and S-Heterocyclic Polycyclic aromatic HydrocarBons

361 Pages·2014·3.98 MB·English

Bitumens and Bitumen emissions,
N S
and some - and -Heterocyclic
Polycyclic aromatic
HydrocarBons
volume 103
iarc monographs
on the evaluation
of carcinogenic risks
to humans
Bitumens and Bitumen emissions,
N S
and some - and -Heterocyclic
Polycyclic aromatic
HydrocarBons
volume 103
this publication represents the views and expert
opinions of an iarc Working Group on the
evaluation of carcinogenic risks to Humans,
which met in lyon, 11-18 october 2011
lyon, france - 2013
iarc monographs
on the evaluation
of carcinogenic risks
to humans

IARC MONOGRAPHS
In 1969, the International Agency for Research on Cancer (IARC) initiated a programme on the evaluation of the carcinogenic
risk of chemicals to humans involving the production of critically evaluated monographs on individual chemicals. The programme
was subsequently expanded to include evaluations of carcinogenic risks associated with exposures to complex mixtures, lifestyle
factors and biological and physical agents, as well as those in specific occupations. The objective of the programme is to elaborate
and publish in the form of monographs critical reviews of data on carcinogenicity for agents to which humans are known to be
exposed and on specific exposure situa tions; to evaluate these data in terms of human risk with the help of international working
groups of experts in chemical carcinogenesis and related fields; and to indicate where additional research efforts are needed. The
lists of IARC evaluations are regularly updated and are available on the Internet at http://monographs.iarc.fr/.
This programme has been supported since 1982 by Cooperative Agreement U01 CA33193 with the United States National
Cancer Institute, Department of Health and Human Services. Additional support has been provided since 1986 by the Health,
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Opportunities, and since 1992 by the United States National Institute of Environmental Health Sciences, Department of Health
and Human Services. The contents of this volume are solely the responsibility of the Working Group and do not necessarily
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This volume was made possible, in part, through Cooperative Agreement CR 834012 with the United States Environmental
Protection Agency, Office of Research and Development. The contents of this volume do not necessarily reflect the views or
policies of the U.S. Environmental Protection Agency.
Published by the International Agency for Research on Cancer,
150 cours Albert Thomas, 69372 Lyon Cedex 08, France
©International Agency for Research on Cancer, 2013
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IARC Library Cataloguing in Publication Data
Bitumens and bitumen emissions, and some N- and S-heterocyclic aromatic hydrocarbons / IARC Working Group
on the Evaluation of Carcinogenic Risks to Humans (2011: Lyon, France)
(IARC monographs on the evaluation of carcinogenic risks to humans ; v. 103)
1. Carcinogens, Environmental – adverse effects 2. Heterocyclic Compounds – adverse effects 3. Neoplasms – chemically
induced 4. Polycyclic Hydrocarbons, Aromatic – adverse effects 5. Vehicle Emissions – toxicity
I. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans II. Series
ISBN 978 92 832 1326 0 (NLM Classification: W1)
ISSN 1017-1606
PRINTED IN FRANCE
CONTENTS
NOTE TO THE READER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
LIST OF PARTICIPANTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
PREAMBLE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
A. GENERAL PRINCIPLES AND PROCEDURES ...................................................................9
1. Background .................................................................................................9
2. Objective and scope. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
3. Selection of agents for review .........................................................................11
4. Data for the Monographs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
5. Meeting participants ....................................................................................12
6. Working procedures .....................................................................................13
B. SCIENTIFIC REVIEW AND EVALUATION ......................................................................14
1. Exposure data ............................................................................................15
2. Studies of cancer in humans ...........................................................................16
3. Studies of cancer in experimental animals ...........................................................20
4. Mechanistic and other relevant data ..................................................................23
5. Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
6. Evaluation and rationale ................................................................................27
References ..........................................................................................................31
GENERAL REMARKS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
BITUMENS AND BITUMEN EMISSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
1. Exposure Data .................................................................................................39
1.1 Identification of the agent: definitions and classifications .........................................39
1.2 Methods of analysis .....................................................................................51
1.3 Production and use ......................................................................................55
1.4 Occurrence and exposure ..............................................................................69
1.5 Regulations and guidelines ............................................................................88
2. Cancer in Humans .............................................................................................90
2.1 Introduction .............................................................................................90
2.2 Cohort studies ...........................................................................................91
2.3 Case–control studies ...................................................................................124
2.4 Meta-analyses ...........................................................................................138
3. Cancer in Experimental Animals ...........................................................................140
3.1 Mouse ....................................................................................................140
III
IARC MONOGRAPHS - 103
3.2 Rat ........................................................................................................153
3.3 Rabbit ....................................................................................................154
3.4 Guinea-pig ...............................................................................................155
4. Mechanistic and Other Relevant Data .....................................................................155
4.1 Overview of the mechanisms of carcinogenesis of PAHs .........................................155
4.2 Absorption, distribution, metabolism, and excretion of bitumens and bitumen fume .......164
4.3 Genetic and related effects ............................................................................170
4.4 Other effects relevant to carcinogenesis ............................................................189
4.5 Mechanistic considerations ...........................................................................193
5. Summary of Data Reported .................................................................................196
5.1 Exposure data ...........................................................................................196
5.2 Human carcinogenicity data ..........................................................................197
5.3 Animal carcinogenicity data ..........................................................................200
5.4 Mechanistic and other relevant data .................................................................202
6. Evaluation .....................................................................................................203
6.1 Cancer in humans ......................................................................................203
6.2 Cancer in experimental animals ......................................................................203
6.3 Mechanistic and other relevant data .................................................................203
6.4 Overall evaluation ......................................................................................204
6.5 Rationale ................................................................................................204
References .....................................................................................................204
SOME N- AND S-HETEROCYCLIC POLYCYCLIC AROMATIC HYDROCARBONS . . . . . . . . . . . . . . . . . . . . . . . . . 221
1. Exposure Data ................................................................................................221
1.1 Identification of the agents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .221
1.2 Analysis ..................................................................................................225
1.3 Production and use .....................................................................................226
1.4 Occurrence and exposure .............................................................................226
1.5 Regulations and guidelines ...........................................................................229
2. Cancer in Humans ............................................................................................229
3. Cancer in Experimental Animals ...........................................................................229
3.1 Benz[a]acridine .........................................................................................229
3.2 Benz[c]acridine ..........................................................................................230
3.3 Dibenz[a,h]acridine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .235
3.4 Dibenz[a,j]acridine .....................................................................................241
3.5 Dibenz[c,h]acridine .....................................................................................246
3.6 Carbazole ................................................................................................248
3.7 7H-Dibenzo[c,g]carbazole .............................................................................252
3.8 Dibenzothiophene .....................................................................................257
3.9 Benzo[b]naphtho[2,1-d]-thiophene ..................................................................257
4. Mechanistic and Other Relevant Data .....................................................................258
4.1 Benz[a]acridine .........................................................................................258
4.2 Benz[c]acridine ..........................................................................................260
4.3 Dibenz[a,h]acridine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .262
4.4 Dibenz[a,j]acridine .....................................................................................266
4.5 Dibenz[c,h]acridine .....................................................................................271
IV
Contents
4.6 Carbazole ................................................................................................274
4.7 7H-Dibenzo[c,g]carbazole .............................................................................275
4.8 Dibenzothiophene .....................................................................................280
4.9 Benzo[b]naphtho[2,1-d]thiophene ...................................................................283
5. Summary of Data Reported .................................................................................285
5.1 Exposure data ...........................................................................................285
5.2 Human carcinogenicity data ..........................................................................285
5.3 Animal carcinogenicity data ..........................................................................285
5.4 Mechanistic and other relevant data .................................................................287
6. Evaluation .....................................................................................................292
6.1 Cancer in humans ......................................................................................292
6.2 Cancer in experimental animals ......................................................................292
6.3 Overall evaluation ......................................................................................292
References .....................................................................................................292
GLOSSARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
LIST OF ABBREVIATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
CUMULATIVE CROSS INDEX TO IARC MONOGRAPHS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
V

NOTE TO THE READER
The term ‘carcinogenic risk’ in the IARC Monographs series is taken to mean that an agent is
capable of causing cancer. The Monographs evaluate cancer hazards, despite the historical presence
of the word ‘risks’ in the title.
Inclusion of an agent in the Monographs does not imply that it is a carcinogen, only that the
published data have been examined. Equally, the fact that an agent has not yet been evaluated in a
Monograph does not mean that it is not carcinogenic. Similarly, identification of cancer sites with
sufficient evidence or limited evidence in humans should not be viewed as precluding the possibility
that an agent may cause cancer at other sites.
The evaluations of carcinogenic risk are made by international working groups of independent
scientists and are qualitative in nature. No recommendation is given for regulation or legislation.
Anyone who is aware of published data that may alter the evaluation of the carcinogenic risk
of an agent to humans is encouraged to make this information available to the Section of IARC
Monographs, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon
Cedex 08, France, in order that the agent may be considered for re-evaluation by a future Working
Group.
Although every effort is made to prepare the Monographs as accurately as possible, mistakes may
occur. Readers are requested to communicate any errors to the Section of IARC Monographs, so that
corrections can be reported in future volumes.
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