Environmental carcinogens, polycyclic aromatic hydrocarbons : chemistry, occurrence, biochemistry, carcinogenicity

272 Pages·1983·17.16 MB·English

by  Grimmer

Environmental
Carcinogens:
Polycyclic Aromatic
Hydrocarbons
Chemistry, Occurrence,
Biochemistry, Carcinogenicity
Editor
Gernot Grimmer, Dr. Chem,
Biochemical Institute for
Environmental Carcinogens
Ahrensburg, West Germany
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
First published 1983 by CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
Reissued 2018 by CRC Press
© 1983 by CRC Press, Inc.
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish
reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the
consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this
publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has
not been acknowledged please write and let us know so we may rectify in any future reprint.
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any
electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any
information storage or retrieval system, without written permission from the publishers.
For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/)
or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit
organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license
by the CCC, a separate system of payment has been arranged.
Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and
explanation without intent to infringe.
Library of Congress Cataloging in Publication Data
Luftqualitätskriterien für ausgewählte poly-
zyklische aromatische Kohlenwasserstoffe.
English.
Environmental carcinogens, polycyclic
aromatic hydrocarbons.
Updated translation of: Luftqualität-
skriterien für ausgewählte polyzyklische
aromatische Kohlenwasserstoffe.
Bibliography: p.
Includes index.
1. Hydrocarbons—Toxicology. 2. Aromatic
compounds—Environmental aspects. 3. Car-
cinogens—Environmental aspects. 4. Envi-
ronmentally induced diseases—Germany (West)
I. Grimmer, G. (Gernot), 1924- . [DNLM:
1. Polycyclic hydrocarbons. 2. Air pollutants.
3. Carcinogens, Environmental. WA 754 E313]
RC268.7.H9E58 65.9’511 82-4210
ISBN 0-8493-6561-9 AACR2
A Library of Congress record exists under LC control number: 82004210
Publisher’s Note
The publisher has gone to great lengths to ensure the quality of this reprint but points out that some imperfections in the original copies
may be apparent.
Disclaimer
The publisher has made every effort to trace copyright holders and welcomes correspondence from those they have been unable to
contact.
ISBN 13: 978-1-315-89265-8 (hbk)
ISBN 13: 978-1-351-07175-8 (ebk)
Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the
CRC Press Web site at http://www.crcpress.com
PREFACE
In the Federal Republic of Germany, as in other countries, the increasing industrial-
ization and urbanization involves a growing hazard to the environment. Therfore,
there is a definite need for measures to protect man and animal and plant life against
harmful environmental influences. The legal bases for such measures are the Federal
Emission Control Law and the Technical Instructions for Maintaining Air Purity, an
administrative regulation that includes, among others, air quality standards for ten
noxious substances. The Federal Environmental Protection Agency (Unweltbunde-
samt) supports the Federal Ministry of the Interior in solving problems of aar quality
control, e.g., by compiling scientific data on the effect of relevant air pollutants. On
the basis of these data, proposals for emission standards are then developed.
Limitation of emissions is often necessary when the emission of a toxic substance
jeopardizes human health. In the case of carcinogenic substances, preventive guidelines
should be laid down even if it is not scientifically justifiable to regard them as author-
itative. Their use may considerably reduce the carcinogenic risk to man.
The group of compounds called polycyclic aromatic hydrocarbons (PAH) is under
strong suspicion of contributing, as an air pollutant, to the frequency of the incidence
of lung cancer. This statement is based on observations in occupational medicine, an-
imal bioassays, and epidemiologic studies. Thus a reduction of the PAH content in
the atmosphere would most probably decrease the frequency of lung cancer.
The present survey comprises today's knowledge of environmental pollution-in
particular of the atmosphere-by PAH and of the biological effects of this class of
substance, putting special emphasis on their carcinogenic activity. The research data
and conclusions derived therefrom are meant to assist the goverment of the Federal
Republic of Germany in determining an air quality standard.
We wish to thank in particular all those scientists who helped to compile this docu-
mentation as well as the members of the working group "Investigations on the Carcin-
ogenic Burden by Air Pollution in Man" and "Inventory and Biological Impact of
Polycyclic Carcinogens in the Environment" who prepared a large amount of the cited
research data.
Dr. Heinrich von Lersner
President of the Federal
Environmental Protection
Agency
INTRODUCTION
D. Schmahl
Environmental protection is an urgent demand of our time. The present industrial
society has confronted physicians, ecologists, and biologists with new problems arising
from this very society. Nevertheless, it should be mentioned that in the Western Hem-
isphere the earliest law on environmental protection was drafted more than 700 years
ago by the Hohenstaufen Emperor Friedrich I1 in the "Constitution of Melfi". It is
relevant to the subject matter of the present volume that this historical constitution
which Friedrich I1 intended to be a clean-air act read: "We endeavour to keep the
health of the air given to us by God clean by providing preventive measures as far as
possible. We therefore decree that nobody is allowed to rinse flax and hemp in waters
less than one mile away from dwellings because this would have a detrimental effect
on the air quality."
Whereas in former times the main concern was to keep the air free from odors and
pathogenic agents of infectious diseases (malaria = malair = bad air), the working
group "Investigations on the carcinogenic burden by air pollution in man" was initi-
ated by the German Federal Ministry of the Interior in 1969 to investigate the problems
arising from carcinogenic agents contained in the air. These agents were to be identified
chemically, tested biologically, and their hazard to man was to be assessed. The initi-
ative of the Federal Ministry of the Interior has to be seen against the background that
for many years the incidence of cancer of the respiratory tract has been growing. Al-
though we know that this increase can be explained predominantly by inhalation of
tobacco smoke, other sources such as heating installations, incinerators, industrial
plants, vehicle exhausts, coal power plants, etc. emit potentially carcinogenic com-
pounds into the atmosphere which may etiologically play a role in carcinogenesis. This
is mainly supported by epidemiological studies in man which are dealt with in a later
chapter.
According to present knowledge, cancer of the respiratory tract must be considered
in most cases as the product of inhaled carcinogens. Since air is our most vital food
- in the truest sense of this word - the responsible legislative authorities must strive
to find ways and means of determining the potential carcinogens in the air we breathe
and either to eliminate them or to reduce them to a level which, according to our
present state of knowledge, causes as little risk as possible. However, those versed in
this field know that it is futile to propose a "zero value" for the concentration of
carcinogenic substances in the air since this is not feasible in our highly industrialized
and technological world. Furthermore, we have to bear in mind that the air contains
natural substances that are considered to be carcinogenic, e.g., the natural level of
radioactivity and some metals and dusts. Due to the given limitations of analytical
detection, a "zero value" per se is not appropriate.
The working groups "Investigations on the carcinogenic burden by air pollution in
man" and "Inventory and biological impact of polycyclic carcinogens in the environ-
ment" were initiated with the aim of adyising the legislative authorities in their legis-
lative action. At the start of our investigations, we had only very little reliable scientific
information which might have served as a basis for legislative initiatives. The scientists
of all participating institutions and their colleagues in the ministeries agreed that it was
impossible to detect, identify, and assess in the air all the potential carcinogens that
lay within the scope of these working groups. We therefore decided to first direct our
attention to the polycyclic aromatic hydrocarbons (PAH) because this class of com-
pounds comprises carcinogens which occur in the atmosphere - sometimes in consid-
erable amounts - and also ubiquitously, even though in varying concentrations. Other
inhalation carcinogens, such as asbestos fibers or N-nitroso compounds could be left
out, all the more so since we knew that other German and foreign groups have dealt
and are dealing with just these substances.
The results obtained by our working groups are included in the present documenta-
tion, which has been accomplished on the initiative of the German Federal Environ-
mental Protection Agency and concerns the complex problems inherent in the carcin-
ogenic activity of polycyclic aromatic hydrocarbons. These problems are dealt with
not only from the restricted vantage point of the two working groups, but also an
attempt is made to assess the risk of PAH as inhalation carcinogens in general, putting
adequate emphasis on the results obtained in model investigations carried out with
automobile exhaust condensates by one of the working groups.
PoIycyclic aromatic hydrocarbons such as benzo[a]pyrene have been proved to be
carcinogenic in a large number of animal species when applied to the skin or injected
subcutaneously. Man is not an exception to this rule. Thus, in 1775, the English phy-
sician Percivall Pott made the first corresponding observation in chimney sweeps
whose skin had come into intensive contact with soot, and PAH were identified as the
carcinogenic substances contained therein. The occupational bronchial carcinoma of
gasworkers and coke plant workers also seems to be induced by PAH generated in the
furnaces. The biological effect of benzo[a]pyrene was demonstrated experimentally in
human skin in 1939. From our present-day knowledge, these PAH exhibit predomi-
nantly a local carcinogenic activity, i.e., they induce malignant tumors at the site of
application and not (or only exceptionally) in distant organs.
Thus it is to be expected that after inhalation they display their carcinogenic activity
in the respiratory tract. That this may be the case is shown in investigations on tobacco
smoke carcinogenesis. Here the carcinogenic substances can be localized predomi-
nantly in the PAH-containing fraction of the tobacco smoke. It seems to be permissible
to reason by analogy that what is true for the tobacco smoke condensate is also appli-
cable to noxious substances derived from other sources of combustion.
Today it is relatively easy to obtain an exact determination of hydrocarbon concen-
trations in various media by a variety of analytical techniques. Furthermore, it is not
difficult to investigate certain hydrocarbons in simply designed experiments, e.g., with
rats and mice, with regard to their carcinogenic activity on skin, when applied topically
or subcutaneously. It is, however, considerably more difficult to test the suspected
compounds with an adequate inhalation technique, because the safety of individuals
working with these substances has to be guaranteed, and animals used in inhalation
experiments should have a structure of the respiratory tract and reaction to harmful
inhalatory substances similar to man. This already hints at the essential difficulty of
all experimental investigations, i.e., the extrapolation of experimental findings to the
human situation.
Despite the problems and difficulties mentioned, there is no alternative to animal
experiments, since for ethical reasons experiments with humans are out of the question,
and prospective epidemiologic studies involving humans would take many years or
even decades. This brings us to a second great difficulty inherent in our subject, i.e.,
the long latency period required for the induction of malignant tumors by chemical
substances. We have to accept this as a fact. Dealing with the assessment of long-term
effects is naturally far more difficult than evaluating short-term effects. Even today
satisfactorily proven results are rare in the field of the toxicological effects of long-
term inhalation because this field of science is comparatively new.
A third difficulty has to be mentioned still: as a rule the etiology of tumors in man
concerns a combination of effects, i.e., the tumor in question was induced not by one
specific noxious substance but by a great number of them. In addition, the constitu-
tional predisposition of the individual and the individual modes of reaction within the
respiratory tract (e.g., destruction of the ciliary function due to nonspecific influences)
may play a role. Beside the substance-related toxicological point of view, we therefore
have to take into account individual-specific considerations which may vary from in-
dividual to individual.
Despite these difficulties and shortcomings, the present documentation attempts to
give a survey of the significance of carcinogenic hydrocarbons as potential hazards to
man. We have tried to present - as comprehensively as possible - the results of
chemical, biological, and epidemiological studies, as well as interpretations given by
other groups of scientists, in considering the above problems. Furthermore, the present
volume is suited to introduce the interested reader to the problems of experimental
and practical ontology, to explain the methods and their necessary fundamentals, and
to show him the manifold difficulties which quite often inhibit the assessment of the
results obtained. In this respect the present documentation exceeds the narrow field of
hydrocarbons and can provide mental stimulations for critical initiatives in other
fields.
North Rhine-
l
women NRW
- - L S
1952 55 60 65 70 75 year
FIGURE 1. Mortality due to malignant tumors of the respiratory organs in North Rhine-
Westphalia and Lower Saxonia from 1952-1976'.
Figure 1 shows the increase of bronchial cancer deaths from 1952 to 1976 using the
German federal states North Rhine-Westphalia and Lower Saxony as examples. The
observed death rates demonstrate that despite intensive efforts in the therapeutic field
considerably more people died of lung cancer annually (1974: about 24,000) than, e.g.,
in road accidents (1974: about 14,600 deaths) in West Germany. This fact justifies the
demand for giving primary prevention of bronchial cancer a higher ranking.
Finally, a word of explanation: due to the subject matter of this study we have had
to give qualitative evaluations in many places, resulting perhaps in discrepancies which,
however, are due to the method of presentation only.
REFERENCE
1. Pott, F. and Dolgner, R., Zur Problematik einer Grenzwertfindung fiir PAH, Staub-Reinhalt. Luft,
39, 12, 1979.
THE EDITOR
Gernot Grimmer, Dr. Chem., earned his Doctoral degree in chemistry from the
University of Hamburg, West Germany in 1952. In 1959 he was appointed university
lecturer in biochemistry at the University and nominated for apl. Professor in 1969.
Since then he has served as chief of the Biochemical Institute of Environmental Carcin-
ogens in Hamburg-Ahrensburg and as a teacher at the University of Hamburg.
Professor Dr. Grimmer has published over 100 articles, mostly related to polycyclic
aromatic hydrocarbons, in journals of chemistry and biochemistry. He is also the edi-
tor of Biochemistry, a textbook for students of medicine and biochemistry, published
by Bibliographisches Institute, Mannheim, West Germany in 1969.
Professor Dr. Grimmer is a member of the German Society of Biological Chemistry,
the German Chemical Society, the German Society of Research on Mineral Oil and
Coal Chemistry, the German Pharmaceutical Society, the German Society of Fat Sci-
ence, and the Commission on Food Chemistry.
CONTRIBUTORS
H. Brune, M.D. U. Mohr, M.D.
Consulting Institute for Preventive Professor
Medicine and Environmental Department of Experimental Pathology
Toxicology Medical University
Hamburg, West Germany Hannover, West Germany
R. P. Deutsch-Wenzel, Ph.D. G. Oberdorster, D.V.M.
Consulting Institute for Preventative Associate Professor
Medicine and Environmental Department of Radiation Biology and
Toxicology Biophysics
Hamburg, West Germany University of Rochester Medical Center
Rochester, New York
S. Dobbertin, D.V.M.
Federal Environmental Agency F. Pott, M.D.
West Berlin, West Germany Professor
Medical Institute for Environmental
G. Grimmer, Dr. Chem.
Hygiene
Professor
University of Dusseldorf
Biochemical Institute for
Dusseldorf, West Germany
Environmental Carcinogens
Ahrensburg, West Germany
D. Schmahl, M.D.
M. Habs, M.D. Professor
Institute for Toxicology and Institute for Toxicology and
Chemotherapy Chemotherapy
German Cancer Research Center German Cancer Research Center
Heidelberg, West Germany Heidelberg, West Germany
J. Jacob, Ph.D.
P. Schneider, M.Sc.
Biochemical Institute for
Department of Experimental Pathology
Environmental Carcinogens
Medical University
Ahrensburg, West Germany
Hannover, West Germany
J. Misfeld, Ph.D.
Professor D. Steinhoff, M.D.
Institute for Mathematics Institute for Experimental Toxicology
University of Hannover Bayer AG
Hannover, West Germany Wuppertal-Elberfeld, West Germany
TABLE OF CONTENTS
Chapter 1
Environmental Carcinogens: A Risk for Man? Concept and Strategy of the
Identification of Carcinogens in the Environment. .............................. 1
G. Grimmer and J. Misfeld
Chapter 2
Chemistry ............................................................... 27
G. Grimmer
Chapter 3
OccurrenceofPAH ....................................................... 61
G. Grimmer and F. Pott
Chapter 4
Behavior of PAH in the Organism. ......................................... 129
F. Pott, B. Oberdorster, J. Jacob, and G. Grimmer
Chapter 5
Biological Activity ....................................................... 157
D. Schmahl, R. P. Deutsch-Wenzel, H. Brune, P. Schneider, U. Mohr, M. Habs,
F. Pott, and D. Steinhoff
Chapter 6
Epidemiology ........................................................... 221
J. Misfeld
Chapter 7
Extrapolation of Experimental Results to Man .............................. .237
D. Schmahl and M. Habs
Chapter 8
Conclusions ............................................................ 247
S. Dobbertin
Index .................................................................. 2 51