WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE ORGANIZATION ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION ET L'AGRICULTURE VBC/DS/78.37 ORIGINAL: ENGLISH DATA SHEETS ON PESTICIDES No. 37 June 1978 2,4-D It must be noted that the issue of a Data Sheet for a particular pesticide does not imply endorsement of the pesticide by WHO or FAO for any particular use, or exclude its use for other purposes not stated. While the information provided is believed to be accurate according to data available at the time when the sheet was compiled, neither WHO nor FAO are responsible for any errors or omissions, or any consequences therefrom. The issue of this document does Ce document ne constitue pas une not constitute formal publication. Il ne doit faire publication. It should not be l'objet d'aucun compte rendu ou reviewed, abstracted or quoted résumé ni d'aucune citation sans without the agreement of the l'autorisation de l'Organisation Food and Agriculture des Nations Unies pour Organization of the United l'Alimentation et l'Agriculture Nations or of the World Health ou de l'Organisation Mondiale de Organization. la Santé. CLASSIFICATION: Primary Use: Herbicide Secondary Use: None Chemical Group: Chlorophenoxy compound Date Issued: June 1978 1. GENERAL INFORMATION 1.1 COMMON NAME 2,4-D (ISO) 1.1.1 Identity: 2,4-dichlorophenoxyacetic acid 1.1.2 Synonyms: 2,4-PA DCPA Local synonyms: 1.2 SYNOPSIS 2,4-D is a herbicide of moderate mammalian toxicity. Its toxicity varies according to which salt or ester is present. It is relatively rapidly excreted from the body, mostly as unchanged compound. 1.3 SELECTED PROPERTIES 1.3.1 Physical characteristics A white powder with a slightly phenolic odour of m.p. 140.5°C. The isopropyl ester is an almost colourless liquid of b.p. 130°C at 1 mmHg which crystallizes in two forms, one at 5-10°C and the second at 20-25°C. The melting point of the various amine salts ranges from 85-87°C for dimethylamine to 179-181°C ammonia. 1.3.2 Solubility The solubility of the acid at 25°C in water is 620 mg/l. It is soluble in aqueous alkali and in alcohols, but insoluble in petroleum oils. Its sodium salt has a solubility in water of 45 g/l at room temperature, and the widely used isopropyl ester is practically insoluble in water, but soluble in alcohols and most oils. The solubility of its amine salts varies from 12 g/l for allylamine up to 4400 g/l for triethanolamine, at 30-32°C. 1.3.3 Stability It is non-hygroscopic, but corrosive. 1.3.4 Vapour pressure 0.4 mmHg at 160°C. Isopropyl ester: 10.5 x 10-3 mmHg at 25°C. 1.4 AGRICULTURE, HORTICULTURE AND FORESTRY 1.4.1 Common formulations Used as solid alkali salt concentrate, or as salt based water-miscible solution, or as ester based emulsifiable concentrate; also used in mixtures with other herbicides. 1.4.2 Susceptible pests Broad leaved weeds in general. 1.4.3 Used pattern Used to control broad leaved weeds in cereals, green crops, roadside verges, and around farm buildings. Application to cereals must be after the crop is sown but before it has started to shoot. Application rates: 1 to 1-1/2 lb acid equivalent per acre applied high or low volume rate 10-100 gal per acre; otherwise, salts 0.5-1.0 kg/ha, esters 0.3-0.6 kg/ha. 1.4.4 Unintended effects Can damage some undersown crops; spray drift can be dangerous, application to water courses can lead to pollution. 1.5 PUBLIC HEALTH PROGRAMME Not used in public health programmes. 1.6 HOUSEHOLD USE Used as a garden herbicide. 2. TOXICOLOGY AND RISKS 2.1 TOXICOLOGY - MAMMALS 2.1.1 Absorption route May be absorbed from the gastrointestinal tract, by inhalation or through the intact skin; however, skin absorption is relatively unimportant. 2.1.2 Mode of action Studies in vivo on liver mitochondria have demonstrated that 2,4-D uncouples oxidative phosphorylation at levels as low as 5 x 10-5M. It has been shown in vivo that 2,4-D produces a dose-related decrease in acetate metabolism. 2.1.3 Excretion products After oral administration of 5 mg/kg of 2,4-D in a male human subject, 73% of the dose was excreted in the urine in 48 hours. After administration of 14C-labelled material, only 0.25% of the dose was altered to an unidentified metabolite, found in the liver; the remainder was excreted or found in body tissues as unchanged 2,4-D. In rats given 1, 5 or 10 mg/kg of 14C 2,4-D, 94-99% was excreted in 72 hours; however, when given 100 mg/kg, 75.5% was excreted in 144 hours. 2.1.4 Toxicity, single dose Oral: Rats (M) 375 mg/kg 2,4-D acid Rats (F) 805 mg/kg 2,4-D sodium salt Rats (M & F) 700 mg/kg 2,4-D isopropyl ester Rats (F) 620 mg/kg 2,4-D mixed butyl esters Most susceptible species: dog, oral LD50 100 mg/kg. 2.1.5 Toxicity, repeated doses Oral: Young female rats were given 0, 3, 10, 30, 100 or 300 mg/kg orally by stomach tube, five times a week for up to four weeks. The animals which received 30 mg/kg or less showed no adverse effects, as judged by gross appearance, haematology, or histopathology. Those on 100 mg/kg showed varying degrees of gastrointestinal irritation, slight cloudy swelling of the liver and depressed growth rate. The animals given 300 mg/kg died rapidly, principally of severe gastrointestinal irritation. Cumulation of compound: 2,4-D is not cumulative in body tissues. It has been estimated that the clearance rate in men for excretion of 2,4-D is approximately 1 mg/kg/day. Cumulation of effect: Cumulation of effect may occur in the form of liver or kidney damage; however, there is no clear-cut biochemical lesion associated with prolonged exposure. 2.1.6 Dietary studies Short-term: Young female rats were fed dietary levels of 0, 100, 300, 1000, 3000 or 10 000 mg/kg diet for periods of up to 113 days. The animals fed at the 300 level or less, showed no adverse effects on gross appearance, haematological parameters, blood urea nitrogen, gross pathology and histopathology. Those given 1000 mg/kg diet had increased mortality, depressed growth rate, slightly increased liver weight and slight cloudy swelling of the liver. The animals given 3000 or 10 000 mg/kg diet were sacrificed after 12 days because of food refusal and rapid weight loss. Autopsy revealed increased liver and kidney weights and there were slight pathological changes in the organs. Long-term: Female rats were fed at levels of 0, 5, 25, 125, 625, or 1250 mg/kg diet for up to two years. There was no significant difference in mortality between test and control groups. At autopsy of those animals that had survived for the two, year period, there was no difference in body weight. The blood picture was normal except at the final examination, after 22 months, which revealed a possible tendency to macrocytosis, polychromasia and hypochromasia in the groups fed 5, 625 and 1250 ppm of 2,4-D. Bile duct proliferation, slight hepatitis and nephritis occurred slightly more often in the groups fed 2,4-D than in the controls. The "no ill-effect" level was 625 mg/kg diet:, equivalent to an intake of 31 mg/kg bw/day. 2.1.7 Supplementary studies of toxicity Carcinogenicity: 2,4-D is not considered to be a carcinogen. In a two-year feeding experiment in rats, a slight dose-related increase in rumour incidence in female rats was observed; however, the data was imprecise, and since the tumours affected a wide variety of sites the authors stated that the raw data did not support the view that 2,4-D was carcinogenic for the rat. Other experiments including a multigeneration reproduction study and a two-year feeding study in dogs, have shown no increased incidence of tumours. Teratogenicity: A number of experiments have been carried out to ascertain the teratogenicity of 2,4-D involving rats, guinea-pigs, hamsters and mice. At high doses, there appeared to be an increase in the incidence of minor skeletal variants and some skeletal abnormalities; however, these effects were not dose related. The no-effect level with respect to foetal body weight and formation of abnormal off-spring is given as 25 mg/kg/day. Mutagenicity: 2,4-D in the range of 50-500 µg/ml had a dose-dependent inhibitory effect on cell growth of L929 cells in monolayer cultures. With 350-500 µg/ml, complete inhibition of growth occurred after 24 hours incubation. On removal of 2,4-D, a rapid resumption of cell multiplication took place. Neurotoxicity: In man, a few cases of peripheral neuropathy, and in one case of successful suicide, degeneration of ganglion cells of the brain have been recorded. These findings have not been confirmed in other investigations. 2.2 TOXICOLOGY - MAN 2.2.1 Absorption 2,4-D may be absorbed from the gastrointestinal tract, by inhalation and, to a lesser extent, by the intact skin. 2.2.2 Dangerous doses Single: An oral dose of 3.6 g has caused acute illness and a self-administered dose of not less than 6.5 g led to death. Repeated: A man consumed 500 mg of purified 2,4-D for 21 days without ill effect. An adult given 18 intravenous doses of 2,4-D over a period of 33 days showed no side effects, even though 12 of these doses were of 800 mg and the final dose was 2000 mg. 2.2.3 Observations of occupationally exposed workers Observations were made on 220 men exposed from 0.5 to 22 years to 30-40 mg per day of 2,4-D in a manufacturing plant. Medical evaluation revealed no difference when compared to a control group of 4600 men. In the exposed group 10 men were karyotyped. There was no effect on the structural integrity or arrangement of the genetic material of the lymphocyte chromosomes. In a second study, there were complaints of general weakness, rapid fatiguability, frequent headache and vertigo among a number of workers at a plant manufacturing the amine salt and butyl ester of 2,4-D. Cases of arterial hypotension were encountered. There were possible indications of liver dysfunction, encountered more frequently amongst workers with long exposure to herbicides. In two groups of agricultural workers, 250 and 45 respectively, excessive fatigue, epigastric pains, anorexia, occasional upper respiratory tract symptoms and impaired taste sensitivity were reported. 2.2.4 Observations on exposure of the general population Since the major uses of 2,4-D are not directly on food crops, exposure of the general population should be very slight. In a number of total diet studies, no 2,4-D has been detected using methods of analysis sensitive to 0.01 mg/kg sample. In one study, herbicide chemicals were found infrequently, averaging an intake of 0.01 mg/kg bw, of which one-third was 2,4-D. The WHO/FAO maximum acceptable daily intake is 0.3 mg/µg/day. 2.2.5 Observations on volunteers Oral administration of a single dose of 5 mg/µg of 2,4-D in a male human subject resulted in a plasma level of 35 µg/ml two hours after administration, which decreased slowly to 25 µg/ml after 24 hours and 3.5 µg/ml after 48 hours. A total of 7370 of the dose was excreted in the urine within 48 hours of treatment. 2.2.6 Reported mishaps Reported cases of poisoning have been mainly the result of accidental or suicidal ingestion. Peripheral neuropathy has been reported on one occasion and contact dermatitis has been reported in a few cases. 2.3 TOXICITY TO NON-MAMMALIAN SPECIES 2.3.1 Fish Moderately toxic to toxic according to concentration, species and test method. 2.3.2 Birds Moderately toxic (pheasants, pigeons, 300-800 mg/kg) (mallards 2000 mg/kg). 2.3.3 Other species Non-toxic to mammals at phytotoxic concentrations but moderately toxic at higher concentrations (male deer 400-800 mg/kg). No 2,4-D was detected in the milk of a cow fed more than 450 g over a six-week period. 3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF COMPOUND 3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY (for definition of categories, see introduction). All formulations above 10%, Category 4. All formulations 10% or less, Category 5. 3.2 TRANSPORTATION AND STORAGE All formulations in Category 4 - Should be transported in clearly labelled rigid and leakproof containers. No food or drink should be transported or stored in the same compartment. Storage should be under lock and key, and secure from access by unauthorized persons and children. Formulations in Category 5 - Should be transported or stored in clearly labelled leakproof containers, out of reach of children, away from food and drink. 3.3 HANDLING All formulations in Category 4 - Protective clothing should be used by those handling concentrates. Adequate washing facilities should be available close at hand. Eating, drinking and smoking should be prohibited during handling and before washing after handling. Formulations in Category 5 - No facilities other than those needed for the handling of any chemical need be required. 3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINER Container must either be burned or crushed and buried below top soil. Care must be taken to avoid subsequent contamination of water sources. Container may be decontaminated (for method see paragraph 4.3 in Part 4). Decontaminated containers should not be used for food and drink. 3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS Formulations in Category 4 - Training of workers in techniques to avoid contact, essential. Formulations in Category 5 - Warning of workers to minimize contact essential. 3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT All formulations - Pilot and loaders should receive special training in application methods. Use of flagmen not recommended. Flagmen, if used, should wear overalls and be located well away from the dropping zone. 3.7 LABELLING Formulations in Category 4 - Minimum cautionary statement: "Keep well away from food-stuffs, empty foodstuff containers and animal feed. Avoid contamination of seeds and fertilizers." Formulations in Category 5 - Minimum cautionary statement: "Keep well away from foodstuffs, empty foodstuff containers and animal feed." 3.8 RESIDUES IN FOOD Maximum residue limits have been recommended for 2,4-D by the Joint FAO/WHO Meeting on Pesticide Residues. These are subject to change at annual reviews. 4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID 4.1 PRECAUTIONS IN USE 4.1.1 General 2,4-D is a chlorophenoxy herbicide of moderate toxicity. It may be absorbed from the gastrointestinal tract, by inhalation or to a lesser extent through the intact skin. 4.1.2 Manufacture and formulation T.L.V: (ACGIH) 10 mg/m3 (USSR) 1 mg/m3 (acetamide). Closed systems and forced ventilation may be required to reduce as much as possible the exposure of workers to the chemical. 4.1.3 Mixers and applicators When opening the container and when mixing, protective impermeable boots, clean overalls and a face mask should be worn. Mixing, if not mechanical, should always be carried out with a paddle of appropriate length. When spraying above waist level or during aerial application, a face mask should be worn as well as an impermeable hood, clothing, boots and gloves. The applicator should avoid working in spray mists and avoid contact with the mouth. Particular care is needed when equipment is being washed after use. All protective clothing should be washed immediately after use, including the insides of gloves. Splashes must be washed immediately from the skin or eyes with large quantities of water. Before eating, drinking or smoking, hands and other exposed skin should be washed. 4.1.4 Other associated workers (including flagmen in aerial operations) Persons exposed to 2,4-D and associated with its application should wear protective clothing and observe the precautions described in 4.1.3 under "Mixers and applicators". 4.1.5 Other populations likely to be affected With good agricultural practice, subject to 4.2 below, other populations should not be exposed to hazardous amounts of 2,4-D. 4.2 ENTRY OF PERSONS INTO TREATED AREAS Unprotected persons should be kept out of sprayed areas for at least 12 hours. 4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS Residues in containers should be emptied in a diluted form into a deep pit, taking care to avoid contamination of ground waters. The empty container may be decontaminated by rinsing two or three times with water and scrubbing the sides. An additional rinse should be carried out with 5% sodium hydroxide solution which should remain in the container overnight. Impermeable gauntlets should be worn during this work and a soakage pit should be provided for the rinsings. Decontaminated containers should not be used for food and drink. They should never be used, even temporarily, for transfer, mixing, storage of other pesticides intended for use on plants. Spillage of 2,4-D should be removed and the area rinsed with large quantities of water. 4.4 EMERGENCY AID 4.4.1 Early symptoms of poisoning Symptoms of poisoning may include: vomiting, headache, double vision, urinary incontinence, muscular weakness and coma. Terminal symptoms may include convulsions. 4.4.2 Treatment before person is seen by a physician if these symptoms appear following exposure The person should stop work immediately; remove contaminated clothing, wash the affected area with soap and water if available and flush the area with large quantities of water. If swallowed, and the person is conscious, vomiting should be induced by stimulating the back of the throat. 5. FOR MEDICAL AND LABORATORY PERSONNEL 5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING 5.1.1 General information A chlorphenoxy herbicide of moderate toxicity which may be absorbed from the gastrointestinal tract, by inhalation or to a lesser extent through the intact skin. 2,4-D is not metabolized in the body and is excreted relatively rapidly as unchanged 2,4-D in the urine. While its use has involved little hazard to exposed workers, a number of accidental and deliberate poisonings have been described. 5.1.2 Symptoms and signs Symptoms of poisoning include headache, double vision, vomiting, fibrillation in some muscles, hyporeflexia, urinary incontinence, muscular weakness and coma. There may be terminal convulsions and changes in body temperature. Cardiac arrhythmia and peripheral neuropathy have also been reported in a few cases. 5.1.3 Laboratory The presence of 2,4-D in the urine is indicative of exposure to this compound. 2,4-D may also be found in plasma for the first 48 hours after exposure. There are no other specific biochemical tests which can confirm exposure, though liver function and ECG examination may be useful in determining the severity of poisoning. 5.1.4 Treatment If the pesticide has been ingested, prompt gastric lavage should be performed using 5% sodium bicarbonate solution, if available. Further treatment should be symptomatic. Artificial respiration may be required. 5.1.5 Prognosis If the acute effects are survived, the prognosis is good. 5.1.6 References of previously reported cases Dudley, A. W., jr et al. (1972) Arch. Path., 94(3), 270-275; Berwick, P. J. (1970) Am. Med. Assoc., 214(6), 1114-1117; Brandt, M. R. (1971) Ugeskrift Laeger, 133(11), 500-503 (Danish); Hayes, J. R., jr (1963) Clinical Handbook on Economic Poisons, United States Department of Health, Education and Welfare, Atlanta, Georgia; Nielsen, K. et al. (1965) Acta. Pharmacol. Toxicol., 22, 224-234. 5.2 SURVEILLANCE TESTS There are no specific surveillance tests for monitoring exposure to 2,4-D. The presence of 2,4-D in urine or plasma is indicative of exposure. In acute exposure, estimation of SGOT and SGPT and other liver function enzyme tests may be useful. 5.3 LABORATORY METHODS 5.3.1 Detection and assay of compound References are given only. Details of methods for the assay of 2,4-D by both colorimetric and gas chromatographic methods can be found in: Marquarot, R. P. et al. (1964) Analytical methods for pesticides. Plant growth regulators and food additives. Vol. IV Herbicides. Edited by G. Zweig. Academic Press, pp. 95-116. The sensitivity of the colorimetric method is in the order of 0.05 ppm and by gas chromatography 0.01 ppm. Further details of gas chromatographic methods are given in: Analytical methods for pesticide and plant growth regulators. Gas chromatographic analysis, Vol. VI. Edited by G. Zweig. Academic Press, 1972. A method specific for the determination of 2,4-D in animal tissues by gas chromatography sensitive to 0.05 ppm is given by: Clark, D. E. et al. (1967) J. Ag. Food Chem., 15 (1), 171-173. 5.3.2 Other tests in cases of poisoning Estimation of SGOT, SGPT, serum lactic dehydrogenose, serum aldose creatine phosphokinase, haemoglobinuria and myoglobinuria may prove of some value in acute exposure to this compound.
See Also: 2,4-Dichlorophenoxyacetic acid (2,4-D) (EHC 29, 1984)