VOLUME 99 Some Aromatic Amines, Organic Dyes, and - IARC

706 Pages·2011·4.45 MB·English

WORLD HEALTH ORGANIZATION
INTERNATIONAL AGENCY FOR RESEARCH ON CANCER

IARC Monographs on the Evaluation of
Carcinogenic Risks to Humans
VOLUME 99
Some Aromatic Amines, Organic Dyes,
and Related Exposures
LYON, FRANCE
2010

WORLD HEALTH ORGANIZATION

INTERNATIONAL AGENCY FOR RESEARCH ON CANCER

IARC Monographs on the Evaluation of

Carcinogenic Risks to Humans

VOLUME 99

Some Aromatic Amines, Organic Dyes,

and Related Exposures

This publication represents the views and expert opinions

of an IARC Monographs Working Group on the

Evaluation of Carcinogenic Risks to Humans,

which met in Lyon,

5–12 February 2008

2010
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 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 the Internet at http://monographs.iarc.fr/.
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This volume was made possible, in part, through Cooperative Agreement CR 834012 with the United States
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Published by the International Agency for Research on Cancer,
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©International Agency for Research on Cancer, 2010
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IARC Library Cataloguing in Publication Data
Some aromatic amines, organic dyes, and related exposures / IARC Working Group on the
Evaluation of Carcinogenic Risks to Humans (2008: Lyon, France)
(IARC monographs on the evaluation of carcinogenic risks to humans; v. 99)
1. Amines – toxicity 2. Barbering 3. Carcinogens 4. Colouring Agents – toxicity
5. Hair Dyes – toxicity 6. Occupational Exposure 7. Urinary Bladder Neoplasms – chemically induced.
I. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans II. Series
ISBN 978 92 832 1299 7 (NLM Classification: W1)
ISSN 1017-1606
PRINTED IN FRANCE
Cover: The composite structure brings together many of the chemical agents discussed and
evaluated in this Volume; the background photograph illustrates occupational exposures of
hairdressers and barbers, and personal use of hair colourants.

Cover photograph and design: Roland Dray (IARC). We gratefully acknowledge the gracious
help of three of our colleagues in realizing the background photograph.

CONTENTS
NOTE TO THE READER..................................................................................................1

LIST OF PARTICIPANTS.................................................................................................3

PREAMBLE........................................................................................................................7
A. GENERAL PRINCIPLES AND PROCEDURES........................................................9
1. Background..............................................................................................................9
2. Objective and scope...............................................................................................10
3. Selection of agents for review...............................................................................12
4. Data for the Monographs......................................................................................12
5. Meeting participants..............................................................................................13
6. Working procedures..............................................................................................14

B. SCIENTIFIC REVIEW AND EVALUATION..........................................................15
1. Exposure data........................................................................................................16
2. Studies of cancer in humans..................................................................................18
3. Studies of cancer in experimental animals............................................................23
4. Mechanistic and other relevant data......................................................................26
5. Summary................................................................................................................30
6. Evaluation and rationale........................................................................................31

References..........................................................................................................................36

GENERAL REMARKS....................................................................................................39

GENERAL DISCUSSION OF COMMON MECHANISMS FOR
AROMATIC AMINES.....................................................................................................41

GENERAL INTRODUCTION TO THE CHEMISTRY OF DYES..............................55

–v–
vi IARC MONOGRAPHS VOLUME 99
THE MONOGRAPHS......................................................................................................69
4-Aminobiphenyl..............................................................................................................71
1. Exposure Data........................................................................................................71
2. Studies of Cancer in Humans................................................................................79
3. Studies of Cancer in Experimental Animals.........................................................80
4. Mechanistic and Other Relevant Data..................................................................85
5. Summary of Data Reported...................................................................................98
6. Evaluation............................................................................................................100
7. References............................................................................................................100
Auramine and Auramine Production.........................................................................111
1. Exposure Data......................................................................................................111
2. Studies of Cancer in Humans..............................................................................120
3. Studies of Cancer in Experimental Animals.......................................................121
4. Mechanistic and Other Relevant Data................................................................125
5. Summary of Data Reported.................................................................................133
6. Evaluation............................................................................................................134
7. References............................................................................................................135
Benzidine.........................................................................................................................141
1. Exposure Data......................................................................................................141
2. Studies of Cancer in Humans..............................................................................180
3. Studies of Cancer in Experimental Animals.......................................................198
4. Mechanistic and Other Relevant Data................................................................221
5. Summary of Data Reported.................................................................................241
6. Evaluation............................................................................................................245
7. References............................................................................................................246
Dyes Metabolized to Benzidine....................................................................................263
1. Exposure Data......................................................................................................263
2. Studies of Cancer in Humans..............................................................................263
3. Studies of Cancer in Experimental Animals.......................................................276
4. Mechanistic and Other Relevant Data................................................................283
5. Summary of Data Reported.................................................................................290
6. Evaluation............................................................................................................292
7. References............................................................................................................293
Magenta and Magenta Production..............................................................................297
1. Exposure Data......................................................................................................297
2. Studies of Cancer in Humans..............................................................................305
3. Studies of Cancer in Experimental Animals.......................................................307
4. Mechanistic and Other Relevant Data................................................................310
CONTENTS vii
5. Summary of Data Reported.................................................................................318
6. Evaluation............................................................................................................320
7. References............................................................................................................320
4,4'-Methylenebis(2-chloroaniline)..............................................................................325
1. Exposure Data......................................................................................................325
2. Studies of Cancer in Humans..............................................................................342
3. Studies of Cancer in Experimental Animals.......................................................343
4. Mechanistic and Other Relevant Data................................................................348
5. Summary of Data Reported.................................................................................357
6. Evaluation and Rationale.....................................................................................359
7. References............................................................................................................360
2-Naphthylamine............................................................................................................369
1. Exposure Data......................................................................................................369
2. Studies of Cancer in Humans..............................................................................376
3. Studies of Cancer in Experimental Animals.......................................................380
4. Mechanistic and Other Relevant Data................................................................387
5. Summary of Data Reported.................................................................................395
6. Evaluation............................................................................................................396
7. References............................................................................................................397
ortho-Toluidine...............................................................................................................407
1. Exposure Data......................................................................................................407
2. Studies of Cancer in Humans..............................................................................416
3. Studies of Cancer in Experimental Animals.......................................................423
4. Mechanistic and Other Relevant Data................................................................427
5. Summary of Data Reported.................................................................................449
6. Evaluation............................................................................................................451
7. References............................................................................................................451
4-Chloro-ortho-toluidine...............................................................................................471
1. Exposure Data......................................................................................................471
2. Studies of Cancer in Humans..............................................................................478
3. Studies of Cancer in Experimental Animals.......................................................480
4. Mechanistic and Other Relevant Data................................................................481
5. Summary of Data Reported.................................................................................491
6. Evaluation............................................................................................................493
7. References............................................................................................................493
viii IARC MONOGRAPHS VOLUME 99
Occupational exposures of hairdressers and barbers and personal use of hair
colourants........................................................................................................................499
1. Exposure Data......................................................................................................499
2. Studies of Cancer in Humans..............................................................................520
3. Studies of Cancer in Experimental Animals.......................................................630
4. Mechanistic and Other Relevant Data................................................................634
5. Summary of Data Reported.................................................................................641
6. Evaluation............................................................................................................646
7. References............................................................................................................646
CUMULATIVE INDEX TO THE MONOGRAPHS SERIES......................................659