Table Of ContentENVIRONMENTAL SGIENGES
An Interdisciplinary Monograph Series
Editors: DOUGLAS H. K. LEE, E. WENDELL HEWSON, and DANIEL OKU Ν
A complete list of titles in this series appears at the end of this volume.
Asbestos and Disease
By
Irving J. Selikoff
Director, Environmental Sciences Laboratory
Mount Sinai School of Medicine of the City University of New York
New York, New York
Douglas H. K. Lee
Consultant, Mount Sinai School of Medicine of the City University of New York
New York, New York
formerly Associate Director, National
Institute of Environmental Health Sciences
Research Triangle Park
North Carolina
with the active collaboration of
Henry A. Anderson Ε. Cuyler Hammond Coleman B. Rabin
Philip Chahinian Duncan A. Holaday Arthur N. Röhl
Jacob Churg Milton Kannerstein Robert J. Schnitzer
Susan Daum Arthur M. Langer Herbert Seidman
Theodore Ehrenreich Ruth Lilis Yasunosuke Suzuki
Alf Fischbein William J. Nicholson Alvin S. Teirstein
Mount Sinai School of Medicine of the City University of New York
New York, New York
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Library of Congress Cataloging in Publication Data
Selikoff, Irving J
Asbestos and disease.
(Environmental sciences)
Bibliography: p.
1. Asbestosis. 2. Asbestos—Toxicology.
3. Asbestos industry—Hygienic aspects. I. Lee,
Douglas Harry Kedgwin, 1905- joint author.
II. Title. III. Series. [DNLM: 1. Asbestos—
Adverse effects. 2. Disease—Etiology. QV610S465a]
RC775.A8S44 615.9'25'39224 77-25735
ISBN 0-12-636050-2
PRINTED IN THE UNITED STATES OF AMERICA
80 81 82 9 8 7 6 5 4 3 2
Foreword
The essence of the relationship of man to his environment is the ratio
of benefit to risk. Asbestos, a naturally occurring fibrous material, is a
startling example of a material at once uniquely useful, because of its
physical and chemical properties, and at the same time potentially
hazardous to man. Evidence linking inhalation of asbestos fiber to the
development of a group of diseases is generating ever-growing concern.
The demonstrated risks involve the worker exposed in manufacture and
use of asbestos, residents of neighborhoods of asbestos manufacturing
plants, and the members of households of the asbestos worker. The
benefits of asbestos, however, merit an assessment of the nature of the
hazard, the extent of the hazard, and the possibilities for control of the
hazard.
Asbestos exposure can result in both inflammatory and neoplastic
disease: asbestosis, lung cancer, and mesothelioma. Epidemiologic
studies show a minimal but consistent increased risk to cancer of the
gastrointestinal tract in workers with asbestosis. The identification of
neoplastic disease as a consequence of asbestos fiber inhalation resulted
in two findings of major significance to students of occupational and
environmental disease. The first relates to the universally recognized
concept of multiple causes of cancer of all sites in man, e.g., lung cancer,
and the second to the appearance in significant numbers of a heretofore
rare form of cancer, mesothelioma.
Evaluating the many factors critical to the causation and control of
asbestos-related disease requires
1. Study of its distribution and prevalence in man
2. Analysis of the specific host and environment interface (work-
place, general ambient environment, consumer product) within the
more general compartments of the environment (air, water, food)
xi
xii Foreword
3. Determination of the sequential response of the lungs and other
target organs with particular emphasis on changes crucial to the evolu-
tion of disease
4. Measurement of the impact of efforts to control exposure to
asbestos
Determining the extent of asbestos-related disease, i.e., the scope of
the populations at risk, the attack rate, and the identification of specific
diseases, is currently the major task at hand. Factors such as the follow-
ing must be considered:
1. Dose response and threshold/no adverse effect level. This highly
controversial, generic issue in carcinogenesis has special relevance to
asbestos-related disease in view of the occurrence of cancer in those
paraoccupationally exposed. In experimental models as well as in man,
dose response and no adverse effect levels of exposure have been
demonstrated.
2. Extrapolation from animal to man and from high-dose to low-dose
exposure. The relevance of experimental animal data for man and the
extrapolation of findings from high-dose exposure to low-dose expo-
sure is critical for new agents to be introduced into the environment
and, for asbestos, is of importance as a factor in establishing acceptable
levels of exposure.
3. Interaction of environmental agents in the causation of cancer. Lung
cancer rates in asbestos workers clearly reflect the combined effect of
cigarette smoking and asbestos exposure. This observation is fully
compatible with the principles of cofactors in cancer causation and with
the current information on the pathogenesis of this disease.
Controlling hazards and evaluating the effectiveness of such controls
also involve a number of problems, one of which is the difference in the
epidemiologic data available for various groups within the population
at risk and, in particular, the lack of reliable data with respect to the
general population. The lack of exposure data at the time of initiation
and during the latency of asbestos-related disease is frustrating, and the
authors of this text have clearly and responsibly addressed this issue.
Also, effective control must be a joint effort of management, labor,
and government. Even when the scientific and technological compo-
nents are all considered, regulation is still primarily a social determina-
tion, and the changing attitude of society toward risk is another factor
that complicates an already complex situation.
This book affords a much-needed comprehensive compendium and
presentation of accumulated information on asbestos and disease. De-
spite the necessity for the authors to take one or another side of the
Foreword xiii
controversial aspects of asbestos-related disease, the text is one that
addresses the problems and lessons to be learned from an agent as-
sociated with hazard to man during uncontrolled exposure. Throughout
the text one finds a continuous thread of extensive experience in the
field and authority.
Paul Kotin
Johns-Manville Corporation
Denver, Colorado
Preface
It is said that there are only two occasions on which it is justifiable to
write of a country: after three weeks of residence when one is impressed
by the opening of new vistas and not aware of subtleties that may
inhibit firm conclusions, or after thirty years of residence when the
nuances have been experienced and a mature judgment is possible.
Much the same could be said for writing a monograph on an environ-
mentally induced disease: either an early exposition of some newly
recognized disease effect as was done in 1974 for vinyl chloride, or a
comprehensive review of the situation revealed by extensive observa-
tion and research on a continuing problem.
The time has come when such a comprehensive review of disease
caused by exposure to asbestos is not merely possible but badly
needed. With the number of articles on the subject in the world litera-
ture at about the three thousand mark, it is manifestly absurd to expect
every person who has some responsibility for or interest in disease
prevention to be familiar with all of the aspects covered, or to be forced
to resolve many of the conflicting views presented. Even those who
have expert knowledge of one aspect, be it clinical effects or engineer-
ing control, may well need guidance on other aspects.
With this realization in mind, we decided to take advantage of the
wide range of specialists available at the Mount Sinai School of
Medicine, not only in the Environmental Sciences Laboratory but also
in the various divisions of the School, and prepare an account that
would place the entire problem in perspective and help the various
specialists communicate and cooperate more easily than they may have
been able to do in the past. Their range of interests is wide indeed:
physicians, laboratory aides, industrial hygienists, plant managers,
XV
xvi Preface
legal representatives, organized labor, environmentalists, public health
officers, economists, and (most importantly) students in any of these
fields.
The major aims of this work are to provide nonspecialists in each of
the fields listed above with easily comprehensible and meaningful data;
with knowledge that will enable them to discuss problems intelligently
with their colleagues and help them appreciate the value of their con-
tributions as well as the limitations of their current knowledge; and
with access to technology other than their own without swamping them
and discouraging them with excessive detail. To include all of the detail
that specialists in a field would consider relevant would result in a set of
volumes, not a useful monograph. In any case, specialists have their
own sources of information and would be unlikely to turn to a review
for guidance in their field. We have sought, therefore, to digest the
specialist information applicable to the asbestos problem, and to pre-
sent it in a manner that will be easily understood by the person trained
in some other field, while at the same time indicating the current
limitations as well as the strengths of the information available. In this
spirit, the radiographs as well as the figures and plates are simply
illustrative of points made in the text. An exhaustive presentation
would have required a volume of its own.
To permit, even to encourage, the reader to probe further, we have
included a fairly extensive Bibliography that covers historical as well as
current information and lists sources that include the various issues of
some complex and still incompletely resolved problems. Some selection
has been exercised, of course, since it would have been impractical to
list all of the some three thousand references in our files, and even the
diligent search of the literature that we have made will inevitably have
missed some relevant and potentially important items. In an Adden-
dum we have noted some of the highlights of information that became
available to us between submission of the manuscript and the finaliza-
tion of page proofs. The symbol [A] at the end of a paragraph indicates
that additional information is included in the Addendum.
In the process of organizing the available clinical and etiological
information, it became clear that the ground rules for judging the
information had never really been defined. An attempt to formulate
such rules for our own use led us to the famed Koch postulates that
provided the judgmental framework for so many generations of bac-
teriologists and clinicians. While the phrasing of the original postulates
(in whatever version one selects) was too rigid for our purposes, they
did suggest a modified version that would be applicable to agents
producing chronic, environmentally induced diseases such as those
that attend exposure to asbestos. These are set out in Chapter 6, and we
Preface xvii
have followed them in reviewing evidence for the incrimination of
asbestos in each of the four disease processes: parenchymal asbestosis,
pleural asbestosis, mesothelioma, and carcinoma associated with expo-
sure to asbestos. We believe that in doing so we have presented a model
for etiological judgment on long term environmental effects in general.
The recognition of four chronic disease processes induced by asbes-
tos is not new, but we hope that our insistence on the separation of the
processes will help clarify future considerations of the clinical response.
In Chapters 7 through 12 we have reviewed the pathological and clinical
consequences of these four processes separately; but, as set out at the
end of Chapter 6, an individual case may be found to have almost any
combination of the four. The analysis into four processes is essential for
the understanding of disease responses, but the acceptance of combina-
tion is equally essential for clinical assessment of the individual case.
As in almost any medical field, and perhaps more than in most,
controversy still exists on some matters of both causation and control.
As individuals, we naturally have come to our own conclusions, but we
have tried to present the evidence for and against the various interpre-
tations, so that readers can attempt their own assessments if they wish.
As new evidence emerges, opinions must necessarily change to ac-
commodate it. While not pretending to be a concordia discordantium, the
book does aspire to present a reasonable resolution of some outstanding
conflicts of opinion. What is presented in this book is the current set of
conclusions we have drawn from evidence that has built up over the
years; new demonstrations could change them, but they are believed to
represent the ones most justified by what we now know. Summariza-
tion of technical information invariably leads to the elimination of some
information deemed unessential to the statement. If in doing so we
have omitted an item that some specialist cherishes more warmly, we
can only claim editorial privilege for such lapses from grace.
It will be evident to the reader that we have adopted a historical
approach in many instances, particularly in matters of etiology. We
hope the reader will find these as interesting and as fascinating as we
did, even though they may again fight some forgotten battles. Insofar as
information derived from the Mount Sinai investigations is concerned,
we have given references where the material has already appeared in
print, but we have generally refrained from citing unpublished reports
and working documents prepared for granting and other agencies. Data
for which bibliographic references are not given can be taken as
emanating from our own studies.
As with all reviewers, our debt to past writers is enormous. It would
be impossible at this stage to determine the exact influence exerted by
each and every one of the documents we have read; their substance has
xviii Preface
long since melded with memories of things read and opinions formed.
The list of names in the Bibliography covers only a fraction of those to
whose ideas we have been exposed. We apologize to those who may
feel that they, too, should have been cited by name. As for those who
have materially aided us in the preparation of this book, our indebted-
ness is almost as extensive. From the long list we must select Mrs. Julia
Roberts, who amended and reamended many magnetic card versions
with remarkable equanimity and skill; Mrs. Doris Fleisher, who or-
ganized and coordinated the various aspects of production; and Mrs.
Janet Kaffenburgh who traced many of the historical references that we
sought. We gratefully acknowledge the excellent drafting of the figures
by Lewis Hollander.
Finally, we must draw attention to the active role played by the
collaborators listed on the title page. Where they prepared definitive
sections, their names have been cited in the text; but their contributions
went far beyond that in reading all of the manuscript, often in more
than one version, and in making numerous suggestions for revision,
many of them vital. In truth, they are part authors of this book, whose
names would appear as such did publishing technicalities permit. We
are very appreciative of the willingness with which Dr. John Harington
and Dr. Paul Kotin accepted the onerous task of going through ad-
vanced revisions of the manuscript and of giving us their advice on
both substance and form. They, like our collaborators, are absolved
from any responsibility for the final version, for which we must accept
complete responsibility.
The preparation of the book was supported by a grant (R-53B) from
the American Cancer Society, but the work of the Laboratory has had
support from numerous sources beside the Mount Sinai School of
Medicine, notably in recent years from the National Institute of En-
vironmental Health Sciences, Department of Health, Education and
Welfare (Grant No. ES 00928). For all of this support we are deeply
grateful. Very special appreciation must be accorded the officers of the
International Association of Heat and Frost Insulators and Asbestos
Workers (IAHFIAW), and those of the Locals that cooperated in many of
the studies carried out by Mt. Sinai investigators. Without this coopera-
tion, our understanding of the disease processes would have been
greatly retarded.
Irving J. Selikoff
Douglas H. K. Lee*
* Present address: Nazareth 5-1, Deer Hill Road, St. Thomas, U.S. Virgin Islands 00801.
