Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene

601 Pages·2002·2.88 MB·English

by  The International Agency for Research on Cancer

WORLD HEALTH ORGANIZATION
INTERNATIONAL AGENCY FOR RESEARCH ON CANCER
IARC MONOGRAPHS
ON THE EVALUATION
OF CARCINOGENIC
RISKS TO HUMANS
VOLUME 82
SOME TRADITIONAL HERBAL MEDICINES,
SOME MYCOTOXINS, NAPHTHALENE
AND STYRENE
2002
IARCPress
L Y O N
F R A N C E
WORLD HEALTH ORGANIZATION
INTERNATIONAL AGENCY FOR RESEARCH ON CANCER
IARC MONOGRAPHS
ON THE
EVALUATION OF CARCINOGENIC
RISKS TO HUMANS
Some Traditional Herbal Medicines,
Some Mycotoxins, Naphthalene
and Styrene
VOLUME 82
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,
12–19 February 2002
2002
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, life-style 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 situations; 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 Internet:
http://monographs.iarc.fr/
This project was supported by Cooperative Agreement 5 UO1 CA33193 awarded by the
United States National Cancer Institute, Department of Health and Human Services, and was
funded in part by the European Commission, Directorate-General EMPL (Employment, and
Social Affairs), Health, Safety and Hygiene at Work Unit. Additional support has been
provided since 1993 by the United States National Institute of Environmental Health Sciences.
©
International Agency for Research on Cancer, 2002
Distributed by IARCPress (Fax: [phone]; E-mail:
CONTENTS
NOTE TO THE READER............................................................................................1
LIST OF PARTICIPANTS............................................................................................3
PREAMBLE ................................................................................................................9
1. Background........................................................................................................9
2. Objective and Scope ..........................................................................................9
3. Selection of Topics for Monographs ..............................................................10
4. Data for Monographs ......................................................................................11
5. The Working Group ........................................................................................11
6. Working Procedures ........................................................................................11
7. Exposure Data..................................................................................................12
8. Studies of Cancer in Humans ..........................................................................14
9. Studies of Cancer in Experimental Animals ..................................................17
10. Other Data Relevant to an Evaluation of Carcinogenicity
and its Mechanisms ....................................................................................20
11. Summary of Data Reported ............................................................................22
12. Evaluation ........................................................................................................23
13. References........................................................................................................28
GENERAL REMARKS..............................................................................................33
THE MONOGRAPHS................................................................................................39
SOME TRADITIONAL HERBAL MEDICINES......................................................41
A. Introduction ....................................................................................................43
1. History of use of traditional herbal medicines ........................................43
1.1 The role of herbal medicines in traditional healing..........................43
1.2 Introduction of traditional herbal medicines into Europe, the USA
and other developed countries ..........................................................44
2. Use of traditional herbal medicines in developed countries ....................46
2.1 Origin, type and botanical data ........................................................46
2.2 Medicinal applications, beneficial effects and active components ..46
2.3 Trends in use ....................................................................................46
3. Awareness, control, regulation and legislation on use ............................50
3.1 WHO guidelines for herbal medicines..............................................50
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iv IARC MONOGRAPHS VOLUME 82
3.2 The European Union ........................................................................51
3.3 Individual countries ..........................................................................55
4. References ................................................................................................66
B. Aristolochia species and aristolochic acids ..................................................69
1. Exposure data............................................................................................69
1.1 Origin, type and botanical data ........................................................69
1.2 Use ....................................................................................................76
1.3 Chemical constituents ......................................................................76
1.4 Active components............................................................................78
1.5 Sales and consumption......................................................................79
1.6 Components with potential cancer hazard: aristolochic acids..........79
2. Studies of cancer in humans ....................................................................84
2.1 Case reports ......................................................................................85
2.2 Prevalence of urothelial cancers among patients with Chinese
herb nephropathy ..............................................................................86
3. Studies of cancer in experimental animals ..............................................87
3.1 Oral administration............................................................................87
3.2 Intraperitoneal administration ..........................................................88
3.3 Subcutaneous administration ............................................................88
4. Other data relevant to an evaluation of carcinogenicity and
its mechanisms..........................................................................................89
4.1 Absorption, distribution, metabolism and excretion ........................89
4.2 Toxic effects ......................................................................................91
4.3 Reproductive and developmental effects ..........................................94
4.4 Genetic and related effects................................................................96
4.5 Mechanistic considerations ............................................................115
5. Summary of data reported and evaluation ..............................................116
5.1 Exposure data ..................................................................................116
5.2 Human carcinogenicity data............................................................117
5.3 Animal carcinogenicity data ..........................................................117
5.4 Other relevant data ..........................................................................117
5.5 Evaluation........................................................................................118
6. References ..............................................................................................118
C. Rubia tinctorum, Morinda officinalis and anthraquinones..........................129
1. Exposure data..........................................................................................129
1.1 Origin, type and botanical data ......................................................129
1.2 Use ..................................................................................................130
1.3 Chemical constituents ....................................................................131
1.4 Sales and consumption....................................................................132
1.5 Component(s) with potential hazard (1-hydroxyanthraquinone;
1,3-dihydroxy-2-hydroxymethylanthraquinone (lucidin))..............132
CONTENTS v
2. Studies of cancer in humans ..................................................................135
Case−control studies ..............................................................................136
3. Studies of cancer in experimental animals ............................................138
3.1 1-Hydroxyanthraquinone ................................................................138
3.2 1,3-Dihydroxy-2-hydroxymethylanthraquinone (lucidin) ..............139
4. Other data relevant to an evaluation of carcinogenicity and
its mechanisms........................................................................................139
4.1 Absorption, distribution, metabolism and excretion ......................139
4.2 Toxic effects ....................................................................................140
4.3 Reproductive and developmental effects ........................................142
4.4 Genetic and related effects..............................................................142
4.5 Mechanistic considerations ............................................................145
5. Summary of data reported and evaluation..............................................146
5.1 Exposure data ..................................................................................146
5.2 Human carcinogenicity data............................................................146
5.3 Animal carcinogenicity data ..........................................................146
5.4 Other relevant data ..........................................................................147
5.5 Evaluation ......................................................................................147
6. References ..............................................................................................147
D. Senecio species and riddelliine ....................................................................153
1. Exposure data..........................................................................................153
1.1 Origin, type and botanical data ......................................................153
1.2 Use ..................................................................................................153
1.3 Chemical constituents ....................................................................153
1.4 Sales and consumption....................................................................154
1.5 Component(s) with potential cancer hazard (riddelliine) ..............154
2. Studies of cancer in humans ..................................................................155
3. Studies of cancer in experimental animals ............................................156
4. Other data relevant to an evaluation of carcinogenicity and
its mechanisms........................................................................................157
4.1 Absorption, distribution, metabolism and excretion ......................157
4.2 Toxic effects ....................................................................................158
4.3 Reproductive and developmental effects ........................................160
4.4 Genetic and related effects..............................................................160
4.5 Mechanistic considerations ............................................................163
5. Summary of data reported and evaluation..............................................163
5.1 Exposure data ..................................................................................163
5.2 Human carcinogenicity data............................................................163
5.3 Animal carcinogenicity data ..........................................................165
5.4 Other relevant data ..........................................................................165
5.5 Evaluation ......................................................................................165
6. References ..............................................................................................165
vi IARC MONOGRAPHS VOLUME 82
SOME MYCOTOXINS............................................................................................169
AFLATOXINS ....................................................................................................171
1. Exposure data..........................................................................................171
2. Studies of cancer in humans ..................................................................193
3. Studies of cancer in experimental animals ............................................210
4. Other data relevant to an evaluation of carcinogenicity
and its mechanisms ................................................................................215
5. Summary of data reported ......................................................................245
6. References ..............................................................................................249
Annex. Aflatoxins in foods and feeds: fungal sources, formation
and strategies for reduction....................................................................275
FUMONISIN B ..................................................................................................301
1
1. Exposure data ........................................................................................301
2. Studies of cancer in humans ..................................................................309
3. Studies of cancer in experimental animals ............................................311
4. Other data relevant to an evaluation of carcinogenicity
and its mechanisms ................................................................................316
5. Summary of data reported and evaluation..............................................343
6. References ..............................................................................................345
NAPHTHALENE ....................................................................................................367
1. Exposure data ........................................................................................367
2. Studies of cancer in humans ..................................................................385
3. Studies of cancer in experimental animals ............................................385
4. Other data relevant to an evaluation of carcinogenicity
and its mechanisms ................................................................................389
5. Summary of data reported and evaluation..............................................416
6. References ..............................................................................................418
STYRENE ................................................................................................................437
1. Exposure data ........................................................................................437
2. Studies of cancer in humans ..................................................................463
3. Studies of cancer in experimental animals ............................................475
4. Other data relevant to an evaluation of carcinogenicity
and its mechanisms ................................................................................479
5. Summary of data reported and evaluation..............................................518
6. References ..............................................................................................522
SUMMARY OF FINAL EVALUATIONS ..............................................................551
LIST OF ABBREVIATIONS USED IN THIS VOLUME ......................................553
CUMULATIVE INDEX TO THE MONOGRAPHS SERIES..................................557
NOTE TO THE READER
The term ‘carcinogenic risk’ in the IARC Monographs series is taken to mean the
probability that exposure to an agent will lead to cancer in humans.
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.
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 carcino-
genic risk of an agent to humans is encouraged to make this information available to the
Unit of Carcinogen Identification and Evaluation, 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 Unit of
Carcinogen Identification and Evaluation, so that corrections can be reported in future
volumes.
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IARC WORKING GROUP ON THE EVALUATION
OF CARCINOGENIC RISKS TO HUMANS:
SOME TRADITIONAL HERBAL MEDICINES, SOME
MYCOTOXINS, NAPHTHALENE AND STYRENE
Lyon, 12–19 February 2002
LIST OF PARTICIPANTS
Members
Ahti Anttila, Finnish Cancer Registry, Institute for Statistical and Epidemiological
Cancer Research, Liisankatu 21 B, 00170 Helsinki, Finland
Ramesh V. Bhat, National Institute of Nutrition, Indian Council of Medical Research,
Jamai-Osmania PO, Hyderabad-500 007 AP, India
James A. Bond, Chemico-Biological Interactions, Toxcon, 5505 Frenchmans Creek,
Durham, NC 27713, USA
Susan J. Borghoff, CIIT Centers for Health Research, 6 Davis Drive, Box 12137,
Research Triangle Park, NC 27709-2127, USA
F. Xavier Bosch, Epidemiology Unit and Cancer Registry, Catalan Institute of Onco-
logy, Av. Gran via s/n, Km. 2.7, 08907 L’Hospitalet del Llobregat, Spain
Gary P. Carlson, School of Health Sciences, 1338 Civil Engineering Building, Purdue
University, West Lafayette, IN 47907-1338, USA
Marcel Castegnaro, Les Collanges, 07240 Saint-Jean-Chambre, France
George Cruzan, ToxWorks, 1153 Roadstown Road, Bridgeton, NJ 08302-6640, USA
Wentzel C.A. Gelderblom, Programme on Mycotoxins and Experimental Carcinogenesis,
Medical Research Council (MRC), PO Box 19070, Tygerberg, South Africa 7505
Ulla Hass, Institute of Food Safety and Toxicology, Mørkhøj Bygade 19, 2860 Søborg,
Denmark
Sara H. Henry, 5100 Paint Branch Parkway, College Park, MD 20740-3835, USA
Ronald A. Herbert, Laboratory of Experimental Pathology, National Institute of Environ-
mental Health Sciences, PO Box 12233, Mail Drop B3-08, Research Triangle Park,
NC 27709-2233, USA
Marc Jackson, Integrated Laboratory Systems, Inc., PO Box 13501, Research Triangle
Park, NC 27709, USA
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