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.