Environmental Health Criteria 58 SELENIUM Please note that the layout and pagination of this web version are not identical with the printed version. Selenium (EHC 58, 1986) INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY ENVIRONMENTAL HEALTH CRITERIA 58 SELENIUM 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 Organisation, 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 Orgnization Geneva, 1987 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 objective of the IPCS is to carry out and disseminate evaluations of the effects of chemicals on human health and the quality of the environment. 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. ISBN 92 4 154258 6 The World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in full. Applications and enquiries should be addressed to the Office of Publications, World Health Organization, Geneva, Switzerland, which will be glad to provide the latest information on any changes made to the text, plans for new editions, and reprints and translations Page 1 of 222 Selenium (EHC 58, 1986) already available. (c) World Health Organization 1987 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 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. CONTENTS ENVIRONMENTAL HEATH CRITERIA FOR SELENIUM 1. SUMMARY AND RECOMMENDATIONS FOR FURTHER RESEARCH 1.1. Summary 1.1.1. Properties and analytical methods 1.1.2. Sources, environmental transport, and distribution 1.1.3. Environmental levels and exposures 1.1.4. Selenium metabolism 1.1.4.1 Absorption 1.1.4.2 Total human body selenium content 1.1.4.3 Distribution 1.1.4.4 Metabolic pools of selenium in the body 1.1.4.5 Metabolic conversion 1.1.4.6 Effect of chemical form of selenium on its metabolism 1.1.4.7 Selenium excretion 1.1.5. Effects on animals 1.1.5.1 Selenium toxicity 1.1.5.2 Selenium deficiency 1.1.6. Effects on man 1.1.6.1 General population exposure 1.1.6.2 Occupational exposure 1.2. Recommendations for further activities 2. CHEMICAL AND PHYSICAL PROPERTIES; ANALYTICAL METHODS 2.1. Properties 2.2. Analytical methods 2.2.1. Sample collection, processing, and storage 2.2.2. Sample decomposition or other preliminary treatment 2.2.2.1 Wet digestion 2.2.2.2 Predigestion 2.2.2.3 Combustion 2.2.2.4 Fusion 2.2.2.5 Concentration 2.2.3. Removal from interfering substances 2.2.4. Detection and identification of selenium Page 2 of 222 Selenium (EHC 58, 1986) 2.2.5. Measurement of selenium 2.2.5.1 Fluorometric analysis 2.2.5.2 Neutron activation analysis 2.2.5.3 Atomic absorption spectrometry 2.2.5.4 Other methods 3. SOURCES, TRANSPORT, AND CYCLING OF SELENIUM IN THE ENVIRONMENT 3.1. Natural sources 3.1.1. Rocks and soils 3.1.2. Natural selenium in the food chain 3.l.3 Water and air 3.2. Man-made sources 3.2.1. Agriculture 3.2.2. Industry 3.3. Environmental transport 3.4. Biological selenium cycle 4. LEVELS IN ENVIRONMENTAL MEDIA 4.1. Levels and chemical forms of selenium in food 4.1.1. Levels in food 4.1.1.1 Natural differences among food commodities 4.1.1.2 Effects of natural differences in the availability of selenium in the environment on levels in food 4.1.1.3 Man-induced changes in selenium levels in food 4.1.2. Chemical forms of selenium in food 4.2. Drinking-water 4.3. Air 5. HUMAN EXPOSURE 5.1. Estimate of general population exposure 5.1.1. Food 5.1.1.1 Geographical variation 5.1.1.2 Food habits (consumption patterns) 5.1.1.3 Elderly people 5.1.1.4 Infants and children 5.1.1.5 Special medical diets 5.2. Occupational exposure 5.2.1. Levels in the workplace air 5.2.2. Biological monitoring 6. METABOLISM OF SELENIUM 6.1. Absorption 6.1.1. Gastrointestinal absorption 6.1.1.1 Animal studies 6.1.1.2 Human studies 6.1.2. Absorption by inhalation 6.1.3. Absorption through the skin 6.2. Distribution in the organism 6.2.1. Transport 6.2.2. Organs 6.2.2.1 Animal studies 6.2.2.2 Human studies 6.2.3. Blood 6.2.4. Total-body selenium content 6.3. Excretion in urine, faeces, and expired air 6.3.1. Animal studies 6.3.2. Human studies Page 3 of 222 Selenium (EHC 58, 1986) 6.3.2.1 Excretion of selenium 6.3.2.2 Balance studies 6.4. Retention and turnover 6.4.1. Animal studies 6.4.2. Controlled human studies 6.5. Metabolic transformation 6.5.1. Animal studies 6.5.1.1 Reduction and methylation 6.5.1.2 Form in proteins 6.5.1.3 Conversion of selenium compounds to nutritionally-active forms of selenium 6.5.2. Human studies 7. EFFECTS OF SELENIUM ON ANIMALS 7.1. Selenium toxicity 7.1.1. Farm animal diseases associated with a high selenium intake 7.1.2. Toxicity in experimental animals 7.1.2.1 Acute and subacute toxicity - single or repeated exposure studies with oral, intraperitoneal, or cutaneous administration 7.1.2.2 Effects of long-term oral exposure 7.1.2.3 Inhalation toxicity 7.1.3. Blood levels in toxicity 7.1.4. Effects on reproduction 7.1.5. Effects on dental caries 7.1.6. Factors influencing toxicity 7.1.6.1 Form of selenium 7.1.6.2 Nutritional factors 7.1.6.3 Arsenic 7.1.6.4 Sulfate 7.1.6.5 Adaptation 7.1.7. Mechanism of toxicity 7.2. Selenium deficiency 7.2.1. Animal diseases 7.2.2. Intakes needed to prevent deficiency 7.2.2.1 Quantitative dietary levels 7.2.2.2 Bioavailability 7.2.3. Blood and tissue levels in deficiency 7.2.4. Physiological role: glutathione peroxidase 7.2.4.1 Function of selenium and relationship to vitamin E 7.2.4.2 Effect of selenium intake on tissue- glutathione peroxidase, activity 7.2.4.3 Relationship between blood-selenium levels and erythrocyte-glutathione peroxidase activity 7.2.4.4 Gluthathione peroxidase as an indicator of selenium status 7.2.5. Other possible physiological roles 7.2.5.1 Homeostasis of hepatic haem 7.2.5.2 Microsomal and mitochondrial electron transport 7.2.5.3 The immune response 7.2.5.4 Selenium and vision 7.2.6. Effects on reproduction 7.2.7. Factors influencing deficiency 7.2.7.1 Form of selenium 7.2.7.2 Vitamin E 7.2.7.3 Heavy metals and other minerals Page 4 of 222 Selenium (EHC 58, 1986) 7.2.7.4 Xenobiotics 7.2.7.5 Exercise stress 7.3. Ratio between toxic and sufficient exposures 7.4. Protection against heavy metal toxicity 7.4.1. Mercury 7.4.2. Cadmium 7.4.3. Other heavy metals 7.5. Cytotoxicity, mutagenicity, and anti-mutagenicity 7.5.1. Cytotoxicity and mutagenicity 7.5.2. Anti-mutagenicity 7.6. Teratogenicity 7.7. Carcinogenicity and anti-carcinogenicity 7.7.1. Selenium as a possible carcinogen 7.7.2. Selenium as a possible anti-carcinogen 8. EFFECTS OF SELENIUM ON MAN 8.1. High selenium intake 8.1.1. General population 8.1.1.1 Signs and symptoms 8.1.1.2 Attempts to associate high selenium intake with human diseases 8.1.2. Reports on health effects associated with occupational exposure 8.1.2.1 Fumes and dust of selenium and its compounds 8.1.2.1.1 Selenium dioxide 8.1.2.1.2 Hydrogen selenide 8.1.2.1.3 Selenium oxychloride 8.2. Low selenium intake 8.2.1. Evidence supporting the possible essentiality of selenium in man 8.2.2. Signs and symptoms of low intake 8.2.3. Dietary levels consistent with good nutrition 8.2.3.1 Quantitative estimates 8.2.3.2 Nutritional bioavailability 8.2.4. Blood and urine levels typical of low intake 8.2.5. Relationship between blood-selenium levels and erythrocyte-glutathione peroxidase activity 8.2.6. Attempts to associate low selenium intake with human diseases 8.2.6.1 Keshan disease 8.2.6.2 Kashin-Beck disease 8.2.6.3 Cancer 8.2.6.4 Heart disease 9.