3.9 0.2 12.1* 007 1g750
Cotinine (ng/ml)
in plasma
0.8
0.3
2.0*
0.7
275
d
~
in sal iva
in urine
0.7
1.6
0.2
0.1
2.5**
7,7**
0.8
0.6
310
1,390 w
~
rt
e
d
0
:3
0
aDifferences between nonsmokers exposed to ETS compared with nonsmokers without exposure: (r
*p<0.01; **
p<0.001. ~
N-
rt
M
EGO-raZzO~OZ
Table 2 continued.
No. o f
ETS-Conditions Passive
Smokers
Room - 16 m3
4 cigarettes con-
currently and con-
tinuously smoked for
80 min; 6 air exch./hr.
(200 g nicotine/m3;
20 ppm CO)
6
Results
Investigators
Time during exposure Nicotine Cotinine Hoffmann et al., 1984
ng ml ng ml (30)
0 Saliva 3 1.0
Plasma 0.2 0.9
Urine 17 14
80 min. Saliva 730 1.4
Plasma 0.5 1.3
Urine 84 28
Time following exposure
30 min. Saliva 148 1.7
Plasma 0.4 1.8
150 " Saliva 17 3.1
Pl asma 0.7 2.9
Urine 100 45
300 " Saliva 7 3.5
Plasma 0.6 3.2
Urine 48 55
*Nicotine and cotinine were measured in urine as ng/mg creatinine.
tsoszzovoz
t
4
Table 2.
"
Uptake of nicotine by nonsmokers exposed to BTS under controlled conditions
FTS-Conditions
No ~ of
Passive
Smokers
Room - 170 m3 (11 smokers)
(a 100 cigarettes were 7
smoked during 2 hrs;
no ventilation
(30 ppm CO)
(b) same conditions as above 7
(a) but with ventilation
(5 ppm CO)
Room - 66 m3 (4 cigarette smokers)
(a) Day 1, nonsmoking 2
°" 2, 98 cig ° s smoked
" 3, 121
m
m
2
IN 4, 98
If 5, 88
(b) Day 1, 97
"° 2, 96
of 3, 94
°° 4, 103
m
m
m
m
m
Room - 43 m3
smo ers consumed
80 cigarettes + 2 cigars
no ventilation
(38 ppm CO)
m
m
m
12
Results
Urinar excretion
Nicotine: 1016.8 Ug 6 hrs.
Cotinine: 35*34.5 pq/6 hrs®
Nicotine: 1817 pg/6 hrs.
Continine: 19:t9.4 Ug/6 hrs.
Nicotine/Urine (pg/24 hrs)
0 - 0
35 - 44
50 - 61
62.5 - 70
47 - 50
23 - 34
22.5 - 58
47.5 - 69
32 - 65
Nicotine/Plasma (ug/ml)
Before exposure: 0o7311.6
After 78 min. exposure: 0091 0.29
Nicotine/Urine (ng/ml)
15 mino after exposure: 80.0¢58.7
Investigator(s)
Cano et al. (28)
e
d
0
Russell and p
Feyerabend rQ'
(29) ~.
rt
m
0
continued ... ~
12
0
rr
M
SGOISZ~aV0~
Draft - Do not cite or quote
,rable 1.
Toxic and tumorigenic agents in MS and SS
Cigarette
Smoke Smoke
Constituent streama A (NF) B (F) C (F) D (PF)
Tar
(mg)
Nicotine
(mg) MS
SS
MS
SS 20.1
22.6
2.04
4.62 15.6
24.4
1.50
4.14 6.8
20.0
0.81
3.54 0.9
14.1
0.15
3.16
---------------------------------------------
CO
(mg) MS
SS 13.2
28.3 13.7
36.6 9.5
33.2 1.8
26.8
---------------------------------------------
Catechol
(µg) MS
SS 41.9
58.2 71.2
89.9 26.9
69.5 9.1
117
---------------------------------------------
BaP MS 26.2 17.8 12.2 2.2
(ng) SS 67.0 45.7 51.7 44.8
---------------------------------------------
Ammonia MS 76.0 19.4 34.0 40.4
(ug) SS 524 893 213 236
---------------------------------------------
NDMA MS 31.1 4.3 12.1 4.1
(ng) SS 735 597 611 685
NPYR MS 64.5 10.2 32.7 13.2
(mg) SS 117 139 233 234
NNN MS 1007 488 273 66.3
(ng) SS 857 3G7 185 338
---------------------------------------------
NNK MS 425 180 56.2 17.3
(ng) SS 1444 752 430 386*
a Abbreviations: NF, nonfilter cigarette; F, filter ciga-
rette; PF, cigarette with perforated filter tip; BaP, benzo-
(a)pyrene; NDMA, N-nitrosodimethylamine; NPYR, N-nitrosopyr-
rolidine; NNN, N'-nitrosonornicotine; NNK, 4-(methylnitros-
amino)-1-(3-pyridyl)-1-butanone.
Draft - Do not cite or quote
CHAPTER 5
ENVIRONMENTAL TOBACCO SMOKE AND CANCER
Jonathan M. Samet, M. D.
Pulmonary Division
Department of Medicine
University of New Mexico
Albuquerque, NM 87131
Introduction
Lung cancer, an uncommon malignancy at the start of the century,
has become the leading cause of cancer death in the United States
(U.S. DHHS 1982). The American Cancer Society estimates that
approximately 157,000 lung cancer cases will occur in the United
States in 1990. Most cases are rapidly fatal and only a small
proportion are cured by surgery or chemotherapy; five-year survival
following diagnosis is less than 10 percent. Most lung cancers
arise in the larger airways of the lung, the predominant site of
deposition of inhaled particles in the size range of 0.5 to 3.0
microns in aerodynamic diameter. Primary cancer of the lung occurs
in multiple histopathological patterns that are generally distinct
and classifiable by conventional light microscopy. The principal
types of lung cancer are squamous cell carcinoma, small cell
carcinoma, adenocarcinoma, and large cell carcinoma; in the general
population, these four types account for approximately 30 percent,
20 percent, 25 percent, and 15 percent, respectively, of all lung
cancers (Butler et al. 1987). Dronchioloalveolar cell carcinoma
represents about 5 percent of all lung cancers. The cellular
origins of the various cell types have not been established, and
controversy remains concerning the specificity of associations
between certain cell types and specific etiologic agents. However,
in nonsmokers, adenocarcinoma is the predominant type and small
cell cancers occur only rarely.
The epidemic rise of lung cancer during this century stimulated
laboratory and epidemiological investigation of its causes. Most
of the early epidemiological evidence indicated that tobacco smoke
was a potent respiratory carcinogen, and in 1964 the Advisory
Committee to the Surgeon General of the U.S. Public Health Service
concluded that cigarette smoking is a cause of lung cancer (U.S.
PHS 1964). The numerous investigations performed subsequently have
been consistent with this conclusion. The association of lung
cancer with cigarette smoking is strongest for squamous cell and
small cell cancers, but the other major types are also caused by
cigarette smoking. In active cigarette smokers, the risk of lung
cancer increases with both the amount smoked on a daily basis and
67
Draft - Do not cite or quote
with the duration of smoking (U.S. DHHS 1982; Doll and Peto 1978;
Pathak et al. 1986). A threshold level of smoking that must be
exceeded to cause lung cancer has never been demonstrated; any
cigarette smoking is considered to increase lung cancer risk beyond
that of the lifelong nonsmoker. In former smokers, the relative
risk of lung cancer declines exponentially in comparison with those
who continue to smoke.
Agents other than tobacco smoke may also cause lung cancer, and
cases occur in lifelong nonsmokers. A recent study in New Mexico
showed that the lifetime risks of lung cancer were 0.5 percent and
1.1 percent in female and male nonsmokers, respectively (Samet et
al. 1988). Occupational exposures to arsenic, asbestos,
chloromethyl ethers, chromium, coke oven fumes, nickel, and radon
daughters have been linked to increased lung cancer risk, and many
other occupational agents are suspect respiratory carcinogens. A
family history of lung cancer is also associated with increased
lung cancer risk, although a clear pattern of genetic
susceptibility to lung cancer has not been demonstrated.. Outdoor
air pollution may contain carcinogens and indoor air may have high
levels of radon, which causes cancer in exposed underground miners.
Animal and human studies suggest that low consumption of vitamin
A or its precursor, beta-carotene, may also increase-lung cancer
risk.
While studies linking active smoking to lung cancer were first
published in the late 1940s and early 1950s (U.S. PHS 1964),
involuntary exposure of nonsmokers to tobacco smoke was not
considered as a cause of lung cancer in nonsmokers until 1981, when
the first two scientific papers on this subject were published.
Subsequently, many additional reports have addressed involuntary
smoking as a cause of lung cancer in nonsmokers. The World Health
Organization (1986) , the U.S. Surgeon General (U.S. DHHS 1986) , and
the National Research Council (1986) have reviewed the evidence on
involuntary smoking and lung cancer from human populations and
judged it sufficient to support the conclusion that involuntary
inhalation of tobacco smoke by nonsmokers causes cancer. This
chapter reviews that evidence and the conclusions of the research
organizations. The chapter also addressess the more limited
evidence on involuntary smoking and cancer at sites other than the
lung.
The Epidemiological Approach
Epidemiology is the scientific method used to describe the
occurrence of disease in human populations and to determine the
causes of disease by studying populations. Descriptive measures
of disease occurrence include the incidence rate, which is the rate
at which new cases of disease develop; the mortality rate, or rate
of death; and the prevalence rate, which is the proportion of the
population with disease. To identify the causes of disease,
epidemiologists generally perform either cohort or case-control
68
Draft - Do not cite or quote
studies. Each type of study provides an estimate of relative risk
as a measure of the association between exposure and disease. The
relative risk describes the comparative occurrence of disease in
exposed compared with nonexposed persons.
In a cohort study, the subjects are selected on the basis of
their exposure history and followed over time for the development
of disease. For example, a study of involuntary smoking and lung
cancer might be performed by enrolling nonsmokers married to
smokers and another group of nonsmokers married to nonsmokers.
The lung cancer risk associated with marriage to a smoker would be
estimated by comparing incidence of or mortality from lung cancer
in the two groups.
In a case-control study, cases with the disease of interest and
controls without the disease are identified and their past
exposures to factors of interest are assessed, often by interview.
For example, a case-control study of lung cancer and involuntary
smoking might be conducted by identifying nonsmokers with lung
cancer and a suitable control group, and then interviewing the
subjects concerning the smoking habits of their spouses, other
household members, and colleagues at work.
e-
Each type of study has advantages and disadvantages, and the
results of both types may be distorted by bias. Misclassification
of exposure is of particular concern in studying lung cancer and
involuntary smoking. Misclassification of exposure refers to the
incorrect categorization of actually exposed subjects as nonexposed
and of nonexposed as exposed. When misclassification occurs
randomly, it tends to bias studies towards no association, that'is
showing negative results; if nonrandom, it may exaggerate or reduce
the apparent effect of an exposure. With regard to involuntary
smoking and lung cancer, two types of misclassification are of
concern. Subjects classified as nonsmokers may have actually been
active smokers and-the degree of exposure of nonsmokers to the
smoking of others may not be accurately classified.
Misclassification of both types is discussed below in relation to
specific studies.
The diagnosis of lung cancer is also subject to misclas-
sification; a cancer that originated at another primary site and
then spread to the lung may be incorrectly diagnosed as a primary
cancer of the lung. For example, in the case-control study
reported by,Garfinkel and colleagues (Garfinkel et al. 1985), 13
percent of cases originally diagnosed as lung cancer were reclas-
sified to other sites after histological review: With regard to
exposure misclassification in this study, 40 percent of the cases
initially classified as nonsmokers on the basis of information in
medical charts were found to be smokers on interview. Confounding
refers to bias that occurs when the effect of another risk factor
is mixed with the effect of the exposure of interest; thus a
confounding factor is a risk factor for disease that is associated
69
Draft - Do not cite or quote
with the exposure under investigation. For lung cancer in
nonsmokers, potential confounding factors include indoor air
pollution by radon and combustion products other than environmental
tobacco smoke, ambient air pollution, and occupational exposures.
Although confounding always merits consideration as an explanation
for association, the diversity of the populations in which passive
smoking and lung cancer have been associated argues strongly
against confounding as the source of the association. Although
individual studies may be affected by one or more biases, the
totality of the epidemiological evidence as well as other relevant
research are considered in judging whether an exposure adversely
affects health. A bias potentially important in one study may be
unimportant or adequately controlled in another. Thus review of
all pertinent literature may show that bias cannot satisfactorily
explain an association between exposure and disease.
Epidemioloaical Evidence on Involuntary Smoking and Lung Cancer
Evidence concerning involuntary smoking and lung cancer has been
sought indirectly in descriptive data on mortality rates and
directly with case-control and cohort studies. Time trends of lung
cancer mortality across this century in nonsmokers have been
examined with the rationale that temporally increasing exposure to
environmental tobacco smoke should be paralleled by increasing
mortality rates (Enstrom 1979; Garfinkel 1981) . These data can
only provide indirect evidence on the lung cancer risk associated
with involuntary exposure to tobacco smoke. Enstrom (1979) cal-
culated lung cancer mortality rates from various nationwide sources
for the period 1914-1968 and concluded that'a real increase had
occurred among nonsmoking males after 1935. In contrast, Garfinkel
(1981) found no time trends of lung cancer mortality in nonsmoking
participants in two cohort studies, the Dorn Study of U.S.
veterans, 1954-1969, and the American Cancer Society study, 1960-
1972.
Most of the case-control and the cohort studies indicate in-
creased lung cancer risk in nonsmokers married to smokers, but
these studies do not uniformly show increased risk for sources of
exposure other than smoking by the spouse (Tables 1 and 2). The
first two major epidemiological studies were reported in 1981 by
Hirayama and Trichopoulos and colleagues (Tables.~ 1 and 2).
Hirayama conducted a cohort study of 91,540 nonsmoking women in
Japan. Mortality in these women was assessed over a 14-year
follow-up period. The ratio of the observed to expected numbers
of lung cancer deaths increased in a statistically significant
pattern with the amount smoked by the husbands. The findings could
not be explained by other factors, such as age and occupation of
the husband, and were unchanged when the follow-up was extended by
several years (Hirayama 1984). After its publication, the report
of this study received intensive scrutiny, and correspondence in
the British Medical Journal, which had published it, raised concern
70
Draft - Do not cite or quote
about various aspects of the study's methods and findings. In his
responses to the correspondence, Hirayama satisfactorily answered
most of the criticisms, although he could not eliminate the
possibility of unreported smoking by women classified as
nonsmokers. If self-reported nonsmokers married to smokers were
actually more likely to be smokers, then the resulting bias would
tend to indicate an increased risk from marriage to a smoker.
Based on the same population, Hirayama has also reported
significantly increased risk of lung cancer for nonsmoking married
men whose wives smoke (Hirayama 1984).
In 1981, Trichopoulos and coworkers (1981) also reported in-
creased lung cancer risk in nonsmoking women married to cigarette
smokers (Table 2). These investigators conducted a case-control
study in Athens, Greece, that included selected histological types
of lung cancer and control subjects ascertained at a hospital for
orthopedic disorders. The finding of increased risk was unchanged
when the case and control series were enlarged (Trichopoulos et al.
1983).
1
The results of subsequently reported case-control studies have
~lso demonstrate& significantly increased risk of lung cancer in
nonsmokers exposed to environmental tobacco smoke (Table 2). The
findings from the more recent reports based on studies throughout
the world greatly strengthen the evidence from the earlier studies.
Several of the newer studies included relatively large numbers of
nonsmokers (Garfinkel et al. 1985; Akiba et al. 1986; Dalager et
al. 1986; Lam et al. 1987; Gao et al. 1987). Furthermore, in most
of the newer studies, involuntary smoking was assessed in greater
detail than in the earlier reports.
The results of two other investigations have also been
interpreted as showing an increased lung cancer risk associated
with involuntary smoking, but both of these studies have
lim~'ttations. Knoth and coworkers (1983), in Germany, described 59
lung cancer cases in females of whom 39 were nonsmokers. Based on
census data, these investigators projected that a much greater than
expected proportion of the nonsmokers had lived in households with
smokers. In another report, Gillis et al. (1984) described the
preliminary results of a cohort study of 16,171 males and females
in western Scotland (Table 1); exposure to tobacco smoke in the
home increased the lung cancer risk for nonsmoking men but not for
nonsmoking women. This observation was based on-only 16 cases of
lung cancer in nonsmokers, however.
Other investigations indicate lesser or no effects of exposure
to environmental tobacco smoke on lung cancer risk (Tables 1 and
2). In these studies, however, the statistical uncertainty is
large because of the relatively small numbers of subjects; ac-
cordingly, the apparently negative findings are statistically
compatible with the findings of those studies judged as positive.
Two separate case-control studies in Hong Kong, where lung cancer
71
Draft - Do not cite or quote
incidence rates in females are particularly high, did not indicate
excess risk from involuntary smoking (Chan et al. 1979; Chan and
Fung 1982; Koo et al. 1984; 1985; 1987). In the more recent of the
two studies, the investigators comprehensively assessed cumulative
exposure from home and workplace sources, but misclassification of
exposure may have biased towards the negative results. A
subsequent study in Hong Kong did find a significant association
of spouse smoking and lung cancer risk (Lam et al. 1987). Lee and
coworkers (Lee et al. 1986) in England reported a small case-
control study with negative findings, but the statistical power of
that study is limited. Another recent hospital-based case-control
study, conducted in Japan, also failed to show an association be-
tween lung cancer risk and spouse smoking (Shimizu et al. 1988).
The results of the American Cancer Society's cohort study of
lung cancer mortality in 176,139 nonsmoking women have also been
considered by many as not showing an increased risk in those par-
ticipants married to smokers (Garfinkel 1981). However, the risks
for the nonsmoking women with smoking husbands were increased
somewhat, but the increase was not statistically significant.
Misclassification of exposure from active and involuntary smoking
may have affected the results of this study. Preliminary results
from a nationwide case-control study also did not demonstrate
increased lung cancer risk from domestic exposure to tobacco smoke
(Kabat and Wynder 1984), but the number of subjects was small. Two
case-control studies of nonsmokers and smokers with selected
histological types of lung cancer did not provide strong evidence
for increased risk from involuntary smoking (Wu et al. 1985;.
Brownson et al. 1987). However, both studies included only small
numbers of nonsmokers.
Conclusions on Involuntary Smoking and Luna Cancer
Scientists draw on a wide range of evidence in judging whether
an agent, such as environmental tobacco smoke, causes disease. In
addition to epidemiological data, the findings of laboratory
studies involving in-vitro systems and of animal studies involving
exposure to the agent are often relevant. Criteria have been
developed for guidance in making judgments on the causality of
exposure-disease relationships, but these criteria only provide
guidelines, not strict rules of evidence (U.S. PHS 1964; Rothman
1986). Interpretation of the evidence on particular exposure-
disease relationships often requires review by multidisciplinary
panels of scientists who are instructed to reach a consensus, often
in a setting of substantial uncertainty. For example, the World
Health Organization regularly convenes panels of scientists to
address the carcinogenicity of environmental agents.
For environmental tobacco smoke and lung cancer, the evidence
has been considered by scientists convened by the International
72
Draft - Do not cite or quote
Agency for Research on Cancer of the World Health Organization,
the National Research Council, and the U.S. Surgeon General (Table
3). All three groups concluded that environmental tobacco smoke
causes lung cancer among nonsmokers, although the approach used by
each group was different. Consensus among the three groups, in
spite of differing methodology, strengthens the determination that
involuntary smoking causes lung cancer. For all three types, the
biological plausibility of this association was supported by the
evidence on active smoking and lung cancer, knowledge of the
constituents of environmental tobacco smoke, and data demonstrating
the uptake of tobacco smoke by nonsmokers.
The International Agency for Research on Cancer of the World
Health Organization (1986) reviewed the evidence available through
the end of 1984. It reached its conclusion concerning involuntary
smoking and lung cancer largely on the basis of biological
plausibility.- The agency cited the characteristics of sidestream
and mainstream smoke, the absorption of tobacco smoke materials
during involuntary smoking, and the nature of dose-response
relationships for carcinogenesis, which project some risk for any
level of exposure.
In reaching its conclusion, the National Research Council
committee considered the biological plausibility of an association
between environmental tobacco smoke exposure and lung cancer and
the supporting epidemiological evidence, available through mid-
1986. The committee carefully considered the sources of bias that
may have affected the epidemiological studies and concluded that
the association documented in the studies could not be attributed
solely to bias. Based on a pooled analysis of the epidemiological
data and adjustment for bias, the report's authors concluded that
the best estimate for the excess risk of lung cancer in nonsmokers
married to smokers was 25%.
The 1986 report of the U.S. Surgeon General also characterized
involuntary smoking as a cause of lung cancer in nonsmokers. This
conclusion was based on the extensive information already available
on the carcinogenicity of active smoking, on the qualitative
similarities between environmental tobacco smoke and mainstream
smoke, and on the epidemiologic data on involuntary smoking.
The extent of the lung cancer hazard associated with involuntary
smoking in the United States has appeared uncertain. (U.S. DHHS
1986; Weiss 1986). The epidemiological studies provide varying and
imprecise measures of the risk (Tables 1 and 2),- and exposures to
environmental tobacco smoke have not been characterized for large
and representative population samples. Thus, any risk assessments
for involuntary smoking and lung cancer are subject to substantial
uncertainty. Nevertheless, risk assessment can provide insight
into the magnitude of the lung cancer problem posed by involuntary
smoking.
73
Draft - Do not cite or quote
Repace and Lowrey (1985) used data on lung cancer mortality in
Seventh Day Adventists, a nonsmoking group, to estimate the effect
of exposure to environmental tobacco smoke in increasing lung
cancer risk. Their analysis led to an estimate of 4,666 lung
cancer deaths per year attributable to environmental tobacco smoke
exposure. A later estimate gave 3,450 female lung cancer deaths and
1,440 male lung cancer deaths per year.(Repace and Lowrey, 1986)
An appendix to the National Research Council's 1986 report provides
estimates of the numbers of lung cancer deaths attributable to
passive smoking. For the year 1985, the risk assessment projects
approximately 1,000 lung cancer deaths in males and 2,000 to 3,000
lung cancer deaths in females attributable to environmental tobacco
smoke. Wells (1988) attributed 3,000 lung cancer cases annually
in the U.S. to involuntary smoking. A recent review of 9 published
risk assessments of environmental tobacco smoke and lung cancer
found they averaged about 4,500 ± 2,800 lung cancer deaths per year
(Repace & Lowrey, 1990).
Further epidemiological studies of involuntary smoking and lung
cancer are in progress. These studies should refine our
understanding of exposure-response relationships for lung cancer
and exposure to environmental tobacco smoke. Other investigations
are addressing the characteristics and toxicity of environmental
tobacco smoke and patterns of exposure to environmental tobacco
smoke. While the results of these new studies will provide needed
information for scientific purposes, the available data and the
conclusions of the scientific community already provide a
compelling rationale for reducing involuntary exposure to
environmental tobacco smoke.
Involuntary Smoking and Cancer at Sites Other Than the Lung
Several reports have suggested that exposure to environmental
tobacco smoke may increase risk of cancer at sites other than the
lung. One study found that in children, maternal exposure to
environmental tobacco smoke during pregnancy was associated with
increased risk of brain tumors (Preston-Martin et al. 1982), and
in another study paternal but not maternal smoking increased the
risk of childhood rhabdomyosarcoma, a cancer of the soft tissues
(Grufferman et al. 1982).
In adults, involuntary smoking has been linked to a generally
increased risk of malignancy (Miller 1984). Several studies have
examined excess risk at specific sites. Sandler and colleagues
(Sandher, Everson, and Wilcox 1985a; 1985b; Sandler, Wilcox, and
Everson 1985) conducted a case-control study on the effects of
exposures to environmental tobacco smoke during childhood and
adulthood on the risk of cancer. The cases included cancers of all
types other than usual forms of skin cancer. For all sites
combined, a statistically significant increase in risk was found
for exposure to smoking by a parent (crude relative risk = 1.6) and
74
Draft - Do not cite or quote
by a spouse (crude relative risk = 1.5); the effects of these two
sources of exposure were independent (Sandler, Wilcox, and Everson
1985). Statistically significant associations were also found for
some individual sites. These provocative findings will require
replication in additional studies. In a case-control study, such
as reported by Sandler and colleagues, biased information on
exposure to environmental tobacco smoke is of particular concern.
In the cohort study in Japan, Hirayama (1984) found significantly
increased mortality from nasal sinus cancers and from brain tumors
in nonsmoking women married to smokers. In a case-control study
of bladder cancer, involuntary smoking at.home and at work did not
increase risk (Kabat et al. 1986). Cervical cancer, which has been
linked to active smoking, was associated with duration of
involuntary smoking in a case-control study in Utah (Slattery et
al. 1989) This unconfirmed finding needs additional investigation.
These associations of involuntary smoking with cancer at diverse
sites other than the lung cannot be readily supported with
arguments for biological plausibility based on evidence from active
smokers. Increased risks at some of the sites, e.g., cancer of the
nasal sinus and female breast cancer, have not been found in active
Vmokers (U.So DHHS 1982). In fact, the International Agency for
Research on Cancer (WHO 1986) has concluded that effects would not
be produced in involuntary smokers that would not be produced to
a larger extent in active smokers.
SUMXARY
1. For exposure to environmental tobacco smoke and lung cancer, the
evidence has been considered by scientists convened by the
International Agency for Research on Cancer of the World Health
Organization, the National Research Council, and the U.S. Surgeon
General. All three groups concluded that environmental tobacco
smoke causes lung cancer among nonsmokers.
2. Further research in involuntary smoking and lung cancer will
refine our understanding and are scientifically necessary;
however, existing scientific conclusions already provide a
compelling rationale for reducing involuntary exposure to
environmental tobacco smoke.
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79
Draft - Do not cite or quote
FIGURES AND TABLES, CHAPTER 5
Draft - Do not cite or qu®te.
TABLE 1
Cohort Studies of Involuntary Smoking and Lung Cancer
Study -
Findings
Comments
91,540 nonsmoking
females, 1966-1981,
Japan (Hirayama
1981).
176,139 nonsmoking
females, 1960-1972,
U.S. (Garfinkel
1981).
:..
8,128 males and
females, 1972-1982,
Scotland (Gillis
et a1,. 1984).
Age-o~cupation adjust-
ed RR by husbands'
smoking:
Nonsmokers - 1.00~
Exsmokers - 1.36
Current smokers
< 20/day - 1.45
> 20/day - 1.91
Age-adjusted RR by
husbands' smoking:
Nonsmokers - 1.00+
Current smokers
< 20/day - 1.27
t > 20/day - 1.10
Age-adjusted RR for
exposure to a tobacco
smoker in the home:
Males - 3.25
Females - 1.00
Trend statistically
significant. All
histological types
of lung cancer.
All histologies.
Effect of husbands'
smoking not stat-
istically signifi-
cant.
Preliminary, small
numbers of cases.
~RR = relative risk, as estimated by the ratio of observed to expected
number of lung cancer deaths.
+reference category, risk arbitrarily set to unity as the
reference point for comparison.
TABLE 2
Draft - Do not cite or quote
Case-control Studies of Involuntary Smoking and Lung Cancer
Study.
40 nonsmoking female
cases, 149 controls,
1978-1980, Greece
(Trichopoulos et al.
1981).
84 female cases and
139 controls, 1976-
1977, Hong Kong
(Chan et al. 1979;
Chan and Fung 1982).
22 female and 8 male
nonsmoking cases,
133 female and 180
male controls, U.S.
(Correa et al. 1983).
19 male and 94
female nonsmoking
cases, and 110 male
and 270 female non-
smoking controls,
Japan (Akiba et al.
1986).
99 nonsmoking cases
and 736 controls,
Louisiana, Texas,
New Jersey (Dalager
et al 1986).
28 nonsmoking
controls, New Mexico
(Humble et al. 1987).
77 nonsmoking cases,
2 matched control
series, Sweden
(Pershagen et al.
1987).
Findings Comments
RR* by husband smoking: Trend statistically
Nonsmokers - 1.0
Exsmokers - 1.8 significant.
tologies other His-
than
Current smokers adenocarcinoma and
< 20/day - 2.4
> 20/day - 3.4
bronchioloalveolar
carcinoma.
RR of 0.75 associated
with smoking spouse,
compared to 1.0 for a
nonsmoking spouse.
RR by spouse smoking:
f Nonsmokers - 1.00
< 40 pack years - 1.48
>_ 41 pack years - 3.11
For females, RR of 1.5
if husband smoked; for
males, RR of 1.8 if
wife smoked.
All histologies.
Two reports are
inconsistent on the
exposure variable.
Significant increase
for >_ 41 pack years.
Bronchioloalveolar
carcinoma excluded.
Clinical or radio-
logical diagnosis
for 43%. All types
of lung cancer.
,
RR for marriage to a
smoking spouse was 1.5
Nearly 100% histo-
logical confirma-
tion. All types of
lung cancer.
RR for marriage to a
smoking spouse was 3.2
No effect in active
smokers.
RR for marriage to a
smoker was 3.3 for
squamous small cell
carcinomas.
All types other
than bronchiolo-
alveolar carcinoma.
No effect of expo-
sure for other
types. Study based
within a cohort.
Draft - Do not cite or quote
TABLE 2 (continued)
Case-control Studies of Involuntary Smoking and Lung Cancer
Study _..
,
Findings
Comments
102 adenocarcinoma
cases, 50 males and
females, and 131
controls, Colorado
(Brownson et al.
1987).
25 male and 53
female nonsmoking
cases with matched
controls, 1971m1980,
U.S. (Kabat and
Wynder 1984).
~
88 nonsmoking female
cases, 1981-1982,-
Hong Kong (Koo et al.
1984, and 1985).
31 nonsmoking and
189 smoking female
cases, U.S. (Wu et
al. 1985).
-61
134 nonsmoking
female cases,.U.S.
(Garfinkel et al.
1985).
15 male and 32
female nonsmoking
cases, and 30 male
and 66 female non-
smokinq controls,
England (Lee et al.,
1986).
No effect in entire
group. In nonsmoking
women, RR of 1.7 for
exposure >_ 4 hrs/day,
versus 1.0 for <3
hrs/day.
RR not significantly
increased for current
exposure at home:
Males - 1.26
Females - 0.92
RR of 1.24 (not stat-
istically significant)
for combined home and
workplace exposure ver-
sus 1.0 for nonexposed.
No association with
cumulative hours of
exposure.
No significant effects
of exposure from par-
ents, spouse, or work-
place in smokers and
nonsmokers.
Nonsignificant Rt of
1.22 if husband smoked.
Significantly increased
RR of 2.11 if husband
smoked 20 or more cig-
arettes daily at home.
Significant trend of RR
with number of cigarettes
smoked at home by the
husband.
Overall FtR for spouse
smoking of 1.1.
Involuntary smoking
effect not signifi-
cant in nonsmoking
women, but only 19
such cases included.
All types. Findings
negative for spouse
smoking variable as
well.
All types of lung
cancer.
Adenocarcinoma and
squamous cell carci®
noma only.
All types of lung
cancer. Careful ex-
clusion of smokers
from the case group.
Hospital-based
study.
*RR = relative risk as estimated by the odds ratio.
Draft - Do not cite or quote
TABLE 3
Conclusions of the World Health Organization,
National Research Council and U.S. Surgeon General
on Involuntary Smoking and Lung Cancer
World Health Organization
"Knowledge of the nature of sidestream and mainstream smoke, of
the materials absorbed during "passive" smoking, and of the
quantitative relationships between dose and.effect that are
commonly observed from exposure to carcinogens, however, leads
to the conclusion that passive smoking gives rise to some risk
of cancer:"
National Research Council
"The weight of eviden}ce derived from epidemiologic studies shows
an association between ETS exposure of nonsmokers and lung
cancer that, taken as a whole, is unlikely to be due to chance
or systematic bias. The observed estimate of increased risk is
34%, largely for spouses of smokers compared with spouses of
nonsmokers."
U.S. Surgeon General
"InvolLuntary smoking can cause lung cancer in nonsmokers." "The
absence of a threshold for respiratory carcinogenesis in active
smoking, the presence of the same carcinogens in mainstream and
sidestream smoke, the demonstrated uptake of tobacco smoke
constituents by involuntary smokers, and thc rieinonstration of an
increased lung cancer risk in some populations with exposures to
ETS leads to the conclusion that involuntary smoking is a cause
of lung cancer."
