THE ENVIRONMENTAL HEALTH CRITERIA SERIES Acrolein (No. 127, 1991) 2,4-Dichlorophenoxyacetic acid - Acrylamide (No. 49, 1985) environmental aspects (No. 84, 1989) Acrylonitrile (No. 28, 1983) DDT and its derivatives (No.9, 1979) Aldicarb (No. 121, 1991) DDT and its derivatives - environmental Aldrin and dieldrin (No. 91 , 1989) aspects (No. 83, 1989) Allethrins (No. 87, 1989) Deltamethrin (No. 97, 1990) Alpha-cypermethrin (No. 142, 1992) Diaminotoluenes (No. 74, 1987) Ammonia (No. 54, 1986) Dichlorvos (No. 79, 1988) Arsenic (No. 18, 1981) Diethylhexyl phthalate (No. 131, 1992) Asbestos and other natural mineral fibres Dimethoate (No. 90, 1989) (No. 53 , 1986) Dimethylformamide (No. 114, 1991) Barium (No. 107 , 1990) Dimethyl sulfate (No. 48, 1985) Beryllium (No. 106, 1990) Diseases of suspected chemical etiology and Biotoxins, aquatic (marine and freshwater) their prevention, principles of studif,s on (No. 37, 1984) (No. 72 , 1987) Butanols - four isomers (No. 65, 1987) Dithiocarbamate pesticides, ethylenethio­ Cadmium (No. 134, 1992) urea, and propylenethiourea: a general Cadmium- environmental aspects (No. 135, introduction (No. 78 , 1988) 1992) Electromagnetic Fields (No. 137, 1992) Camphechlor (No. 45, 1984) Endosulfan (No. 40, 1984) Carbamate pesticides: a general introduction Endrin (No. 130, 1992) (No. 64, 1986) Environmental epidemiology, guidelines on Carbon disulfide (No. I 0, 1979) studies in (No. 27, 1983) Carbon monoxide (No. 13, 1979) Epichlorohydrin (No. 33, 1984) Carcinogens, summary report on the evalu­ Ethylene oxide (No. 55 , 1985) ation of short-term in vitro tests (No. 47, Extremely low frequency (ELF) fields 1985) (No. 35, 1984) Carcinogens, summary report on the evalu­ Fenitrothion (No. 133, 1992) ation of short-term in vivo tests (No. 109, Fenvalerate (No. 95, 1990) 1990) Fluorine and fluorides (No. 36, 1984) Chlordane (No. 34, 1984) Food additives and contaminants in food, Chlordecone (No. 43, 1984) principles for the safety assessment of Chlorine and hydrogen chloride (No. 21, (No. 70, 1987) 1982) Formaldehyde (No. 89, 1989) Chlorobenzenes other than hexachloro­ Genetic effects in human populations, benzene (No. 128, 1991) guidelines for the study of (No. 46 , 1985) Chlorofluorocarbons, fully halogenated Heptachlor (No. 38, 1984) (No. 113, 1990) Alpha- and beta- hexachlorocyclohexanes Chlorofluorocarbons, partially halogenated (No. 123, 1991) (ethane derivatives) (No. 139, 1992) Hexachlorocyclopentadiene (No. 120, 1991) Chlorofluorocarbons, partially halogenated n-Hexane (No. 122, 1991) (methane derivatives) (No. 126, 1991) Hydrazine (No. 68, 1987) Chlorophenols (No. 93 , 1989) Hydrogen sulfide (No. 19, 1981) Chromium (No. 61, 1988) Infancy and early childhood, principles for Cyhalothrin (No. 99, 1990) evaluating health risks from chemicals Cypermethrin (No. 82, 1989) during (No. 59, 1986) 1,2-Dichloroethane (No. 62 , 1987) lsobenzan (No. 129, 1991) 2,4-Dichlorophenoxyacetic acid (2,4 - D) Kelevan (No. 66, 1986) (No. 29, 1984) Lasers and optical radiation (No. 23, 1982) • Out of print continued inside back cover This report contains the collective views of an in­ ternational group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the Interna­ tional Labour Organisation, or the World Health Organization Environmental Health Criteria 101 METHYLMERCURY Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization World Health Organization Geneva, 1990 The International Programme on Chemical Safety (IPCS) is a joint venture of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization. The main objec­ tive of the IPCS is to carry out and disseminate evaluations of the effects of chemicals on human health and the quality of the environ­ ment. Supporting activities include the development of epidemiological, experimental laboratory, and risk-assessment methods that could produce internationally comparable results, and the development of manpower in the field of toxicology. Other activities carried out by the IPCS include the development of know-how for coping with chemical accidents, coordination of laboratory testing and epidemiological studies, and promotion of research on the mechanisms of the biological action of chemicals. WHO Library Cataloguing in Publication Data Methylmercury. (Environmental health criteria 101) I. Methylmercury compounds 2. Mercury poisoning I. Series ISBN 92 4 157101 2 (NLM Classification: QV 293) ISSN 0250-863X ©World Health Organization 1990 Reprinted 1993 Publications of the World Health Organization enjoy copyright pro­ tection in accordance with the provisions of Protocol 2 of the Univer­ sal 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 con­ cerning 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. PRINTED IN FINLAND 89/83I5- VAMMALA- 5000 93/9578 - VAMMALA - 1000 CONTENTS ENVIRONMENTAL HEALTH CRITERIA FOR METHYLMERCURY 1. SUMMARY AND CONCLUSIONS 11 1.1 Identity, physical and chemical properties, analytical methods 11 1.2 Sources of human and environmental exposure 11 1.3 Environmental transport, distribution, and transformation 12 1.4 Environmental levels and human exposure 13 1.5 Kinetics and metabolism 13 1.6 Effects on experimental animals and in vitro systems 15 1.7 Effects on man - mechanism of action 15 1.8 Conclusions 17 2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS 18 2.1 Identity 18 2.2 Physical and chemical properties 18 2.3 Conversion factors 19 2.4 Analytical methods 19 2.4.1 Sampling 19 2.4.2 Analytical procedures 21 2.4.3 Quality control and quality assurance 23 3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE 24 3.1 Natural occurrence 24 3.2 Man-made sources 24 3.3 Uses 26 4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION 28 4.1 Transport and distribution between media 28 4.2 Biotransformation 29 4.3 Interaction with other physical, chemical, or biological factors 31 3 5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE 35 5.1 Environmental levels 35 5.1.1 Air 35 5.1.2 Water 36 5.1.3 Food 36 5.2 General population exposure 37 5.2.1 Estimated daily intakes 37 6. KINETICS AND METABOLISM 42 6.1 Absorption 42 6.2 Distribution 42 6.3 Metabolic transformation 43 6.4 Elimination and excretion 47 6.5 Retention and turnover 49 6.6 Reference or normal levels in indicator media 52 6.7 Reaction with body components 57 7. EFFECTS ON ORGANISMS IN THE ENVIRONMENT 59 8. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS 60 8.1 Neurotoxicity and nephrotoxicity 60 8.2 Reproduction, embryotoxicity, and teratogenicity 62 8.3 Mutagenicity and related end-points 64 8.4 Carcinogenicity 64 8.5 Special studies 65 8.6 Factors modifying toxicity; toxicity of metabolites 65 9. EFFECTS ON MAN 68 9.1 General population exposure 68 9.1.1 Effects on adults 68 9.1.1.1 Effects on the nervous system 68 9.1.1.2 Effects on non-nervous tissue 69 9.1.2 Effects on developing tissues 69 9.1.2.1 Effects on the nervous system 69 9.2 Occupational exposure 70 9.3 Mechanisms of toxicity 71 9.3.1 The mature organism 71 4 9.3.l.l Mechanism of selective damage 71 9.3.1.2 The latent period 71 9.3.1.3 Cellular and molecular mechanisms 72 9.3.2 Developing tissues 74 9.3.3 Summary 76 9.4 Dose-effect and dose-response relationships in human beings 76 9.4.1 Adult exposure 76 9.4.1.1 The Minamata and Niigata outbreaks 77 9.4.1.2 The Iraqi outbreak 78 9.4.1.3 Exposed populations in Canada 83 9.4.1.4 Other fish-eating populations 84 9.4.1.5 Special groups 84 9.4.1.6 Summary 85 9.4.2 Prenatal exposure 85 9.4.2.1 Iraq 86 9.4.2.2 Canada 93 9.4.2.3 New Zealand 96 9.4.2.4 Summary 98 10. EVALUATION OF HUMAN HEALTH RISKS 100 10.1 Exposure levels and routes 100 10.2 Toxic effects 100 10.2.1 Adults 100 10.2.2 Prenatal exposure 101 10.3 Conclusions 102 11. RECOMMENDATIONS 104 11.1 Gaps in knowledge 104 11.2 Preventive measures 104 12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES 106 REFERENCES 107 APPENDIX 143 5 WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR METHYLMERCURY Members Dr L. Albert, Centro de Ecodesarrollo, Xalapa, Vera Cruz, Mexico Dr L. Amin-Zaki, Al-Damluji Clinic, Al-Nasr Street, Abu Dhabi, United Arab Emirates Professor S. Araki, Kumamoto University Medical School, First Department of Internal Medicine, Kumamoto, Japan Professor M. Berlin, Department of Environmental Medicine, University of Lund, Lund, Sweden (Chairman) Dr P.M. Bolger, Food and Drug Administration, Public Health Service, Center for Food Safety and Applied Nutrition, Division of Toxicological Review, Washington, DC, USA Dr T. Clarkson, The University of Rochester, Environmental Health Sciences Center, Rochester, New Yorka Dr D. Dimitroff, Health and Welfare Canada, Environmental Health Services, Medical Services Branch, Ottawa, Ontario, Canada Dr L. Magos, Medical Research Council, MRC Toxicology Unit, Carshalton, Surrey, United Kingdom (Rapporteur) Dr D. Marsh, The University of Rochester, Department of Neurology, Rochester, New York, USA Dr J.