States Science Advisory Board EPA-SAB-lAQC-93-003
Environmental A-101 November 1932
Protection Agancy Washington, DC
oEPA AN SAB REPORT:
REVIEW OF DRAFT
PASSIVE SMOKING
HEALTH EFFECTS
DOCUMENT
REVIEW, BY THE INDOOR AIR
QUALITY AND TOTAL HUMAN
EXPOSURE COMMITTEE, OF THE
OFFICE OF RESEARCH AND
DEVELOPMENT'S DRAFT REPORT:
"RESPIRATORY HEALTH EFFECTS
OF PASSIVE SMOKING: LUNG
CANCER AND OTHER DISORDERS"
(EPA/600/6-90/006B)
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UNHFED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON D.C, 20460
November 20, 1992
OFFICE OF
1HE ADMINISTRATOR
SCIENCE ADVISOR* BOARD
EPA-SAB-IAQC-93-003
Honorable William K. Reilly
Administrator
U.S, Environmental Protection Agency
401 M Street, SW
Washington, DC 20460
Subject: Review of the Environmental Tobacco Smoke Risk
Assessment - Respiratory Health Effects of Passim
Smoking: Lung Cancer and Other Disorders (EPA/600/6-
90/006B)
Dear Mr. ReOIy;
The Science Advisory Board's (SAB) Indoor Air and Total Human Exposure
Committee (IAQTHEC) met on July 21-22, 1992 to review the draft EPA
document Respiratory Health Effects of Passive Smoking: Lung Cancer and Other
Disorders (EPA/600/6-90/006B, May 1992 SAB Review Draft). TMs is the second
review conducted by this committee on this issue; the Erst being conducted on
December 4-5, 1990, The Committee reported its earlier findings to you in our
April 1991 report, ATI SAB Report: Review of Draft Environmental Tobacco Smoke
Health Effects Document (EPA-SAB-IAQC-91-007, April 1991). This second draft
document is much revised and expanded from the first document we reviewed! and,
for the most part, reflects the advice presented in our April 1991 report. As a
result of ow recent public review, the Committee provided to the EPA Staff
detailed editorial and substance comments on the draft document. The attached
report contains the Committee's broad recommendations and its responses to
fifteen specific questions.
The Committee is pleased to note the great improvement in the discussion
and analysis of effects of environmental tobacco smoke (ETS) on the health of
children. The coverage of the pertinent literature is much more complete, and the
specification and quantitation of the identifiable health risks are presented in a
clear and defensible manner. This new material provides a basis for the Agency to
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issue an overall risk assessment on ETS that gives an appropriate emphasis to
non-cancer health effects. We also nrote that the revised draft has an improved
presentation, discussion, and analysis of ETS as a lung carcinogen, providing a
firmer basis for the designation of ETS as an EPA Class A Carcinogen, The
Committee was unanimous in endorsing this classification.
This second draft, as a whole, is a very substantially improved document
and, in general, does a good job of presenting the scientific evidence that supports
the judgment that exposure to ETS causes lung cancer and other adverse
respiratory health effects, It presents the data and relevant analysis in greater
detail than is available in any other single source. In general, the findings are
well substantiated, although further improvements are recommended for the new
Chapter 3, Other changes made from the first draft to the cuirent draft were
carefully thought out and generally appropriate. Also, the authors have done a
commendable job in addressing the points raised by the Committee in its review of
the first draft. TMs document will be an invaluable source of information for
health professionals and policy makers for years to come.
We appreciate the opportunity to review this draft document and look
forward to your response to our advice contained in the attached report.
Sincerely,
5r» Kaymond C, J-eeiflPTChair Dr. Morton Lippmann, Chair
Science Advisory Board Indoor Air Quality and Total
Human Exposure Committee
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ABSTRACT
The Science Advisory Board's (SAB) Indoor Air and Total Human Exposure
Committee (IAQTHEC) met on July 21-22, 1992 to review the draft EPA document
Respiratory Health Effects of Passive Smoking; Lung Cancer and Other Disorders
(EPA/600/6-90/OQ6B, May 1992 SAB Review Draft). The Committee provided
responses to fifteen specific questions and provided commentary on chapters of the
draft document. The Committee noted the great improvement in the discussion
and analysis of effects of environmental tobacco smoke (ETS) on the health of
chfldren. The coverage of the pertinent literature is much more complete in this
draft than in the previous draft, and the specification and quantitation of the
identifiable health risks is presented in a clear and defensible manner. This new
material provides a basis for the Agency to issue an overall risk assessment on ETS
that gives an appropriate emphasis to non-cancer health effects. The Committee
also noted that the revised draft has an improved presentation, discussion, and
analysis of ETS as a lung carcinogen, providing a firmer basis for the designation
of ETS as an EPA Class A Carcinogen. The Committee was unanimous in
endorsing this classification.
KEYWORpg; Environmental Tobacco Smoke; ETS; Carcinogenicity; Passive
Smoking; Sidestream Smoke; Mainstream Smoke; Confounders; Lung Cancer;
Respiratory Disease
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NOTICE
This report has been written as a part of the activities of the Science Advisory
Board, a public advisory group providing extramural scientific information and
advice to the Administrator and other officials of the Environmental Protection
Agency, The Board is structured to provide balanced, expert assessment of
scientific matters related to problems facing the Agency, This report has not been
reviewed for approval by the Agency and, hence, the contents of this report do not
necessarily represent the views and policies of the Environmental Protection
Agency, nor of other agencies in the Executive Branch of the Federal government,
nor does mention of trade names or commercial products constitute a
recommendation for use.
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U.S. Environmental Protection Agency
Science Advisory Board
Indoor Air Quality and Total Human Exposure Committee
Environmental Tobacco Smoke Review
Dr. Morton Lippmann, Institute of Environmental Medicine, New York University
Medical Center, Tuxedo, New York
Vice Chair
Dr. Jan AJF, Stolwjjk, School of Medicine, Department of Epidemiology and Public
Health, Yale University, New Haven, Connecticut
Members
Dr. Joan Daisey, Indoor Environment Program, Lawrence Berkeley Laboratory,
Berkeley, California
Dr. Timothy Larson, Environmental Science and Engineering Program, Department
of Civil Engineering, University of Washington, Seattle, Washington
Dr. Victor G. Lattea, Environmental Health Sciences Center, University of
Rochester School of Medicine and Dentistry, Rochester, New York
Dr. Paul Lioy, Department of Environmental and Community Medicine, Robert
Wood Johnson School of Medicine, Piseataway, New Jersey
Dr. Jonathan M. Samet, Department of Medicine, The University of New Mexico
School of Medicine, and The New Mexico Tumor Registry, Albuquerque, New
Mexico
Dr. Jerome J. WesolowsM, Air and Industrial Hygiene Laboratory, California
Department of Health, Berkeley, California
Dr. James E. Woods, Jr., College of Architecture and Urban Studies, Virginia
Polytechnic Institute and State University, Bkcksburg, Virginia
> the Committee
Dr. Neal L. Benowitz, Division of Clinical Pharmacology and Experimental
Therapeutics, University of California - San Francisco, San Francisco,
California
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Dr. William 3. Blot, National Cancer Institute, Bethesda, Maryland (Federal Liaison
to the Committee)
Dr. David Burns, Department of Medicine, University of California, San Diego
Medical Center, San Diego, California
Dr. Delbert Eatough, Department of Chemistry, Brigham Young University, Provo,
Utah
Dr. S. Katharine Hammond, Environmental Health Sciences Program, Department
of Family and Community Medicine, University of Massachusetts Medical
School, North Worcester, Massachusetts
Dr. Geoffrey Rabat, American Health Foundation, New York, New York
Dr. Michael D, Lebowitz, University of Arizona College of Medicine, Division of
Respiratory Sciences, Tucson, Arizona
Dr. Howard Hoekette, School of Public Health, University of Pittsburgh, Pittsburgh,
Pennsylvania
Dr. Scott T. Weiss, Harvard University School of Medicine, Boston, Massachusetts
Board Staff
Mr, A, Bobert FJaak, Assistant Staff Director and Designated Federal Official,
Science Advisory Board (A-101F), U.S. Environmental Protection Agency, 401
M Street, SW, Washington, DC 20460
Ms. Carolyn Qsborne, Program Assistant, Science Advisory Board (A-1Q1F), U-S.
Environmental Protection Agency, 401 M Street, SW, Washington, DC 20460
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TABLE OF CONTENTS
1, EXECUTIVE SUMMARY 1
2, INTRODUCTION . 7
2.1 Background . . . , 7
2.2 Charge to the Committee . 8
2.3 Format of this report ,.....,... 10
3. RESPONSES TO THE QUESTIONS IN THE CHABGE 11
3.1 Questions Concerning ETS Exposure (Chapter 3) 11
3.2 Questions Concerning Lung Cancer • Hazard Identification
(Chapters 4 and 5) . 13
3.3 Questions Concerning Lung Cancer - Population Impact
(Chapter 6) 15
3.4 Questions Concerning Noncancer Respiratory Disorders - Hazard
Identification (Chapter 7; Sections 8.1 and 8.2) 16
3.5 Questions Concerning Noncancer Respiratory Disorders -
Population Impact (Chapter 8) 17
4. COMMENTS ON THE DRAFT DOCUMENT 19
4.1 Chapter 1 - Summary and Conclusions ,,...,.,... , 19
4.2 Chapter 2 - Introduction . 20
4,3 Chapter 3 • Estimation of Environmental Tobacco Smoke
Exposure 20
4.3,1 The composition of toxic compounds in ETS ...... 21
4.3.2 The rate of removal of nicotine in indoor
environments 21
4.3.3 The relative amounts of ETS and non-ETS particles
in indoor environments 21
4.4 Chapter 4 - Hazard Identification I; Lung Cancer in Active
Smokers, Long-term Animal Bioassays, and Genotosdc Studies ... 21
4.5 Chapter 5 - Hazard Identification II: Interpretation of
Epidemiologic Studies on ETS and Lung Cancer 22
4,6 Chapter 6 - Population Risk of Lung Cancer from Passive
Smoking 23
4.7 Chapter 7 • Passive Smoking and Respiratory Disorders Other
Than Cancer 21
4.8 Chapter 8 - Assessment of Increased Risk for Respiratory
Illnesses in Children from Environmental Tobacco Smoke 27
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1. EXECUTIVE SUMMARY
The Science Advisory Board's (SAB) Indoor Air and Total Human Exposure
Committee (IAQTHEC) met on July 21-22, 1992 to review the draft EPA document
Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders
(EPA/6Q0/6-90/OQ6B, May 1992 SAB Eeview Draft). This is the second review
conducted by this committee on this issue; the first being conducted on December
4-5, 19iO. The Committee reported its findings to the EPA Administrator in our
April 1991 report, An SAB Report: Review of Draft Environmental Tobacco Smoke
Health Effects Document (EPA-SAB-IAQC-91-007, April 1991). The Committee
made a number of substantive as well as structural recommendations, most of
which have been addressed in the present draft document.
The Committee is pleased to note the great improvement in the discussion
and analysis of effects of environmental tobacco smoke (ETS) on the health of
children. The coverage of the pertinent literature is much more complete, and the
specification and quantitation of the identifiable health risks are presented in a
clear and defensible manner. This new material provides a basis for the Agency to
issue an overall risk assessment on ETS that gives an appropriate emphasis to non-
cancer health effects. We also note that the revised draft has an improved
presentation, discussion, and analysis of ETS as a lung carcinogen, providing: a
firmer basis for the designation of ETS as an EPA Class A Carcinogen, The
Committee was unanimous in endorsing this classification.
As a result of the public review, the Committee provided to the EPA Staff
detailed editorial and substance comments on the draft document. This report
contains the Committee's broad recommendations and its responses to fifteen
specific questions in several categories from the charge to the Committee:
ETS Exposure
a) Do the conclusions on the chemical similarities of ETS and
mainstream smoke (MS) warrant the toxicologies! comparison between
passive and active smoking made as part of the biological plausibility
arguments for lung cancer (Chapter 4) and non-cancer respiratory
disorders (Chapter 7)?
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Yes, All of the major carcinogenic and toxic agents found in mainstream
smoke are also present in ETS, albeit at lower concentrations. The combustion of
tobacco to form sidestream smoke (SS) actually results in slightly higher amounts
of many toxic and carcinogenic compounds per gram of tobacco burned than when
the tobacco is burned to produce mainstream smoke, However, Chapter 3, as
written, dMmt adequately make this case and requires some modification. The
following issues should be addressed in Chapter 3 to support this similarity.
* Many of the same carcinogenic compounds are found in MS and
SS and ETS (measured in smoky rooms), i.e,, the polycyelie
aromatic hydrocarbons, the N-nitrosamJnes, and 4-
amlnobiphenyL Many of these compounds are substantially
enriched in SS relative to MS by factors ranging from about 2 to
100, although overall exposure to ETS will be much lower than
to MS, Thus, as a complex mixture, SS might be expected to be
somewhat more potent as a carcinogenic mixture,
• Extracts of particulate matter from combustion mixtures have
consistently been shown to be carcinogenic in animal bioassays,
mutagenic in short-term in vitro bioassays, and carcinogenic in
humans, although potencies can vary.
• Many of the individual organic compounds in MS, SS and ETS
have also been found to be carcinogenic in animals, e.g., many of
the polycyclic aromatic hydrocarbons, the N-nitrosamines and
4-aminobiphenyl.
b) Is the extent_ of ETS exposure in various environments adequately
characterized?
Yes. ETS exposure has been characterized in several different ways, in many
environments. ETS is virtually ubiquitous, and concentrations and other
characteristics have been consistently demonstrated in a very larp number of
environments. It is unlikely that further quantitative and qualitative description
would provide much critical additional or different insights that would impact on
the overall conclusions of the risk assessment.
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c) Are the methods of assessing ETS exposure and the uncertainties
associated with each accurately described?
Yes, The methods, and the problems and limitations are well described.
Given the caveats and uncertainties, the different methods produce results which
are confirmatory of each other. The questionnaire method, which has the inherent
problem of information bias, has been validated, and the misclassification has been
estimated in several studies. The degree of misclassification is different in different
studies, as one would expect with instruments and study protocols that are
different,
Lung Cancer - Hazard Identification
d) Is the evidence for the lung carcmogenicity of ETS presented
adequately?
Yes, The report has been strengthened by the addition of Chapter 4 which
reviews toxicologic evidence and highlights the evidence on active smoking. The
epidemiologic data are adequately described, although formal criteria should be set
forth for assigning the studies to tiers.
e) Does any of the new information alter the SAB conclusion regarding
the categorization of ETS as an EPA Group A carcinogen?
No. The conclusion that ETS should be categorized as a Group A
carcinogen, made in the initial EPA draft, remains valid with the addition of the
new information in the revised draft. Despite the uncertainly about the magnitude
of the risk of lung cancer due to passive smoking, the overall evidence is sufficient
to declare that prolonged exposure to ETS is etiolpgicaUy related to lung cancer
and that ETS should be regarded as an EPA Group A carcinogen,
Lung Cancer • Population Impact
f) Is the approach used to derive estimates of U.S. female never-smoker
lung cancer risk scientifically defensible?
Yes. The combination of U,S, epidemiologic studies of non-smoking women
married to smokers provides an appropriate and sound basis for estimating the
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relative risk of lung cancer associated with ETS among American women who have
never smoked cigarettes.
g) Is the approach used to extrapolate lung cancer risk from female
never-smokers to male never-smokers and former smokers of both
sexes scientifically defensible?
Yes, Although alternative approaches also might have merit, the approach of
extrapolating lung cancer mortality rates among women to men, which was used in
the draft document, is scientifically defensible. However, the uncertainties should
be further acknowledged. On the other hand, we advise caution in extending the
risk assessment to ex-smokers who are known to remain at increased risk of lung
cancer well beyond 5 years following cessation of smoking.
h) Are the assumptions used to derive these lung cancer population
estimates and the uncertainties involved characterized adequately?
Yes. While the overall point estimate of approximately 3,000 total lung
cancer deaths (LCDs) due to ETS exposure annually in the United States is based
on reasonable assumptions, the citation of a range of 2,500 to 3,300 ETS-related
LCDs, based on varying only one of the parameters involved in the estimation, is
misleading and implies a greater degree of precision in the estimation than is
warranted. The document would be strengthened by additional acknowledgement
and characterization of these uncertainties.
i) Is the degree of confidence in these estimates as stated appropriately
characterized?
No. The confidence in these estimates, represented by the range of 2,500 to
3,300 deaths due to ETS, understates the uncertainties associated with each of the
assumptions that went into the risk assessment. It indicates a much higher degree
of precision than the 90% confidence interval surrounding the summary relative
risk for spousal smoking in the ILS. of 1,19. There are other assumptions used in
the risk assessment that increase the uncertainty.
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Non-Cancer Respiratory Disorders
j) Have the biological plausibility arguments been adequately presented?
Yes, Biological plausibility has been adequately presented, except for the
importance of bronchial responsiveness, especially in relation to lung function
growth and decline,
k) Have the most important confounders been property addressed?
Yes, most of them have. Low birth weight is a eonfounder that is not
adequately considered by many studies. Also, ETS exposure in childhood and
adolescence should be included in assessing the effects of ETS on lung functions in
adults,
1) Has the weight of evidence been properly characterized? Are the
conclusions scientifically defensible?
Yes. The weight of evidence has been properly characterized for most
sections in Chapter 7, but the evidence for adult pulmonary function does not take
into account the potential confounders of childhood respiratory diseases or
exposures to parental smoking. The weight of evidence for asthma and sudden
infant death syndrome (SIDS) is properly characterized, concluding causality for
increased episodes and exacerbation of symptoms in asthmatics, but insufficient
evidence for causality for asthma induction or SIDS.
m) Is the evidence with respect to maternal smoking and sudden infant
death syndrome properly characterized? Should this evidence be
included in this report?
Yes. The evidence is appropriately characterized in terms of the strong
association and the Centers for Disease Control (CDC, 1991) Risk Assessment,
Given the existing data, one cannot determine whether this is an m utero effect or
an effect of environmental smoke exposure.
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Population Impact
n) Is the presented population impact of ETS on lower respiratory
infections and asthma in children scientifically defensible?
Yes. The issues related to asthma are clearly based on current knowledge.
The focus should be on the exacerbation of asthmatic attacks because the etiology
of the disease is difficult to define. The issue of childhood respiratory illnesses
carries significant weight in the conclusions. It could be expanded, especially for
population impact above age 18 months. Potential impact of both asthma and
respiratory illnesses on adult lung function and disease could be explored further.
The presentatipn of both a threshold and a non-threshold analysis is balanced, and
the levels ascribed are consistent.
o) Are the assumptions, uncertainties, and degree of confidence in the
ranges of population impact estimates adequately characterized?
Yes, for the most part. There is a complete description of the assumptions
and uncertainties hi the dataset. This is an enormous improvement from the first
draft of this document, and provides a solid scientifically defensible base upon
which to draw the conclusions made by the document.
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2. INTRODUCTION
2.1 Background
The Science Advisoiy Board's (SAB) Indoor Air and Total Human Exposure
Committee (IAQTHEC) met in public session on July 21-22, 1992 in Arlington,
Virginia to review the draft EPA document Respiratory Health Effects of Passive
Smoking: Lung Cancer and Other Disorders (EPA/600/6-90/006B, May 1992 SAB
Review Draft), At this public meeting, the Committee received presentations from
Agency staff concerning the draft document, and public comments from 15
individuals representing themselves or various groups with an interest in this
matter, including the R. J, Reynolds Company, the Tobacco Institute, Action on
Smoking and Health, the Coalition on Smoking OR Health, and the Centers for
Disease Control, The Committee also received written comments from 27
individuals or groups. Since the Agency did not initiate a formal public comment
period, the SAB was the sole recipient of formal public comments under the
provisions of the Federal Advisory Committee Act, Copies of all written comments
were provided to the Committee prior to the public meeting, as well as to Agency
staff for their consideration in revising the draft document.
This constitutes the second review conducted by this committee on this issue.
This draft document is a revision of an earlier EPA draft report formerly titled,
Health Effects of Passive Smoking; Assessment of Lung Cancer in Adults and
Respiratory Disorders in Children, which the Committee reviewed on December 4
and 5, 1990. Our earlier findinp (An SAS Report: Review of Draft Environmental
Tobacco Smoke Health Effects Document, EPA-SAB-1AQC-91-007, April 1991)
concurred with EPA's conclusions that ETS should be designated a Group A or
known human carcinogen, but suggested that the conclusions on respiratory
disorders in children could be made stronger. Our report also suggested several
areas in which the health risk assessment could be improved, and offered to provide
additional advice on a revised document.
The draft document has been significantly revised from the 1990 draft, and is
quite different in size as well as format. The current draft is about 600 pages in
length, compared to the 350 of the earlier draft. The increased size is the result of
several changes, including: a new Chapter (3) on physical/chemical components and
assessing exposure to ETS; a new Chapter (4) on the relationship of active smoking
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and lung cancer; an expanded Appendix (Appendix A), which includes a review of
all the pertinent ETS lung cancer studies in non-smoking women; a rewrite of the
noncancer respiratory disorders Chapter (7) to include approximately thirty more
studies than did the 1990 draft; and a new quantitative risk assessment Chapter (8)
on noncancer respiratory effects.
As a result of our earlier review, two appendices from the EPA initial draft
were dropped in the revision. These dealt mostly with lung deposition modelling
and active to passive smoking dose-response modelling. As we suggested in our
earlier report, some of the material from these appendices was extracted and
included in Chapters 3 and 4 of the revised draft,
2.2 Charge to the Committee
The Agency sought the advice of the SAB on the accuracy and completeness
of the entire document and on whether the Agency has been responsive to the
Committee's previous recommendations. In addition, the SAB was asked to address
the following specific issues;
A - ETS EXPOSURE (Chapter 3)
a) Do the conclusions on the chemical similarities of ETS
and MS warrant the toxicological comparison between
passive and active smoking made as part of the biological
plausibility arguments for lung cancer (Chapter 4) and
non-cancer respiratory disorders (Chapter 7)?
b) Is the extent of ETS exposure in various environments
adequately characterized?
c) Are the methods of assessing ETS exposure and the
uncertainties associated with each accurately described?
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B - LUNG CANCER
1. HAZARD IDENTIFICATION (Chapters 4 and 5)
a) Is the evidence for the lung careinogenieity of ETS
presented adequately?
b) Does any of the new information alter the SAB conclusion
regarding the categorization of ETS as an EPA Group A
carcinogen?
2. POPULATION IMPACT (Chapter 6)
a) Is the approach used to derive estimates of U,S. female
never-smoker lung cancer risk scientifically defensible?
b) In the approach used to extrapolate lung cancer risk from
female never-smokers to male never-smokers and former
smoker of both sexes scientifically defensible?
c) Are title assumptions used to derive these lung cancer
population estimates and the uncertainties involved
characterized adequately?
d) Is the degree of confidence in these estimates as stated
appropriately characterized?
C - NON-CANCER RESPIRATORY DISORDERS
1. HAZARD IDENTIFICATION (Chapter 7; Sections 8,1 and 8.2)
a) Have the biological plausibility arguments been adequately
presented?
b) Have the most important confounders been property
addressed?
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c) Has the weight of evidence been properly characterized?
Are the conclusions scientifically defensible?
d) Is the evidence with respect to maternal smoking and
sudden infant death syndrome properly characterized?
Should this evidence be included in this report?
2, POPULATION IMPACT (Chapter 8)
a) Is the presented population impact of ETS on lower
respiratory infections and asthma in children scientifically
defensible?
b) Are the assumptions, uncertainties, and degree of
confidence in the ranges of population impact estimates
adequately characterized?
2.3 Format of this report
Although a major focus of the Committee's review is the response to the
questions in the charge, the Committee also provided detailed commentary on each
chapter of the document, both in the meeting transcript and in written comments.
This report consists of 4 major chapters. An Executive Summary> an Introduction,
Responses to the Questions in the Charge, and Comments on the Draft Document,
Detailed editorial comments were omitted,
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3. RESPONSES TO THE QUESTIONS IN THE CHARGE
3,1 Questions Concerning ETS Exposure (Chapter 3}
a) Do the conclusions on the chemical similarities of ETS and
mainstream smoke (MS) warrant the toxicological comparison between
passive and active smoking made as part of the biological plausibility
arguments for lung cancer (Chapter 4) and non-cancer respiratory
disorders (Chapter 7)7
Yes, all of the major carcinogenic and toxic agents found in MS are also
present in ETS, albeit at lower concentrations. The combustion of tobacco to form
ETS actually results in slightly higher amounts of many toxic and carcinogenic
compounds per gram of tobacco burned than when the tobacco is burned to produce
mainstream smoke. There are substantial differences in the relative composition of
the smoke formed between mainstream and sidestream smoke, similar to the
differences between the MS formed by different currently manufactured cigarettes,
but there is no reason to suppose that the qualitative toxicities of ETS and MS are
substantively different. In comparing these two agents the differences are largely
ones of dose and duration of exposure rather than fundamental differences in the
toxieity or carcinogenicity of the agent in question. However, Chapter 3» as
written, did not adequately make this case and requires some modification. The
following issues should be addressed in Chapter 3 to support this similarity,
• Many of the same carcinogenic compounds are found in MS and
SS and ETS (measured in smoky rooms), ie., the polycyclic
aromatic hydrocarbons, the N-nitrosamines, and 4-
aminobiphenyl. Many of these compounds are substantially
enriched in SS relative to MS by factors ranging from about 2 to
100, although overall exposure to ETS will be much lower than
to MS. Thus, as a complex mixture, SS might be expected to be
somewhat more potent as a carcinogenic mixture.
• Extracts of particulate matter from combustion mixtures have
consistently been shown to be carcinogenic in animal bioassays,
mutagenic in short-term in vitro bioassays, and carcinogenic in
humans, although potencies can vary.
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• Many of the individual organic compounds in MS, SS and ETS
have also been found to be carcinogenic in animals, e.g., many of
the polycyclic aromatic hydrocarbons, the N-nitrosamines and
4-aminobiphenyl,
b) Is the extent of ETS exposure in various environments adequately
characterized?
Adequate is a relative word. ETS exposure has been characterized in several
different ways, in many environments, ETS is virtually ubiquitous, and
concentrations and other characteristics have been consistently demonstrated in a
very large number of environments. It is unlikely that further quantitative and
qualitative description would provide much critical additional or different insight
that would impact on the overall conclusions of the risk assessment.
Precise calculation of the expected risk due to ETS exposure would require
detailed estimates on a population base for all of the United States for various ETS
exposures. This database does not exist. However, there is a vast array of data on
samples of the population and samples of the environments that can be
extrapolated to the U.S. general population with an acceptable degree of certainty.
These measures include traditional atmospheric measures of constituents of the
smoke as well as individual dosimetry from individual monitors and from samples
of biologic fluids for constituents of tobacco smoke and/or metabolic products of
such constituents. As the report describes, one would expect some variation in the
U.S. population in the degree of exposure to these agents, and the report describes
the process for taking into account this variability in calculating numbers of deaths
that are presented in the document. The data on exposure to the population in
question are adequate to make the risk assessments that have been made, and are
substantially more complete than the exposure estimates that are available for
many other Class A carcinogens.
c) Are the methods of assessing ETS exposure and the uncertainties
associated with each accurately described?
The methods, and the problems and limitations are well described. Given
the caveats and uncertainties, the different methods produce results which are
confirmatory of each other. The questionnaire method, which has inherent
problems of information bias, has been validated, and the misclassiflcation has been
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The evidence for the earemogemcity of ETS is presented in several logical
components: evidence^for MS inhalation being causal for lung Cancer in proportion
to dose, evidence for the reduction in risk following cessation of smoking, animal
evidence for the careinogenieity of MS ind ETS, and evidence of rautagenicity of
MS end ETS components. Finally the results of a large number of epidemiological
studies of ETS exposures in non-smoking and never-smoking populations, and the
increase in lung cancer risk associated with such exposures, are presented in great
detail. These community exposures are shared by a very large fraction of the
population and, although the risks are small compared to the risks of active
smoking, they are quite consistent. Any studies involving low relative risks are
likely to be controversial: there always are methodological short-comings,
b) Does any of the new information alter the SAB conclusion regarding
the categorization of ETS as an EPA Group A carcinogen?
The conclusion that ETS should be categorized as a Group A carcinogen,
made in the initial EFA draft, remains valid with the addition of the new
information in the revised draft. The totality of epidemiologie evidence indicates
that non-smoking women married to smokers have experienced an increased risk of
lung cancer. Increased risks have been observed in most of the investigations in
various parts of the world, including the United States. Biomarker studies have
shown that nonsmokers exposed to ETS inhale and metabolize compounds in
cigarette smoke, leaving no doubt that some of the various classes of carcinogens in
tobacco smoke reach bodily tissues. Although concentrations of tobacco smoke
components are much lower in ETS than in mainstream cigarette smoke, ETS and
-- MS share many qualitative chemical similarities and, for many carcinogens, the
relative proportion in ETS is enriched. Because cigarette smoking is such a well-
•estabUshed risk factor for lung cancer, and one that exhibits no evidence for a
threshold, it is biologically plausible that prolonged inhalation of ETS results in
some increase in risk of lung cancer among nonsmokers. Thus, despite the
uncertainty about the magnitude of the risk of lung cancer due to passive smoking,
the overall evidence is sufficient to declare that prolonged exposure to ETS is
ecologically related to lung cancer and that ETS should be regarded as an EFA
Group A carcinogen.
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estimated in several studies. The degree of miselassifkation is different in, different
studies, as one would expect with instruments and study protocols that are
different.
Although several possible markers for ETS are mentioned, two, respirable
suspended particulate matter (RSP) and nicotine, are discussed most fully. The
major uncertainties related to RSP as a marker are that the other sources of RSP
in all environments vary from environment to environment. At low smoking levels,
the ESP attributable to ETS is difficult to determine directly, and estimates of ETS
in these cases are unstable. By contrast, ETS is the only source of nicotine in most
environments, so that even at low smoking levels nicotine can be quantified and
attributed entirely to ETS, The major limitations of vapor phase nicotine are that
it is deposited onto surfaces more quickly than other components of ETS and also
is re-emitted from these surfaces. On the other hand, the successful use of these
two markers in field studies argues that these uncertainties are relatively small.
The wide range of ETS concentrations reported in human environments where
smoking occurs—over two and up to three orders of magnitude—indicate that the
current degree of uncertainty in assessing ETS exposures can be tolerated.
Of the possible biomarkers of ETS exposure, cotinine and nicotine in body
fluids (saliva, blood, and urine) are discussed most extensively. The advantages and
Limitations of these are accurately described, except that there should be some
discussion of the possible dietary sources of nicotine and cotinine, and the
contribution these might make to measured levels of these compounds in
nonsmokers.
3.2 Questions Concerning Lung Cancer - Hazard Identification (Chapters
4 and 5)
a) Is the evidence for the lung carcinogenicity of ETS presented
adequately?
Yes, the report has been strengthened by the addition of Chapter 4 which
reviews toxicologic evidence and highlights the evidence on active smoking. The
epidemlologic data are adequately described, although formal criteria should be set
forth for assigning the studies to tiers.
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3.3 Questions Concerning Lung Cancer - Population Impact (Chapter 6)
a) Is the approach used to derive estimates of U.S. female never-smoker
lung cancer risk scientifically defensible?
The combination of U.S. epidemiologic studies of non-smoking women
married to smokers provides an appropriate and sound basis for estimating the
relative -risk of lung cancer associated with ETS among American women who have
never smoked cigarettes. The procedures used to estimate the numbers of lung
cancer deaths due to ETS among female nonsmokers in the United States are based
on a series of reasonable assumptions, and yield a point estimate that is
scientifically defensible.
b) Is the approach used to extrapolate lung cancer risk from female
never-smokers to male never-smokers and former smokers of both
sexes scientifically defensible?
The use of data among non-smoking women to estimate lung cancer deaths
(LCDs) due to ETS among non-smoking men offers the advantage of the much
greater stability of the estimated effect of ETS among non-smoking women. The
epidemiologic studies in the United States have included over 1,000 non-smoking
women with lung cancer, but the numbers of non-smoking male cases studied are
nearly an order of magnitude smaller, and probably too few to provide an adequate
basis for national projections of ETS-related LCDs. Information to make direct
estimates of ETS effects among former smokers is even more limited and should
take into account their residual risk. Thus, although alternative approaches also
might have merit, the approach of extrapolating lung cancer mortality rates among
women to men, which was used in the draft document, is scientifically defensible.
However, the uncertainties should be further acknowledged. On the other hand, we
advise caution in extending the risk assessment to ex-smokers who are known to
remain at increased risk of lung cancer well beyond 5 years following cessation of
smoking,
c) Are the assumptions used to derive these lung cancer population
estimates and the uncertainties involved characterized adequately?
The estimated numbers of lung cancer deaths (LCDs) due to ETS in the
United States are based upon several assumptions. For never-smoking women, the
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numbers rely on, estimates of the relative risk of lung cancer among non-smoking
women married to smokers vs. nonsmokers, the effect of potential miselassifleation
of ETS exposure, the relative increase above background in ETS exposure among
non-smoking women married to smokers, the proportions of women in various
marital/ETS/smoking exposure categories, and the relative risk of lung cancer
among female active smokers. Assumptions associated with procedures to derive
these estimates are provided, but the draft document does not adequately convey
the extent of uncertainty in the resulting estimated numbers of ETS-induced LCDs
among never-smoking women. Uncertainties for the estimates among
never-smoking males or former smokers are even greater. While the overall point
estimate of approximately 3,000 total LCDs due to ETS exposure annually in the
United States is based on reasonable assumptions, the citation of a range of 2,500
to 3,300 ETS-related LCDs, based on varying only one of the parameters involved
in the estimation, is misleading and implies a greater degree of precision in the
estimation than is warranted, The document would be strengthened by additional
acknowledgement and characterization of these uncertainties.
d) Is the degree of confidence in these estimates as stated appropriately
characterized?
The confidence in these estimates, represented by the range of 2,500 to 3,300
deaths due to ETS, understates the uncertainties associated with each of the
assumptions that went into the risk assessment. It indicates a much higher degree
of precision than the 90% confidence interval surrounding the summary relative
risk for spousal smoking in the U.S. of 1.19. There are other assumptions used in
the risk assessment that Increase the uncertainty.
3.4 Questions Concerning Noncancer Respiratory Disorders - Hazard
Identification (Chapter 7; Sections 8.1 and 8,2)
a) Have the biological plausibility arguments been adequately presented?
Biological plausibility has been adequately presented, except for the
importance of bronchial responsiveness, especially in relation to lung function
growth and decline.
b) Have the most important confounders been properly addressed?
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Most of them ham Low birth weight is a confounder that is not adequately
considered by many studies. Also, ETS exposure in childhood and adolescence
should be included in assessing the effects of ETS on lung function in adults.
c) Has the weight of evidence bten properly characterized? Are the
conclusions scientifically defensible?
Yes. The weight of evidence has been property characterized for most
sections in Chapter 7, but the evidence for adult pulmonary function does not take
into account the potential confounders of childhood respiratory diseases or
exposures to parental smoking. The weight of evidence for asthma and sudden
infant death syndrome (SIDS) is properly characterized, concluding causality for
increased episodes and exacerbation of symptoms in asthmatics, but insufficient
evidence for causality for asthma induction or SIDS.
d) Is the evidence with respect to maternal smoking and sudden infant
death syndrome properly characterized? Should this evidence be
included in this report?
The evidence is appropriately characterized in terms of the strong association
and the suggestion that it is impossible, given the existing data, to determine
whether this is an in utero effect or an effect of environmental smoke exposure.
3.5 Questions Concerning Noncancer Respiratory Disorders - Population Impact
(Chapter 8}
a) Is the presented population impact of ETS on lower respiratory
infections and asthma in children scientifically defensible?
Yes. The issues related to asthma are clearly discussed based on current
knowledge. The focus should be on the exacerbation of asthmatic attacks because
the etiology of the disease is difficult to define. The issue of childhood respiratory
illnesses carries significant weight in the conclusions. It could be expanded,
especially for population impact above age 18 months. Potential impact of both
asthma and respiratory illnesses on adult lung function and disease could be
explored further. The presentation of both a threshold and a non-threshold
analysis is balanced, and the levels ascribed are consistent.
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b) Are the assumptions, uncertainties, and degree of confidence in the
ranges of population impact estimates adequately characterized?
Yes, there is a complete description of the assumptions and uncertainties in
the data set. This is a enormous improvement from the first draft of this
document, and provides a solid scientifically defensible base upon which to form the
conclusions drawn by the document.
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4. COMMENTS ON THE DRAFT DOCUMENT
This second draft as a whole, is a very substantially improved document and,
in general, does a good job of presenting the scientific evidence that supports the
judgment that exposure to ETS causes lung cancer and other adverse respiratory
health effects. It presents the data and relevant analysis in greater detail than is
available in any other single source. The findings in general are well substantiated.
The changes made from the first draft to the current draft were carefully thought
out and generally appropriate. Also, the authors have done a commendable job in
addressing the points raised by the Committee in its review of the first draft. This
document will be an invaluable source of information for health professionals and
policy makers for years to come.
. In preparing the final draft, the Committee recommends that EPA consider a
change in organization that we believe would better clarify the nature of the report
and its findings. We suggest that Chapters 4, 5 and 6 cover the health effects of
ETS on adults, and Chapters f and 8 cover the health effects of children rather
than having Chapters 4-6 devoted to cancer and Chapters 7 and 8 devoted to other
disorders.
4.1 Chapter 1 - Summary and Conclusions
The summary and conclusions of the report are clearly described with a brief
and appropriate discussion of substantiating evidence. Both the strengths and
limitations of the data on which conclusions are based are described. The addition
of comments on the relative strengths of the conclusions is also helpful. This
chapter will be very useful to the reader who does not have time or the expertise to
read the entire document.
A problem with this chapter is that although the findings and conclusions are
accurately reported from the document, summary comments and conclusion
comments are not clearly separated. The authors may wish to examine summary
and conclusions chapters from Surgeon General's reports (DHHS, 1984; 1986} to
give them an idea how better to organize this material. Clearly these two should
be separated. It would also be helpful to have each summary statement stand
alone, be in paragraph form, or be highlighted. In addition, it would also be
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helpful if some clearly stated overall objective for the document and specific
objectives for each chapter were outlined,
Because of the importance of this Chapter, the conclusions should be clearly
highlighted, or a new chapter on Conclusiojas_.and Recommendations should be
added. At a minimum, we recommend that a new section: 1.3 Conclusions be added
in which the conclusions reached as a result of analyses of findings are
summarized.
4.2 Chapter 2 - Introduction
This chapter does provide a brief statement of the problem of health risks
related to tobacco use. This introductory chapter should clearly establish why ETS
is an important problem. The terms "passive smoking," "ETS," and "in utero vs.
post-natal exposure" need to be more clearly defined. Specifically, it is important to
distinguish between passive smoking and ETS. Chapter 2 suffers from excessive
use of epidemiologic statistical and risk assessment jargon. It is critical for the
general understanding and acceptance of this EPA report that clear language be
presented in these chapters to make complex scientific issues accessible and
understandable to a lay audience.
4,3 Chapter 3 - Estimation of Environmental Tobacco Smoke Exposure
This chapter does a good job of covering the included material. However,
there are some important points related to the estimation of exposure to ETS that
are not included in the review. These points are important because they affect the
interpretation of the exposure and risk estimates.
The introduction to the chapter correctly points out the various factors that
can affect the composition of ETS including the variability of emission rates,
frequency of smoking, types of products combusted, other sources of the measured
components, ventilation rates and effects due to chemistry and deposition losses.
However, the review then treats ETS as a material having constant composition
with little regard to some of these factors. Three points with respect to the
chemical composition of ETS in indoor environments seem especially important.
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4.3.1 The composition of toxic compounds in WHS
The review should point to the expectation that the toxic potential of a unit
mass of ETS is expected to be greater than that of MS, This discussion might also
include some comments on the known changes in the chemical composition of ETS
as it ages and the unknown impact these changes have on toxicology,
4.3 J The rate of removal of nicotine in indoor environments
Nicotine has been the component of choice as a tracer of ETS in many
studies of environmental tobacco smoke because of its uniqueness to ETS and ease
of measurement. However, it has also been shown by several investigators that
nicotine is the component of ETS that is most rapidly removed in indoor
environments. The end result of its removal will be the underestimation of
exposure to most other components of ETS when the estimate is based on the
concentration of nicotine present in an indoor environment, with the '
underestimation becoming more severe as the exposure approaches zero.
Underestimation will have the same effect as random misclassificatioji, driving the
data, towards the null hypothesis. This effect should not be ignored.
4.3.3 The relative amounts of ETS and non-ETS particles in Indoor
environments
The text frequently emphasizes the average excess of ETS particulate matter
seen in indoor environments where smoking is present, but does not put these
numbers into proper context. The impression given is that the bulk of particulate
matter in typical indoor environments is from ETS, with high concentrations being
rarely measured in the absence of smoking. The average contribution, however, is
that about half of the fine particulate matter in a typical indoor environment where
smoking is present comes from ETS.
44 Chapter 4 - Hazard Identification I: Lung Cancer in Active Smokers, Long-
term Animal Bioaasays, and Genotoxic Studies
This chapter provides a concise and adequate summary of relevant but
indirect evidence supporting the biological plausibility for a causal association
between long-term exposure to ETS and an elevated risk for lung cancer. The clear
dose-related association of lung cancer risk with exposure to MS smoke, the
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presence of essentially all of the same known carcinogens in both MS and SS
smoke, the laryngeal cancers produced by inhaled MS smoke in the Syrian hamster,
and the greater carcinogenic potency of SS tar than MS tar in the mouse skin, all
are consistent with an elevated risk of lung cancer in nonsmokers chronically
exposed to ETS.
4.5 Chapter 5 - Hazard Identification II: Interpretation of Epidemiologic Studies
on ETS and Lung Cancer
This chapter provides an overview of 31 epidemiologic studies of ETS and
lung cancer, an evaluation of these studies, and a meta-analysis. Summary analyses
are presented by geographic region and study quality. The chapter ends with an
overall evaluation of the evidence and a conclusion that ETS is a Group A human
carcinogen. We support the general approach of reviewing the studies, classifying
them by quality, and calculating a pooled measure of association. However, a
number of specific problems should be addressed.
a) Lack of a general jepidemiologic framework: The chapter fails to set
out a general framework for evaluating the studies. The introductory
portions of the chapter, in addition to considering the issue of
statistical significance, should systematically review the types of bias
that may affect case-control and cohort studies. The framework could
then be used for evaluating the individual studies. The types of
relevant bias can be readily Mated: selection bias, information bias
resulting in either differential or non-differential misclassification, and
confounding. Improper control group selection and statistical power
are two additional limitations. We suggest an overall discussion of
each of these, methodological limitations and the potential consequences
for interpreting the studies. This approach would lend itself to
evaluating the individual studies.
b) Lack of framework for reviewing individual studies: A second concern,
failure to develop a systematic framework for reviewing the individual
studies, would be satisfactorily addressed by the approach suggested
above.
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c) Editing: The text needs further editing. In many instances
cpidemiologic terminology has been used inappropriately. This
imprecision of language may lead to unneeded ambiguity.
d) Confounding: A substantial portion of the text is directed at potential
bias introduced by confounding. As noted by the authors, confounding
variables are themselves risk factors but are also associated with the
exposure of interest. We presently know little about causes of lung
cancer in persons who have never smoked. Some occupational factors
are causally linked to lung cancer in never smokers but other risk
factors have not yet been well established. For example, while diet is
emphasized as a potential confbunder in the chapter, we are still
awaiting confirmation that dietary factors are of importance in the
high proportion of lung cases occurring in smokers.
46 Chapter 6 - Population Risk of Lung Cancer from Passive Smoking
Chapter 6 provides estimates of the numbers of lung cancer deaths (LCD)
among nonsmokers in the United States attributed to ETS exposure. Estimates are
presented first for female nonsmokers, the group with the largest quantity of
relevant data on the effects of ETS. The estimated number of LCDs depends upon
the estimate, presented and discussed in Chapter 5, of 1.19 for the relative risk of
lung cancer among American non-smoking women married to smokers compared to
non-smoking women married to nonsmokers, and the relative risk estimate of 1.59
for these same women corrected for background GTS exposure. Based on these two
..., estimates, and estimates of the relative risk of lung cancer among female smokers
compared to nonsmokers, the proportions of non-smoking women exposed to
•spousal ETS, and the proportion of women who are nonsmokers, the report
partitions the approximately 38,000 LCDs in American women in 1985 into about
32,000 due to active smoking, 1,500 due to ETS (1,030 due to background ETS and
470 due to spousal ETS), and about 5,000 due to other causes. No confidence
limits are placed about the 1,500 ETS-related LCDs to take into account inherent
sampling variation. The report then estimates the numbers of LCDs in 1985
attributed to ETS among male nonsmokers. Limited data on relative risks of lung
cancer among non-smoking men married to smoking women are available from 11
studies (7 in the United States), with an overall average relative risk of about 1.6
(1.4 for U.S. studies), but the report does not use these estimates to estimate LCDs
attributed to ETS among men. Instead it extrapolates from the more stable
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estimated lung cancer mortality rates among non-smoking women married to
smokers vs. nonsmokers. So doing yields an estimate of 500 LCDs due to ETS
among male nonsmokers.
A similar extrapolation technique is used to estimate the number of LCDs in
1985 due to ETS among male and female former smokers, where former smokers
are defined as those who quit smoking 5 or more years ago. The estimated number
of ETS-related LCDs among these former smokers is 1,060. The grand total of
LCDs attributed to ETS is thus 3,060.
Data from the large, multi-center ease-control study of lung cancer among
non-imofcing women by Fontham et al. (1991) are then used in place of the
combined U.S. data to produce alternative total estimates of 2,480 and 3,300 ETS--
induced LCDs. The two estimates from this case-control study arise from use of
two different estimates (one based on means, the other based on medians) of the
ratio of ETS exposure in non-smoking women married to smokers vs. nonsmokers.
The use of data only from American studies to estimate LCDs in the United
States seems justifiable. Data from other countries bolster the conclusion that ETS
exposure can increase risk of lung cancer in humans (i.e., that ETS is a class A
carcinogen), but the magnitude of the effect in the United States seems better
estimable using the U.S. data alone. The use of data among non-smoking women
to estimate LCDs due to ETS among non-smoking men offers the advantage of the
much greater stability of the estimated effect of ETS among non-smoking women.
The U,S. studies included over 1,000 non-smoking women with lung cancer, but the
number of non-smoking male cases studied appears to be nearly an order of
magnitude smaller, and probably too few to provide an adequate basis for national
projections of ETS-related LCDs. The chapter cites problems in adjustment for
misclassification as the rationale for not using the male data, but a stronger case
might be made on grounds of limited information among males and the
considerably greater precision of the female data. Nevertheless, the text should
more fully discuss the claim that misclassification bias may be greater for male
than female nonsmokers, and acknowledge the possibility that the number of ETS—
related LCDs among male nonsmokers may be less than, in addition to greater
than, the estimate of 500.
The decision to not use cigarette-equivalent lowdose interpolation techniques
to estimate the numbers of LCDs due to ETS seems appropriate. It is not clear
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which one or several of the many carcinogens in cigarette smoke is responsible for
the increased risk of lung cancer in active smokers, nor how variation in bodily
cotinine concentration relates to variation in lung exposurl Wthese carcinogens.
Thus, there would be considerable uncertainty in using cotinine or other biomarker
data to translate ETS exposure by lionsmokers into cigarette-equivalent exposures.
The biomarker data clearly show that nonsmokers inhale and metabolize
components of tobacco smoke, and help establish that exposure to ETS can increase
the risk- of cancer, but they are less useful in estimating the number of cancers
induced by ITS,
The type of risk estimation done in this section is always subject to error
because of inadequate knowledge in many of the parameters and the need to make
various assumptions about the relationship of these parameters to one another.
The estimates obtained in this section appear reasonable and the assumptions are
clearly stated. Analytically it would seem difficult to place confidence Intervals that
can be interpreted in the conventional context of a sample size. Some indication in
this regard could be accomplished with a simulation study. The sensitivity analysis
serves to convey the high degree of variability in the estimates but considers
primarily one variable at a time. The approach used to estimate lung cancer due to
ETS in non-smoking women appears reasonable although the parameters used are
presently based on untestable assumptions. The extrapolation to males and
ex-smokers requires additional assumptions and, thus, is more difficult to defend
scientifically. However, the report states the assumptions made to obtain the
estimates.
4.7 Chapter 7 - Passive Smoking and Respiratory Disorders Other Than Cancer
This chapter Is an important component to the report. This chapter is
substantially improved from the previous draft. Section 7.2.2 presents evidence that
the in utero exposure to cigarette smoke via the mother significantly affects
neonatal pulmonary function both in animals and humans. While the evidence is
fragmentary, the effects are consistent and convincing overall.
Section 7.2.S indicates that reduced airway size and reduced respiratory flow
rates in neonates are associated with an increased of risk of pulmonary infection
during infancy, and possibly a predisposition to chronic obstructive lung disease in
adulthood. The section provides an important theoretical link between in utero or
25
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early life exposure to cigarette smoke and possible abnormal lung function and
pulmonary morbidity in later life.
Sections 7.2,4 and 7.2,5. provide evidence that parental smoking, at least
heavy smoking, enhances the likelihood of bronchial hyper-responsiveness and other
atopic illnesses in children. These findings are even more striking in light of the
"healthy smoker effect". Overall, Section 7.2 provides an excellent overview of
biological mechanisms that may underlie the ETS-resprratory disease association.
New data reviewed in Section 7.3 support prior conclusions of the Surgeon
General's Report (DHHS, 1986) and the National Research Council (NEC, 1986)
report that parental smoking is associated with increased risk of respiratory tract
infections in infants. The Chen (1989), Chen et al. (1986; 1988) and Woodward et
al. (1990) data demonstrating that in utero exposure via maternal cigarette smoking
is not the sole explanation for the increased risk represent a valuable new
observation. Several potential confounders were discussed and convincingly argued
not to account for the observed risk of BTS exposure; these included low birth
weight. Low birth weight, the risk of which has been reported to be increased by
ETS exposure, would be expected to raise the risk of respiratory infection during
infancy.
Section 7,5. The recent studies on cough, phlegm or wheezing and ETS are
particularly impressive in that so many studies performed in different countries and
with veiy different methodologies have arrived at similar conclusions. Potential
confounders are thoroughly discussed. The conclusion that ETS exposure is
associated with an increased prevalence of respiratory symptoms in infants and the
young is highly reasonable.
Section 7.6. The new studies in this area offer support for the conclusion
that ETS exposure aggravates asthma in children. The discussion that it is more
likely chronic rather than acute exposure to ETS that increases airway
responsiveness, the importance of high levels of exposure (which may vary
seasonally), and the socioeconomic influences on exposure are important for our
understanding of the nature of the relationship between ETS and asthma, as well
as for developing prevention strategies.
Section 7.7, The studies on maternal smoking and risk of sudden infant
death syndrome (SIDS) and the Centers for Disease Control (CDC, 1991) Risk
26
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Assessment are remarkably consistent in showing an increased risk, even though
patients were studied in different areas in the XLS, and in different countries
around the world. The association between maternal smoking" and SIDS persists
after controlling for a variety of potential confounders, including low birth weight
However, the relative risks of prenatal and postnatal cigarette smoke exposure
cannot be distinguished.
Section 7,8. As noted, the data on ETS and pulmonary health in adults are
inconsistent from study to study and potentially confounded by exposure to other
respiratory irritants that are linked to socioeconomic class and/or to a greater
tolerance by ETS-exposed individuals of other noxious airborne chemicals. Not
mentioned in the discussion of potential confounders is the issue of childhood
exposure that could influence pulmonary function in adulthood. It is likely that
children whose parents smoked, even if they did not become smokers themselves,
are more likely to marry a smoker compared to children whose parents do not
smoke. Also relevant to the issue is the study of Janerich et al. (1990) indicating
that a substantial fraction of life-long environmental ETS exposure occurs during
childhood and adolescence.
4*8 Chapter 8 - Assessment of Increased Risk for Respiratory Illnesses in
Children from Environmental Tobacco Smoke
In general, the risk assessments in this chapter are well done, and tend to be
on the conservative side. For one thing, there is a tendency toward an
underestimation of the risk associated with the use of cotinine as a measure of
exposure to ETS. For another, the risk assessment was limited, for LRI's to those
under age 18 months, for asthmatic attacks on children and only those exposed at
home and requiring some type of urgent care; it did not include the risk associated
with bronchial responsiveness nor the risk associated with ETS-induced respiratory
effects in childhood which have high probabilities of producrng/impacting on adult
respiratory problems.
27
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References Cited
CDC. (1991) SmoMttg-attributable mortality and years of potential life lost-United
States. Centers for Disease Control. MMWE 40:62-71.
Chen, Y. (1989) Synergistic effect of passive smoking and artificial feeding on
hospitalization for respiratory illness in early childhood. Chest 95:1004-1007.
Chen, Y., Li, W. and Yu, S. (1986) Influence of passive smoking on admissions for
respiratory illness in early childhood. Br. Med. J. 293:303-306.
Chen, Y., Li» W., S, Yu and W. Qian, (1988) Chamg-Ning epidemlologieal study of
children's health: I Passive smoking and children's respiratory diseases. Int,
J. Epidemic!. 17:348-355,
DHHS. (1984) The health consequences of smoking: chronic obstructive lung
disease. A report of the Surgeon General. DHHS Pub, No. (PHS3 84-50205.
U.S. Department of Health and Human Services, Washington, DC.
DHHS, (1986) The health consequences of involuntary smoking. A report of the
Surgeon General, DHHS Pub. No. (PHS) 87-8398. U,S. Department of
Health and Human Services, Washington, DC.
Fontham, E.T.H., Correa, P., Wu-Wffliams, A,» Reynolds, P.t Greenberg, R.S.,
Buffler, PA,, Chen, V.W., Boyd, P., Alterman, T.» Austin, D.P., Liff, J. and
S.D. Greenberg. (1991) Lung cancer in nonsmoking women: a multicenter
ease-control study. Cancer Epidemiol. Biomarkers and Prev. l(l):35-44.
Janerich, D.T., Thompson, W.D., Varela, L.R., ft al (1990) Lung cancer and
exposure to tobacco smoke in the household. N. Eng. J. Med. 323:632-636.
NRC, (1986) Environmental tobacco smoke: measuring exposures and assessing
health effects. National Research Council, Washington, C. National
Academy Press.
Woodward, A,, Douglas, E.M., Graham, N.M.H. and H. Miles, (1990) Acute
respiratory illness in Adelaide children: breast feeding modifies the effect of
passive smoking. J. Epidemiol. Community Health 44:224-30.
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