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Environmental Health Criteria 63 ORGANOPHOSPHORUS INSECTICIDES: A GENERAL INTRODUCTION Please note that the layout and pagination of this web version are not identical with the printed version. Organophophorus insecticides: a general introduction (EHC 63, 1986) INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY ENVIRONMENTAL HEALTH CRITERIA 63 ORGANOPHOSPHORUS INSECTICIDES: A GENERAL INTRODUCTION 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, 1986 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 154263 2 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 already available. Page 1 of 135 Organophophorus insecticides: a general introduction (EHC 63, 1986) (c) World Health Organization 1986 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 ORGANOPHOSPHOROUS INSECTICIDES - A GENERAL INTRODUCTION PREFACE 1. SUMMARY AND RECOMMENDATIONS 1.1. Summary 1.1.1. General 1.1.2. Properties and analytical methods 1.1.3. Sources; environmental transport and distribution 1.1.4. Environmental levels and exposure 1.1.5. Effects on organisms in the environment 1.1.6. Metabolism 1.1.7. Mode of action 1.1.8. Effects on experimental animals and in vitro test systems 1.1.9. Effects on human beings 1.1.10. Therapy of poisoning 1.2. Recommendations 2. PROPERTIES AND ANALYTICAL METHODS 2.1. Chemical and physical properties 2.1.1. Effects of light 2.1.2. Effects of solutes and solvents 2.2. Analytical methods 3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE, ENVIRONMENTAL TRANSPORT AND DISTRIBUTION, EXPOSURE LEVELS 3.1. Sources of pollution 3.2. Environmental transport and distribution 3.2.1. Distribution in air and water 3.2.2. Distribution in food 3.3. Bioaccumulation and degradation in the environment 3.4. Exposure levels 3.4.1. Exposure of the general population 3.4.2. Occupational exposure Page 2 of 135 Organophophorus insecticides: a general introduction (EHC 63, 1986) 4. METABOLISM AND MODE OF ACTION 4.1. Uptake 4.1.1. Dermal uptake 4.1.2. Gastrointestinal tract 4.1.3. Inhalation 4.2. Distribution and storage 4.2.1. Experimental animal studies on distribution and storage 4.3. Biotransformation 4.3.1. Mixed-function oxidases (MFOs) 4.3.1.1 Oxidative desulfuration 4.3.1.2 Oxidative N - dealkylation 4.3.1.3 Oxidative O -dealkylation 4.3.1.4 Oxidative de-arylation 4.3.1.5 Thioether oxidation 4.3.1.6 Side-chain oxidation 4.3.2. Hydrolases 4.3.3. Transferases 4.3.3.1 Transferases handling primary metabolites 4.3.4. Tissue binding 4.4. Elimination 4.5. Mode of action 4.5.1. Inhibition of esterases 4.5.2. Possible alkylation of biological macromolecules 5. EFFECTS ON ORGANISMS IN THE ENVIRONMENT 5.1. Aquatic organisms 6. EFFECTS ON ANIMALS 6.1. Effects on the nervous system 6.1.1. Effects attributed to interaction with esterases 6.1.1.1 Cholinergic effects 6.1.1.2 Delayed neuropathic effects 6.1.2. Behavioural and other effects on the nervous system 6.2. Other effects 6.2.1. Mutagenic and carcinogenic effects 6.2.2. Teratogenic effects 6.2.3. Effects on the immune system 6.2.4. Effects on tissue carboxyesterases 6.2.5. Sundry other effects of organophosphorus pesticides 6.2.5.1 Effects on hormones 6.2.5.2 Effects on the reproductive system 6.2.5.3 Effects on the retina 6.2.5.4 Porphyric effect 6.2.5.5 Lipid metabolism 6.2.5.6 Effects causing delayed deaths 6.2.5.7 Selective inhibition of thermogenesis 6.3. Factors influencing organophosphorus insecticide toxicity 6.3.1. Dosage-effect 6.3.2. Age and sex 6.3.3. Nutrition 6.3.4. Effects of impurities and of storage 6.3.4.1 Impurities toxic in their own right 6.3.4.2 Impurities potentiating the toxicity of the major ingredient 6.3.5. Effects of other pesticides and of drugs 6.3.6. Species 6.3.7. Other factors 6.4. Acquisition of tolerance to organophosphorus Page 3 of 135 Organophophorus insecticides: a general introduction (EHC 63, 1986) insecticides 6.5. Therapy of experimental organophosphorus poisoning 6.5.1. Palliation 6.5.2. Antagonism of effects of ACh 6.5.3. Reactivation of inhibited AChE 6.5.4. Efficacy of therapy 7. EFFECTS ON MAN 7.1. Acute cholinergic poisoning 7.1.1. Methods for assessing absorption and effects of organophosphorus insecticides 7.1.1.1 Analysis of urine as a means of monitoring exposed populations 7.1.1.2 Biochemical methods for the measurement of effects 7.1.1.3 Electrophysiological methods for the study of effects 7.1.2. Monitoring studies 7.1.3. Retrospective studies of populations exposed to organophosphorus pesticides: acute and long-term exposure 7.2. Other effects on the nervous and neuromuscular system due to acute or long-term exposure 7.2.1. Delayed neuropathic effects 7.2.2. Behavioural effects 7.3. Effects on other organs and systems 7.4. Treatment of organophosphate insecticide poisoning in man 7.4.1. Minimizing the absorption 7.4.2. General supportive treatment 7.4.3. Specific pharmacological treatment 7.4.3.1 Atropine 7.4.3.2 Oxime reactivators 7.4.3.3 Diazepam 7.4.3.4 Notes on the recommended treatment REFERENCES ANNEX I: NAMES AND STRUCTURES OF SELECTED ORGANOPHOSPHORUS PESTICIDES ANNEX II: ORGANOPHOSPHORUS INSECTICIDES: JMPR REVIEWS, ADIs, EVALUATION BY IARC, CLASSIFICATION BY HAZARD, FAO/WHO DATA SHEETS, IRPTC DATA PROFILE, AND LEGAL FILE ANNEX III: LD50s AND NO-OBSERVED-ADVERSE-EFFECT LEVELS IN ANIMALS ANNEX IV: ABBREVIATIONS USED IN THE DOCUMENT WHO TASK GROUP ON ORGANOPHOSPHOROUS INSECTICIDES Members Dr D. Ecobichon, Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada Dr A.H. El-Sebae, Department of Pesticide Chemistry, Faculty of Agriculture, University of Alexandria, Alexandria, Egypt Dr L. Ivanova-Chemishanska, Institute of Hygiene and Occupational Health, Medical Academy, Sofia, Bulgaria (Vice-Chairman) Dr M.K. Johnson, Toxicology Unit, Medical Research Council Page 4 of 135 Organophophorus insecticides: a general introduction (EHC 63, 1986) Laboratories, Carshalton, Surrey, United Kingdom (Rapporteur) Dr S.K. Kashyap, National Institute of Occupational Health, Ahmedabad, India Dr M. Lotti, Institute of Occupational Health, Padua, Italy Dr L. Martson, All-Union Scientific Research Institute of the Hygiene and Toxicology of Pesticides, Polymers, and Plastics (VNIIGINTOX), Kiev, USSRa Dr U.G. Oleru, College of Medicine, University of Lagos, Lagos, Nigeria Dr W.O. Phoon, Department of Social Medicine and Public Health, National University of Singapore, Outram Hill, Republic of Singapore (Chairman) Dr E. Reiner, Institute for Medical Research and Occupational Health, Zagreb, Yugoslavia Dr A.F. Rahde, Ministry of Public Health, Porto Alegre, Brazil Dr J. Sekizawa, National Institute of Hygienic Sciences, Tokyo, Japan Observers Mr R.J. Lacoste, International Group of National Associations of Pesticide Manufacturers (GIFAP), Brussels, Belgium Dr W.O. Phoon, International Commission on Occupational Health, Geneva, Switzerland Secretariat Mme B. Bender, United Nations Environment Programme, International Register of Potentially Toxic Chemicals, Geneva, Switzerland Secretariat (contd.) Dr J.R.P. Cabral, Unit of Mechanisms of Carcinogenesis, International Agency for Research on Cancer, Lyons, France Dr K.W. Jager, International Programme on Chemical Safety, World
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