INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
ENVIRONMENTAL HEALTH CRITERIA 29
2,4-DICHLOROPHENOXYACETIC ACID (2,4-D)
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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, 1984
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CONTENTS
ENVIRONMENTAL HEALTH CRITERIA FOR 2,4-DICHLOROPHENOXYACETIC ACID
1. SUMMARY AND RECOMMENDATIONS FOR FURTHER STUDIES
1.1. Summary
1.1.1. Analytical methods
1.1.1.1 2,4-D, 2,4-D alkali metal salts or 2,4-D
amine salts and 2,4-D esters
1.1.1.2 Contaminants in 2,4-D herbicides
1.1.2. Sources of environmental pollution
1.1.3. Environmental distribution and transformations
1.1.4. Environmental exposure levels
1.1.5. Uptake and fate of 2,4-D in the body
1.1.6. Effects on animals
1.1.6.1 Acute toxic effects
1.1.6.2 Chronic toxic effects
1.1.6.3 Teratogenic and reproductive effects
1.1.6.4 Mutagenic effects
1.1.6.5 Carcinogenic effects
1.1.7. Effects on human beings
1.1.7.1 Acute toxic effects
1.1.7.2 Chronic toxic effects
1.1.7.3 Teratogenic and reproductive effects
1.1.7.4 Mutagenic effects
1.1.7.5 Carcinogenic effects
1.2. Recommendations for further studies
1.2.1. Analytical methods
1.2.2. Environmental exposure levels
1.2.3. Studies on animals
1.2.4. Studies on human beings
2. PROPERTIES AND ANALYTICAL METHODS
2.1. Physical and chemical properties of 2,4-D
2.1.1. Introduction
2.1.2. Synthesis of 2,4-D
2.1.3. Important chemical reactions of 2,4-D
2.1.4. Composition of technical 2,4-D materials
2.1.5. Volatility of 2,4-D derivatives
2.2. Determination of 2,4-D
2.2.1. General comments
2.2.2. Analysis of technical and formulated 2,4-D products
2.2.3. Determination of 2,4-D residues
2.2.3.1 Sampling, extraction, and clean-up
2.2.4. Derivatization and quantification
2.2.5. Confirmation
3. SOURCES OF ENVIRONMENTAL POLLUTION
3.1. Production of 2,4-D herbicides
3.2. Uses
3.3. Disposal of wastes
3.3.1. Industrial wastes
3.3.2. Agricultural wastes
4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION OF
2,4-D
4.1. Drift and volatilization in the atmosphere
4.2. Movement within and from the soil
4.3. Contamination of water
4.4. Environmental transformation and degradation processes
4.4.1. Metabolism in plants
4.4.1.1 Side-chain degradation
4.4.1.2 Ring hydroxylation
4.4.1.3 Conjugation with plant constituents
4.4.2. Degradation of 2,4-D in the soil
4.4.3. Degradation in the aquatic ecosystem
4.4.4. Photochemical degradation
4.5. Bioconcentration
5. ENVIRONMENTAL LEVELS AND EXPOSURE
5.1. Levels of 2,4-D residues in the environmment
5.1.1. In air
5.1.1.1 Field exposure
5.1.1.2 General environment exposure
5.1.2. In water
5.1.3. In soil
5.1.4. In food sources
5.1.4.1 Residues in retail food supplies
5.1.4.2 Residues in fish and shellfish
5.1.4.3 Residues in wild fruits and mushrooms
5.1.4.4 Residues in food derived from animals
5.2. Occupational exposure to 2,4-D during the production,
handling, and use of chlorophenoxy herbicides
5.2.1. Industrial exposure
5.2.2. Exposure related to herbicide use
5.3. Exposure of bystanders to 2,4-D
5.4. Estimated exposure by the general population in 2,4-D-use
areas
5.4.1. Intake of 2,4-D residues from air
5.4.2. Intake of 2,4-D residues from potable water
5.4.3. Intake of 2,4-D residues from soil
5.4.4. Intake of 2,4-D residues from food
5.4.5. Total exposure by the general population in a
2,4-D-use area
5.4.6. Total exposure of persons occupationally exposed in
agriculture
5.4.7. Total exposure of the general population outside
areas of 2,4-D use
6. CHEMOBIOKINETICS AND METABOLISM
6.1. Uptake via different routes of exposure
6.1.1. Uptake by inhalation
6.1.1.1 Animals
6.1.1.2 Human beings
6.1.2. Dermal uptake
6.1.2.1 Animals
6.1.2.2 Human beings
6.1.3. Oral uptake
6.1.3.1 Animals
6.1.3.2 Human beings
6.2. Distribution and transformation in the body
6.2.1. Animals
6.2.2. Human beings
6.3. 2.4-D levels in body tissues and fluids
6.3.1. Animals
6.3.2. Human beings
6.4. Elimination and biological half life
6.4.1. Animals
6.4.2. Human beings
6.5. Chlorinated dibenzo- p-dioxins (CDDs)
7. EFFECTS OF 2,4-D ON ANIMALS
7.1. General introduction
7.2. Acute effects
7.2.1. Skin and eye irritancy
7.2.2. Skin sensitization
7.2.3. Lethal doses and concentrations (LD50 and LC50)
7.2.3.1 Acute oral LD50
7.2.3.l.l Mammals
7.2.3.1.2 Birds
7.2.3.2 Acute dermal LD50
7.2.3.2.1 Mammals
7.2.3.3 Acute inhalation LC50
7.2.3.4 Parenteral LD50
7.2.4. Acute toxicity in aquatic organisms
7.3. Subchronic and chronic toxicity
7.3.1. Mammals
7.3.1.1 Clinical signs of poisoning
7.3.1.2 Effects on food and water consumption, and
on body weight
7.3.1.3 Effects on the central nervous system
(CNS)
7.3.1.4 Effects on the peripheral nervous system
7.3.1.5 Myotoxic effects
7.3.1.6 Cardiovascular effects
7.3.1.7 Haematological effects
7.3.1.8 Effects on blood chemistry
7.3.1.9 Other biochemical effects observed in vivo
or in vitro
7.3.1.10 Pulmonary effects
7.3.1.11 Hepatotoxic effects
7.3.1.12 Effects on the kidney
7.3.1.13 Effects on endocrine organs
7.3.1.14 Effects on the digestive tract
7.3.2. Birds
7.3.3. Cold-blooded animals
7.4. Fetotoxicity, teratogenicity, and reproductive effects
7.4.1. Rats
7.4.1.1 Effects on adult rats
7.4.1.2 Effects on offspring
7.4.2. Mice
7.4.3. Birds
7.4.4. Cold-blooded animals
7.4.4.1 Amphibians
7.4.4.2 Fish
7.5. Mutagenicity and related effects
7.5.1. 2,4-D and its derivatives
7.6. Carcinogenic effects on experimental animals
7.6.1. 2,4-D and its derivatives
7.6.2. Contaminants in 2,4-D
8. EFFECTS ON MAN, CLINICAL AND EPIDEMIOLOGICAL STUDIES
8.1. Acute poisoning and occupational overexposure
8.1.1. Neurotoxic effects of 2,4-D and related compounds
8.1.1.1 Effects on the central nervous system
8.1.1.2 Effects on the peripheral nervous system
8.1.2. Myotoxic effects of 2,4-D
8.1.3. Cardiopathies and cardiovascular effects
8.1.4. Haematological effects
8.1.5. Blood chemistry effects
8.1.6. Pulmonary effects
8.1.7. Hepatotoxic effects
8.1.8. Nephrotoxic effects
8.1.9. Effects on the digestive tract
8.1.10. Effects on endocrine organs
8.1.11. Irritative and allergenic effects
8.2. Epidemiological studies of the chronic effects of 2,4-D
8.2.1. Reproductive, fetotoxic, and teratogenic effects
8.3. Studies on mutagenic effects in workers exposed to 2,4-D
8.4. Carcinogenic effects
8.4.1. Epidemiological studies
8.4.2. Evidence on the carcinogenicity of 2,4-D
8.5. Treatment of poisoning in human beings
9. EVALUATION OF HEALTH RISKS TO MAN FROM EXPOSURE TO 2,4-D
9.1. General considerations
9.2. Estimated intake of 2,4-D by the population in a 2,4-D-use
area
9.2.1. Intake by bystanders
9.2.2. Occupational intake
9.3. Safety factors
9.3.1. Definitions
9.3.2. Determination of safety factors
9.3.2.1 Acute poisoning
9.3.2.2 Chronic toxicity
9.3.2.3 Embryonic, fetotoxic, and teratogenic
effects
9.3.2.4 Mutagenic effects
9.3.2.5 Carcinogenic effects
9.4. Evaluation of health risks from 2,4-D exposure
9.5. Recommendations on exposure
REFERENCES
NOTE TO READERS OF THE CRITERIA DOCUMENTS
While every effort has been made to present information in the
criteria documents as accurately as possible without unduly
delaying their publication, mistakes might have occurred and are
likely to occur in the future. In the interest of all users of the
environmental health criteria documents, readers are kindly
requested to communicate any errors found to the Manager of the
International Programme on Chemical Safety, World Health
Organization, Geneva, Switzerland, in order that they may be
included in corrigenda, which will appear in subsequent volumes.
In addition, experts in any particular field dealth with in the
criteria documents are kindly requested to make available to the
WHO Secretariat any important published information that may have
inadvertently been omitted and which may change the evaluation of
health risks from exposure to the environmental agent under
examination, so that the information may be considered in the event
of updating and re-evaluation of the conclusions contained in the
criteria documents.
IPCS TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR
2,4-DICHLORPHENOXYACETIC ACID
Members
Dr. E. Astolfi, Faculty of Medicine of Buenos Aires, Buenos Aires,
Argentina (Chairman)
Dr. L.A. Dobrovolski, Kiev Institute of Labour, Hygiene and
Occupational Diseases, Kiev, USSR
Dr. B. Gilbert, Centre for Research of Natural Products, University
of Rio de Janeiro, Rio de Janeiro, Brazil
Dr. D. Grant, Foods Directorate, Health Protection Branch, Health &
Welfare Canada, Ottawa, Ontario, Canada
Dr. O. Hutzinger, University of Amsterdam, Amsterdam, The
Netherlands
Dr. R.N. Khanna, Industrial Toxicology Research Centre, Lucknow
(UP) India
Dr. R.D. Kimbrough, Center for Environmental Health, Center for
Disease Control, Department of Health and Human Services,
Public Health Service, Atlanta, Georgia, USA
Dr. D.G. Lindsay, Ministry of Agriculture, Fisheries & Food,
London, England, (Rapporteur)
Dr. P.J. Madati, Ministry of Health, Dar-es-Salam, Tanzania
Representatives of Other Organizations
Dr. M.L. Leng, International Group of National Associations of
Manufacturers of Agrochemical Products, c/o Dow Chemical
Company, Midland, Michigan, USA
Dr. T.F. McCarthy, Permanent Commission and International
Association on Occupational Health
Secretariat
Dr. D. Riedel, Environmental Health Directorate, Health & Welfare
Canada, Environmental Health Centre, Ottawa, Canda, (Temporary
Advisor)
Dr. F. Valic, World Health Organization, Geneva, Switzerland,
(Secretary)
Mr. J.D. Wilbourn, International Agency for Research on Cancer,
Lyons, France
Observers
Dr. H. Spencer, US Environmental Protection Agency, Washington, DC,
USA
ENVIRONMENTAL HEALTH CRITERIA FOR 2,4-DICHLOROPHENOXYACETIC ACID
(2,4-D)
Further to the recommendations of the Stockholm United Nations
Conference on the Human Environment in 1972, and in response to a
number of World Health Assembly resolutions (WHA23.60, WHA24.47,
WHA25.58, WHA26.68) and the recommendation of the Governing Council
of the United Nations Environment Programme, (UNEP/GC/10,
July 3 1973), a programme on the integrated assessment of the
health effects of environmental pollution was initiated in 1973.
The programme, known as the WHO Environmental Health Criteria
Programme, has been implemented with the support of the Environment
Fund of the United Nations Environment Programme. In 1980, the
Environmental Health Criteria Programme was incorporated into the
International Programme on Chemical Safety (IPCS). The result of
the Environmental Health Criteria Programme is a series of criteria
documents.
The Environmental Health Directorate, Health Protection Branch,
Department of National Health and Welfare, Canada (Director-General
Dr. E. Somers) was responsible, as a Lead Institution of the IPCS,
for the preparation of the first and second drafts of the
Environmental Health Criteria Document on 2,4-D. Dr. D. Riedel
co-ordinated the work.
The Task Group for the Environmental Health Criteria for 2.4-D
met in Ottawa from 4 to 11 July, 1983. The meeting was opened by
Dr. E. Somers. Dr. A.B. Morrison, Assistant Deputy Minister,
Department of National Health and Welfare, Canada welcomed the
participants on behalf of the host government and Dr F. Valic, on
behalf of the 3 co-sponsoring organizations of the IPCS
(UNEP/ILO/WHO). The Task Group reviewed and revised the second
draft criteria document and made an evaluation of the health risks
of exposure to 2,4-D.
The efforts of all who helped in the preparation and the
finalization of the document are gratefully acknowledged.
* * *
Partial financial support for the publication of this criteria
document was kindly provided by the United States Department of
Health and Human Services, through a contract from the National
Insitute of Environmental Health Sciences, Research Triangle Park,
North Carolina, USA - a WHO Collaborating Centre for Environmental
Health Effects.
1. SUMMARY AND RECOMMENDATIONS FOR FURTHER STUDIES
1.1. Summary
1.1.1. Analytical methods
1.1.1.1. 2,4-D, 2,4-D alkali metal salts or 2,4-D amine salts, and
2,4-D esters
The available analytical results concerning 2,4-dichloro-
phenoxyacetic acid (2,4-D) and its derivatives in herbicides and
biological and environmental matrices were collected over a span of
almost 40 years, by diverse and, until fairly recently, not
sufficiently specific or sensitive methods. This makes comparison
of most of the data reported in the literature difficult.
1.1.1.2. Contaminants in 2,4-D herbicides
Adequately specific and sensitive methods for the reliable
identification of such potentially hazardous contaminants as the
di-, tri-, and tetrachlorodibenzo- p-dioxin isomers and
N-nitrosamines have only recently been developed. Available
analytical data are limited to a few manufactured products.
1.1.2. Sources of environmental pollution
Most of the 2,4-D residues result from the production and use
of 2,4-D herbicides. Other possible minor sources of 2,4-D include
the use of 2,4-dichlorophenoxybutyric acid (2,4-DB).
Little information is available on the uses of 2,4-D products
and the amounts used in various parts of the world.
The drifting of vapours of the more volatile short-chain 2,4-D
esters may result in air pollution and crop damage, and these
products are being replaced by less volatile long-chain esters or
by amine salts.
The use of 2,4-D for aquatic weed control may lead to
contamination of sources of irrigation and drinking-water.
Environmental pollution also arises through inadequate disposal
practice.
1.1.3. Environmental distribution and transformations
Various amounts of 2,4-D products applied to a target area may
be distributed in the general environment, within a few hours or
days, by the movements of air, water, or soil, particularly during
periods of rain, high winds, or high temperature.
2,4-D and its derivatives are fairly rapidly broken down by
hydrolysis, photolysis, and by biological action.
Persistence or accumulation of 2,4-D residues from normal use
is occasionally possible, mainly under dry or cold conditions where
there is little biological activity.
Nothing is known about the environmental fate of the impurities
present in 2,4-D herbicides.
1.1.4. Environmental exposure levels
Available data indicate that residues of 2,4-D rarely exceed
1 mg/kg in soil, several µg/litre in water, several µg/m3 in air,
and a few tens of µg/kg in food sources. Exceptions may occur in
the vicinity of 2,4-D herbicide spills, in water treated with
aquatic 2,4-D herbicides, in berries and mushrooms grown in treated
right-of-way areas, or when the herbicide is used in quantities far
in excess of the rates applied in normal agricultural or forestry
practice. No information is available on the corresponding
exposure levels for the contaminants present in 2,4-D herbicides.
Exposure to 2,4-D, in the work environment, of persons
producing, handling, or using herbicides may result in absorption
of detectable amounts of 2,4-D.
1.1.5. Uptake and fate of 2,4-D in the body
2,4-D and its derivatives can be absorbed via the oral, dermal,
and inhalation routes. General population exposure is mainly by
the oral route, but under occupational and bystander exposure
conditions, the dermal route is by far the most important.
Distribution of 2,4-D occurs throughout the body, but there is
no evidence that it is accumulated. Transformation in mammals
appears to occur only to a slight extent and mainly involves the
production of 2,4-D conjugates with sugars or amino acids. A
single dose is excreted within a few days, mainly with the urine,
and to a much lesser extent in the bile and faeces.
Little is known about the uptake and subsequent fate of the
contaminants of 2,4-D other than 2,4-dichlorophenol.
1.1.6. Effects on animals
1.1.6.1. Acute toxic effects
Death may result in mammals and birds administered oral doses
of 2,4-D exceeding approximately 100 - 300 mg/kg body weight.
The most characteristic signs of severe 2,4-D poisoning are
those of myotonia, but various other physiological, haematological,
biochemical, and histological changes have been described.
The no-observed-adverse-effect level for a single dose of 2,4-D
in animals has not been clearly established for all species.
No adequately documented reports of acute accidental 2,4-D
poisoning of mammals or birds have been found.
1.1.6.2. Chronic toxic effects
The no-observed-adverse-effect level for some of the chronic
adverse effects of 2,4-D in mammals has not been established
firmly.
1.1.6.3. Teratogenic and reproductive effects
The no-observed-adverse-effect level for the teratogenic,
embryotoxic, or fetotoxic effects of 2,4-D in mammals and birds
appears to be about 10 mg/kg body weight per day.
1.1.6.4. Mutagenic effects
Studies available at present are not adequate for the
quantitive evaluation of the mutagenic effects of 2,4-D and its
derivatives in short-term tests. However, the evidence does not
suggest that 2,4-D derivatives are potent mutagens.
1.1.6.5. Carcinogenic effects
The carcinogenic potential of 2,4-D and its derivatives such as
the amine salts and esters has not been adequately tested. The
reports on animal bioassays carried out so far are either too brief
for proper evaluation, or have become the subject of scientific
controversy.
1.1.7. Effects on human beings
1.1.7.1. Acute toxic effects
2,4-D drug trials and studies on volunteers have shown that
doses of between 5 and about 30 mg/kg body weight do not cause any
acute toxic effects.
Accidental and intentional 2,4-D poisonings indicate that the
toxic effects of 2,4-D are the same in human beings as in other
mammals. The lethal single oral dose is uncertain.
1.1.7.2. Chronic toxic effects
It is uncertain whether the chronic toxic effects of 2,4-D
products reported in occupationally-exposed people are solely
attributable to 2,4-D.
1.1.7.3. Teratogenic and reproductive effects
Scientifically valid studies have not shown any adverse
reproductive effects in human beings accidentally or occupationally
exposed to 2,4-D.
1.1.7.4. Mutagenic effects
The results of studies suggesting that occupational exposure to
2,4-D may result in chromosome abnormalities are equivocal.
1.1.7.5. Carcinogenic effects
The results of some epidemiological studies have suggested an
association between exposure to phenoxy herbicides and increased
incidences of malignant tumours and tumour mortality. It is not
clear, at present, whether this represents a true association, and
if so, whether it is specifically related to 2,4-D.
1.2. Recommendations for Further Studies
1.2.1. Analytical methods
Methods not requiring highly sophisticated and expensive
equipment are available for the accurate, specific, and sensitive
determination of 2,4-D residues in a wide variety of environmental
and biological materials. However, it would be desirable to
develop simpler but specific methods for the detection and
quantification of dioxin contaminants.
1.2.2. Environmental exposure levels
Further studies should be undertaken to determine the total
2,4-D intake of various sub-populations in areas of 2,4-D use.
It would be desirable to monitor 2,4-D residues in aquatic
organisms taken from lakes or rivers receiving discharges or
treatment with 2,4-D.
Further work on the relationship between the factors
influencing the dermal absorption of various 2,4-D formulated
products in human beings and animals should be carried out.
1.2.3. Studies on animals
More animal studies are desirable to investigate the possible
interactions between 2,4-D and other herbicides commonly used in
conjunction with 2,4-D.
Further work is required to accurately define the no-observed-
adverse-effect level for 2,4-D in long-term exposures.
Where unknown, the chronic toxicity of the alcohols and amines
used in preparing 2,4-D derivatives, should be investigated.
More studies are needed to assess the mutagenic potential of
2,4-D derivatives.
1.2.4. Studies on human beings
In the case of occupationally-exposed workers further
consideration should be given to the chemobiokinetics of 2,4-D
under repeated exposure conditions.
2. PROPERTIES AND ANALYTICAL METHODS
2.1. Physical and Chemical Properties of 2,4-D
2.1.1. Introduction
The structures of 2,4-dichlorophenoxyacetic acid (2,4-D) and of
chemically-related phenoxy herbicides in common use are given in
Fig. 1.
Some physical properties of 2,4-D and of the 2,4-D derivatives
that are used in agriculture are summarized in Table 1.
Table 1. Physical properties of 2,4-D
---------------------------------------------------
Molecular formula: C8H6Cl2O3
Relative molecular mass: 221.0
Melting point: 140-141 °C
Solubility in water: slightly soluble
Solubility in organic solvents: soluble
Vapour pressure: 52.3 Pa at 160 °C
pKa at 25 °C: 2.64-3.31
---------------------------------------------------
2,4-D has growth-regulating and herbicidal properties in
broad-leaved plants. Because of its solubility, 2,4-D is
rarely used in the form of the acid; commercial 2,4-D
herbicide formulations consist of the more soluble forms such
as alkali salts, amine salts, or esters. These are combined
with solvents, carriers, or surfactants and are marketed in
the form of dusts, granules, emulsions, or oil and water
solutions in a wide range of concentrations.
2.1.2. Synthesis of 2,4-D
2,4-D is commonly prepared by the condensation of 2,4-
dichlorophenol with monochloroacetic acid in a strongly alkaline
medium at moderate temperatures (Canada, NRC, 1978; Sittig 1980;
Que Hee & Sutherland, 1981), or by the chlorination of
phenoxyacetic acid, but this method leads to a product with a high
content of 2,4-dichlorophenol and other impurities (Melnikov,
l97l). Higher reaction temperatures and alkaline conditions during
the manufacture of 2,4-D increase the formation of polychlorinated
dibenzo- p-dioxin (CDD) by-products (Fig. 2). The alkali metal
salts of 2,4-D are produced by the reaction of 2,4-D with the
appropriate metal base. Amine salts are obtained by reacting
stoichiometric quantities of amine and 2,4-D in a compatible
solvent (Que Hee & Sutherland, 1974, 1981). Esters are formed by
acid-catalysed esterification with azeotropic distillation of water
(Que Hee & Sutherland, 1981) or by a direct synthesis in which the
appropriate ester of monochloroacetic acid is reacted with
dichlorophenol to form the 2,4-D ester (Canada, NRC, 1978).
2.1.3. Important chemical reactions of 2,4-D
Pyrolysis converts various amine salts of 2,4-D to the
corresponding amides (Que Hee & Sutherland, 1975a). Pyrolysis of
2,4-D and its derivatives is likely to produce certain CDD isomers
(section 2.1.4). 2,4-D is readily photodegraded (section 4.4.4).
2.1.4. Composition of technical 2,4-D materials
Technical 2,4-D may range in purity from less than 90% to 99%.
Typical levels for impurities are listed in Table 2. Trace levels
of CDDs have been found in amine and ester formulations (Table 3).
It can be seen that the amine formulations tend to be less highly
contaminated with di- and tetra-CDD than the ester products. The
structures of these impurities are shown in Fig. 2.
Table 2. Typical levels of 2,4-D and major impurities
in technical 2,4-Da
------------------------------------------------------
Component % range
------------------------------------------------------
2,4-dichlorophenoxyacetic acid 94 - 99
2,6-dichlorophenoxyacetic acid 1.5 - 0.5
2-monochlorophenoxyacetic acid 0.5 - 0.1
4-monochlorophenoxyacetic acid 0.8 - 0.2
bis(2,4-dichlorophenoxy) acetic acid 2.0 - 0.1
phenoxyacetic acid trace - 0.2
2,4-dichlorophenol 0.6 - 0.1
2,6-dichlorophenol 0.048 - 0.001
2,4,6-trichlorophenol 0.14 - 0.001
2-chlorophenol 0.04 - 0.0004
4-chlorophenol 0.005 - 0.0004
water 0.8 - 0.1
------------------------------------------------------
a From: Cochrane (1981).
Table 3. Ranges of levels of chlorinated dibenzo- p-dioxins (CDD)
in 2,4-D amine and ester formulationsa
-------------------------------------------------------------------
CDD isomers found (µg/kg)b
Type of 2,7-di- 1,3,7-tri- 1,3,6,8/ 2,3,7,8-tetra
formulation 1,3,7,9-tetra
-------------------------------------------------------------------
2,4-D amines ndc- 409 nd - 587 nd - 278 nd
2,4-D esters nd - 23815 nd - 450 nd - 8730 nd
-------------------------------------------------------------------
a From: Cochrane et al. (1981).
b Expressed in terms of 2,4-D.
c nd (not detected < 1 µg/kg).
The composition of technical 2,4-D depends on the manufacturing
process and especially on the purity of 2,4-dichlorophenol when
this is the starting material. During 2,4-D synthesis from
monochloroacetic acid and 2,4-dichlorophenol, the latter compound
as well as other ortho-chlorinated by-products can give rise to a
wide variety of chorinated by-products at a high temperature and
high pH. Self condensation of 2,4-dichlorophenol may form 2,7-
dichlorodibenzo- p-dioxin, while trichlorophenols may give rise to
a mixture of 1,3,6,8- and 1,3,7,9-tetrachlorodibenzo- p-dioxins
(but not 2,3,7,8-TCDD) by self-condensation, or to 1,3,7-
trichlorodibenzo- p-dioxin by cross-condensation with 2,4-
dichlorophenol.
A different type of toxic trace impurity, namely N-
nitrosamines, can occur in amine formulations of 2,4-D, especially
when nitrite is added as a corrosion inhibitor for containers.
Dimethyl- N-nitrosamine has been found in some 2,4-D dimethylamine
products at levels of up to 0.3 mg/litre (Ross et al., 1977; Cohen,
et al., 1978).
2.1.5. Volatility of 2,4-D derivatives
2,4-D esters with short-chain alcohols are highly volatile
(Table 1). This influences the effectiveness of their application
to target crops, their effects on neighbouring crops, and the
degree of contamination of the atmosphere. 2,4-D alkali salts or
amine salts are much less volatile than esters (Carter, 1960;
Canada, NRC, 1978; Que Hee & Sutherland, 1981, and section 4.1),
and these products are to be preferred when the use of 2,4-D esters
might lead to evaporative 2,4-D losses and to crop damage.
2.2. Determination of 2,4-D
2.2.1. General comments
General comments on criteria for acceptable analytical methods
and on other pertinent aspects of 2,4-D determination can be found
in the publications of Gunther (1962), Currie (1968), Kaiser
(1973), Carl (1979), Kateman & Pijper (1981), Que Hee & Sutherland
(1981) and Chau et al. (1982).
2.2.2. Analysis of technical and formulated 2,4-D products
In the past, the quality of 2,4-D products was assessed by an
acid-base titration or by a total chlorine determination
(Collaborative International Pesticides Analytical Council, 1970).
These non-specific and thus inaccurate methods have been superseded
by specific gas-liquid chromatography (GLC) or high pressure liquid
chromatography (HPLC), making it possible to determine various by-
products (Henshaw et al., 1975; Bontoyan, 1977; Skelly et al.,
1977; Stevens et al., l978; Cochrane et al., 1982). The isomer-
specific HPLC method is now preferred by many 2,4-D producers and
regulatory agencies. The chlorinated dibenzo- p-dioxins (CDDs) are
usually produced only in trace amounts and are difficult to
separate and identify; highly specialised equipment and skills are
necessary (Crummett & Stehl, 1973; Huckins et al., 1978; Norström
et al., 1979; Baker et al., 1981; Cochrane et al., 1981; Hass et
al., 1981, and National Research Council of Canada, Associate
Committee on Scientific Criteria for Environmental Quality, 1981).
2.2.3. Determination of 2,4-D residues
All exposure determinations and risk assessments ultimately
depend on accurate chemical analyses, and therefore some critical
aspects of analysis for 2,4-D residues have been included in the
present document.
Before 2,4-D residues can be measured, they have to be
quantitatively extracted and purified to remove substances that
could interfere with the final residue determination. They must
then be converted to a stable product (derivative) suitable for
determination with a given type of detector.
When comparing analytical results, it should be kept in mind
that the older methods of extraction and clean-up contained
considerable sources of errors, and that the early methods
for measuring 2,4-D residues, such as colorimetry and
spectrophotometry, were not as sensitive or specific as those
developed in recent years.
2.2.3.1. Sampling, extraction, and clean-up
Methods for the sampling, extraction, and clean-up of 2,4-D
residues in water, air, soil, and biological materials have
recently been reviewed by National Research Council of Canada,
Associate Committee on Scientific Criteria for Environmental
Quality (1978) and by Que Hee & Sutherland (1981). Problems caused
by the conjugate formation of 2,4-D with amino acids, proteins,
sugars, or lipids, or the absorption of 2,4-D onto container
surfaces, including those of glass vessels, have been solved by
Chow et al. (1971), Renberg (1974), Osadchuk et al. (1977), Lokke
(1979), Jensen & Glas (1981), and Bristol et al. (1982). For
sampling and extracting 2,4-D residues, the following references
should also be consulted:
Air: Van Dyk & Visweswariah (1975), Farwell et al. (1976a,b),
Grover et al. (1976), Johnson et al. (1977), Gluck & Melcher
(1980), and Grover & Kerr (1981); water: Suffet (1973a,b), Renberg
(1974), Mierzwa & Witek (1977), Chau & Thomson (1978); soil:
Woodham et al. (1971); Smith (1972, 1976a), Foster & McKercher
(1973); food: Que Hee & Sutherland (1981), Bjerk et al. (1972),
Jensen & Glas (1972), Lokke (1975); biological media: Smith
(1976b), (blood, urine); Senczuk & Pogorzelska (1981).
2.2.4. Derivatization and quantification
At present, gas-liquid chromatography with electron-capture
detection (GLC-EC) is the most commonly used and generally most
sensitive method (picogram level) for measuring 2,4-D residues.
To improve the sensitivity of detection, the 2,4-D has to be
transformed (derivatized), usually to a methyl ester by reacting
with BF3-methanol, diazomethane, or with concentrated sulfuric
acid-methanol; the first method may give the best results (Munro,
1972; Horner et al., 1974; Olson et al., 1978).
For a recent review of derivatization methods and GLC columns
for various substrates see Cochrane (1981).
Thin-layer chromatography (TLC) has been used for herbicide
residue determination (Guardigli et al., 1971, Yip 1975). It has
recently been recommended by Batora et al. (1981) as a simplified
method for determining pesticide residues that requires a minimum
of costly equipment. TLC is suitable for food inspection and could
be of use in the establishment of new residue laboratories in
developing countries.
High-pressure liquid chromatography (HPLC) is less sensitive
than GLC-EC i.e., nanogram (ng) versus picogram levels, but may be
advantageous under some circumstances (Tuinstra et al., 1976;
Arjmand et al., 1978; Connick & Simoneaux, 1982). Using mass
fragmentography with deuterated internal standards it is possible
to determine nanogram amounts of 2,4-D and related compounds in
urine and plasma (De Beer et al., 1981); it is also suitable for
chemobiokinetic studies on subtoxic doses of 2,4-D in blood.
2.2.5. Confirmation
The ultimate confirmatory technique is gas chromatography
coupled with mass spectrometry and specific ion monitoring, with a
sensitivity down to the femtogram level (Farwell et al., 1976a).
3. SOURCES OF ENVIRONMENTAL POLLUTION
3.1. Production of 2,4-D Herbicides
Comprehensive statistics on 2,4-D herbicide production or use
were not available for review. According to the US Department of
Agriculture, 3 x 108 kg of total herbicides were used in the USA
alone, in 1981. In the past, 10% of the herbicide used was 2,4-D,
which would account for a total use in the USA of about 3 x 107 kg.
In 1975, an estimated 5 x 106 kg were produced in the United
Kingdom. World-wide use of herbicides and annual production, which
probably exceeds 5 x 107 kg per year, are increasing, National
Research Council of Canada, Associate Committee on Scientific
Criteria for Environmental Quality, 1978; Bovey & Young, 1980).
3.2. Uses
2,4-D alkali or amine salts or esters are used as agricultural
herbicides against broad-leaf weeds in cereal crops as well as on
pastures and lawns, in parks, and on golf courses at rates of about
0.2 - 2.0 kg active ingredient (acid equivalent) per hectare.
Esters are also used at rates of up to 6 kg (acid equivalent) per
ha to suppress weeds, brush, and deciduous trees along rights-of-
way and in conifer plantations and conifer reafforestation areas.
Granular formulations of 2,4-D are used as aquatic herbicides
in or along irrigation and other canals, in ponds, and lakes at
rates ranging from 1 to 122 kg/ha (Pal'mova & Galuzova, 1963; Smith
& Isom, 1967; National Research Council of Canada, Associate
Committee on Scientific Criteria for Environmental Quality, 1978;
Bovey & Young, 1980).
2,4-D products can be used at very low application rates as
growth regulators by application of aqueous foliar sprays
containing 20 - 40 mg 2,4-D/litre on apple trees to reduce
premature fruit drop, on potato plants to increase the proportion
of medium-size tubers or to intensify the tuber skin colour of the
red varieties (Bristol et al., 1982), and in citrus culture to
reduce pre-harvest fruit drop and to increase fruit storage life.
The highly volatile ethyl, isopropyl, and butyl esters are
being replaced by low-volatile esters or by amine salts to reduce
crop damage resulting from 2,4-D vapour drift, and to decrease
atmospheric pollution.
During recent years, the use of 2,4-D and 2,4,5-T in parks,
forested recreation, and other areas frequently used by the public,
has been reduced in some countries, because of increasing concern
about possible toxic effects, especially in relation to CDDs.
The ecological effects of using high rates of 2,4-D and
repeated treatments have been reviewed by Bovey & Young (1980).
3.3. Disposal of wastes
3.3.1. Industrial Wastes
Environmental pollution with 2,4-D may occur as a result of the
production and disposal of 2,4-D, or of its by-products, and of
industrial effluents. Such pollution will be generally localised
to the production site and to areas of waste dumping, and it is
likely to be more dispersed if disposal or leaching has occurred
into water courses. Combustion of 2,4-D and its by-products at low
temperatures could lead to the formation of CDDs. A temperature
approaching 1000 °C, however, gives almost complete destruction of
2,4-D (Sittig, ed., 1980). The spread of 2,4-D from waste dumps
may be reduced by the use of properly enclosed impermeable clay-
lined pits, away from water sources.
3.3.2. Agricultural wastes
Disposal of unused 2,4-D and washing of equipment may result in
localised land pollution and also pollution of water supplies
through direct contamination or leaching from soil.
4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION OF 2,4-D
2,4-D does not persist or accumulate in the environment, as it
is readily degraded by physical, chemical, and biological action.
It is susceptible to photolysis in air and water, on soil, and on
plant surfaces. Thus, the question of environmental distribution
is limited to the immediate transfer of 2,4-D between compartments
of the environment.
4.1. Drift and Volatilization in the Atmosphere
The atmosphere can be contaminated with 2,4-D during both its
manufacture and use. The production of 2,4-D may result in the
emission into the air of dichlorophenol, chloroacetic acid, and
ammonia (Sittig, ed., 1980), in addition to 2,4-D vapours (Grover
et al., 1976).
According to the formulation of 2,4-D used, environmental
transfer into the atmosphere will occur by either drift (depending
on the particle size of the droplet, the spray technique, and
climatic conditions), or by volatilization, or by a combination of
both. It is very difficult to calculate the extent to which drift
or volatisation occurs, and this is illustrated by the range of
2,4-D concentrations observed in the air after 2,4-D use (Table 4).
The factors affecting the amount of herbicide spray that lands
on a target crop and the proportion that is lost by drifting or
volatilization have been described (Grover et al., 1972; Grover,
1976; Maybank et al., 1978; Que Hee & Sutherland, 1981). Unwanted
residues may be deposited on non-target crops (Akesson & Yates,
1961; Yates & Akesson, 1973). The National Research Council
of Canada, Associate Committee on Scientific Criteria for
Environmental Quality (1978) cited reports of drift damage
caused in susceptible crops by phenoxy herbicide applications,
particularly in cotton, tobacco, tomatoes, grapes, rapeseed,
clover, and a number of horticultural species.
Widespread damage in vineyards and in other crops due to 2,4-D
drift from sprayed wheat fields was reported by Robinson & Fox
(1978) with two different damage patterns, one localized and the
other widespread. The first was characterized by severe localized
damage with a very clear gradient of decreasing severity away from
the zone, following the drift of spray droplets in the immediate
treatment area. The more widespread damage was of greater concern.
It was characterized by more or less uniform symptoms and appeared
to be attributable to the passage of a large cloud of vapour that
may have extended for several km. Both problems could have been
avoided by the use of low-volatile preparations and proper
application methods.
Table 4. Concentrations of total 2,4-D residues in ambient air
------------------------------------------------------------------------------------------------------------------
Days when 2,4-D was 2,4-D residues
Site location µg/m3air Predominant
No. of stations, height ------------------------------------------- type of 2,4-D Reference
Regional characteristics found Sample Meana Max. residue
present time
mean max. h
------------------------------------------------------------------------------------------------------------------
Saskatchewan, Canada not
(1) 150 m (aircraft) stated 1 min 1.0c 2.5 butyl ester Elias (1975)
Saskatchewan, Canada 48 33 36 24 h 0.5c 13.5 butyl ester Grover et al.
(8) 2 m above ground 24 h 0-6d isooctyl ester (1976)e,f
level, wheat area 24 h - - amine salt
California, USA 41 (1973) 24 h 0.4 0.9 high volatile Farwell et al.
(7-8) near ground 73 (1974) 24 h 0.1 0.4 low volatile (1976)
level 24 h 0.1 0.2 non volatile
Washington State, USA 105-106 81 89 24 h 0.2 2.2 isopropyl ester Adams et al.
(2) near ground 65 69 24 h 0.09 2.2 butyl ester (1964)b
level, wheat area 8 11 24 h 0.003 3.1 isooctyl ester
Washington State, 99-102 34 39 24 h 0.08 2.0 isopropyl ester droplets Bamesberger &
(2) near ground 8 15 24 h 0.08 1.3 isopropyl ester vapour Adamsb
level, wheat area 18 22 24 h 0.07 1.0 butyl ester droplets
3 5 24 h 0.03 1.3 butyl ester vapour
1 1 24 h 0.005 0.5 isooctyl ester droplets
- - 24 h - - isooctyl ester vapour
4 5 24 h 0.01 0.5 acid, salts, droplets
5 5 24 h 0.04 5.1 acid, salts, vapour
------------------------------------------------------------------------------------------------------------------
a Values measured at different sites or at different times have been averaged and reduced to a single significant
figure for simplicity.
b At the time of these studies, GLC methods were less highly developed.
c Centre of principal range observed.
d Maximum values recorded in a previous study (Que Hee et al., 1975) were shown to be equivalent to concentrations
existing directly over an open pan of formulated butyl ester; the implication was made that accidental
laboratory contamination could have occurred.
f The results of Maybank & Yoshida (1969), Maybank et al. (1978), and Stanley et al. (1971) could not be adapted
to this table.
Volatilization of 2,4-D products in the air during the spraying
operation and from the surface of plants and the soil is difficult
to distinguish from the drift of spray droplets. Evaporation
occurs to a greater extent with the highly volatile ethyl,
isopropyl, or butyl esters; very little occurs with amine salt
formulations, and it is greatly reduced when 2,4-D is dissolved in
corn oil, cottonseed oil, or diesel oil (Marth & Mitchell, 1949).
In one experiment, no significant amounts of 2,4-D amine, but 20 -
40% of the initially deposited 2,4-D butyl ester, and 10 - 15% of
the octyl ester of 2,4-D vapourized within 2 h of spraying (Grover
et al., 1972); less volatilization occurs with the higher esters of
2,4-D. For this reason, the use of the more volatile esters has
been discontinued in some countries. Studies of 2,4-D aerial drift
following ground spray operations have shown that only 3 - 8% of
the applied herbicides drift as spray droplets when low volatile
preparations are applied as large droplets. However, ultra-low-
volume (ULV) applications by aircraft, or the use of highly
volatile esters may cause as much as 25 - 30% of the 2,4-D sprayed
to drift off the target (Grover et al., 1972; Maas & Kerssen, 1973;
Maybank et al., 1978).
4.2. Movement Within and From the Soil
The movement of pesticides within and from the soil can be
divided into three categories: diffusion, leaching, and surface
movement. Diffusion is a localized process and depends on the
concentration gradient of the pesticide in the soil medium, on the
soil mineral type, and on the organic matter content, temperature,
pH, and other factors. Leaching refers to the movement of
pesticides through the soil profile with percolating water.
Surface movement refers to wind erosion of dust particles and
surface run-off in flowing water.
Examination of the behaviour of 2,4-D in soils (Liu & Cibes-
Viade, 1973; Grover & Smith, 1974; Moreale & Van Bladel, 1980) has
shown that organic matter, soil pH (surface horizons), and
exchangeable aluminium (clay sub-horizons) are the key determinants
for the percentage of 2,4-D adsorbed. As the adsorption/desorption
process is the basic mechanism influencing herbicide availability,
mobility, and degradation in soil, 2,4-D is likely to be more
strongly bound in soils with a high content of organic matter than
in those with a low content.
4.3. Contamination of Water
Residues of 2,4-D in aqueous systems can result from the
deposition of spray drifts, the "washout" of 2,4-D in the vapour or
droplet phase from the atmosphere during rainfall, the run-off from
treated fields, or following the application of 2,4-D to water for
the control of aquatic weeds. Industrial discharges, either from
accidental spills or through sewage systems, may also contribute to
the contamination of water. The National Research Council of
Canada, Associate Committee on Scientific Criteria for
Environmental Quality (1978) has tabulated data that demonstrate
the influence of environmental factors on the clearance of 2,4-D
and its derivatives from water. The principal processes involved
are ester and amine hydrolysis, volatilization, microbial
degradation, photolysis, and sorption. There is little movement of
2,4-D into drainage water in organic soils, because it is strongly
bound to organic materials.
4.4. Environmental Transformation and Degradation Processes
4.4.1. Metabolism in plants
Plants hydrolyse 2,4-D esters to 2,4-D, which is the active
herbicide (Morton et al., 1967; Matsunaka, 1972). Further
metabolism in plants occurs through three mechanisms, namely, side-
chain degradation, hydroxylation of the aromatic ring, and
conjugation with plant constituents (Crafts, 1960; Morre & Rogers,
1960; Erickson et al., 1963).
4.4.1.1. Side-chain degradation
Degradation of the side-chain of 2,4-D has been observed in
many plants (Loos, 1969), but in only a few species or varieties
does it appear to play a major role in herbicide breakdown.
Luckwill & Lloyd Jones (1960a,b) suggested two degradation
pathways leading to the formation of 2,4-dichlorophenol.
4.4.1.2. Ring hydroxylation
Thomas et al. (1964a,b), and, more recently, Feung et al.
(1971, 1972, 1973b) identified 2,5-dichloro-4-hydroxyphenoxyacetic
acid and 2,3-dichloro-4-hydroxyphenoxyacetic acid as major and
minor phenolic acid metabolites, respectively. Evidence was found
by Fleeker & Stein (1971) indicating hydroxylation resulting in the
elimination of the 4-chloro substituent from the aromatic ring, in
addition to migration of the chlorine at the 4-position to an
adjacent carbon on the ring. A small amount of 2-chloro-4-hydroxy-
phenoxyacetic acid was produced from 2,4-D by wild buckwheat, wild
oats, leafy spurge, and yellow foxtail.
4.4.1.3. Conjugation with plant constituents
Studies indicate that resistant crops, i.e., grasses and
cereals, form water-soluble conjugates with sugars, whereas
sensitive broad-leaved crops (such as beans) form mainly water-
insoluble amino acid conjugates (Montgomery et al., 1971; Feung et
al., 1971, 1972, 1973b, 1975).
4.4.2. Degradation of 2,4-D in the soil
Deposition of 2,4-D esters on the soil is followed fairly
rapidly by hydrolysis. Burcar et al. (1966) observed that the
2,4-D isooctyl ester disappeared after 2 weeks, though free acid
could be detected up to 6 weeks after application. The breakdown
of the iso-propyl, n-butyl, and isooctyl esters of 2,4-D on three
Canadian prairie soils was studied by Smith (1972) who found that
after 24 h no iso-propyl or n-butyl esters remained, whereas
20 - 30% of the isooctyl ester was still intact. The author
concluded that an initial rapid phase of hydrolysis of the 2,4-D
esters to the anion in soil was the result of chemical and not
microbial action.
Microbial degradation of phenoxy herbicides does occur and has
been comprehensively reviewed by Loos (1975), Cripps & Roberts
(1978) and The National Research Council of Canada, Associate
Committee on Scientific Criteria for Environmental Quality, (1978).
Early studies of the persistence of 2,4-D in soil indicated that
warm moist conditions and the presence of organic matter favoured
the rapid disappearance of 2,4-D. Sterilization of the soil
inhibited breakdown, indicating that the degradation was microbial.
In addition, Pemberton (1979) reported the discovery of specific
2,4-D plasmids within some bacterial strains, transmitted from one
cell to another, and carrying with them a genetic capability
enabling the bacteria to degrade 2,4-D.
Two principal pathways have been proposed for the microbial
degradation of 2,4-D in soil. Firstly the side chain may be
removed to form 2,4-dichlorophenol, followed by orthohydroxylation
of the phenol to produce a catechol (Bollag et al., 1968). The
catechol may then be cleaved to yield a muconic acid and further
conversion products. The second possible pathway is via a
hydroxyphenoxyacetic acid intermediate (Evans et al., 1971).
4.4.3. Degradation in the aquatic ecosystem
A multitude of variables influence the partitioning and removal
of phenoxy herbicides within an aquatic ecosystem. Detectable
residues have been reported to persist for 4 weeks in some
situations and up to 4 months in others (Frank & Comes, 1967;
Wojtalik et al., 1971; Schultz & Harman, 1974). Photolysis is an
important means of degradation of 2,4-D in natural water and is
more rapid than that of 2,4,5-T (Crosby & Wong, 1973). The
partition of residues between water and sediment will have an
effect on the rate of breakdown, as will temperature and intensity
of light. Anaerobic conditions will favour microbial breakdown.
The effects of some of these factors have been tabulated by the
National Research Council of Canada, Associate Committee on
Scientific Criteria for Environmental Quality (1978).
4.4.4. Photochemical degradation
Photodecomposition of 2,4-D was studied in detail by Crosby &
Tutass (1966), Boval & Smith (1973), and reviewed recently by Que
Hee & Sutherland (1981). It leads to the formation of a variety of
products but commonly involves reductive dechlorination of the
acid, esters, and salts in aqueous or in organic solutions, with
2,4-dichlorophenol acting as a catalyst for the breakdown of
2,4-D, which may involve rupture of the aromatic ring. Que Hee &
Sutherland (1987) studied the vapour and liquid phase photolysis of
the n-butyl ester of 2,4-D and observed dechlorination at the
second position with simultaneous reduction and re-arrangement to
produce a variety of photoproducts. According to Boval & Smith
(1973), carbon dioxide is the final oxidation product when aqueous
solutions of 2,4-D undergo photodecomposition.
4.5. Bioconcentration
There is no evidence that bioconcentration of 2,4-D occurs
through the food chain or in any compartment of the environment.
This has been demonstrated by large-scale monitoring for 2,4-D
residues in soils, foods, feedstuffs, wildlife, and human beings,
and from examinations of the many routes of metabolism and
degradation that exist in ecosystems (sections 5.1.3 and 5.1.4).
5. ENVIRONMENTAL LEVELS AND EXPOSURE
5.1. Levels of 2,4-D Residues in the Environment
Most of the available information on 2,4-D levels in the
environment has been reviewed in detail (National Research Council
of Canada, Associate Committee on Scientific Criteria for
Environmental Quality, 1978; Ramel, 1978; Bovey & Young, 1980;
Canada, Health & Welfare, 1980; Shearer & Halter, 1980; US EPA,
1980a). In comparing early and recent results, it should be kept
in mind that the analytical procedures used before about 1965 were
often unreliable and may have resulted in under- or overestimation
of the actual levels of 2,4-D derivatives. No information is
available on the levels of 2,4-D-related dioxin by-products in the
environment.
5.1.1. In air
Some levels of 2,4-D in ambient air are shown in Table 4.
These 2,4-D residues consist mainly of esters, particularly the
highly volatile butyl esters (Bamesberger & Adams, 1966; Farwell et
al., 1976b; Grover et al., 1976). Total 2,4-D residues in the air
were found to decrease during periods of rain, suggesting a
"washout effect" (Grover et al., 1976). In the majority of cases,
the levels reported were those found shortly after spraying.
5.1.1.1. Field exposure
Concentrations of 2,4-D that occurred during and after
herbicide use in the air of the work zone of people engaged in
herbicide spray operations in various use situations, are given in
Table 5. Workers involved in these operations were exposed to
2,4-D levels of up to 0.2 mg/m3 air during the period of actual
application.
5.1.1.2. General environmental exposure
In large-scale studies in areas of intense 2,4-D use, about 40%
of all air samples were found to contain between 0.01 and 0.1 µg
2,4-D/m3 (Grover et al., 1975). In a similar study undertaken by
Que Hee et al. (1976), much higher levels were recorded in one
urban location, reaching an average of 339 µg/m3 air during 3 days.
However, Grover et al. (1976), in their subsequent work, showed
that such concentrations could only be produced under artificial
conditions that could not reflect environmental conditions. In a
general programme of air monitoring undertaken in citrus-growing
regions in the USA, only one out of 880 samples analysed was found
to contain 2,4-D, at a level of 0.004 mg/m3. The sites were not
chosen in relation to 2,4-D use (Stanley et al., 1971).
Table 5. Concentrations of total 2,4-D in air related to occupational exposure
---------------------------------------------------------------------------------------------------------
Days Mean of 2,4-D
Herbicide Circumstances Type of exposure after concentrations References
product monitoring spraying in air (mg/m3)
---------------------------------------------------------------------------------------------------------
2,4-dimethylamine agricultural spray Analyses of air 0 0.02 Thiele et al.
salt (0.9% aqueous operations with in tractor cabs (1981a,b)
solution) tractor-drawn
equipment
2,4-D butoxyethanol Exposure during Analyses of air 0 0.1-0.2 Kolmodin-Hedman
ester. 2% emulsion forest spray in breathing zone & Erne (1980),
in water operation with of workers Kolmodin-Hedman
tractor driven et al. (1979)
equipment
2,4-D isooctyl- 3-day aerial spray Analyses of air 0 0.002-01a Franklin et al.
ester in diesel oil operation with single in breathing zone (1982)
engine aircraft of pilot and
ground crew
2,4-D PGBE ester Two 1-day aerial Analyses of air 0 <0.00001b Lavy et al.
emulsion in water forest spray in breathing zone (1982)
operations by of ground crew
helicopter
---------------------------------------------------------------------------------------------------------
a Application using large spray droplets.
b One flagman was recorded as being exposed to 0.1 mg/m3.
5.1.2. In water
2,4-D, as well as chlorophenol residues resulting from the
microbial transformation of 2,4-D, may occur in raw and finished
supplies of drinking-water (Faust & Aly, 1963; US EPA, 1976, 1980a;
National Research Council of Canada, Associate Committee on
Scientific Criteria for Environmental Quality, 1978; Bovey & Young,
1980; Canada, Health & Welfare, 1980; Shearer & Halter, 1980).
Information on 2,4-D-related dioxins in water was not
available.
Drinking-water in the USA is routinely analysed by the FDA as
part of the beverage-food group in their "market basket" analysis
programme; 2,4-D has not been detected in these studies, where the
limit of detection is 0.005 mg/litre for beverages (Table 6). This
indicates that drinking-water is not a significant source of human
exposure outside directly sprayed areas.
The same conclusion can be drawn from the results of large-
scale surveys of pesticide residues, including 2,4-D in surface
waters in areas of 2,4-D use (Table 7).
Levels much higher than those found in these studies have been
observed, but only in relation to local spills or direct
contamination (Frank et al., 1979; Frank & Sirons, 1980). A very
wide fluctuation has been found in water samples following
treatment of bodies of water, shores, ditches, or stream banks with
herbicides (Averitt, 1967; Frank & Comes, 1967; Bartley & Hattrup,
1970; Frank et al., 1970; Wojtalik et al., 1970; Frank, 1972;
Whitney et al., 1973; Schultz & Harman, 1974; Schultz & Whitney,
1974; Paderova, 1975; Province of British Columbia, 1981).
Occasional high contamination levels in samples of potable water
have been reported following experimental treatments of reservoirs
with 2,4-D (Wojtalik et al., 1971). However, the mean levels
tended to remain below 2 µg/litre, even in samples of raw or
processed water from 2,4-D-treated reservoirs (Smith & Isom, 1967;
Wojtalik et al., 1971; Province of British Columbia, 1981).
Generally, 2,4-D residues were < 0.1 µg/litre in two large-scale
monitoring programmes of surface waters (Frank & Sirons, 1980;
Gummer, 1980). This is not unexpected in view of the moderately
rapid microbial degradation of 2,4-D in the environment (Robson,
1966; Averitt, 1967; Frank, 1972; Nesbitt & Watson, 1980a,b;
Province of British Columbia, 1981).
2,4-D and especially its transformation product,
dichlorophenol, at levels exceeding 20 µg/litre will impart an
objectionable odour and taste to contaminated water (Pal'mova &
Galuzova, 1963; Faust & Suffet, 1966). This organoleptic effect
may reduce the likelihood of highly contaminated water being
ingested. It is noteworthy that public water supplies containing
"traces" of 2,4-D, and wells contaminated with 2,4-D or other
herbicides have been shut down because of objectionable odours or
tastes (Gribanov, 1968; Kramer & Schmaland, 1974; Frank et al.,
1979).
Table 6. 2,4-D residues reported in market basket samples in the USA
---------------------------------------------------------------------------------------------------------
Types of samples Nature of samples % of samples Residue levels
Years analysed containing residues with residues (mg/kg) References
---------------------------------------------------------------------------------------------------------
1965-65 Total diets sugars and adjunctsa 4.2 < 0.02-0.16 Duggan & Corneliussen
1966-66 leafy vegetables (1) 3.0 < 0.02-0.03 (1972)
low fats
1967-67 leafy vegetables (2) 1.7 0.03
oil fats (1)
1968-68 dairy produce (1) 0.6 0.02-0.13
1969-69 fruits (1), sugars (2) 0.3 < 0.2
1970-70 leafy vegetables (1) 0.3 < 0.02
dairy produce (1)
1970-71 Total diets leafy vegetables (3) - 0.01-0.02 Manske & Corneliussen
(1975)
1971-72 Total diets dairy products (1) - 0.01 Manske & Johnson
(1975)
1973-80 Total diets 0 < 0.01 Manske & Johnson
(1976)
Johnson et al.
(1981a,b)
Johnson et al. (1977)
1972-73 Potatoes from raw, boiled or baked - < 0.02-0.12 Bristol et al. (1982)
fields treated
with herbicide
---------------------------------------------------------------------------------------------------------
a No. of positives not specified.
Table 7. Concentrations of 2,4-D residues in surface water samples following application of 2,4-D to
agricultural landsa
------------------------------------------------------------------------------------------------------
Site No. of samples in 2,4-D applied 2,4-D residues
Number of Stations which 2,4-D was: in watershed (µg/litre) References
Regional Characteristics ----------------- (kg/ha) ---------------
analysed found meanb max.
------------------------------------------------------------------------------------------------------
Ontario, Canada 949 66 0.8 <0.1 3.9e Frank & Sirons (1980)
11
streams
Saskatchewan, Canada 15 10 - 2 21.6 Choi et al. (1976)
5
river
Western Canada 186 10 - 0.5c 4.3d Gummer (1980)
14
diverse sites
------------------------------------------------------------------------------------------------------
a Studies in which the analytical procedures were not described or were considered unreliable have not
been included.
b Values measured at different sites or at different times have been averaged and reduced to a single
significant figure for simplicity.
c Reported data are very close to analytical detection limits.
d The maximum value, which raises the average value considerably, occurred in the effluent of an
industrial plant.
e Levels of 15.9 and 320 µg/litre were recorded at two sites but were related to spillage or actual
spraying at the sampling locality.
5.1.3. In soil
Most of the information available at present concerning 2,4-D
and other chlorophenoxy herbicide residues in soils has been
reviewed by the National Research Council of Canada, Associate
Committee on Scientific Criteria for Environmental Quality (1978),
Bovey (1980a), and by Que Hee & Sutherland (1981). In highly
acidic soils, or in soils in cold or arid regions, 2,4-D
degradation is apparently slow (Lavy et al., 1973; Buslovich &
Milchina, 1976; Ou et al., 1978; Moreale & Van Bladel, 1980;
Nesbitt & Watson, 1980b). However, even at about 20 - 2000 times
the normal agricultural application rates, little or no detectable
2,4-D was left in soils under temperate climatic conditions with
prolonged winters, after intervals of 385 - 440 days (Young et al.,
1974; Stewart & Gaul, 1977; Bovey, 1980a). Furthermore, results of
a laboratory study on 2,4-D degradation in the soil showed a half-
life of 4 days (Altom & Stritzke, 1973). Several soil monitoring
studies in North America, in areas with regular 2,4-D use, have
shown residues in less than 10% of the samples, and at levels of
less than 1 mg/kg (Stevens et al., 1970; Wiersma et al., 1972;
Gowen et al., 1976).
The available data are inadequate for establishing regional and
seasonal profiles of 2,4-D soil residues and of direct population
exposure, but it is likely that direct exposure would be minor,
except during or soon after herbicide application. Indirect
exposure through the transfer of 2,4-D residues from soil to air,
or food sources is assessed separately.
5.1.4. In food sources
Although 2,4-D and its transformation products do not tend to
accumulate in plants and plant products, detectable residues of
2,4-D on food plants may be consumed by human beings or animals and
may thus contribute to the overall exposure of the human population
to this chemical.
The results of pertinent studies on 2,4-D residues on or in
foods, and in food sources for human beings and animals, are
summarized in Tables 8 - 11. Theoretically, some contribution to
the reported 2,4-D residues may have been partly derived from other
phenoxy herbicides, as 2,4-DB undergoes beta-oxidation to 2,4-D in
some plants and fish, and in cattle (Lisk et al., 1963; Gutenmann &
Lisk, 1965; Sundström et al., 1979; Bovey, 1980a).
5.1.4.1. Residues in retail food supplies
The frequency of occurrence and the levels of 2,4-D residues in
over 110 000 samples of a variety of different ready-to-eat foods,
beverages, and infant and young children's diets, have been studied
over the last 20 years in the USA (Lipscomb, 1968; Corneliussen,
1970, 1972; Duggan et al., 1971; Duggan & Corneliussen, 1972;
Johnson et al., 1979, 1981a,b). The 2,4-D residues found in such
samples are reported in Table 6. The theoretical daily intake
resulting from these residues was variously estimated to be < 1 -
5 µg/person per day (Duggan & Corneliusson, 1972).
Studies undertaken since 1970 have failed to detect residues of
2,4-D in any of the US diet samples analysed, except for a single
positive sample in the dairy product food group which was estimated
at 0.01 mg/kg (Manske & Johnson, 1975).
5.1.4.2. Residues in fish and shellfish
Fish and shellfish may be exposed to 2,4-D as a consequence of
aquatic herbicide use, or through the agricultural use of 2,4-D.
The residues in the edible portions of such fish rarely exceed 1
mg/kg wet weight (Erne, 1974, 1975 and Table 8). Residues of 2,4-D
have not been detected in retail samples of fish and shellfish
analysed as part of the US "market basket" studies (section
5.1.4.1).
There is some evidence that the organoleptic properties of the
2,4-D residues may reduce the likelihood of the consumption of fish
flesh contaminated with higher levels of 2,4-D (Gavrilova, 1965;
Folmar, 1979).
5.1.4.3. Residues in wild fruits and mushrooms
Uncultivated fruits and mushrooms taken from areas where 2,4-D
was used, or was likely to have been used, were examined for
residues of 2,4-D by Erne & von Haartman (1973), Erne, (1980),
Sietanen et al. (1981), and Frank et al. (1982). The results in
Table 9 show that residues of 2,4-D in berries in field-trial
studies have been as high as 30 mg/kg immediately after
application, but residues in berries and mushrooms taken from the
wild are generally < 1 mg/kg.
High residues of 2,4-D can produce disagreeable odours or
flavours in wild fruits and vegetables (Ingelög et al., 1977;
McArdle et al., 1961), and this may reduce the likelihood that
highly contaminated foods are ingested.
5.1.4.4. Residues in food derived from animals
Domestic meat-, milk-, and egg-producing animals, and game
animals may consume forage or feed containing 2,4-D residues, and
thus, their tissues and products may contain residues. Published
data on 2,4-D residues in feed and forage from the Northern
Hemisphere are summarized in Table 10. Immediately after
application of phenoxy herbicides, 2,4-D residues in or on grass,
generally average about 100 mg/kg for each kg of herbicide applied
per hectare. Such residues decline with a half-life of about 1 - 2
weeks, to about 20 mg/kg, within 4 weeks after an application of 1
kg/ha (Leng, 1972). Residues in 2,4-D-treated feed grains are
significantly lower than the levels reported above and no residues
would be expected in meat, milk, or eggs from such sources (Table
10).
Table 8. 2,4-D residues reported in field studies on fish and shellfish
-----------------------------------------------------------------------------------------------------
Country Year(s) 2,4-D application Types of samples 2,4-D residues in References
rate tissues (mg/kg)
-----------------------------------------------------------------------------------------------------
USA 1961 0.1 mg/litre oyster (1 species) 1.6-2.0 Butler (1965)
fish (1 species) 0.3-1.0 Cope et al. (1970)
USA 1966 44.8-112 kg/ha mussels < 0.14-1.12 Smith & Isom (1967)
clams < 0.14
fish (5 species) < 0.14
USA 1968 112 kg/ha fish (4 species) < 0.10-0.24 Whitney et al. (1973)
USA 1969 22.4-44.8 kg/ha mussels < 0.05-2.7 Wojtalik et al. (1971)
fish (8 species) < 0.10-0.34
USA 1971 2.24-8.96 kg/ha fish (3 species) < 0.005-1.075 Schultz & Harman (1974)
USA 1971 4.48 kg/ha fish (5 species) 0.000-0.162 Schultz & Whitney (1974)
-----------------------------------------------------------------------------------------------------
Table 9. 2,4-D residues in wild berries and mushrooms collected in fields or forests following application
of phenoxyalkanoic herbicides
--------------------------------------------------------------------------------------------------------------
Country Year(s) Sample 2,4-D application Days after No. samples 2,4-D residues References
rate (kg a.i./ha) treatment analysed (mg/kg)
--------------------------------------------------------------------------------------------------------------
Canadaa 1979-81 raspberries 1.1-3.9 2 124 2.6-31.0 Frank et
14-35 0.1-3.3 al. (1982)
Finlanda 1974-76 vaccinium berries 2.5 10-356 44 Mukula et
jam not known not known 1 2.2 al. (1978)
mushrooms 14-300 28 < 0.05-1.2
Finlanda 1975-76 vaccinium berries 0.25-2.25 365 not stated < 0.05 Siltanen et
al. (1981)
Swedena 1970 raspberries 1.5-2.2 2-32 9 < 0.03-0.9 Erne & Von
vaccinium berries 1.5-2.2 2-32 68 < 0.03-7.7 Haartman
blueberries 1.5-2.2 2-32 19 < 0.03-2.9 (1973)c
mushrooms 1.5-2.2 2-32 15 < 0.03
Swedena 1973-79 vaccinium berriesb 0.25-2.25 365 61 nd (< 0.05) Erne (1980)
raspberries not stated 14 not stated nd-2.5
blueberries not stated 2 not stated nd-10.0
cowberries not stated 1-28 not stated nd-6.0
mushrooms not stated 7 1 0.3
Swedena blueberries 0.4-1.5 1-35 not stated 0.2-5.3 Ingelög et
vaccinium berries 0.4-1.5 30-35 not stated 0.5-4.5 al. (1977)
raspberries 0.4-1.5 1-10 not stated 0.2-2.0
--------------------------------------------------------------------------------------------------------------
a Samples taken from areas treated with 2,4-D.
b Samples entering factory for processing.
c Data from authors' Table 1.
Table 10. 2,4-D residues reported in samples of herbicide-treated forage or feed
--------------------------------------------------------------------------------------------------------------------------
Country Year(s) Type of samples 2,4-D application Post- No. samples 2,4-D residues References
rate, (kg a.i./ha) treatment examined & (mg/kg)
interval, positive
(days)
--------------------------------------------------------------------------------------------------------------------------
Canada 1971 wheat plants 0.42 1-36 ? ? 8.35-0.011 Cochrane & Russell (1975)
Finland 1962-68 green forage 1-4 7.21 ? ? 600-3.7 Finnish State Institute of
(grass and 3.5 7-28 ? ? 13-0.4 Agriculture (1963-1969)
clover)
Finland 1974-76 aspen leaves 2.5 60-300 32 30-0.3 Mukula et al. (1978)
and twigs
birch leaves 60-300 16 31-0.1
and twigs
cowberry plants 365 8 < 26-0.05
Germany, wheat, barley, 0.375-0.735 64-101 ? ? < 0.015-0.01 Maier-Bode (1971)
Federal rye, oat grains
Republic wheat, barley, < 0.34-0.02
of rye, oat straw
Hungary 1971 silo corn 1.4-1.5 56-120 ? ? 0.8-0.075 Bodai et al. (1974)
Sweden 1972-76 barley, oats ? ? 3 2 0.7-0.4 Erne & Rutqvist (1979)
grass 7 1 0.4
lichens ? ? 2 2 0.4-0.2
USA 1949 pasture plants 4.48 1 8 8 14.6-1.65 Grigsby & Farwell (1950)
USA 1967 forage grasses 0.56-2.2 0-112 ? ? 100-1 Morton et al. (1967)
USA 1969 sorghum plants 1.4 2 ? ? 1.06 Ketchersid et al. (1970)
1.4-2.8 30-60 < 5.25-0.2
USA 1969 pasture plants 6.6-8.8 0-28 24 24 700-150 Leng (1972)
--------------------------------------------------------------------------------------------------------------------------
No residues of 2,4-D were detected (detection limit of 0.02 mg)
in the milk of dairy cows fed 2,4-D at a level of 300 mg/kg total
diet (Bjerke et al., 1972; Leng, 1972). A range of 0.06 - 0.08 mg
2,4-D/litre was found in the milk of cows fed for 3 weeks at a
level of 1000 mg 2,4-D/kg total diet.
When young beef cattle were fed 2,4-D at levels of 300, 1000,
and 2000 mg/kg total diet for 28 days, 2,4-D residue levels were
highest in the kidney and liver, but did not exceed 0.1 mg/kg in
muscle and fat, even at the highest dose level (Clark et al., 1975;
Leng, 1972, 1977). 2,4-D residues were not detected in more than
12 000 samples each of meat and dairy products analysed in the USA
between 1963 and 1969 (Duggan et al., 1971).
Results of feeding studies with hares and reindeer in
Scandinavia indicated that 2,4-D levels of 25 - 30 mg/kg forage
(equivalent to an intake of about 1 mg 2,4-D/kg body weight per
day) produce maximum 2,4-D residues of 1.1 mg/kg wet weight in
liver, and 8.9 mg/kg in kidney tissues (Erne, 1974). Residues of
2,4-D were detected in the liver and kidney of a few game animals
shot by hunters, or found dead in or near areas sprayed with
phenoxy herbicides (Table 11, Erne, 1974, 1975). The residues in
muscle tissue were not measured but would be lower than in the
liver and kidney, as indicated by the data summarized in Table 11.
On the whole, the available evidence indicates that 2,4-D is
rarely detected in commercial foods and that residues in food taken
from areas where 2,4-D has been sprayed will usually be < 1 mg/kg
food. The liver and kidney from range animals are possible
exceptions, but these contribute little to the total diet of the
general population.
5.2. Occupational Exposure to 2,4-D During the Production, Handling,
and Use of Chlorophenoxy Herbicides
During occupational exposure to 2,4-D, the chemical may be
absorbed via the inhalation, oral, and dermal routes, but more than
90% of the total amount of 2,4-D or other chlorophenoxy compounds
entering the body under these circumstances appears to be absorbed
through the skin and excreted relatively quantatively in the urine
as the phenoxy acid and readily-hydrolysed conjugates (Kolmodin-
Hedman et al., 1979, 1980; Libich et al., 1981; Draper & Street,
1982; Franklin et al., 1982; Leng et al., 1982; Nash et al., 1982)
(section 6).
Data from occupational exposure studies concerning the amounts
of 2,4-D found on the clothing or on cloth patches worn by workers
are not included in this review because the correlation between
these amounts and amounts absorbed into the body and then excreted
in urine is poor (Franklin et al., 1982; Lavy et al., 1982; Leng et
al., 1982).
Table 11. 2,4-D residues in game and domestic animals and animal products
------------------------------------------------------------------------------------------------------------------
Country Year(s) Species 2,4-D treatment Post- Type of 2,4-D residues References
rate (kg a.i./ha) treatment samples (mg/kg)
interval examined
(days)
------------------------------------------------------------------------------------------------------------------
Sweden 1968 moose (Alces game animals found ? liver and < 0.05-6 Erne (1974,
-1972 alces) dead, or shot by kidney from 1975)
deer (Capreolus hunters in herbicide- 250 animals
capreolus) treated areas found dead
hares (Lepus
lepus)
pheasants ? liver and < 0.05-4.5
grouse kidney from (2,4-D and
130 animals 2,4,5-T)
shot by
hunters
USA 1963 Jersey cow 50 ppm in diet for 4 0-2 milk < 0.1 Bache et al.
days (1964a)
USA 1974(?) adult beef 0, 9, 30 or 60 mg 0 muscle < 0.05-0.07 Clark et al.
cattle 2,4-D acid/kg bw/day 28 fat < 0.13-0.34 (1975)
for days (0, 300, liver < 0.05-0.23
1,000 2000 mg/kg feed) kidney 2.53-10.9
USA 1974(?) adult sheep 2000 mg/kg feed for 0-7 muscle < 0.05-0.06 Clark et al.
28 days fat 0.10-0.15 (1975)
liver 0.29-0.98
kidney 0.37-9.17
USA 1965(?) dairy cows animals grazing on 2 milk 0.01-0.09 Klingman et al.
pasture sprayed with 4 (1966)
herbicide at 2, 24 kg
a.i./ha
USA 1972 dairy cows 30, 300, 1000 mg/kg 0 milk < 0.05-0.16 Bjerke et al.
in feed for 2-3 weeks (1972)
1-3 < 0.05 Leng (1972)
USSR 1975 "livestock" ? ? muscle 0.04 Fyodorova et
liver 0.04 al. (1977)
kidney 0.03 (mean)
------------------------------------------------------------------------------------------------------------------
5.2.1. Industrial exposure
Several studies have been published on the levels of 2,4-D to
which workers producing or packaging 2,4-D herbicides are exposed
(Fetisov, 1966; Johnson, 1971; Juzwiak et al., 1973; Andreasik et
al., 1979). In every case the amount of 2,4-D absorbed by the
workers was uncertain and, therefore, the data are inadequate for
estimating industrial exposure to 2,4-D. Workers manufacturing
2,4-D were also exposed to other chemicals (Assouly, 1951; Bashirov
& Ter-Bagdasarova, 1970).
5.2.2. Exposure related to herbicide use
The available studies on the occupational exposure to 2,4-D of
workers during the use of 2,4-D herbicides are summarized in Table
12. Studies on the exposure of back-pack sprayers to 2,4-D have
not been published. However, comparable exposure data are
available for 2,4,5-T back-pack sprayers, and they have been
included in Table 12 for comparison. The levels of 2,4-D found in
the air of the working zone in these and other studies have already
been referred to in section 5.1.1.1 and Table 5.
In studies undertaken before 1980, only the amounts of 2,4-D in
the air, on the clothing, or on the skin were determined, except
for 2 urinary 2,4-D values reported by Shafik et al. (1971). Thus
the amounts of 2,4-D actually absorbed cannot be reliably estimated
from these early reports and are not included in Table 12.
After 1980, several detailed occupational exposure studies were
carried out to determine the amounts of 2,4-D or other chlorophenoxy
acids absorbed by various members of ground and aerial spray teams,
using a variety of equipment for dispersing aqueous or oil solutions
or emulsions (Kolmodin-Hedman et al., 1979; Kolmodin-Hedman & Erne,
1980; Libich et al., 1981; Draper & Street, 1982; Franklin et al.,
1982; Lavy et al., 1982; Leng et al., 1982; Nash et al., 1982).
The total 2,4-D urinary excretion levels reported in Table 12
reflect a wide variety of uses and show that the excretion does not
usually exceed 0.1 mg 2,4-D/kg body weight per day of exposure.
However, so far, a comprehensive comparison of the relative
exposures resulting from different methods of application and
different 2,4-D derivatives (amine salts and esters) or formulations
(aqueous, oil) cannot be carried out, because the available data are
still incomplete. The amount of 2,4-D absorbed depends on the type
of work performed, and on the degree of care taken to avoid direct
dermal contact with the herbicide concentrate, spray solution, or
spray. The most heavily-exposed workers tend to be the mixer-
loaders, who handle the herbicide concentrate, and the spray
personnel. However, if careful, they may be exposed to less 2,4-D
than, for example, a pilot of a spray plane who is not careful
(Franklin et al., 1982; Leng et al., 1982; Lavy et al., 1982; Nash
et al., 1982). The reports by Libich et al. (1981) and Leng et al.
(1982) on ground spray crews indicate that, even under unfavourable
working conditions, the amount of 2,4-D absorbed may be greatly
reduced simply by wearing clean gloves and overalls, and by making
the workers more aware of the importance of safe work habits.
Table 12. Exposure related to herbicide use
------------------------------------------------------------------------------------------------------------------------
Product No. of Type of Daily concentr- Duration of Total 2,4-D in urine References
people application ation of 2,4-D collection of excreted (mg/kg bw/
exposed in urine 24-h urine day of exposure)
(mg/litre)e samples (days)
------------------------------------------------------------------------------------------------------------------------
2,4-D and dicamba 2 boom spray 1 - 4 - - Draper & Street
dimethylene salts single use (1982)
in aqueous solution 2 repeated use 3 - 20 - -
2,4-D isooctyl 4 3 applications - 4 0.004 - 0.04 Franklin et al.
ester in diesel oil by single- (1982)
engine aircraft
2,4-D/2,4,5-T 4 tractor-drawn 1 - 14 7 - Kolmodin-Hedman
butoxyethyl sprayers, forestry (1979, 1980)
esters as 2% exposure daily,
emulsion in water for one week
2,4-D PGBE ester 26 helicopter in - 5 nd - 0.06a Lavy et al.
26 forestry use - 5 nd - 0.02b (1982)
2,4,5-T PGBE ester 7 Back-pack 5 0.01 - 0.09 Leng et al.
forestry use (2,4,5-T) (1982)
single exposures,
one week apart
2,4-D/2,4-DPc and 23 roadside and < 0.01 - 8 3 - Libich et al.
2,4-D/picloramc right-of-way (one usually (1981)
ground equipment high result
incl. mist blowers of 31)
2,4-Dc 17 aircraft repeated - 7 0.006 - 0.02d Nash et al.
exposure (mean values/day) (1982)
2,4-D amine salt 26 ground equipment - 7 nd - 0.08
and ester (single exposure)
------------------------------------------------------------------------------------------------------------------------
a No special precautions taken.
b Protective clothing worn.
c Preparation used not specified.
d Mean values per day recorded for different individuals.
e It is not possible to calculate the total 2,4-D excretion in urine from these data, because of individual variations
in urine concentrations from day to day from sample to sample.
As the chemobiokinetic profiles of urinary 2,4-D output are
reported in only a few of the studies, summarized in Table 12, it
is not possible to estimate the total 2,4-D intake in all cases.
The results of the studies by Libich et al. (1981) and by
Draper & Street (1982) suggest that using single-exposure studies
to estimate the peak exposure levels reached by workers exposed
several days in succession may give an underestimation.
No information is available on the amounts of chlorinated
dibenzodioxins, or other by-products or contaminants, absorbed as a
consequence of occupational exposure to 2,4-D herbicides.
In one extensive occupational monitoring programme undertaken
in 1979 - 82, about 3000 urine samples were analysed for herbicide
residues (Simpson, 1982). The subjects included pesticide factory
staff, pest control operators, farmers, park workers, and others
potentially exposed to 2,4-D. During the first year of the study,
no 2,4-D was detected (< 0.001 mg/litre) in 735 of 973 samples.
Most of the other samples contained less than 0.1 mg/litre and only
27 contained more than 1 mg/litre. The highest value was 31
mg/litre. The study is continuing.
5.3. Exposure of Bystanders to 2,4-D
Aerial drift and other forms of pesticide transport, as well as
the contamination of surfaces during or after herbicide production,
distribution, or use, may bring 2,4-D into contact with bystanders,
i.e., persons other than those who are occupationally exposed. Few
studies of bystander exposure to 2,4-D or other chlorophenoxy
herbicides have been published. Studies available for review
included that of Lavy et al. (1982) concerning 9 supervisors and
observers present at two helicopter forest spray operations using
2,4-D propyleneglycol butylether (PGBE) ester, respectively, for
unspecified durations. These people excreted a maximum of 1.3 µg
2,4-D/kg body weight. In a forest ground spray operation with
tractor-drawn equipment, 2,4-D was not detected (< 0.05 mg/litre)
in the urine of bystanders (Kolmodin-Hedman et al., 1980).
Additional bystander exposure studies for various 2,4-D use
patterns are desirable. However, the 2,4-D intake of bystanders is
unlikely to exceed the 2,4-D intake during occupational exposure.
5.4. Estimated Exposure of the General Population in 2,4-D-Use Areas
Data useful for estimating the intake by the general population
of 2,4-D residues in the environment including those in food
sources have been generated. The present calculations of the
intake of the general population in an area of 2,4-D use are based
on these data and on a series of stated assumptions aimed at
obtaining a moderate overestimation rather than underestimation of
the actual exposure.
5.4.1. Intake of 2,4-D residues from air
On the basis of available information, it can be assumed that
the general population in areas of 2,4-D herbicide use would rarely
be exposed to 2,4-D concentrations exceeding 0.1 µg/m3 air.
Assuming an air level of 0.1 µg 2,4-D/m3, a body weight of 60
kg, an air intake of 20 m3 per day, and a 100% retention of 2,4-D,
it can be calculated that the respiratory intake would be 0.03 µg
2,4-D/kg body weight per day.
5.4.2. Intake of 2,4-D residues from potable water
The larger surveys of potable water (Table 7) show mean 2,4-D
residues in surface water to be generally < 0.1 µg/litre, but for
the present estimate, it is assumed that potable water from surface
sources or from treatment plants, during a period of about 10 days
after reservoir treatment, can contain an average 2,4-D residue
level of 2 µg/litre (Wojtalik et al., 1971 and Table 7). Assuming
a 2,4-D concentration in water of 2 µg/litre, a body weight of 60
kg, a water intake of 2 litres per day (Canada, Health & Welfare,
1980), and a 100% absorption of the ingested 2,4-D, it can be
calculated that the 2,4-D intake of the general population in a
2,4-D use area resulting from water could approach 0.07 µg/kg body
weight per day, which could occur for about 10 days.
Insufficient data are available to give a reliable estimate of
2,4-D intake from ground water sources, but it is likely to be
lower than the above value.
5.4.3. Intake of 2,4-D residues from soil
2,4-D on soil particles ingested with food or water, or carried
into the air and inhaled, is considered to be part of the exposure
due to residues in air, water, or food and is therefore assumed to
be completely covered in these exposure estimates.
5.4.4. Intake of 2,4-D residues from food
The data in Tables 8 - 11 indicate that there is unlikely to be
any exposure of the general population to 2,4-D residues in retail
food supplies. The possibility that individuals are exposed to
contaminated local sources of food has been assessed in section
5.1.4. In the case of milk or muscle meat, it can be assumed that
no individual will be exposed to levels in excess of 0.02 mg/kg of
these foods, the limit of detection of the method of analysis used.
Assuming a concentration of 0.02 mg 2,4-D/litre in milk, and a
consumption of 1.5 litre per day, the maximum intake from this
source would be 0.0005 mg/kg body weight per day for a 60 kg adult.
Individuals who consume wild berries taken from 2,4-D-treated areas
could be exposed through this food source. Assuming consumption of
100 g of berries per serving and a maximum 2,4-D concentration of 1
mg/kg, the intake from this source would be 0.002 mg/kg body weight
per serving.
5.4.5. Total exposure of the general population in a 2,4-D-use area
The above considerations suggest that the total daily 2,4-D
intake of the population in use areas will not normally exceed
about 0.002 µg/kg body weight during the application period (Table
13).
Table 13. Components of estimasted exposure to 2,4-D
-------------------------------------------------------------------
Estimated amount of
Exposed Group intake (µg 2,4-D/kg Source of 2,4-D
bw/day)
-------------------------------------------------------------------
Occupational
i. Factory workers insufficient data mainly dermal contact
ii. Applicator crews 100a
iii. Bystanders - b
General population in
areas with 2,4-D use 0.03 air
0.07 water
0.5 milk
ND retail food
2.0 wild berries, mushrooms
etc.
-------------------------------------------------------------------
a Based on total urinary output after several days of exposure.
b Unlikely to exceed occupational exposure.
5.4.6. Total exposure of persons occupationally exposed in agriculture
An accurate maximum occupational intake of 2,4-D cannot be
determined on the basis of the limited studies undertaken.
However, the available data suggest that work performed in the
preparation of, and during, agricultural application of 2,4-D
herbicide will probably result in an exposure of not more than
about 0.1 mg 2,4-D/kg body weight per day, providing that minimum
precautions are taken against excessive exposure.
5.4.7. Total exposure of the general population outside areas of 2,4-D use
Monitoring of air, water, and food outside areas of known 2,4-D
use show that intake is below present detection limits.
6. CHEMOBIOKINETICS AND METABOLISM
With the exception of recent occupational exposure studies and
studies on animals published in 1979 or later, the available
information on the uptake, distribution, transformation, and
excretion of 2,4-D by human beings and other mammals has already
been reviewed by Leng (1977), National Research Council of Canada,
Associate Committee on Scientific Criteria for Environmental
Quality (1978), Young et al. (1978), Bovey (1980a,b), Shearer
(1980), and United States Veterans' Administration (1981).
6.1. Uptake via Different Routes of Exposure
6.1.1. Uptake by inhalation
6.1.1.1. Animals
Burton et al. (1974) found that small amounts of 2,4-D
instilled into the rat lung were rapidly absorbed, apparently by a
non-saturable process following first-order kinetics, with an
absorption half time of 1.4 - 1.7 min. The kinetics of the
absorption of 2,4-D vapours or aerosols in the respiratory tract of
animals have not yet been studied.
6.1.1.2. Human beings
The uptake of 2,4-D and of 2,4-D derivatives via the human
respiratory tract does not appear to have been studied under
controlled conditions. However, the observations of Kolmodin-
Hedman & Erne (1980), Libich et al. (1981), Franklin et al. (1982),
and Lavy et al. (1982) on people occupationally exposed to 2,4-D
indicated that only a small percentage of the total amount of 2,4-D
absorbed via all routes of exposure was taken in through the
respiratory tract.
6.1.2. Dermal uptake
6.1.2.1. Animals
Mice whose tails had been immersed in 2,4-D butyl or crotyl
ester solutions, 4 h daily for 3-5 days, absorbed lethal amounts of
the chemicals (Fetisov, 1966). However, the actual doses absorbed
and other details were not given. In contrast, no major ill
effects were reported in studies in which rabbits were treated
percutaneously for 2 or 3 weeks with 130 - 180 mg/kg body
weight/day of a 50% aqueous solution of 2,4-D octyl ester, or with
unspecified amounts of solutions of 2,4-D dimethylamine salt in
water, or oil solutions of 2,4-D isooctyl or butyl ester
(Vinokurova, 1960; Kay et al., 1965).
6.1.2.2. Human beings
Only 5.8% of a dilute solution of 14C-labelled 2,4-D in acetone
applied at a dose of 4 µg a.i./cm2 to the ventral forearm of adults
was excreted in the urine compared with 100% of a small intravenous
dose (Feldmann & Maibach, 1974) (Table 14). The 2,4-D excretion in
urine is delayed and more prolonged after dermal application than
after intraveneous or oral administration (Feldmann & Maibach,
1974; Sauerhoff et al., 1977), and complete elimination may take
about one week (Levy et al., 1982; Leng et al., 1982). Cases of
acute occupational 2,4-D poisoning following combined dermal and
inhalation exposures (Monarca & Divito, 1961; Tsapko, 1966;
Paggiaro et al., 1974), as well as occupational exposure studies
(Table 12), suggest a fairly efficient dermal absorption of 2,4-D.
However, the importance of solvents, surfactants, and other
ingredients of the herbicides in the uptake of 2,4-D via the dermal
route still needs to be defined.
6.1.3. Oral uptake
6.1.3.1. Animals
The uptake of 2,4-D from the gut of rats, mice, guinea-pigs,
cattle, pigs, and sheep appears to be similar in both rapidity and
extent to that observed in human beings (Mitchell et al., 1946;
Lisk et al., 1963; Bache et al., 1964a; Erne, 1966a,b; Milhaud et
al., 1970; Shafik et al., 1971; Buslovich et al., 1973; Fedorova &
Belova, 1974; Clark et al., 1975; Senczuk & Pogorzelska, 1975,
1981; Van Peteghem & Heyndrickx, 1975). In some of the ungulates,
2,4-DB acid, and 2,4-D amine salts or esters are at least partially
converted to 2,4-D in the rumen, before being absorbed (Gutenmann
et al., 1963; Lisk et al., 1963). Some of the esters may be less
well absorbed from the gut than the acid or its alkali or amine
salts (Erne, 1966a; Buslovich et al., 1973), but the uptake
mechanisms for 2,4-D and its salts or esters is not known, and thus
deserves further study.
6.1.3.2. Human beings
Information on the uptake of 2,4-D by human beings via the
oral route has been gathered in studies on two groups of 5 - 6
volunteers each, who ingested single doses of 5 mg 2,4-D/kg body
weight (Table 14), and by chemobiokinetic studies on individuals
who, with suicidal intent, swallowed lethal or non-lethal amounts
of various 2,4-D herbicides (Geldmacher-Von Mallinckrodt &
Lautenbach, 1966; Rivers et al., 1970; Kohli et al., 1974;
Sauerhoff et al., 1976, 1977; Khanna & Kohli, 1977; Young & Haley,
1977; Prescott et al., 1979) (Table 15). These results show that
single doses of 2,4-D are fairly rapidly and completely absorbed
from the human digestive tract, unless the dose is so large that
toxic effects interfere with absorption. However, in the two
studies on volunteers, considerable individual variation in the
rate and extent of absorption from the digestive tract was
observed. The absorption mechanism appears to involve first-order
kinetics (Kohli et al., 1974; Khanna & Kohli, 1977) and may fit a
single- or multi-compartment chemobiokinetic model, depending on
individual characteristics (Sauerhoff et al., 1977).
Table 14. Chemobiokinetics of 2,4-D in human beings following administration under controlled conditions
--------------------------------------------------------------------------------------------------------------------------
Product Dose and dosing Subjects Observations Toxic effects References
schedule EL NOELa
(mg/kg bw)
single dose
--------------------------------------------------------------------------------------------------------------------------
14C-2,4-D 1) Intravenous injection: 6 (sex & Scintillation counting ? ? Feldmann &
(New England Dose (7 µCi) not stated as age not 1) 100% of dose excreted in urine Maibach
Co., and 2,4-D/weight unit stated) urine in 120 h Mean t0.5 = 13 h (1974)
Amersham 2) Dermal application: 6 (sex & 2) 5.8% of applied dose excreted ? ?
Searle Co.) 1 x 4 µg 2,4-D (in acetone)/ age not in 120 h
cm2 of skin of forearm. stated)
Application site was not
washed for 24 h
2,4-D, 99% Oral administration: 6 gas chromatography of blood & ? 5 Khanna &
pure (Dow 1 x 2, 3, or 5 mg/kg bw, in (adult M) urine samples; no ill effects; no Kohli (1977);
Chemical gelatin capsule, with water, changes in clinical parameters: Kohli et al.
Co.) following breakfast blood pressure, pulse rate, Hb, WBC (1974)
counts (total & differential); mean
plasma clearance t0.5 = 33 ± 3.1 h;
peak plasma conc. at 7-24 h = 40
mg/litre; ~75% of dose excreted
in urine in 96 h
"no metabolic transformation
at up to 5 mg/kg"
2,4-D, Oral administration: 6 gas chromatography - mass ? 5 Sauerhoff
analytical 1 x 5 mg/kg bw as a slurry (adult M, spectrometry of blood & urine et al.
grade in milk, or in powder form, 70-90 kg) samples; no ill effects; (1976, 1977)
with some water, following essentially all of the dose
breakfast absorbed; peak plasma conc. = 10-30
mg/litre within 24 h; mean plasma
clearance t0.5 = 11.6 h; mean
urinary excretion t0.5 = 17.7 h;
total excreted amount ~82% of dose
administered; 4.8-27.1% of
excreted compound was conjugated
--------------------------------------------------------------------------------------------------------------------------
a NOEL = No-observed-adverse-effect level.
Table 15. Chemobiokinetics of 2,4-D by human beings following accidental or intentional ingestion of herbicides
----------------------------------------------------------------------------------------------------------------
Products Circum- Subject Observations References
stances
----------------------------------------------------------------------------------------------------------------
2,4-D suicide; F, 33 death in about 30 h; post mortem 2,4-D Geldmacher-Von
ingestion years concentration: Mallinckrodt &
of unknown mg/litre mg/kg Lautenbach (1966)
amount of blood urine brain liver lung heart
herbicide 23 164 100 116 88 63
no metabolites were identified
Herbicide suicide; F, 51 death in about 96 h; concentration of 2,4-D
containing ingestion years, plus MCPA:
2,4-D plus of unknown 66 kg mg/litre mg/kg
MCPA amount of blood urine liver kidney muscle
("U46 COMBI") herbicide 42 420 100 trace 40
(BASF 2,4-dichlorophenol not detected; s