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Environmental Health Criteria 88 Polychlorinated Dibenzo-Para Environmental Health Criteria 88 Polychlorinated dibenzo-para-dioxins and dibenzofurans Please note that the layout and pagination of this web version are not identical with the printed version. Polychlorinated dibenzo-p-dioxins and dibenzofurans (EHC 88, 1989) INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY ENVIRONMENTAL HEALTH CRITERIA 88 POLYCHLORINATED DIBENSO- PARA-DIOXINS AND DIBENZOFURANS 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 1989 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 9241542888 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 Page 1 of 286 Polychlorinated dibenzo-p-dioxins and dibenzofurans (EHC 88, 1989) 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 already available. (c) World Health Organization 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 HEALTH CRITERIA FOR POLYCHLORINATED DIBENZO-PARA-DIOXINS AND DIBENZOFURANS 1. SUMMARY AND RECOMMENDATIONS 1.1. Summary 1.1.1. Sources 1.1.2. Ambient levels and routes of exposure 1.1.3. Toxicokinetics, biotransformation, and biological monitoring 1.1.4. Health effects 1.1.4.1 Animals 1.1.4.2 Humans 1.1.5. Conclusion 1.2. Recommendations 2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS 2.1. Identity 2.2. Physical and chemical properties 2.3. Analytical methods 2.3.1. General aspects 2.3.2. Sampling strategy and sampling methods 2.3.3. Extraction procedures 2.3.4. Sample clean-up 2.3.5. Isomer identification 2.3.6. Quantification 2.3.7. Confirmation 2.3.8. Other analytical methods 3. SOURCES OF ENVIRONMENTAL POLLUTION 3.1. Production, synthesis, and use 3.2. Industrial processes 3.3. Contamination of commercial products 3.3.1. Chlorophenoxyacetic acid herbicides 3.3.2. Hexachlorophene Page 2 of 286 Polychlorinated dibenzo-p-dioxins and dibenzofurans (EHC 88, 1989) 3.3.3. Chlorophenols 3.3.4. Polychlorinated biphenyls (PCBs) 3.3.5. Chlorodiphenyl ether herbicides 3.3.6. Hexachlorobenzene 3.3.7. Rice oil 3.4. Sources of heavy environmental pollution 3.4.1. Industrial accidents 3.4.2. Improper disposal of industrial waste 3.4.3. Heavy use of chemicals 3.5. Other sources of PCDDs and PCDFs in the environment 3.5.1. Thermal degradation of technical products 3.5.2. Incineration of municipal waste 3.5.3. Incineration of sewage sludge 3.5.4. Incineration of hospital waste 3.5.5. Incineration of hazardous waste 3.5.6. Metal industry and metal treatment industry 3.5.7. Wire reclamation 3.5.8. Traffic 3.5.9. Fires and accidents in PCB-filled electrical equipment 3.5.10. Pulp and paper industry 3.5.11. Incineration of coal, peat, and wood 3.5.12. Inorganic chlorine precursors 3.5.13. Photochemical processes 3.6. Comparison of isomeric pattern and congener profiles from various sources 4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATIONS 4.1. Environmental transport 4.1.1. Air 4.1.2. Water 4.1.3. Soil and sediments 4.2. Environmental transformation 4.2.1. Abiotic transformation 4.2.2. Biotransformation and biodegradation 4.3. Bioaccumulation 4.4. Levels in biota 4.4.1. Vegetation 4.4.2. Aquatic organisms 4.4.3. Terrestrial animals 4.4.4. Human data 4.4.4.1 Adipose tissue 4.4.4.2 Blood plasma 5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE 5.1. Air 5.2. Water and leachate 5.3. Soil and sediment 5.4. Food 5.4.1. Meat and bovine milk 5.4.2. Human milk 5.4.3. Rice 5.5. Yusho and Yu-cheng episodes 6. KINETICS AND METABOLISM OF 2,3,7,8-TETRACHLORODIBENZO- P-DIOXIN (TCDD) AND OTHER PCDDs Page 3 of 286 Polychlorinated dibenzo-p-dioxins and dibenzofurans (EHC 88, 1989) 6.1. Uptake, distribution, and excretion 6.1.1. Studies on rats 6.1.2. Studies on mice 6.1.3. Studies on guinea-pigs 6.1.4. Studies on hamsters 6.1.5. Studies on monkeys 6.1.6. Studies on dogs 6.1.7. Studies on cows 6.1.8. In vitro studies 6.2. Metabolic transformation 6.2.1. Studies on mammals 6.2.1.1 In vivo studies 6.2.1.2 In vitro studies 6.3. Transfer via placenta and/or milk 6.4. Matrix effects on the uptake ("bio-availability") 7. EFFECTS OF TCDD AND OTHER PCDDs ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS 7.1. Acute toxicity 7.1.1. In vivo studies on mammals 7.1.2. In vitro studies on mammalian cells 7.1.3. Studies on birds 7.1.4. Toxicity of metabolites 7.1.5. Modulation of the acute toxicity 7.2. Short-term toxicity 7.2.1. Studies on rats 7.2.2. Studies on mice 7.2.3. Studies on guinea-pigs 7.2.4. Studies on hamsters 7.2.5. Studies on monkeys 7.3. Long-term toxicity 7.3.1. Studies on rats 7.3.2. Studies on mice 7.3.3. Studies on monkeys 7.4. Effects detected by special studies 7.4.1. Wasting syndrome 7.4.2. Hepatotoxicity 7.4.2.1 Morphological alterations 7.4.2.2 Hepatic plasma membrane function 7.4.2.3 Biliary excretion 7.4.3. Porphyria 7.4.4. Epidermal effects 7.4.4.1 In vivo studies 7.4.4.2 In vitro studies 7.4.5. Effects on the immune system 7.4.5.1 Histopathology 7.4.5.2 Humoral-mediated immunity 7.4.5.3 Cell-mediated immunity 7.4.5.4 Macrophage function 7.4.6. Myelotoxicity 7.4.7. Effects on the intermediary metabolism 7.4.8. Enzyme induction 7.4.8.1 Studies on rats 7.4.8.2 Studies on mice 7.4.8.3 Studies on guinea-pigs 7.4.8.4 Studies on rabbits 7.4.8.5 Studies on hamsters 7.4.8.6 Studies on cows Page 4 of 286 Polychlorinated dibenzo-p-dioxins and dibenzofurans (EHC 88, 1989) 7.4.8.7 Studies on chick embryos 7.4.8.8 Studies on cell cultures 7.4.9. Endocrine effects 7.4.10. Vitamin A storage 7.5. Embryotoxicity and reproductive effects 7.5.1. Studies on rats 7.5.2. Studies on mice 7.5.3. Studies on rabbits 7.5.4. Studies on monkeys 7.5.5. Studies on chickens 7.6. Mutagenicity and related end-points 7.6.1. Mutagenicity 7.6.1.1 Studies on bacteria 7.6.1.2 Studies on eukaryotic cells 7.6.1.3 In vivo studies 7.6.2. Interaction with nucleic acids 7.6.3. Cytogenetic effects 7.6.4. Cell transformation 7.7. Carcinogenicity 7.7.1. Long-term animal studies on single compounds 7.7.2. Long-term animal studies with mixed compounds 7.7.3. Short-term and interaction studies 7.8. Mechanisms of action 7.8.1. Receptor-mediated effects 7.8.2. Toxicokinetics 7.8.3. Impairment of normal cellular regulatory systems 7.8.3.1 Endocrine imbalance 7.8.3.2 Body weight regulation 7.8.3.3 Plasma membrane function 7.8.3.4 Impaired vitamin A storage 7.8.4. Lipid peroxidation 8. EFFECTS OF PCDDs ON HUMAN BEINGS - EPIDEMIOLOGICAL AND CASE STUDIES 8.1. Occupational studies - historical perspective 8.2. General population studies 8.2.1. Missouri, USA 8.2.2. Seveso, Italy 8.2.3. Viet Nam 8.3. Signs and symptoms in humans associated with TCDD exposure 8.3.1. Skin manifestations 8.3.2. Systemic effects 8.3.3. Neurological effects 8.3.4. Psychiatric effects 8.4. Epidemiological studies 8.5. Human experimental studies 9. TOXICOKINETICS OF PCDFs 9.1. Uptake, distribution, and excretion 9.1.1.
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