Environmental Health Criteria 18 ARSENIC Please note that the layout and pagination of this web version are not identical with the printed version. Arsenic (EHC 18, 1981) IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY ENVIRONMENTAL HEALTH CRITERIA 18 ARSENIC 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. Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization World Health Organization Geneva, 1981 ISBN 92 4 154078 8 (c) World Health Organization 1981 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. For rights of reproduction or translation of WHO publications, in part or in toto, application should be made to the Office of Publications, World Health Organization, Geneva, Switzerland. The World Health Organization welcomes such applications. 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. Page 1 of 149 Arsenic (EHC 18, 1981) CONTENTS ENVIRONMENTAL HEALTH CRITERIA FOR ARSENIC 1. SUMMARY AND RECOMMENDATIONS FOR FURTHER RESEARCH 1.1. Summary 1.1.1. Properties, uses, and analytical procedures 1.1.1.1 Properties and uses 1.1.1.2 Analytical procedures 1.1.2. Environmental transport and distribution 1.1.3. Exposure 1.1.4. Metabolism 1.1.5. Normal levels in man and biological indicators of exposure 1.1.6. Effects and evaluation of health risks 1.1.6.1 Inorganic arsenic compounds 1.1.6.2 Organic arsenic compounds 1.2. Recommendations for further research 1.2.1. Sampling and determination 1.2.2. Exposure 1.2.3. Metabolism and indicators of exposure 1.2.4. Effects 2. PROPERTIES AND ANALYTICAL PROCEDURES 2.1. Chemical and physical properties of arsenic compounds 2.1.1. Inorganic arsenic compounds 2.1.2. Organic arsenic compounds 2.2. Analytical procedures 2.2.1. Sampling and sample treatment 2.2.1.1 Natural waters 2.2.1.2 Air 2.2.1.3 Biological materials 2.2.2. Analytical methods 2.2.2.1 Methods for total arsenic 2.2.2.2 Analyses for specific arsenic compounds 3. SOURCES AND OCCURRENCE OF ARSENIC IN THE ENVIRONMENT 3.1. Natural occurrence 3.1.1. Rocks, soils, and sediments 3.1.2. Air 3.1.3. Water 3.1.4. Biota 3.2. Industrial production and uses of arsenic 3.2.1. Industrial production 3.2.2. Uses of arsenic compounds 3.2.3. Sources of environmental pollution 4. ENVIRONMENTAL TRANSPORT AND DISTRIBUTION 4.1. General 4.2. Aquatic systems 4.3. Air-soil systems 5. LEVELS OF EXPOSURE TO ARSENIC AND ITS COMPOUNDS 5.1. General population exposure through air, drinking water, food, and beverages 5.1.1. Air 5.1.2. Drinking water 5.1.3. Food and beverages 5.1.4. Tobacco Page 2 of 149 Arsenic (EHC 18, 1981) 5.1.5. Drugs 5.1.6. Total daily intake in the general population 5.2. Occupational exposure 6. METABOLISM OF ARSENIC 6.1. Inorganic arsenic 6.1.1. Absorption 6.1.1.1 Respiratory deposition and absorption 6.1.1.1.1 Animals 6.1.1.1.2 Man 6.1.1.2 Gastrointestinal absorption 6.1.1.2.1 Animals 6.1.1.2.2 Man 6.1.1.3 Skin absorption 6.1.1.3.1 Animals 6.1.1.3.2 Man 6.1.1.4 Placental transfer 6.1.1.4.1 Animals 6.1.1.4.2 Man 6.1.2. Distribution in organisms 6.1.2.1 Fate of arsenic in blood 6.1.2.1.1 Animals 6.1.2.1.2 Man 6.1.2.2 Tissue distribution 6.1.2.2.1 Animals 6.1.2.2.2 Man 6.1.3. Elimination 6.1.3.1 Animals 6.1.3.2 Man 6.1.4. Biotransformation 6.1.4.1 Animals 6.1.4.2 Man 6.2. Organic arsenic compounds 6.2.1. Absorption 6.2.1.1 Respiratory absorption 6.2.1.1.1 Animals 6.2.1.1.2 Man 6.2.1.2 Gastrointestinal absorption 6.2.1.2.1 Animals 6.2.1.2.2 Man 6.2.1.3 Skin absorption 6.2.1.4 Placental transfer 6.2.1.4.1 Animals 6.2.1.4.2 Man 6.2.2. Distribution in organisms 6.2.2.1 Fate of organic arsenic in blood 6.2.2.1.1 Animals 6.2.2.1.2 Man 6.2.2.2 Tissue distribution of organic arsenic 6.2.2.2.1 Animals 6.2.2.2.2 Man 6.2.3. Elimination 6.2.3.1 Animals 6.2.3.2 Man 6.2.4. Biotransformation 6.2.4.1 Animals 6.2.4.2 Man 7. NORMAL LEVELS IN MAN AND BIOLOGICAL INDICATORS OF EXPOSURE 7.1. Blood 7.2. Urine Page 3 of 149 Arsenic (EHC 18, 1981) 7.3. Hair 7.4. Other tissues 8. EFFECTS AND DOSE-RESPONSE RELATIONSHIPS OF INORGANIC ARSENIC 8.1. Acute and subacute effects after short-term exposure 8.1.1. Man 8.1.2. Animals 8.2. Effects on reproduction and teratogenicity 8.2.1. Man 8.2.2. Animals 8.3. Noncarcinogenic effects after long-term exposure and sequelae of short-term exposure to inorganic arsenic 8.3.1. Effects on the respiratory system 8.3.1.1 Man 8.3.1.2 Animals 8.3.2. Effects on skin 8.3.2.1 Man 8.3.2.2 Animals 8.3.3. Effects on the liver 8.3.3.1 Man 8.3.3.2 Animals 8.3.4. Effects on the cardiovascular system 8.3.4.1 Man 8.3.4.2 Animals 8.3.5. Effects on the nervous system 8.3.5.1 Man 8.3.5.2 Animals 8.3.6. Effects on other organs 8.3.6.1 Man 8.3.6.2 Animals 8.4. Carcinogenicity 8.4.1. Man 8.4.1.1 Cancer of the respiratory system 8.4.1.2 Cancer of the skin 8.4.1.3 Cancer of the liver 8.4.1.4 Leukaemia and tumours of the haematopoietic system 8.4.1.5 Cancer of other organs 8.4.2. Experimental animal studies 8.4.2.1 Cancer of the respiratory system 8.4.2.2 Skin application 8.4.2.3 Oral administration 8.4.2.4 Other experimental systems 8.5. Mutagenicity 8.6. Mechanisms of toxicity 9. EFFECTS AND DOSE-RESPONSE RELATIONSHIPS OF ORGANIC ARSENIC COMPOUNDS 9.1. Acute and chronic toxicity 9.1.1. Man 9.1.2. Animals 9.2. Teratogenicity 9.3. Carcinogenicity 9.3.1. Animals 9.4. Mutagenicity 9.5. Mechanisms of toxicity 10. INTERACTIONS WITH OTHER CHEMICALS 10.1. Thiol-compounds 10.2. Selenium Page 4 of 149 Arsenic (EHC 18, 1981) 10.3. Cadmium and lead 11. EVALUATION OF HEALTH RISKS TO MAN FROM EXPOSURE TO ARSENIC 11.1. Introduction 11.2. Exposure 11.3. Inorganic arsenic compounds 11.3.1. Acute and subacute effects after short-term exposure 11.3.2. Noncarcinogenic effects after long-term exposure and sequelae of short-term exposure 11.3.2.1 Skin effects 11.3.2.2 Cardiovascular effects 11.3.2.3 Neurological effects 11.3.3. Carcinogenicity 11.3.3.1 Cancer of the respiratory system 11.3.3.2 Skin cancer 11.4. Organic arsenic compounds 11.5. Assessment of the cancer risk for man from exposure to inorganic arsenic REFERENCES NOTE TO READERS OF THE CRITERIA DOCUMENTS While every effort has been made to present information in the criteria documents as accurately as possible without unduly delaying their publication, mistakes might have occurred and are likely to occur in the future. In the interest of all users of the environmental health criteria documents, readers are kindly requested to communicate any errors found to the Division of Environmental Health, World Health Organization, Geneva, Switzerland, in order that they may be included in corrigenda which will appear in subsequent volumes. In addition, experts in any particular field dealt with in the criteria documents are kindly requested to make available to the WHO Secretariat any important published information that may have inadvertently been omitted and which may change the evaluation of health risks from exposure to the environmental agent under examination, so that the information may be considered in the event of updating and re-evaluation of the conclusions contained in the criteria documents. WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR ARSENIC Members Dr R. Albert, Institute of Environmental Medicine, New York University Medical Center, New York, NY, USA (Chairman of Subgroup 2) Dr V. Bencko, Department of General and Environmental Hygiene, Medical Faculty of Hygiene, Charles University, Prague, Czechoslovakia Dr G. Corey, Department of Environment Programs, Ministry of Health, Santiago, Chile Dr L.