Volume 100 of the IARC Monographs, A Review of Human Carcinogens, covers all agents previously classified by IARC as "carcinogenic to humans (Group 1)" and was developed by six separate Working Groups: Pharmaceuticals; Biological agents; Arsenic, Metals, Fibres, and Dusts; Radiation; Personal Habits and Indoor Combustions; Chemical Agents and Related Occupations.

This Volume 100A covers Pharmaceuticals, specifically Busulfan, Chlorambucil, Methyl-CCNU, Cyclophosphamide, Etoposide in combination with Cisplatin and Bleomycin, Melphalan, MOPP, Tamoxifen, Thiotepa, Treosulfan, Diethylstilbestrol, Estrogen-only Menopausal Therapy, Combined Estrogen-Progestogen Menopausal Therapy, Combined Estrogen-Progestogen Contraceptives, Azathioprine, Chlornaphazine, Ciclosporin, Plants containing Aristolochic Acid, Methoxsalen plus Ultraviolet A Radiation, and Phenacetin.

Because the scope of Volume 100 is so broad, its Monographs are focused on key information. Each Monograph presents a description of a carcinogenic agent and how people are exposed, critical overviews of the epidemiological studies and animal cancer bioassays, and a concise review of the agent's toxicokinetics, plausible mechanisms of carcinogenesis, and potentially susceptible populations, and life-stages. Details of the design and results of individual epidemiological studies and animal cancer bioassays are summarized in tables. Short tables that highlight key results are printed in Volume 100, and more extensive tables that include all studies appear on the Monographs programme website (http://monographs.iarc.fr).

It is hoped that this volume, by compiling the knowledge accumulated through several decades of cancer research, will stimulate cancer prevention activities worldwide, and will be a valued resource for future research to identify other agents suspected of causing cancer in humans.

Contents

• NOTE TO THE READER
• List of Participants
  • Members
  • Observers
  • IARC Secretariat
  • Pre-meeting Scientific Assistance
  • Post-Meeting Scientific Assistance
  • Administrative Assistance
  • Production Team
• PREAMBLE
  • A. GENERAL PRINCIPLES AND PROCEDURES
  • B. SCIENTIFIC REVIEW AND EVALUATION
  • References
• General remarks
  • Volume 100 – General Information
  • Specific remarks about the review of pharmaceutical agents in this volume
  • Phenacetin, etoposide, and plants containing aristolochic acid
  • References
• BUSULFAN
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• CHLORAMBUCIL
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• METHYL-CCNU
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• CYCLOPHOSPHAMIDE
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• ETOPOSIDE IN COMBINATION WITH CISPLATIN AND BLEOMYCIN
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• MELPHALAN
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• MOPP
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• TAMOXIFEN
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• THIOTEPA
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• TREOSULFAN
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• DIETHYLSTILBESTROL
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• ESTROGEN-ONLY MENOPAUSAL THERAPY
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• COMBINED ESTROGEN–PROGESTOGEN MENOPAUSAL THERAPY
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• COMBINED ESTROGEN–PROGESTOGEN CONTRACEPTIVES
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• AZATHIOPRINE
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• CHLORNAPHAZINE
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• CICLOSPORIN
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• PLANTS CONTAINING ARISTOLOCHIC ACID
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• METHOXSALEN PLUS ULTRAVIOLET A RADIATION
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• PHENACETIN
  • 1. Exposure Data
  • 2. Cancer in Humans
  • 3. Cancer in Experimental Animals
  • 4. Other Relevant Data
  • 5. Evaluation
  • References
• LIST OF ABBREVIATIONS

Corrigenda to the IARC Monographs are published online at http://monographs.iarc.fr/ENG/Publications/corrigenda.php.

Corrigenda to Volume 100A. (PDF, 69K)

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, 14-21 October 2008

Lyon, France - 2012

Lorenzo Tomatis, MD, with other colleagues knowledgeable in primary prevention and environmental carcinogenesis, perceived in the 1960s the growing need to objectively evaluate carcinogenic risks by international groups of experts in chemical carcinogenesis. His vision and determination to provide a reliable source of knowledge and information on environmental and occupational causes of cancer led to his creating the IARC Monographs Programme for evaluating cancer risks to humans from exposures to chemicals. The first meeting, held in Geneva in December 1971, resulted in Volume 1 of the IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man [1972], a series known affectionately since as the “orange books”. As a champion of chemical carcinogenesis bioassays, Tomatis defined and promoted the applicability and utility of experimental animal findings for identifying carcinogens and for preventing cancers in humans, especially in workers and children, and to eliminate inequalities in judging cancer risks between industrialized and developing countries. Tomatis’ foresight, guidance, leadership, and staunch belief in primary prevention continued to influence the IARC Monographs as they expanded to encompass personal habits, as well as physical and biological agents. Lorenzo Tomatis had a distinguished career at the Agency, arriving in 1967 and heading the Unit of Chemical Carcinogenesis, before being Director from 1982 to 1993.

Volume 100 of the IARC Monographs Series is respectfully dedicated to him.

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/.

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, Safety and Hygiene at Work Unit of the European Commission Directorate-General for Employment, Social Affairs and Equal 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 represent the official views of the U.S. National Cancer Institute, the U.S. National Institute of Environmental Health Sciences, the U.S. Department of Health and Human Services, or the European Commission Directorate-General for Employment, Social Affairs and Equal Opportunities.

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, 2012
• Distributed by WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: tni.ohw@sredrokoob).
• Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved.

The International Agency for Research on Cancer welcomes requests for permission to reproduce or translate its publications, in part or in full. Requests for permission to reproduce or translate IARC publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; email: tni.ohw@snoissimrep).

The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.

The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.

The IARC Monographs Working Group alone is responsible for the views expressed in this publication.