CICAD 58 - Chloroform Version 11 - WHO

1 This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour organization , or the world health organization . Concise International Chemical Assessment Document 58 Chloroform Please note that the layout and pagination of this pdf file are not identical to the Version in press First draft prepared by Mr Peter Watts, Toxicology Advice & Consulting Ltd, Sutton, Surrey, United Kingdom; Mr G. Long, health Canada, Ottawa, Canada; and Ms Meek, health Canada, Ottawa, Canada Published under the joint sponsorship of the United Nations Environment Programme, the International Labour organization , and the world health organization , and produced within the framework of the Inter- organization Programme for the Sound Management of Chemicals.

2 world health organization Geneva, 2004 The International Programme on Chemical Safety (IPCS), established in 1980, is a joint venture of the United Nations Environment Programme (UNEP), the International Labour organization (ILO), and the world health organization (WHO). The overall objectives of the IPCS are to establish the scientific basis for assessment of the risk to human health and the environment from exposure to chemicals, through international peer review processes, as a prerequisite for the promotion of chemical safety, and to provide technical assistance in strengthening national capacities for the sound management of chemicals. The Inter- organization Programme for the Sound Management of Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and Agriculture organization of the United Nations, WHO, the United Nations Industrial Development organization , the United Nations Institute for Training and Research, and the Organisation for Economic Co-operation and Development (Participating Organizations), following recommendations made by the 1992 UN Conference on Environment and Development to strengthen cooperation and increase coordination in the field of chemical safety.

3 The purpose of the IOMC is to promote coordination of the policies and activities pursued by the Participating Organizations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment. WHO Library Cataloguing-in-Publication Data Chloroform . (Concise international chemical assessment document ; 58) - adverse effects assessment exposure Programme on Chemical Safety ISBN 92 4 153058 8 (LC/NLM Classification: QV 81) ISSN 1020-6167 world health organization 2004 All rights reserved. Publications of the world health organization can be obtained from Marketing and Dissemination, world health organization , 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: +41 22 791 2476; fax: +41 22 791 4857; email: Requests for permission to reproduce or translate WHO publications whether for sale or for noncommercial distribution should be addressed to Publications, at the above address (fax: +41 22 791 4806.))

4 Email: 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 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. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. 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.

5 The world health organization does not warrant that the information contained in this publication is complete and correct and shall not be liable for any damages incurred as a result of its use. Risk assessment activities of the International Programme on Chemical Safety, including the production of Concise International Chemical Assessment Documents, are supported financially by the Department of health and Department for Environment, Food & Rural Affairs, UK, Environmental Protection Agency, Food and Drug Administration, and National Institute of Environmental health Sciences, USA, European Commission, German Federal Ministry of Environment, Nature Conservation and Nuclear Safety, health Canada, Japanese Ministry of health , Labour and Welfare, and the Swiss Agency for Environment, Forests and Landscape.

6 Technically and linguistically edited by Marla Sheffer, Ottawa, Canada, and printed by Wissenchaftliche Verlagsgesellschaft mbH, Stuttgart, Germany iii TABLE OF CONTENTS FOREWORD ..1 1. EXECUTIVE SUMMARY ..4 2. IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES ..5 3. ANALYTICAL METHODS ..6 4. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE ..6 Natural sources ..6 Anthropogenic sources ..7 Production and 5. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION ..7 Water ..8 Soil ..8 Biota ..8 Environmental 6. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE.

7 9 Environmental levels ..9 Ambient air ..9 Indoor air ..9 Surface Drinking-water ..10 Sediment and soil ..10 Human exposure: Human exposure: occupational ..12 7. COMPARATIVE KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS ..13 General metabolism ..13 PBPK 8. EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS ..16 Single exposure ..16 Short-term Ingestion ..16 Inhalation ..16 Medium-term Ingestion ..18 Inhalation ..18 Long-term exposure and Overview of carcinogenicity.

8 19 Liver ..20 Kidney ..20 Thyroid ..22 Concise International Chemical Assessment Document 58 iv Initiation/promotion Genotoxicity and related Reproductive Effects on fertility ..23 Developmental Other toxicity ..24 Mode of action ..24 9. EFFECTS ON HUMANS ..26 10. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD ..27 Aquatic Terrestrial environment ..28 11. EFFECTS Evaluation of health effects ..28 Hazard Criteria for setting tolerable Sample risk characterization ..30 Uncertainties in the evaluation of health risks ..31 Evaluation of environmental Assessment Sample environmental risk characterization.

9 32 Terrestrial organisms ..32 Aquatic organisms ..32 Uncertainties in the evaluation of environmental 12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES ..35 APPENDIX 1 SOURCE DOCUMENT ..46 APPENDIX 2 CICAD PEER APPENDIX 3 CICAD FINAL REVIEW BOARD ..48 APPENDIX 4 ABBREVIATIONS AND ACRONYMS ..49 APPENDIX 5 DERIVATION OF TOLERABLE INTAKES/CONCENTRATIONS FOR Chloroform ..50 INTERNATIONAL CHEMICAL SAFETY CARD ..53 R SUM D ORIENTATION ..55 RESUMEN DE ORIENTACI 1 FOREWORD Concise International Chemical Assessment Documents (CICADs) are the latest in a family of publications from the International Programme on Chemical Safety (IPCS) a cooperative programme of the world health organization (WHO), the International Labour organization (ILO), and the United Nations Environment Programme (UNEP).

10 CICADs join the Environmental health Criteria documents (EHCs) as authoritative documents on the risk assessment of chemicals. International Chemical Safety Cards on the relevant chemical(s) are attached at the end of the CICAD , to provide the reader with concise information on the protection of human health and on emergency action. They are produced in a separate peer-reviewed procedure at IPCS. They may be complemented by information from IPCS Poison Information Monographs (PIM), similarly produced separately from the CICAD process. CICADs are concise documents that provide sum-maries of the relevant scientific information concerning the potential effects of chemicals upon human health and/or the environment. They are usually based on selected national or regional evaluation documents or on existing EHCs.