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    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     rsum 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 Sant.

                             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

    CHEMICAL STRUCTURE

    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. 140.5C. The
    isopropyl ester is an almost colourless liquid of b.p. 130C at
    1 mmHg which crystallizes in two forms, one at 5-10C and the second
    at 20-25C. The melting point of the various amine salts ranges from
    85-87C for dimethylamine to 179-181C ammonia.

    1.3.2  Solubility

    The solubility of the acid at 25C 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 30-32C.

    1.3.3  Stability

    It is non-hygroscopic, but corrosive.

    1.3.4  Vapour pressure

    0.4 mmHg at 160C.  Isopropyl ester: 10.5 x 10-3 mmHg at 25C.

    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 g/ml had a
    dose-dependent inhibitory effect on cell growth of L929 cells in
    monolayer cultures. With 350-500 g/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/g/day.

    2.2.5  Observations on volunteers

    Oral administration of a single dose of 5 mg/g of 2,4-D in a male
    human subject resulted in a plasma level of 35 g/ml two hours after
    administration, which decreased slowly to 25 g/ml after 24 hours
    and 3.5 g/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:
       Toxicological Abbreviations
       D, 2,4- (AGP:1970/M/12/1)
       D, 2,4- (WHO Pesticide Residues Series 1)
       D, 2,4- (WHO Pesticide Residues Series 4)
       D, 2,4- (WHO Pesticide Residues Series 5)
       D, 2,4- (Pesticide residues in food: 1980 evaluations)