2 ,4-Dichlorophenoxyacetic Acid (2,4-D)
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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 Pro- gramme, the International Labour Organisa- tion, or the World Health Organization Environmental Health Criteria 29 2 ,4-DICHLOROPHENOXYACETIC ACID (2,4-D) Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization World Health Organization Geneva, 1984 The International Programme on Chemical Safety IPCS) is a joint venture of the United Nations Environment Programme, the Interna- tional 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, experi- mental laboratory, and risk-assessment methods that could produce inter- nationally comparable results, and the development of manpower in the field of toxicology. Other activities carried Out by IPCS include the devel- opment of know-how for coping with chemical accidents, coordination of laboratory testing and epiderniological studies, and promotion of research on the mechanisms of the biological action of chemicals. ISBN 92 4 154089 3 World Health Organization 1984 Publications of the World Health Organization enjoy copyright protec- tion in accordance with the provisions of Protocol 2 of the Universal Copy- right Convention. For rights of reproduction or translation of WHO publica- tions, in part or in toto, application should be made to the Office of Publica- tions, 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 con- cerning 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 men- tioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. PRINTED IN FINLAND 8315998- VAMIvIALA- 5500 -3- CONTENTS ENVIRONMENTAL HEALTH CRITERIA FOR 2,4-DICHLOROPHENOXYACETIC ACID Page SUMMARY AND RECOMMENDATIONS FOR FURTHER STUDIES . 11 1.1 Summary ........................ 11 1.1.1 Analytical methods 11 1.1.1.1 2,4-D, 2,4-D alkali metal salts or 2,4-D amine salts and 2,4-D esters . 11 11 1.1.1.2 Contaminants in 2,4-D herbicides ..... 1.1.2 SourceS of environmental pollution 11 1.1.3 Environmental distribution and transformations ................ 11 1.1.4 Environmental exposure levels ......... 12 1.1.5 Uptake and fate of 2,4-D in the body 12 12 1.1.6 Effects on animals 1.1.6.1 Acute toxic effects 12 13 1.1.6.2 Chronic toxic effects 1.1.6.3 Teratogenic and reproductive effects 13 1.1.6.4 Mutagenic effects 13 1.1.6.5 Carcinogenic effects ........... 13 1.1.7 Effects on human beings ............ 13 13 1.1.7.1 Acute toxic effects 14 1.1.7.2 Chronic toxic effects 14 1.1.7.3 Teratogenic and reproductive effects 1.1.7.4 Mutagenic effects 14 1.1.7.5 Carcinogenic effects ........... 14 14 1.2 Recommendations for further studies ......... 1.2.1 Analytical methods 14 14 1.2.2 Environmental exposure levels ......... 1.2.3 Studies on animals 15 1.2.4 Studies on human beings ............ 15 PROPERTIES AND ANALYTICAL METHODS ..........17 2.1 Physical and chemical properties of 2,4-D ......17 2.1.1 Introduction .................17 2.1.2 Synthesis of 2,4-D ..............17 2.1.3 Important chemical reactions of 2,4-D . 18 2.1.4 Composition of technical 2,4-D materials . 18 2.1.5 Volatility of 2,4-D derivatives .........20 2.2 Determination of 2,4-D ...............21 2.2.1 General comments ...............21 -4- Page 2.2.2 Analysis of technical and formulated 2,4-D products ................ 21 2.2.3 Determination of 2,4-D residues ........ 21 2.2.3.1 Sampling, extraction, and clean-up . 22 2.2.4 Derivatization and quantification ....... 22 2.2.5 Confirmation ................. 23 3. SOURCES OF ENVIRONMENTAL POLLUTION .......... 24 3.1 Production of 2,4-D herbicides ........... 24 3.2 Uses ........................ 24 3.3 Disposal of wastes ................. 25 3.3.1 Industrial wastes ............... 25 3.3.2 Agricultural wastes .............. 25 4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION OF 2,4-D ............... 26 4.1 Drift and volatilization in the atmosphere ..... 26 4.2 Movement within and from the soil .......... 29 4.3 Contamination of water ............... 30 4.4 Environmental transformation and degradation processes ...................... 30 4,4.1 Metabolism in plants .............. 30 4.4.1.1 Side-chain degradation .......... 30 4.4.1.2 Ring hydroxylation ............ 30 4.4.1.3 Conjugation with plant constituents * . 31 4.4.2 Degradation of 2,4-D in the soil ........ 31 4.4.3 Degradation in the aquatic ecosystem ..... 32 4.4.4 Photochemical degradation ........... 32 4.5 Bioconcentration .................. 32 5. ENVIRONMENTAL LEVELS AND EXPOSURE ..........33 5.1 Levels of 2,4-D residues in the environmment ..... 33 5.1.1 In air .................... 33 5.1.1.1 Field exposure ............ 33 5.1.1.2 General environment exposure ..... 33 5.1.2 In water ................... 35 5.1.3 In soil .................... 38 5.1.4 In food sources ................ 38 5.1.4.1 Residues in retail food supplies ............... 39 5.1.4.2 Residues in fish and shellfish ............... 39 5.1.4.3 Residues in wild fruits and mushrooms ............. 39 -5-. 5.1.4.4 Residues in food derived from animals ............. 41 5.2 Occupational exposure to 2,4-fl during the production, handling and use of chlorophenoxy herbicides . 46 5.2.1 Industrial exposure .............. 46 5.2.2 Exposure related to herbicide use ....... 46 5.3 Exposure of bystanders to 2,4-fl........... 50 5.4 Estimated exposure by the general population in 2,4-D-use areas ............. 50 5.4.1 Intake of 2,4-D residues from air ....... 51 5.4.2 Intake of 2,4-fl residues from potable water . 51 5.4.3 Intake of 2,4-D residues from soil ...... 51 5.4.4 Intake of 2,4-fl residues from food ...... 51 5.4.5 Total exposure by the general population in a 2,4-fl-use area ............... 52 5.4.6 Total exposure of persons occupationally exposed in agriculture ............ 52 5.4.7 Total exposure of the general population outside areas of 2,4-D use .......... 53 6. CHEMOBIOKINETICS AND METABOLISM ........... 54 6.1 Uptake via different routes of exposure ....... 54 6.1.1 Uptake by inhalation .............. 54 6.1.1.1 Animals ................. 54 - 6.1.1.2 Human beings ............... 54 6.1.2 Dermal uptake ................. 54 6.1.2.1 Animals ................. 54 6.1.2.2 Human beings ............... 55 6.1.3. Oral uptake ................. 55 6.1.3.1 Animals ................. 55 6.1.3.2 Human beings ............... 55 6.2 Distribution and transformation in the body ..... 57 6.2.1 Animals .................... 57 6.2.2 Human beings ................. 59 6.3 2.4-D levels in body tissues and fluids ....... 60 6.3.1 Animals .................... 60 6.3.2 Human beings ................. 60 6.4 Elimination and biological half life ......... 61 6.4.1 Animals .................... 61 6.4.2 Human beings ................. 62 6.5 Chlorinated dibenzo-2-dioxins (CDDs) ......... 62 7. EFFECTS OF 2,4-fl ON ANIMALS ............. 63 7.1 General introductjn ................. 63 7.2 Acute effects ................... 64 -6- 7.2.1 Skin and eye irritancy ............ 64 7.2.2 Skin sensitization .............. 64 7.2.3 Lethal doses and concentrations (LID50 and LC 50 ) ................... 64 7.2.3.1 Acute oral LD50 ............. 65 7.2.3.1.1 ltarrrisals ............... 65 7.2.3.1.2 Birds ................ 65 7.2.3.2 Acute dermal LED50 ............ 67 7.2.3.2.1 Mammals ............... 67 7.2.3.3 Acute inhalation LC50 .......... 67 7.2.3.4 Parenteral LID50 ............. 67 7.2.4 Acute toxicity in aquatic organisms ...... 67 7.3 Subchronic and Chronic toxitity ........... 68 7.3.1 Mammals .................... 68 7.3.1.1 Clinical signs of poisoning ....... 68 7.3.1.2 Effects on food and water consumption, and on body weight ............ 69 7.3.1.3 Effects on the central nervous system (CNS) .................. 70 7.3.1.4 Effects on the peripheral nervous system 70 7.3.1.5 Myotoxic effects ............. 71 7.3.1.6 Cardiovascular effects .......... 71 7.3.1.7 Haematological effects .......... 71 7.3.1.8 Effects on blood chemistry ........ 72 7.3.1.9 Other biochemical effects observed in vivo or in Vitro .............. 72 7.3.1.10 Pulmonary effects ............ 72 7,3.1.11 Hepatotoxic effects ........... 73 7.3.1.12 Effects on the kidney .......... 73 7.3.1.13 Effects on endocrine organs ....... 74 7.3.1.14 Effects on the digestive tract ...... 74 7.3.2 Birds ..................... 74 7,3.3 Cold-blooded animals ............. 76 7.4 Fetotoxicity, teratogenicity, and reproductive effects ................ 76 7.4.1 Rats ..................... 77 7.4.1.1 Effects on adult rats .......... 77 7.4.1.2 Effects on offspring ........... 77 7.4.2 Mice ..................... 79 7.4.3 birds ..................... 79 7.4.4 Cold-blooded animals ............. 80 7.4.4.1 Amphibians ................ 80 7.4.4.2 Fish .................... 80 7.5 Mutagenicity and related effects .........