This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment 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

         The International Programme on Chemical Safety (IPCS) is a
    joint venture of the United Nations Environment Programme, the
    International Labour Organisation, and the World Health
    Organization. The main objective of the IPCS is to carry out and
    disseminate evaluations of the effects of chemicals on human health
    and the quality of the environment. Supporting activities include
    the development of epidemiological, experimental laboratory, and
    risk-assessment methods that could produce internationally
    comparable results, and the development of manpower in the field of
    toxicology. Other activities carried out by the IPCS include the
    development of know-how for coping with chemical accidents,
    coordination of laboratory testing and epidemiological studies, and
    promotion of research on the mechanisms of the biological action of

        ISBN 92 4 154089 3 

         The World Health Organization welcomes requests for permission
    to reproduce or translate its publications, in part or in full.
    Applications and enquiries should be addressed to the Office of
    Publications, World Health Organization, Geneva, Switzerland, which
    will be glad to provide the latest information on any changes made
    to the text, plans for new editions, and reprints and translations
    already available.

    (c) World Health Organization 1984

         Publications of the World Health Organization enjoy copyright
    protection in accordance with the provisions of Protocol 2 of the
    Universal Copyright Convention. All rights reserved.

         The designations employed and the presentation of the material
    in this publication do not imply the expression of any opinion
    whatsoever on the part of the Secretariat of the World Health
    Organization concerning the legal status of any country, territory,
    city or area or of its authorities, or concerning the delimitation
    of its frontiers or boundaries.

         The mention of specific companies or of certain manufacturers'
    products does not imply that they are endorsed or recommended by the
    World Health Organization in preference to others of a similar
    nature that are not mentioned. Errors and omissions excepted, the
    names of proprietary products are distinguished by initial capital




    1.1. Summary
         1.1.1. Analytical methods
        2,4-D, 2,4-D alkali metal salts or 2,4-D 
                         amine salts and 2,4-D esters
        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
        Acute toxic effects
        Chronic toxic effects
        Teratogenic and reproductive effects
        Mutagenic effects
        Carcinogenic effects
         1.1.7. Effects on human beings
        Acute toxic effects
        Chronic toxic effects
        Teratogenic and reproductive effects
        Mutagenic effects
        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

    2.1. 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
        Sampling, extraction, and clean-up
         2.2.4. Derivatization and quantification
         2.2.5. Confirmation


    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


    4.1. 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
        Side-chain degradation
        Ring hydroxylation
        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


    5.1. Levels of 2,4-D residues in the environmment
         5.1.1. In air
        Field exposure
        General environment exposure
         5.1.2. In water
         5.1.3. In soil
         5.1.4. In food sources
        Residues in retail food supplies
        Residues in fish and shellfish
        Residues in wild fruits and mushrooms
        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 
         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 
         5.4.7. Total exposure of the general population outside 
                areas of 2,4-D use


    6.1. Uptake via different routes of exposure
         6.1.1. Uptake by inhalation
        Human beings
         6.1.2. Dermal uptake
        Human beings

         6.1.3. Oral uptake
        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)


    7.1. 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)
        Acute oral LD50
                         7.2.3.l.l  Mammals
        Acute dermal LD50
        Acute inhalation LC50
        Parenteral LD50
         7.2.4. Acute toxicity in aquatic organisms
    7.3. Subchronic and chronic toxicity
         7.3.1. Mammals
        Clinical signs of poisoning
        Effects on food and water consumption, and 
                         on body weight
        Effects on the central nervous system 
        Effects on the peripheral nervous system
        Myotoxic effects
        Cardiovascular effects
        Haematological effects
        Effects on blood chemistry
        Other biochemical effects observed  in vivo  
                         or  in vitro 
       Pulmonary effects
       Hepatotoxic effects
       Effects on the kidney
       Effects on endocrine organs
       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
        Effects on adult rats
        Effects on offspring
         7.4.2. Mice

         7.4.3. Birds
         7.4.4. Cold-blooded animals
    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


    8.1. Acute poisoning and occupational overexposure
         8.1.1. Neurotoxic effects of 2,4-D and related compounds
        Effects on the central nervous system
        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


    9.1. General considerations
    9.2. Estimated intake of 2,4-D by the population in a 2,4-D-use 
         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  
       Acute poisoning   
       Chronic toxicity  
       Embryonic, fetotoxic, and teratogenic 
       Mutagenic effects
       Carcinogenic effects
    9.4. Evaluation of health risks from 2,4-D exposure
    9.5. Recommendations on exposure



    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. 



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 

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


Dr. D. Riedel, Environmental Health Directorate, Health & Welfare 
    Canada, Environmental Health Centre, Ottawa, Canda,  (Temporary 

Dr. F. Valic, World Health Organization, Geneva, Switzerland,

Mr. J.D. Wilbourn, International Agency for Research on Cancer, 
    Lyons, France 


Dr. H. Spencer, US Environmental Protection Agency, Washington, DC, 


    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 

    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. 


1.1.  Summary

1.1.1.  Analytical methods  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.  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 

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  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.  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.  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.  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.  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 

1.1.7.  Effects on human beings  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.  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.  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.  Mutagenic effects

    The results of studies suggesting that occupational exposure to 
2,4-D may result in chromosome abnormalities are equivocal.  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. 


2.1.  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-

    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.  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). 


3.1.  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. 


    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).  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.  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.  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). 


5.1.  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 

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.  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.  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                                                 

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)

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                           
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 

    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., 

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

1971-72  Total diets       dairy products (1)      -              0.01            Manske & Johnson

1973-80  Total diets                               0              < 0.01          Manske & Johnson
                                                                                  Johnson et al. 
                                                                                  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)

Saskatchewan, Canada      15          10     -              2          21.6   Choi et al. (1976)

Western Canada            186         10     -              0.5c       4.3d   Gummer (1980)
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).  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).  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 

    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).  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.  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 

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    
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)

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
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                        
                  pheasants                                ?          liver and    < 0.05-4.5
                  grouse                                              kidney from  (2,4-D and
                                                                      130 animals  2,4,5-T)
                                                                      shot by

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
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 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 

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

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
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. 


    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  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.  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  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).  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  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.  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
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; several
Ludwigshafen)                       other metabolites or herbicide by-products
                                    found, but not identified

Herbicide      suicide     M, 39    severe toxic effects; unconsciousness;            Prescott et al. (1979)
containing     attempt;    years    recovery within 11 days following treatment by
2,4-D plus     ingestion            alkaline diuresis; initial plasma concentration:
mecoprop       of 6.7 g             2,4-D = 400 mg/litre, mecoprop = 750 mg/litre;
(10%) + (20%)  2,4-D and            no pretreatment change in 2,4-D level following
               7.6 g                alkaline diuresis; plasma clearance t0.5 = 3.7 h
               mecoprop             for 2,4-D, 11-28 h for mecoprop
6.2.  Distribution and Transformation in the Body

6.2.1.  Animals

    The absorption and distribution kinetics and metabolism of pure 
2,4-D and of a variety of pure or commercial 2,4-D or 2,4-DB amine 
salts and esters have been repeatedly studied both  in vivo and  in
 vitro in a wide variety of animals including rats, mice, rabbits, 
guinea-pigs, cattle, sheep, goats, pigs, chickens, fish, and spiny 
lobsters (Gutenmann & Lisk, 1965; Erne & Sperber, 1974; Guarino & 
Arnold, 1979; James, 1979; Koschier & Pritchard, 1979; Pritchard 
& James, 1979; Pritchard & Miller 1980).  The considerable 
differences observed in the relative amounts of residues found in 
the cells and plasma of mouse, rat, and horse blood, after dosing 
animals or after  in vitro addition of 2,4-D (Erne, 1966a; Jenssen 
& Renberg, 1976), in different tissues of rats, mice, and sheep 
(Erne, 1966a,b; Lindquist & Ullberg, 1971; Milhaud et al., 1970; 
Buslovich et al., 1973; Clark et al., 1975; Elo & Ylitalo, 1979), 
and in the soluble and particulate fractions of rat tissues (Khanna 
& Fang, 1974) support the idea that there is more than one 
physiological compartment for 2,4-D storage.  The distribution 
volumes appear to be equivalent to the volume occupied by about 
25 - 50% of the body mass (Erne, 1966a). 

    2,4-D is reversibly bound to blood plasma proteins, 
particularly albumins, possibly at sites for which it competes with 
related compounds.  The same sites are apparently also binding 
sites for palmitic acid and thyroxine.  The extent of 2,4-D binding 
depends, in part, on pH and 2,4-D concentration (Florsheim et al., 
1963; Erne, 1966b; Kolberg et al., 1973; Hacque et al., 1975; 
Mason, 1975; Orberg, 1980a), and may affect the rate and extent of 
renal 2,4-D excretion (Pritchard & James, 1979; Pritchard & Miller, 
1980) and thus the toxicity of 2,4-D. 
    In pregnant mammals, up to about 17% of a single dose of 2,4-D 
may rapidly cross the placenta to reach the embryos or fetuses 
(Lindquist & Ullberg, 1971; Fedorova & Belova, 1974; Antonenko, 

    Pigs and rats hydrolyse 2,4-D esters both in the gut and after 
absorption in the body (Erne, 1966a,b).  Observations from several 
studies indicate that 2,4-D is not significantly metabolized in 
animals, except in ruminants.  No 14CO2 was produced by rats given 
C1- or C2-labelled 14C-2,4-D (Khanna & Fang, 1966).  No 2,4-
dichlorophenol (2,4-DCP) was detected in the tissues of mice or 
rats dosed by various routes with 2,4-D (Zielinski & Fishbein, 
1967; Shafik et al., 1971; Federova & Belova, 1974; Grunow & Böhme, 
1974).  However, residues of 2,4-DCP were detected in the milk of 
dairy cows fed 100 mg 2,4-D/kg diet for 3 weeks (Bjerke et al., 
1972; Leng, 1972), and in the livers and kidneys of cattle and 
sheep fed up to 2000 mg/kg diet for 4 weeks (Clark, 1975; Leng, 
1972, 1977).  These 2,4-DCP residues probably resulted from the 
bacterial degradation of 2,4-D in the rumen of the animals.  
Bacterial degradation may also account for the 2,4-DCP reported by 
Antonenko (1977) in pregnant or lactating rats and rat fetuses. 

    Other investigators did not detect 2,4-DCP in the tissues of 
mice or rats dosed with 2,4-D by various routes (Zielinski & 
Fishbein, 1967; Shafik et al., 1971; Fedorova & Belova, 1974; 
Grunow & Böhme, 1974). 

    Results of studies on experimental animals have suggested that 
2,4-D conjugates are formed in the kidney tubules (Erne, 1966a,b; 
Erne & Sperber, 1974; Grunow & Böhme, 1974). 

    Taurine and glycine conjugates, as well as various other 
unidentified conjugates of 2,4-D have been found in the urine of 
rats, pigs, chickens, and the dogfish shark  (Squalus acanthias)  
(Erne, 1966b; Erne & Sperber, 1974; Grunow & Böhme, 1974; Koschier 
& Pritchard, 1979).  However, in rats and pigs, only about 10-20%, 
and in the chicken, less than 5% of the total amount of 2,4-D 
appeared to be excreted in this form. In the dogfish shark, the 
taurine conjugate may be primarily formed in the tubular cells of 
the kidney (Koschier & Pritchard, 1979).  The site and mechanism of 
2,4-D conjugation seem to be unknown in the other species. 

6.2.2.  Human beings

    Studies on human volunteers who ingested pure 2,4-D, and on 
cases of accidental or voluntary acute poisoning with various 2,4-D 
herbicides have shown that 2,4-D is very rapidly absorbed from the 
gut and carried in the blood to cells and tissues throughout the 
body, but that is not extensively transformed (Tables 14, 15) 
(Curry, 1962; Herbich & Machata, 1963; Nielsen et al., 1965; Dudley 
& Thapar, 1972; Coutselinis et al., 1977).  The kinetics following 
ingestion suggest a 1- or 2-compartment distribution, depending on 
individual characteristics (Sauerhoff et al., 1977; Young & Haley, 
1977).  Following absorption of purified 2,4-D, or of herbicides 
containing only 2,4-D, no transformation products, including 2,4-
dichlorophenol, were found in blood or tissues.  After ingestion of 
herbicides containing 2,4-D and other compounds, some 2,4-D 
metabolites or manufacturing by-products were detected in tissues, 
but were not identified (Geldmacher-Von Mallinckrodt & Lautenbach, 
1966; Prescott et al., 1979).  Unidentified 2,4-D conjugates were 
also found in urine following ingestion of pure 2,4-D.  These 
conjugates represented up to 27% of the 2,4-D ingested (Sauerhoff 
et al., 1976, 1977).  Of the 5 North American volunteers studied by 
these authors, only one did not produce a conjugate; in contrast, 
apparently none of the 6 Indian subjects studied by Kohli et al. 
(1974) and by Khanna & Kohli (1977) produced 2,4-D metabolites. 

6.3.  2,4-D Levels in Body Tissues and Fluids

6.3.1.  Animals

    2,4-D levels in the blood and organs of mammals have been 
determined, e.g., by Erne (1966a,b), Milhaud (1970), Buslovich et 
al. (1973), Khanna & Fang (1974), Clark et al. (1975), Jenssen & 
Renberg (1976), and Elo & Ylitalo (1979).  The highest residue 
levels were usually found in liver, kidney, lungs, spleen, and 
heart.  In a study by Fedorova & Belova (1974), 6 - 8% of the 

amount of 2,4-D administered was found in all of the tissues 
examined in rats dosed orally 26 - 35 days previously with this 
chemical.  However, the 2,4-D residue levels quoted were close to 
the limit of detection for the analytical method used. 

6.3.2.  Human beings

    In volunteers, each of whom ingested a single dose of 5 mg 
2,4-D/kg body weight, the 2,4-D levels in blood plasma reached 
peaks of about 10 - 45 mg/litre within about 7 - 24 h, and then 
declined (Kohli et al., 1974; Khanna & Kohli, 1977; Sauerhoff et 
al., 1977).  In one group of workers occupationally exposed to 
2,4-D for one week while using ground equipment for spraying 
(Kolmodin-Hedman et al., 1979), plasma levels ranged from the 
detection limit (0.02 mg/ml) to 0.2 mg/ml, while urinary levels 
ranged from 1 to 14 mg/litre.  Urinary 2,4-D levels reported in 
other occupational exposure studies are summarized in Table 12.  
However, it should be noted that analysis of single urine specimens 
is not adequate for estimating the dose absorbed by individuals, 
because excretion follows a diurnal pattern and continues for 
several days after dermal exposure (Leng et al., 1977; Sauerhoff et 
al., 1979; Lavy et al., 1982).  Thus, levels found after several 
days of spraying will probably be higher than first day levels, as 
reported by Libich et al. (1981) and Draper & Street (1982). 
However, excretion of 2,4-D should be completed within one week 
following the last exposure (Feldmann & Maibach, 1974; Lavy et al., 
1982; Leng et al., 1982). 

    The toxic and lethal levels of 2,4-D in human blood and tissues 
are still not well defined.  A woman with reportedly 335 mg 
2,4-D/litre plasma did not show any signs of poisoning; in general, 
the acute lethal levels of 2,4-D appear to lie between 447 and 826 
mg/litre plasma (Herbich & Machata, 1963; Nielsen et al., 
1965; Geldmacher-Von Mallinckrodt & Lautenbach, 1966; Coutselinis 
et al., 1977; Prescott et al., 1979).  The lowest lethal 2,4-D 
levels in blood or tissues were recorded several days after the 
chemical was ingested, i.e., after most of the 2,4-D had probably 
been eliminated.  Among the different organs examined  post mortem 
in cases of fatal 2,4-D poisoning, liver and kidney tended to 
contain the highest concentrations of 2,4-D, while brain and other 
fatty organs, and muscle including the heart, usually had lower 
2,4-D levels (Table 15) (Curry, 1962; Herbich & Machata, 1963; 
Nielsen et al., 1965; Geldmacher-Von Mallinckrodt & Lautenbach, 
1966; Dudley & Thapar, 1972; Coutselinis et al., 1977).  As in the 
case of blood, the values for the different tissues may vary 
according to the proportion of 2,4-D eliminated by the time death 

6.4.  Elimination and Biological Half-Life

    The term "biological half-life" will be used to indicate the 
time required to eliminate one half of a single dose of 2,4-D, or 
to reduce 2,4-D residues in the body fluids or tissues to one-half 
of the peak concentration.  Biological half-life, as defined here, 
is a useful concept with which it is possible to make rough 

comparisons of the elimination rate of 2,4-D with that of other 
toxic chemicals. 

6.4.1.  Animals

    The half-life values recorded in mammals fall into the range 
observed in the rat (Erne, 1966a,b; Federova & Belova, 1974; Khanna 
& Fang, 1974), with the exception of the very low value for 2,4-D 
butyl ester in whole mouse carcasses (0.85 - 1.11 h) observed by 
Zielinski & Fishbein (1967).  Results of the investigations 
conducted by these authors also suggest that prior dosing with 
2,4-D ("priming") may increase the rate of elimination of 2,4-D 
butyl ester in mice, presumably through stimulation of the renal 
excretory mechanism. 

    An important correlation between diet and 2,4-D elimination 
rate was observed by Orberg (1980b) in the goat.  A protein-poor 
diet reduced the 2,4-D plasma clearance rate by about 20 - 50%, 
possibly because of decreased renal size and renal blood flow. 

    The many species-related factors known to affect the rate of 
2,4-D elimination make interspecies comparisons difficult, and 
often the published reports do not include such details as diet, 
age, sex, and body weight of the test animals, type and purity of 
the test compounds, and important environmental factors such as the 
ambient temperature, which are necessary for valid comparisons. 

6.4.2.  Human beings

    The studies on volunteers and on cases of accidental or 
voluntary 2,4-D poisoning summarized in Tables 14 and 15 show that 
human beings excrete 2,4-D mainly in the urine, and that the 
blood plasma clearance times depend on the dose, individual 
characteristics, and the presence or absence of compounds that may 
competitively inhibit 2,4-D excretion.  For single oral doses of 
2,4-D, the biological half-life in blood plasma is about one day, 
depending on the circumstances.  However, forced alkaline diuresis 
may reduce this to as little as 3.7 h (Sauerhoff et al., 1977; 
Prescott et al., 1979). 

    In occupationally-exposed people, absorption of successive 
daily doses of 2,4-D makes its biological half-life difficult to 
determine, but for single occupational exposures it has been 
estimated to be 35-48 h (Nash et al., 1982). 

6.5.  Chlorinated Dibenzo- p-Dioxins (CDDs)

    The metabolism in the rat of several dibenzo- p-dioxins, 
including the 2,7-CDD found in 2,4-D, was described by Tulp & 
Hutzinger (1978).  The primary pathway of transformation appears 
to involve hydroxylation at the 2-, 3-, 7-, or 8-position in the 
molecule; some sulfur-containing conversion products have also been 


7.1.  General Introduction

    Many studies of the toxicity of 2,4-D were carried out before 
the possible toxicological importance of manufacturing by-products, 
such as 2,6-dichlorophenoxyacetic acid, 2,4,6-trichlorophenoxy-
acetic acid (2,6-D and 2,4,6-T) monochlorophenoxyacetic acid, or 
 N-nitroso compounds, was known or appreciated. 

    Furthermore, 2,4-D may be contaminated with several chlorinated 
dibenzo- p-dioxins (section 2.1.4).  The toxicity of a number of 
these contaminants has not been examined in detail, but whether or 
not their presence would affect the toxicity of 2,4-D and its 
derivatives would depend on the amount of CDD present in the 
product, and on the inherent toxicity of the particular CDD 
isomers.  The most toxic CDD isomer, namely 2,3,7,8-TCDD (Schwetz 
et al., 1973; McConnell et al., 1978; Leng, 1979; Kociba & Schwetz, 
1982), is not normally found in 2,4-D products (see also section 
2.1.4).  However, there have been instances in which the same 
manufacturing equipment was used to produce both 2,4,5-T and 2,4-D, 
resulting in cross-contamination of 2,4-D with 2,4,5-T and 2,3,7,8-
TCDD (US EPA, 1982). 

    Studies of structure-activity relationships using  in vitro 
systems have shown that the CDDs that may be present in 2,4-D and 
its derivatives have a much lower biological activity than 2,3,7,8-
TCDD (Poland & Glover, 1973; Poland & Kende, 1974; Poland et al., 
1976; Bradlaw et al., 1980; Knutson & Poland, 1980).  However, 
except for a study of the carcinogenic potential of 2,7-
dichlorodibenzodioxin (2,7-DCDD) (US National Cancer Institute, 
1979), the chronic toxicity of the CDD detected in 2,4-D and its 
derivatives has not been studied. 

    2,4-D has been in use as a herbicide for nearly 40 years, and 
during this time a great deal of literature on the toxicology of 
this chemical has accumulated.  The extent to which its toxicity to 
various organisms has been tested, and the types of 2,4-D products 
used for such testing have varied over the years.  Earlier 2,4-D 
products probably contained higher concentrations of trace 
contaminants than the 2,4-D in use today, and therefore it may have 
been found to be more toxic in earlier than in more recent studies.  
In addition, the generally accepted standards and protocols for 
pesticide toxicity tests have changed, making some of the older 
tests inadequate by present day standards.  For these reasons, 
attention has been focused on the more recent studies.  The older 
studies are, in many instances, only cited for completeness and 
should be used with caution, especially when ascribing specific 
toxic effects to unspecified 2,4-D products and when establishing 
an effect level or no-observed-adverse-effect level for adverse 
effects of 2,4-D.  The Task Group noted that a number of additional 
studies on 2,4-D are at present in progress.  As the additional 
information becomes available, the present document will need to be 

7.2.  Acute Effects

    The reports of experimental studies to define the toxic and 
other effects of 2,4-D or its derivatives cover a wide range of 
organisms commonly referred to as "animals", including worms, 
molluscs, arthropods, lower vertebrates, birds, and mammals.  Much 
of this information, especially on acute toxic effects, was 
recently tabulated by the National Research Council of Canada, 
Associate Committee on Scientific Criteria for Environmental 
Quality (1978), Schneider (1979), Bovey & Young (1980), Shearer & 
Halter (1980), and the Commission of the European Communities (CEC, 

    The usual mandatory acute and subacute safety tests for 
pesticides include assays for eye and skin irritancy and for skin 
sensitization, and determinations of the acute oral, percutaneous, 
and parenteral lethal doses, or of the corresponding lethal 
concentrations in the air, diet, or water. 

7.2.1.  Skin and eye irritancy

    2,4-D does not appear to be an eye or skin irritant (Schneider, 
l979).  Adequate tests of the potential irritative properties of 
2,4-D derivatives have not been reported in the literature. 

7.2.2.  Skin sensitization

    No adequate published information is available on the dermal 
sensitization potential of 2,4-D and its derivatives in mammals. 

7.2.3.  Lethal doses and concentrations (LD50 and L50)

    The lethal potential of a chemical is usually measured as the 
dose (mg/kg body weight), or as the concentration in the air, diet, 
or water (mg/kg, mg/m3, mg/litre, respectively) that will kill 50% 
of the test animals in a specified time interval.  These amounts 
are referred to as the LD50 or LC50.  For 2,4-D and its derivatives, 
and for 2,4-D herbicide formulations, these statistically estimated 
values vary depending on the test product, the test species, and 
the route and frequency of administration (Tables 16 and 17).  Acute oral LD50  Mammals

    Published acute oral LD50 values vary for different 2,4-D 
products and test species (Table 16).  It appears that 2,4-D has a 
moderate acute toxicity for mammals (WHO, 1976).  Birds

    Table 17 shows published oral LD50 values for chickens. 

Table 16.  Acute oral toxicity of 2,4-D, esters, and salts
Compound          Species     Sex    LD50        Reference
                                     (mg/kg bw)
2,4-D             mouse       M      375         Hill & Carlisle (1947)
                  mouse       M      368         Rowe & Hymas (1954)
                  rat         M      375         Rowe & Hymas (1954)
                  rat                666         Hill & Carlisle (1947)
                  guinea-pig  M & F  469         Rowe & Hymas (1954)
                  guinea-pig         1000        Hill & Carlisle (1947)
                  rabbit             800         Hill & Carlisle (1947)
                  dog                100         Drill & Hiratzka (1953)

butyl ester       mouse              380         Konstantinova (1970)
                  rat                1500        Schillinger (1960)
                  rat                920         Konstantinova (1970)
                  cat                820         Konstantinova (1970)

esters of mono-,  rat         F      570         Rowe & Hymas (1954)
di-, and tripro-
pylene glycol
butyl ethers

isopropyl ester   mouse       M      541         Rowe & Hymas (1954)
                  rat         M & F  700         Rowe & Hymas (1954)
                  guinea-pig  M      550         Rowe & Hymas (1954)

mixed butyl       mouse       F      713         Rowe & Hymas (1954)
esters            rat         F      620         Rowe & Hymas (1954)
                  guinea-pig  F      848         Rowe & Hymas (1954)
                  rabbit      M & F  1420        Rowe & Hymas (1954)
sodium salt       mouse              375         Rowe & Hymas (1954)
                  rat         F      805         Rowe & Hymas (1954)
                  rat                2000        Schillinger (1960)
                  guinea-pig  M      551         Rowe & Hymas (1954)
                  rabbit             800         Rowe & Hymas (1954)
------------------------------------------------------------------------  Acute dermal LD50  Mammals

    Reports by Buslovich (1963) and Fetisov (1966) indicate that, 
under extreme test conditions, mice and rats may absorb lethal 
amounts of 2,4-D amine salts and esters through their skin, but no 
acute dermal LD50 values were available for review.  Acute inhalation LC50

    No accurate measurements of acute inhalation LC50 values
for 2,4-D products were available.


Table 17.  Acute LD50 for various 2,4-D products in domestic chickens  (Gallus domesticus)
Product                 Animals          Procedure           LD50              Acid        References
                                                             (mg/kg bw)        equivalent
2,4-D                   chick, M & F     P.O., in olive oil  541 (358-817)     541         Rowe & Hymas (1954)

2,4-D Na salt           adult hen        P.O., in water      655               646         Loktionov et al. (1973)

2,4-D alkanolamine      chick            P.O., in water      > 380 < 765       368         Bjorn & Northern (1948)
salts                                                                                      Rowe & Hymas (1954)

2,4-D amine salt        6-month chicken  P.O., in water      1950              1238        Loktionov et al. (1973)

2,4-D butyl esters      chick, M & F     P.O., undiluted     2000 (1350-2960)  1503        Rowe & Hymas (1954)

2,4-D butoxyethyl       chick, 330 g     P.O., in food       900               588         Whitehead & Pettigrew
esters                                                                                     (1972)

2,4-D isopropyl esters  chick, M & F     P.O., in olive oil  1420 (1127-1789)  1145        Rowe & Hymas (1954)

2,4-D/2,4,5-T (1:1),    chick, M & F     P.O., undiluted     4000 (2700-5900)  -           Rowe & Hymas (1954)
butyl ester             3 weeks old
------------------------------------------------------------------------------------------------------------------  Parenteral LD50

    The acute parenteral LD50 values reported for various
laboratory animals and 2,4-D products ranged from 220 to 666 mg 
a.i./kg body weight (National Research Council of Canada, Associate 
Committee on Scientific Criteria for Environmental Quality, 1978; 
Young et al., 1978; Schneider, 1979). 

7.2.4.  Acute toxicity in aquatic organisms

    The available reports indicate great differences in acute LC50 
values obtained with different test species, and with different 
2,4-D derivatives and test formulations.  The esters appear to be 
considerably more toxic than the water-soluble salts.  For fish, 
the LC50 for various 2,4-D isooctyl ester products may range from 5 
to 68 mg/litre for bluegill sunfish  (Lepomis spp.) and from 62 to 
153 mg/litre for rainbow trout  (Salmo gairdneri) (Schneider, 
1979).  This variability may, in part, be due to differences in 
test animal species and strains, in test conditions (temperature, 
pH, 02 tension, mineral content of water), and, in part, to the 
effects of chemicals other than 2,4-D in the herbicide 
formulations, or of 2,4-dichlorophenol, which may occur in water 
as a decomposition product of 2,4-D (Holcombe et al., 1980). 
Discussions on this variablility can be found in numerous reviews: 
Way (1969), Katz et al. (1972), National Research Council of 
Canada, Associate Committee on Scientific Criteria for 
Environmental Quality (1978), and of Halter (1980), as well as in 
the reports of studies by Harrisson & Rees (1946), King & Penfound 
(1946), Lopez (1961), Hughes & Davis (1963), Butler (1965), 
Hiltibran (1967), Mount & Stephan (1967), Alabaster (1969), Sanders 
(1970a), Andrushaitis (1972), Cooke (1972), Shim & Self (1973), 
Fabacher & Chambers (1974), Meehan et al. (1974), Nishiuchi & 
Yoshida (1974), Rehwoldt et al. (1977), Vardia & Durve (1981), and 
particularly in the extensive and methodical investigation of 
Pravda (1973). 

    Similar information on aquatic invertebrates is available in 
the review of Mackenthun & Keup (1972) and in the studies of Hooper 
(1958), Sudak & Claff (1960), Beaven et al. (1962), Rawls (1965), 
Sanders (1970b), Klekowski & Zvirgzds (1971), Wierzbicka (1974a,b), 
and Caldwell et al. (1979). 

    The observations of Hansen et al. (1972, 1973) and Folmar
(1976) indicate that fish and aquatic invertebrates will try
to avoid water containing toxic amounts of 2,4-D products.

7.3.  Subchronic and Chronic Toxicity

7.3.1.  Mammals

    Most of the published long-term studies with mammals have 
already been reviewed by Bodyagin et al. (1969), Way (1969), IARC 
(1977, 1982), National Research Council of Canada, Associate 
Committee on Scientific Criteria for Environmental Quality (1978), 
Young et al. (1978), Bovey & Young (1980), Shearer (1980), and US 
Veterans' Administration (1981). 

    In the long-term as in the short-term studies on mammals, the 
test products were mainly administered orally.  The composition of 
the test products was not adequately known by present standards, 
but many of the tests were carried out with more or less purified 
2,4-D or its alkali salts.  It is difficult to decide to what 
extent the available results reflect the toxicological properties 
of the present 2,4-D products, in which the maximum contents of CDD 
and other toxic by-products are kept at very low levels. 

    A long-term feeding study in the rat (Hansen, 1971) was 
evaluated by FAO/WHO JMPR in 1971 (FAO/WHO, 1972).  It was 
concluded that a no-observed-adverse-effect level in the rat was 
equivalent to 31 mg/kg body weight per day.  However, new studies 
on mice and rats are in progress.  Clinical signs of poisoning

    Signs of toxic effects on the digestive tract, such as 
diarrhoea, vomiting, dysphagia, decreased gut motility, irritation, 
or necrotic changes (in dogs including necrosis of oral tissues) 
are likely to appear in animals following the absorption of high 
doses of 2,4-D or its derivatives by the oral, dermal, or 
inhalation routes, and after parenteral injections (Bucher, 1946; 
Hill & Carlisle, 1947; Drill & Hiratzka, 1953; Rowe & Hymas, 1954; 
Thomssen, 1958; Björklund & Erne, 1966; Erne, 1966a; Palmer & 
Radeleff, 1969).  Blood-tinged discharges from the nose, and in 
dogs also nasal and eye irritation and skin lesions may also occur 
(Bucher, 1946; Hill & Carlisle, 1947; Kosyan et al., 1974).  Cattle 
may suffer from tympanitis, and may show signs of thirst (Björklund 
& Erne, 1966).  However, some of the signs of "2,4-D poisoning" 
reported in herbivores pastured on 2,4-D-treated vegetation may 
have been caused by the ingestion of inherently poisonous plants 
(Maclean & Davidson, 1970).  Pigs may refuse to eat feed containing 
high amounts of 2,4-D (Strach & Bohosiewicz, 1964), but sheep have 
been reported to feed avidly on 2,4-D-treated vegetation (Sadykov 
et al., 1972). 

    Characteristic signs of severe 2,4-D poisoning in mammals 
appear to be muscular weakness, stiffness, stilted gait, and muscle 
spasms (myotonia), alleviated by exercise and exacerbated by rest.  
There may also be muscular incoordination progressing to paralysis 
especially in the hind limbs; in rodents, caudal rigidity has also 
been observed.  These clinical signs are the result of the myotoxic 
action of 2,4-D discussed below, which, through its effects on the 
heart, may also lead to hypo- or hypertension, cardiac 
fibrillation, and death.  Prolonged inactivity may also occur and 
may lead to pulmonary congestion, emphysema, and pneumonia (Bucher, 
1946; Hill & Carlisle, 1947; Drill & Hiratzka, 1953; Vinokurova, 
1960; Björklund & Erne, 1966; Gorshkov, 1972; Sadykov et al., 1972; 
Kosyan et al., 1974). 

    At high doses, 2,4-D and its derivatives may act as a central 
nervous system depressant and cause lethargy, slowed respiration, 
stupor, coma, and death (Bucher, 1946; Hill & Carlisle, 1947; Drill 
& Hiratzka, 1953; Vinokurova, 1960; Desi et Sos, 1962a,b; Desi et 
al., 1962a,b; Kosyan et al., 1974; Elo & Ylitalo, 1977, 1979).  Effects on food and water consumption, and on body weight

    Relatively high concentrations of 2,4-D or its derivatives in 
the diet or drinking water, or given by capsule, gavage, or 
parenterally, may cause a reduction in food and water consumption, 
and weight loss or reduced body weight gain in rats (Rowe & Hymas, 
1954; Thomssen, 1958; Björklund & Erne, 1966; Chang et al., 1974; 
Chen et al., 1981; Gorshkov, 1972), as well as in dogs (Bucher, 
1946; Drill & Hiratzka, 1953), in pigs (Strach & Bohosiewicz, 1964; 
Björklund & Erne, l966), in rabbits (Loktionov et al., 1973), in 
cattle (Rowe & Hymas, 1954; Björklund & Erne, 1966; Palmer & 
Radeleff, 1969; McLennan, 1974), and sheep (Palmer & Radeleff, 
1969).  However, the same authors, as well as Guseva (1956) and 
Hansen et al. (1971) did not observe these effects at low doses or 
low dietary concentrations of 2,4-D.  In fact, in the studies by 
Raoul & Marnay (1948) and Strach & Bohosiewicz (1964) on rats and 
piglets fed low dietary concentrations of 2,4-D, an unimpaired 
appetite and an improved body weight gain was seen in some groups 
of animals.  In these studies, the dosages ranged between 15 and 
119 mg 2,4-D/kg body weight. 

    Observations of Thomssen (1958), Strach & Bohosiewicz (1964), 
Martynov (1970), Gorshkov (1972), Sadykov et al. (1972), and Erne 
(1974), on hares  (Lepus timidus), European elk, pigs, and rats 
suggest that, given a choice, animals will refuse to eat food or to 
drink water containing more than a certain amount of 2,4-D, and 
that this may, in part, be because of the strong characteristic 
odour and taste of this compound, or of organic solvents such as 
diesel fuel that are used in herbicide formulations or as diluents.  Effects on the central nervous system (CNS)

    It has been suggested that the signs of central nervous system 
depression in animals severely poisoned with 2,4-D are related to a 
partial breakdown of the blood-brain barrier, possibly as a result 
of damage to capillary vessels, and a subsequent accumulation of 
2,4-D in the CNS (Desi & Sos, 1962a,b; Elo & Ylitalo, 1977, 1979). 

    However, further studies are needed to clarify the mechanism(s) 
by which 2,4-D acts on the central nervous system.  Effects on the peripheral nervous system

    No peripheral neuropathy was attributed to 2,4-D in the 
available reports on short-term and long-term studies with 2,4-D in 
a variety of animals (Shillinger & Naumova, 1957; Stupnikov, 1959).  
The partial or complete paralysis, especially of the hind legs, of 
2,4-D poisoned animals reported already by Bucher (1946) and Hill & 
Carlisle (1947) may be a myotoxic rather than a neurotoxic effect 
of 2,4-D.  Moreover, in severe 2,4-D poisoning, a general weakness 
may lead to inactivity that might be interpreted as paralysis. 

    No signs of neuropathy were reported by Kay et al. (1965) in 
rabbits given large percutaneous doses of 2,4-D dimethylamine salt, 
2,4-D butyl ester, or 2,4-D isooctyl ester.  In similar studies in 

which rats or rabbits were exposed by the dermal route, Buslovich 
(1963) reported myotonia and death in rats given unspecified doses 
of 2,4-D amine salt or 2,4-D butyl ester, but no peripheral 
neuropathy, while Vinokurova (1960) found 130 - 180 mg of a 50% 
aqueous emulsion of 2,4-D octyl ester/kg body weight to have "no 
systemic effect" on rabbits. 

    The neurotoxic effects in animals of 2,4-D and of other related 
compounds have not been adequately studied.  Further research is 
required to elucidate the mechanism of the neurotoxic and myotoxic 
action of 2,4-D in animals.  Myotoxic effects

    Most of the studies of the effects of 2,4-D on vertebrate 
muscles were carried out because the 2,4-D-induced abnormalities 
resemble a heritable muscle disorder in human beings, namely 
myotonia congenita (Hofmann et al., 1966; Laskowski & Dettbarn, 
1977).  As a rule, high doses of 2,4-D (1/4 to 1/2 LD50) are 
required to obtain severe and prolonged myotonia.  The effects of 
2,4-D on muscle cells are complex, and include disturbances in:  
the activity of various enzymes (leading, for example, to increased 
lactate production); potassium levels; membrane resistance; and in 
chloride conductance.  There are also shifts in calcium-binding 
sites, changes in muscle and nerve cell electrical potentials, and 
mitochondrial structural and ultrastructural degenerative changes 
in muscle (Eyzaguirre et al., 1948; Kuhn & Stein, 1964, 1965, 1966; 
Heene 1966, 1968, 1975; Hofmann et al., 1966; Kenigsberg, 1968; 
Stein & Kuhn, 1968; Bodem et al., 1971; Preiss & Rossner, 1971; 
Seiler, 1971; Buslovich & Koldobskaya, 1972; Rüdiger et al., 1972; 
Senges & Rüdel, 1972; Brody, 1973; Danon et al., 1976; Iyer et al., 
1976; Bretag & Caputo, 1978; Dux et al. 1978; De Reuck et al., 
1979; Eberstein & Goodgold, 1979; Mazarean et al., 1979a,b). 
Similar effects are produced by the chlorophenoxy drug clofibrate 
(atromid) (Pierides et al., 1975; Smals et al., 1977).  None of the 
available studies on 2,4-D-induced myotonia were designed to 
establish no-observed-adverse-effect levels for the various 
myotoxic effects in intact animals, and therefore additional 
studies should be carried out for this purpose.  Cardiovascular effects

    As part of its myotoxic action, 2,4-D and its derivatives may 
in high doses cause biochemical, physiological, and structural 
damage to the myocardium  in vitro and  in vivo (Bodem et al., 1971; 
Preiss & Rossner, 1971; Rüdiger et al., 1972; Mazarean et al., 
1979a,b).  Haematological effects

    Shifts have been reported in the number or types of 
erythrocytes, leukocytes, or bone marrow cells, or changes in 
haemoglobin levels, in a variety of laboratory and domestic mammals 
given 2,4-D or 2,4-D derivatives  (Bucher, 1946; Hill & Carlisle, 
1947; Drill & Hiratzka, 1953; Shillinger & Naumova, 1957; 

Schillinger, 1960; Björklund & Erne, 1966; Hansen et al., 1971; 
Sadykov et al., 1972; Loktionov et al., 1973; Kosyan et al., 1974; 
and Halliop et al., 1980).  Effects on blood chemistry

    Rowe & Hymas (1954) were apparently the first investigators to 
monitor blood chemistry in 2,4-D-treated animals.  They did not 
observe any adverse effects at 2,4-D dietary levels as high as 300 
mg 2,4-D/kg in rats treated for 113 days. 

    Other investigators noted changes in various serum, plasma, or 
erythrocyte enzyme activity levels, and shifts in the levels of 
electrolytes, glucose, blood proteins, or other chemicals in 
response to treatment with 2,4-D or 2,4-D derivatives in rats, 
rabbits, cattle, pigs, or sheep, or in blood from such animals to 
which 2,4-D was added  in vitro (Shillinger & Naumova, 1957; 
Schillinger, 1960; Björklund & Erne, 1966; Shevchenko, 1966; 
Dzhaparov & Tsilikov, 1969; Hunt et al., 1970; Szöcs et al., 1970; 
Gorshkov, 1972; Kosyan et al., 1974; Kuzminskaya & Bersan, 1975; 
Chen et al., 1981).  Some of the changes in transaminase (SGOT, 
SGPT), blood urea nitrogen (BUN), or glucose levels appeared to be 
secondary to myotoxic, nephrotoxic, or hepatotoxic effects of high 
doses of 2,4-D.  Other biochemical effects observed  in vivo or  in vitro

    Sufficiently high doses of 2,4-D may induce changes in 
mitochondrial oxygen consumption and oxidative phosphorylation, in 
electrolyte, ascorbic acid, glycogen, lipid, and nucleic acid 
contents of organs, tissues, cells, organelles, or cell fractions 
from a variety of mammals (Brody, 1952, 1973; Guseva, 1956; Baker 
et al., 1960; Kuhn & Stein, 1964; Heene, 1966, 1967, 1968; 
Shevchenko, 1966; Philleo & Fang, 1967; Kenigsberg, 1968; Dzhaparov 
& Tsilikov, 1969; Stanosz, 1969; Buslovich & Koldobskaya, 1972; 
Graff et al., 1972; Buslovich et al., 1973; Abo-khatwa & 
Hollingworth, 1974; Chang et al., 1974; Nikandrov, 1974; Venkaiah & 
Patwardhan, 1978; Podolak, 1979).  Pulmonary effects

    No pulmonary abnormalities were reported in studies with mice, 
rabbits, rats, or dogs conducted by Bucher (1946), Drill & Hiratzka 
(1953), Rowe & Hymas (1954), Shillinger & Naumova (1957), 
Schillinger (1960), or Björklund & Erne (1966).  In contrast, Hill 
& Carlisle (1947) and Palmer (1972) noted congestion of pulmonary 
vessels, pulmonary petechial haemorrhages, and pulmonary edema or 
emphysema in mice, rats, dogs, cattle, or sheep that died of 2,4-D 
poisoning.  Hepatotoxic effects

    Rabbits, rats, mice, dogs, cattle, or sheep treated for a 
prolonged period with toxic doses of 2,4-D were found to develop a 
subacute toxic hepatitis with congestion of hepatic blood vessels, 

and cloudy swelling, fatty infiltration, local necrosis, 
degeneration, or atrophy of hepatocytes, especially of the 
parenchyma in the centrolobular areas (Bucher, 1946; Hill & 
Carlisle, 1947; Drill & Hiratzka, 1953; Rowe & Hymas, 1954; 
Björklund & Erne, 1966; Szöcs et al., 1970; Palmer, 1972).  High 
doses of 2,4-D may induce a proliferation of peroxisomes and 
increased levels of mixed function oxidases in liver cells of rats 
and hamsters (Buslovich et al., 1982; Vainio et al., 1982, 1983). 

    Changes in the levels of certain liver enzymes such as maleate 
or succinic dehydrogenase, and in ascorbic acid or glycogen content 
or hippuric acid production have also been reported (Shillinger & 
Naumova, 1957; Baker et al., 1960; Dzhaparov & Tsilikov, 1969; 
Szöcs et al., 1970; Buslovich et al., 1973; Chang et al. 1974; 
Nikandrov, 1974).  Some of the results concerning liver glycogen 
levels in rats suggest a reverse trend at high doses, as Dzhaparov 
& Tsilikov (1969) found that a dose equivalent to 1/16 LD50 per day 
lowered the liver glycogen content, while Chang et al. (1974) 
observed the opposite effect at doses of about 100 mg/rat per day.  Effects on the kidney

    In early studies with high doses of 2,4-D, signs of impaired 
kidney function, increased relative kidney weight, and of gross and 
histological abnormalities (parenchymatous degeneration, 
hypertrophy, and hyperplasia, cloudy swelling especially in the 
cells of the proximal convoluted tubules, and glomerular lesions) 
were noted in mice, rats, and dogs (Bucher, 1946; Hill & Carlisle, 
1947; Drill & Hiratzka, 1953; Rowe & Hymas, 1954).  That the kidney 
is a target organ for the structural, physiological, and chemical 
effects of 2,4-D was confirmed repeatedly by later and more 
detailed studies on a wider range of test species including pigs, 
goats, and sheep (Schillinger, 1960; Björklund & Erne, 1966; Erne, 
1966a; Stanosz, 1969; Hunt et al., 1970; Milhaud et al., 1970; 
Gorshkov, 1972; Palmer, 1972; Senczuk & Pogorzelska, 1975; Koschier 
et al., 1978; Orberg, 1980a).  In a recent 13-week study on rats, 
the no-observed-adverse-effect level for histological changes 
induced with pure 2,4-D in mammalian kidney appeared to be 15 mg/kg 
body weight per day (Chen et al., 1981).  Effects on endocrine organs

    Swelling and congestion of the thyroid were noted by Palmer 
(1972) in cattle and sheep fatally poisoned with various 2,4-D 
products.  Effects of 2,4-D on iodide uptake by the thyroid gland 
were first decribed by Sos & Kertai (1958) and studied further by 
Florsheim & Velcoff (1962), Florsheim et al. (1963), Tsilikov 
(1969), and Gorshkov (1972).  Their results indicate that doses of 
5 - 250 mg 2,4-D sodium salt or equivalent/kg body weight per day 
have a stimulatory effect on thyroid function. 

    Effects of 2,4-D on adrenal function and its relationship to 
muscle carbohydrate metabolism and 2,4-D-induced myotonia have been 
studied by Kenigsberg (1968), and by Buslovich & Koldobskaya 
(1972).  2,4-D-induced changes in adrenal or thyroid function may 
also be implicated in the abnormal temperature regulation in 2,4-D-

treated rats described by Sudak et al. (1966).  However, it is 
noteworthy that Buslovich (1963) was unable to induce a change in 
the body temperature of rats by giving 15 - 20 oral doses of 2,4-D 
sodium salt, amine salt, or butyl ester at a level of 1/10 or 1/5 
LD50/day.  Effects on the digestive tract

    Vomiting, diarrhoea, hyperaemia, bloody exudates in the gut, 
necrotic changes in the mucosa, and other non-acute toxic effects 
on the digestive tract have been reported after administration of 
high doses of 2,4-D by either the oral or parenteral route in mice, 
rats, and dogs (Bucher, 1946; Hill & Carlisle, 1947; Drill & 
Hiratzka, 1953; Kosyan et al., 1974).  However, Hansen et al. 
(1971) did not observe any such effects in a 2-year feeding study 
at dietary levels of 2,4-D corresponding to about 37.5 and 67.5 mg 
2,4-D/kg body weight per day, respectively, for rats and dogs.  
Their observations on dogs contrast with those of Drill & Hiratzka 
(1953) who found repeated doses of 20 mg 2,4-D/kg body weight per 
day to be fatal in 3 out of 4 dogs studied by them. 

7.3.2.  Birds

    The published reports on the toxic effects of 2,4-D and 2,4-D 
products in birds deal mainly with chickens  (Gallus domesticus)  
and game birds.  The available data on cumulative oral lethal doses 
for game birds have been summarized in Table 18; studies on the 
reproductive, embryotoxic, and teratogenic effects of 2,4-D are 
dealt with in section 7.3.6. 
Table 18.  Cumulative oral lethal doses of 2,4-D herbicides for game birds
Product        Species               Dietary LC50  Cumulative LD50   References
                                     (mg a.i./kg   (mg a.i./kg bw)a
2,4-D          quail (young)         5000          28 000            Dewitt et al. 
dimethylamine                                                        (1962)
               mallard duck          5000          8250
               (young)               5000          8250
               (adult)               > 2500        > 34 000

2,4-D          quail
butoxyethanol  (young)               5000          38 000
ester          (adult)               5000          40 700

               pheasant (young)      5000          29 500
               mallard duck (adult)  5000          > 33 000
a a.i. = active ingredient
    The clinical signs of 2,4-D poisoning in birds appear to be 
similar to those in mammals, and the kidney seems to be the most 
sensitive organ.  No adverse effects were reported in chickens fed 

dietary levels of 1000 mg/kg for 21 days (142 mg/kg body weight) 
whereas kidney enlargement occurred in chickens fed 5000 mg/kg of 
diet for 21 days (Whitehead & Pettigrew, 1972).                 

7.3.3.  Cold-blooded animals

    The literature on the chronic effects of 2,4-D and its 
derivatives on cold-blooded animals (poikilotherms) was not 
reviewed in detail.  The available reports indicate that for 
aquatic vertebrates in general, 2,4-D esters are more toxic than 
2,4-D amines, and that the overall no-observed-adverse-effect level 
for toxic effects on fish for the esters is at or near 1 mg/litre 
(King & Penfound, 1946; Zhiteneva & Chesnokova, 1973; Fabacher & 
Chambers, 1974; Meehan et al., 1974).  2,4-dichlorophenol, which 
may occur in water as a by-product or transformation product of 
2,4-D, is similarly toxic to fish (Holcombe et al., 1980). 

7.4.  Fetotoxicity, Teratogenicity, and Reproductive Effects

    The scientific literature contains a fairly large number of 
reports on the fetotoxic, teratogenic, and reproductive effects of 
2,4-D in livestock and in laboratory animals.  However, most of the 
observations on livestock are either too sketchy to be useful or 
neglect to take into account various confounding factors.  Examples 
of this are studies by Björklund & Erne (1966) on a single pregnant 
pig, by Sadykov et al. (1972) on sheep grazing on pastures 
apparently containing a high percentage of poisonous plants, and 
the report by Bodai et al., (1974), on reproductive disturbances in 
cattle feeding on either 2,4-D-treated vegetation possibly 
including poisonous plants, or on contaminated silage. 

    Some of the studies carried out with rodents under laboratory 
conditions also provide little useful information, either because 
it is difficult or impossible to determine the dose levels used in 
the studies (Weinmann, 1957; Schuphan, 1963, 1965, 1969; Schiller, 
1964; Buslovich et al., 1976); or because the information provided 
is insufficient and the studies cannot be properly evaluated 
(Bucher, 1946; Hansen et al., 1971; King et al., 1971).  The study 
by Weinmann (1957) can be considered invalid, as a high mortality 
occurred in both control and experimental animals, when they were 
exposed to cold stress because of construction work affecting the 
animal quarters during the winter months.  Moreover, Weinmann 
(1957) and several other authors, including Schuphan (1963, 1965, 
1969) Schiller (1964), Schillinger (1960), and Shillinger & Naumova 
(1957) did not in fact examine the effects of 2,4-D, but rather the 
effects of foods or food extracts prepared from crops that had been 
sprayed with 2,4-D, and, in some cases, also with other plant 
growth substances.  As none of these authors appears to have 
carried out an analysis to demonstrate the presence of 2,4-D 
residues in the test material, it is questionable whether the test 
animals ingested any 2,4-D or 2,4-D residues, and these studies are 
therefore not reviewed in detail.  Buslovich et al. (1976) tested 
only a single dose level (1/2 LD50) and this reduces the usefulness 
of their study.  Pertinent reports are discussed below. 

7.4.1.  Rats  Effects on adult rats

    No deleterious effects on the health or fertility of rats 
receiving the maximum tolerated dose of 87.5 mg/kg body weight in 
terms of 2,4-D or its molar equivalent of the isooctyl ester or the 
propylene glycol butyl ether ester per day, on days 6 - 15 of 
pregnancy, were reported by Schwetz et al. (1971) and Unger et al. 
(1980).  Even higher amounts of 2,4-D or its equivalent in 2,4-D 
derivatives were used by Björklund & Erne (1966), Hansen et al., 
(1971) and Khera & McKinley (1972) with similar results. 

    Reduced testis and prostate size, abnormal spermatogenesis (and 
also liver and kidney damage) were reported by Schillinger (1960) 
in some of the male rats given 375 mg/kg body weight per day (about 
1/4 LD50) of a Soviet-made 2,4-D butyl ether formulation containing 
polyethylene glycol alkyl phenyl ether surfactant.  These effects 
were not noted at 1/10 of this dose level, i.e., at 37.5 mg/kg body 
weight per day. Some of the toxic effects reported by Schillinger 
(1960) may have been caused by the surfactant, but as a surfactant 
control group was not included in this study, this cannot be 
confirmed.  Thus, the available studies suggest that the no-
observed-adverse-effect level for reproducing adult rats lies 
between 37.5 and 87.5 mg 2,4-D/kg body weight per day.  Effects on offspring

    Björklund & Erne (1966) gave pregnant rats a 2,4-D 
concentration in drinking-water of 1000 mg/litre during pregnancy, 
and for the following 10 months.  No effects on reproduction were 

    Hansen et al. (1971) fed male and female rats dietary levels of 
technical 2,4-D of 100, 500, and 1500 mg/kg (ppm), and the rats 
were bred through 3 successive generations.  At dietary levels of 
100 and 500 mg/kg, no effects were noted.  However, at a dietary 
level of 1500 mg/kg, survival of pups to weaning was reduced.  The 
number of pups surviving ranged from 70 - 97% in the control group 
and from 60 - 93% at the 100 and 500 mg/kg (ppm) dietary levels; 
survival at the highest dose ranged from 20 - 62%. 

    Resorptions, reduced fetal weight and size, enlarged ventricles 
of the brain and haemoperitoneum were found by Buslovich et al. 
(1976) in the offspring of rats treated with two different 2,4-D 
derivatives at a dose of one-half LD50 (value unspecified).  
Schwetz et al. (1971) dosed female rats from day 6 - 15 of 
pregnancy by gavage at dose levels of 0, 12.5, 25, 50, and 87.5 
mg/kg body weight per day with 2,4-D or equimolar dose levels of 
the propylene glycol butyl ether (PGBE) and the isooctyl esters 
(IO).  At doses of 50 and 87.5 mg/kg, a decrease in fetal body 
weight was noted for all three compounds. 

    Subcutaneous oedema, delayed ossification of sternebrae, 
sternebrae with split centres of ossification, wavy ribs, and 
lumbar ribs increased with increasing doses, for at least one of 
the agents studied.  However, these anomalies were not 
significantly increased at the 12.5 or 25 mg/kg dose level for the 
3 compounds.  A small but significant increase in the incidence of 
subcutaneous oedema was observed in fetuses from dams receiving 
12.5 mg/kg molar equivalent of IO.  The incidence of missing 
sternebrae was significantly increased at dose levels of 87.5 mg/kg 
for 2,4-D and 12.5 and 87.5 mg/kg for PGBE. 

    Unger et al. (1980), in a later study, using the same dosing 
regimens for 2,4-D IO and 2,4-D PGBE did not observe the effects 
reported by Schwetz et al., except for a statistically significant 
increase in rib buds at the highest dose (87.5 mg/kg) tested for 
both compounds ( P < 0.05). 

    Khera & McKinley (1972) dosed female rats from day 6 - 15 of 
pregnancy by gavage with 2,4-D, 2,4-D IO, 2,4-D butyl ester, 2,4-D 
butoxyethanol ester and 2,4-D dimethylamine salt.  The butyl and 
isooctyl ester depressed fetal weight and decreased fetal viability 
at the highest dose of 150 mg/kg body weight.  Wavy ribs, 
additional ribs, retarded ossification and sternal defects, fused 
ribs, small-sized distorted scapula and micromelia were observed as 
anomalies among the treated groups.  A statistically significant 
increase in malformed fetuses was noted at 2,4-D levels of 25 mg/kg 
body weight ( P < 0.05) and at levels of 150 mg/kg or more for the 
other compounds. 

    Konstantinova et al. (1975) reported hemorrhage into internal 
organs in the fetuses of rats treated with a 2,4-D level of 50 
mg/kg body weight. 

    The results of all these studies suggest that dosage levels of 
less than 12.5 mg/kg body weight for the various 2,4-D derivatives 
do not cause fetotoxic or teratological effects in rats, and the 
results of the more recent study by Unger et al. (1980) indicate 
that higher doses may be without deleterious effects on the 

    Thus, at present, a daily dose level of 10 mg 2,4-D or 2,4-D 
acid equivalent/kg body weight can be considered to be without 
significant fetotoxic or teratogenic effects in rats. 

7.4.2.  Mice

    The report by Courtney (1977) indicated that in CD-1 mice, 
doses of 1 mM/kg body weight of 2,4-D and its n-butyl and PGBE 
esters reduced fetal body weight, and increased fetal mortality.  
The compounds were also teratogenic, inducing cleft palates, at 
levels of 124 mg/kg body weight per day (2,4-D or acid equivalent) 
or more.  However, the 2,4-D isopropyl and isooctyl esters appeared 
to be less teratogenic than 2,4-D, as they did not induce birth 
defects at a 2,4-D equivalent level of 124 mg/kg body weight per 
day.  Furthermore, the 2 esters did not induce fetal death in CD-1 
mice at doses of 2,4-D equivalent up to 221 mg/kg body weight per 

7.4.3.  Birds

    In the 1960s and 1970s, a number of tests of the embryotoxic, 
teratogenic, and other reproductive effects of 2,4-D were carried 
out on birds' eggs and embryos.  These results may not apply to 
mammals, because bird embryos develop in a closed environment 
different from that of mammalian embryos, and because birds differ 
anatomically from mammals. 

    Lutz-Ostertag & Lutz (1970, 1974) reported mortality and severe 
deformities in wild bird embryos exposed to 2,4-D amine salt, but 
they did not provide crucial experimental details, and other 
investigators (Dunachie & Fletcher, 1967, 1970; Kopischke, 1972; 
Grolleau et al., 1974; Gyrd-Hansen & Dalgaard-Mikkelsen, 1974; 
Somers et al., 1974a,b,c; Hilbig et al., 1976a,b; Spittler, 1976) 
were unable to duplicate their results either with 2,4-D amine 
salts or esters.  Some of the teratogenic effects attributed to 
2,4-D by Lutz-Ostertag & Lutz (1970, 1974) resemble those induced 
by excessively high incubation temperatures (Nielsen, 1968), and 
may thus have been experimental artifacts. 

    On the whole, the available studies on bird embryos indicate 
that the no-observed-adverse-effect level for 2,4-D-induced 
embryotoxic and teratogenic effects lies near 0.5 mg active 
ingredient/egg (equivalent to about 10 mg/kg) and is thus similar 
to that in mammals. 

7.4.4.  Cold-blooded animals

    The available literature contained little information 
concerning the possible reproductive, embryotoxic, or teratogenic 
effects of 2,4-D or 2,4-D derivatives on cold-blooded animals.  Amphibians

    Lopez (1961) noted that the motility of frog spermatozoa was 
not affected by low concentrations of 2,4-D or its sodium salt, and 
that the inhibition of movement, or the lysis observed under some 
conditions were caused by changes in the pH of the test solution.  
Aqueous solutions of less than 0.05% 2,4-D sodium salt did not 
induce any macroscopic abnormalities in developing frog eggs or 
embryos (Lhoste & Roth, 1946), while Cooke (1972) did not find 
either toxic effects or 2,4-D residues in frog tadpoles exposed for 
1 or 2 days to up to 50 mg 2,4-D/litre.  According to Sanders 
(1970a) a commercial 2,4-D dimethylamine salt had an LC50 of 100 
mg/litre for frog tadpoles.  Fish

    Only three brief reports were available on the effects of 2,4-D 
on developing fish eggs and embryos.  Andrusaitis (1972) found that 
2,4-D reduced the oxygen consumption of 32-cell blastomeres, and 
increased the oxygen consumption in 64 - 128 cell blastomeres of 
 Misgurnus fossilis.  In a study by Mount & Stephan (1967), 2,4-D 

butoxyethanol ester (BEE) at a concentration of up to 0.31 
mg/litre, or 2,4-D at 0.80 mg/litre did not reduce the reproduction 
rate in fathead minnows  (Pimephales promelas), whereas 2,4-D BEE 
at 1.5 mg/litre killed minnow eggs in 48 h.  Rehwoldt et al. (1977) 
similarly found that 0.1 mg 2,4-D/litre did not have any adverse 
effect on reproduction in guppies. 

    These reports suggest that the no-observed-adverse-effect level 
of 2,4-D BEE for the reproductive or teratogenic effects of 2,4-D 
in fish may be about 1 mg a.i./litre water. 

7.5.  Mutagenicity and Related Effects

7.5.1.  2,4-D and its derivatives

    Studies on the mutagenicity of 2,4-D and its derivatives have 
been reviewed by Andersen et al. (1972), National Research Council 
of Canada, Associate Committee on Scientific Criteria for 
Environmental Quality (1978), Ramel (1978), Seiler (1978), 
Vachkova-Petrova (1978), Kas'yanenko & Koroleva (1979), Murthy 
(1979), Shearer (1980), US Veterans' Administration (1981), Waters 
et al. (1981), and Linainmaa (1983). 

    A recent IARC Working Group (IARC, 1982) evaluated the activity 
of 2,4-D and derivatives in short-term tests.  It was reported that 
2,4-D induced unscheduled DNA synthesis in cultured human 
fibroblasts (Ahmed et al., 1977a), but not in rat hepatocytes 
(Probst et al., 1981).  2,4-D was not mutagenic in bacterial 
systems (Andersen et al., 1972; Sherasen et al., Zetterberg, 1977; 
Moriya et al., 1983).  2,4-D was mutagenic in yeast, when tested at 
low pH (Zetterberg et al., 1977), but was not active under other 
conditions (Zetterberg, 1977) or in a host-mediated assay 
(Zetterberg et al., 1977).  Results of four studies on  Drosophila 
 melanogaster were reported to be positive (Rasmuson & Persson-
Svahalin, 1978):  results of three other studies were negative 
Berin & Buslovich, 1971; (Vogel & Chandler, 1974; Magnusson et al., 
1977; Rasmuson & Svahlin, 1978). 

    2,4-D was reportedly mutagenic in cultured Chinese hamster 
ovary (CHO) cells (Ahmed et al., 1977b), but did not induce a 
statistically significant increase in sister chromatid exchanges 
(SCEs) in CHO cells  in vitro (Linainmaa, 1983).  Chromosomal 
effects have been reported in plants (Khalatkar & Bhargava, 1982). 

    Chromosomal aberrations or SCEs were found in cultured human 
lymphocytes (Pilinskaya, 1974; Korte & Jatal, 1982), but 
chromosomal aberrations were not found in cultured embryonic bovine 
kidney cells (Bongso & Basrur, 1973). 

    In mice, single oral doses of 100 - 300 mg 2,4-D/kg body weight 
reportedly induced chromosomal aberrations (Pilinskaja, 1974), but 
micronuclei were not found in mice after ip injection of single 
doses of 100 mg 2,4-D/kg body weight (Jenssen & Renberg, 1976).  
2,4-D was not active in a dominant lethal test in mice (Epstein et 
al., 1972), and did not induce SCEs in rats after oral 

administration of 2,4-D amine salt at daily doses of 100 mg/kg body 
weight for two weeks (Linnainmaa et al., 1983).  Recent evidence 
(Buslovich et al., 1982; Vainio et al., 1982) suggests that 2,4-D 
may have an indirect effect on genetic material via the production 
of active oxygen radicals derived from peroxisome proliferation, 
which has been demonstrated in  in vivo and  in vitro studies in 
liver cells of rats and hamsters (Reddy et al., 1980, 1982; Vainio 
et al., 1982; Gray et al., 1983). 

    At present, available studies are inadequate to evaluate the 
genetic effects of 2,4-D and its derivatives in short-term tests 
(IARC, 1982).  No data on cell transformation are available. 

7.6.  Carcinogenic Effects on Experimental Animals

7.6.1.  2,4-D and its derivatives

    A number of studies have been carried out on mice and rats to 
assess the potential carcinogenic effects of 2,4-D and its 
derivatives.  Two IARC Working Groups have reviewed these studies 
(IARC, 1977, 1982) and concluded that it was not possible to make 
an evaluation on the basis of the available data.  2,4-D and 
several of its esters were tested by oral administration and by a 
single sc injection in the newborn of 2 strains of mice (Innes et 
al., 1969); 2,4-D or its amine salts were also tested in rats by 
oral administration (Arkhipov & Kozlova, 1974; Hansen et al., 

    Nearly 20 years have passed since these studies were carried 
out and because of basic flaws in their design and execution, it is 
unlikely that further reviews of these studies will lead to 
generally accepted conclusions.  The Task Group was aware that 
further long-term studies in mice and rats were in progress, and 
these should prove useful in the future evaluation of the potential 
carcinogenicity of 2,4-D. 

7.6.2.  Contaminants in 2,4-D

    2,7-DCDD was tested for carcinogenicity in mice and rats fed 
dietary levels of 5000 and 10 000 mg/kg for 90 weeks, followed by a 
short observation period of about 1 - 10 weeks, at which time all 
animals were killed.  Sufficient numbers of animals survived to 
evaluate the development of late-appearing tumours.  Although an 
increased incidence of hepatocellular adenomas and carcinomas was 
observed in treated male mice (20/50 in the low dose and 17/42 in 
the high dose compared with 8/49 in matched controls), it was noted 
that the incidence of liver tumours in historical controls ranged 
from 16 - 32%.  No tumorigenic effects were found in rats (US 
National Cancer Institute, 1979). 


    The available clinical and epidemiological studies fall into 4 
groups:  (a) studies on patients treated with 2,4-D as an 
anticancer drug (Apffel, 1959a) or antibiotic (Seabury, 1963), (b) 
reports on acute 2,4-D poisoning due to voluntary or accidental 
ingestion of herbicides (Tables 19 and 20), (c) reports on workers 
(mainly men) overexposed to 2,4-D during the manufacture, 
processing, or use of 2,4-D herbicides, and (d) epidemiological 
studies on groups of people who were actually or potentially 
exposed as a result of herbicide spray programmes, or who lived in 
areas in which herbicides were used.  With the exception of the 
case studies of Apffel (1959a) and Seabury (1963), almost all of 
the reports deal with mixed exposures to 2,4-D and other chemicals, 
and therefore it is often unclear to what extent 2,4-D, its alkali 
or amine salts, or its esters contributed to the effects reported 
by the authors of the studies. 

    Much of the literature on acute poisonings and on the health 
effects of occupational overexposure to 2,4-D or other 
chlorophenoxy compounds or their toxic by-products has been 
recently reviewed by Pocchiari et al. (1979), Bovey & Young (1980), 
Huff et al. (1980), National Research Council of Canada, Associate 
Committee on Scientific Criteria for Environmental Quality (1981), 
CEC (1981), Rappe & Buser (198l), US Veterans' Administraton 
(1981), Coggon & Acheson (1982), Hay (1982), IARC (1982, 1983), and 
Dobrovolski (unpublished data, 1983).  However, most of these 
reviews concentrated on 2,4,5-T, Agent Orange, and other herbicides 
used in the Vietnam war, or on industrial accidents resulting in 
massive exposures to largely undefined mixtures of chlorophenols, 
chlorinated dibenzodioxins, and other reaction products.  In 
contrast, the present review focuses mainly on 2,4-D herbicides. 

    In evaluating human exposure to mixtures of chemicals that 
include 2,4-D and various concentrations of contaminants of 2,4-D, 
it is in many instances difficult or impossible to determine 
whether any of the described effects can actually be attributed to 
the exposure to 2,4-D or its derivatives. 

8.1.  Acute Poisoning and Occupational Overexposure

    Pertinent reports on acute poisoning with 2,4-D, or of the 
effects of occupational overexposure to 2,4-D herbicides are 
summarized or cited in Tables 19 and 20. 

    Signs and symptoms of acute overexposure to 2,4-D or its 
derivatives occurred after ingestion or absorption of large 
amounts, or where poor occupational hygiene was practised leading 
to pronounced dermal absorption of the material.  It is unlikely 
that, with good agricultural practice, good personal protection, 
and occupational hygiene, resulting in exposures to low 
concentrations of 2,4-D, any of the acute symptoms and signs 
reported below would be expected to occur. 

Table 19.  Acute toxicity of 2,4-D, fatal poisonings with herbicides containing 2,4-D
Product(s)       Circum-       Sex of  Body     Dose ingested    2,4-D          Effects and outcomes    References
                 stances       victim  weight                    concentration  
                                       or age                    in tissues     
a)  Fatal poisonings

2,4-D diethyl    not stated    F       50.8 kg  60-90 g          40-400         coma; death in about    Curry (1962)
ester                                           (1180-1770 mg                   2 days; degeneration
(DICOTEX EXTRA)                                 DOCOTOX/kg bw)                  of convoluted kidney

"2,4-D"          suicide       M       ?        ~ 125 ml         ?              loss of consciousness,  Delarrard &
400 g                                                            (< 400 bw)     coma, generalized       Barbaste (1969)
a.i./litre                                                                      muscular hypotonia,
                                                                                loss of all reflexes,
                                                                                proteinuria; death in
                                                                                12 h

"pure" 2,4-D     suicide       M       55 kg    ?                57.6-407.9     coma, myotonia, fever,  Dudley &
acid in                                                                         pulmonary emphysema     Thapar (1972)
kerosene                                                                        and edema, liver 
                                                                                necrosis, degeneration
                                                                                of kidney tubules;
                                                                                death in 6 days
"2,4-D"          suicide       F       ?        ?                20-116         loss of consciousness,  Geldmacher-Van
                                                                                vomiting, uterine       Mallinckrodt &
                                                                                bleeding, tachycardia,  Lautenbach 
                                                                                and circulatory         (1966)
                                                                                failure; death in 
                                                                                about 30 h; edema and 
                                                                                congestion of brain;
                                                                                fatty liver cell 
                                                                                changes; fatty changes 
                                                                                in kidney tubules;
                                                                                pulmonary hyperaemia &
                                                                                edema with isolated
Table 19.  (contd.)
Product(s)       Circum-       Sex of  Body     Dose ingested    2,4-D          Effects and outcomes    References
                 stances       victim  weight                    concentration  
                                       or age                    in tissues     
"2,4-D"          suicide       M       ?        "at least"                      stiffness in legs,      Herbich &
                                                13.5 g                          vomiting, loss of       Machata
                                                                                consciousness; death    (1963)
                                                                                in 14 h; hyperaemia
                                                                                and edema of brain;
                                                                                pulmonary edema

2,4-D            suicide       M       75 kg    120 ml           12.5-7700      vomiting; congestion,   Nielsen et al.
dimethylamine                                   (80 mg/kg)                      pulmonary emphysema;    (1965)
formulation                                                                     CNS congestion &       
                                                                                haemorrhages, severe
                                                                                degeneration of          
                                                                                ganglion cells; death
                                                                                within hours of
Herbicide        suicide       M       26       360 ml 2,4-D      plasma         clinical and            Osterloh et al.
containing                             years    and mecoprop     321 (1.5 h)    pharmacokinetic         (1983)
2,4-D, mecoprop                                 amine salt       540.9 (21 h)   study coma with            
(MCPP) and                                      (10.6%, 11.6%    480.8 (30 h)   pin-point pupils                   
chlorpyrifos                                    a.i.) and 360                   tachycardia,         
                                                ml chlorpyrifos  urine (on      hypertension,                
                                                in kerosene       admission):    myoclonus, diarrhoea,          
                                                (6.7% a.i.)      230.3          then hypotension,              
                                                plus few                        cardiac arrhythmias,            
                                                granules         gastric        asystole, and death            
                                                Warfarin (0.025  content (on    after 30 h                     
                                                % a.i.) (2,4-D    admission):   
                                                = 600 mg/kg bw;  108.2        
                                                mecoprop = 600      
                                                mg/kg bw)        tissues
                                                                  (post mortem)
                                                                 brain: 186.4
                                                                 blood: 389.5
                                                                 liver: 293.5
                                                                 heart: 301.2
                                                                 kidney: 315.0

Table 19.  (contd.)
Product(s)       Circum-       Sex of  Body     Dose ingested    2,4-D          Effects and outcomes    References
                 stances       victim  weight                    concentration  
                                       or age                    in tissues     
b)  Non-fatal poisonings
"2,4-D"          accidental    M       ? (5-    ?                ?              drowsiness,             Duric et al.
"DEHERBAN A"     ingestion             year                                     unsteadiness,           (1979)
herbicide                              old                                      difficulties with          
formulation,                           child)                                   speech; dilated pupils;             
400 g                                                                           on fourth day, toxic   
a.i./litre                                                                      myocarditis with      
                                                                                abnormal ECG; kidney      
                                                                                damage indicated by         
                                                                                increased blood urea
                                                                                levels; no liver      
                                                                                damage; complete         
                                                                                recovery within about          
                                                                                one month     
herbicide        suicide       F       58       ?                ?              no signs of toxicity    Prescott et al.
containing       attempt;              years                                    on admission to         (1979)    
2,4-D plus       ingestion of                                                   hospital with plasma         
dichlorprop      unspecified                                                    concentration of
(16.1% + 21.4%)  amount of                                                      335 mg 2,4-D/litre &
                 herbicide                                                      400 mg mecoprop/litre;
                                                                                plasma clearance
                                                                                t = 143 h for 
                                                                                2,4-D vs 95 h for 
                                                                                dichlorprop; 91% of
                                                                                ingested 2,4-D and 
                                                                                70% of ingested 
                                                                                dichlorprop excreted
                                                                                unchanged; metabolites
                                                                                not identified
-----------------------------------------------------------------------------------------------------------------------                                                                                not identified

Table 19.  (contd.)
Product(s)       Circum-       Sex of  Body     Dose ingested    2,4-D          Effects and outcomes    References
                 stances       victim  weight                    concentration  
                                       or age                    in tissues     
herbicide        suicide       F       30.2 kg  100 ml           ?              pharmacokinetic study   Rivers et al. 
containing       attempt                        herbicide                       of 2,4-D/dicamba        (1970)
salts of 2,4-D                                  (13.6 g 2,4-D)                  excretion; no           Young & Haley
(20.1%) and                                                                     information on toxic    (1977)
dicamba (1.9%)                                                                  effects; excretion of
                                                                                2,4-D initially slowed
                                                                                by competitive
                                                                                excretion of dicamba;
                                                                                small amounts of 2,4-D
                                                                                still excreted 3 weeks
                                                                                after ingestion; only
                                                                                52% of ingested 2,4-D
                                                                                excreted in urine;
                                                                                rest assumed to have
                                                                                been excreted by 
                                                                                faecal route; plasma
                                                                                clearance t = 59.2 h
                                                                                initially, and 16.7 h
                                                                                after most of the 
                                                                                dicamba was excreted
Table 20.  Acute or non-acute effects attributed to occupational or bystander overexposure to 2,4-D 
Target organ  Types of effects                       References
or organ
Central       i)   unconsciousness                   Radionov et al. (1967); Paggiaro et al. (1974)
nervous       ii)  electroencephalograph changes     Kontek et al. (1973); Andreasik et al. (1979)
system        iii) subjective symptoms               Assouly (1951); Goldstein et al. (1959); Monarco &
                                                     Divito (1961); Foissac-Gegoux et al. (1962);
                                                     Berkley & Magee (1963); Belomyttseva (1965);
                                                     Fetisov (1966); Radionov et al. (1967); Bashirov
                                                     (1969); SARE (1972); Andreasik et al. (1979);
                                                     Kuzyk (1979)

Peripheral    i)   polyneuritis                      Foissac-Gegoux et al. (1962); Todd (1962);
nervous                                              Belomyttseva & Karimova (1963); Bashirov (1969)
              ii)  partial paralysis                 Monarca & Divito (1961); Foissac-Gegoux et al.
                                                     (1962); Todd (1962)
              iii) functional changes                Monarca & Divito (1961); Foissac-Gegoux et al.
                                                     (1962); Berkley & Magee (1963); Belomyttseva
                                                     (1967); Wallis et al. (1970); Andreasik et al.
                                                     (1979); Singer et al. (1982)
              iv)  subjective symptoms

Skeletal      i)   myotonia, myokymia, fibrillation  Foissac-Gegoux et al. (1962) Berkley & Magee
muscles            stiffness                         (1963); Wallis et al. (1970); Paggiaro et al.
              ii)  muscle damage or atrophy          Wallis et al. (1970)
              iii) subjective symptoms               Assouly (1951); Foissac-Gegoux et al. (1962); Todd
                                                     (1962); Fetisov (1966); Radionov et al. (1967);
                                                     Bashirov (1969); Wallis et al. (1970)

Digestive     i)   vomiting, diarrhoea               Goldstein et al. (1959); Monarca & Divito (1961);
system                                               Todd (1962); Belomyttseva (1967); Radionov et al.
                                                     (1967); Paggiaro et al. (1974); Dennis (1976)
              ii)  various functional disorders or   Assouly (1951); Monarca & Divito (1961); Bashirov
                   subjective symptoms               (1969); Wallis et al. (1970); Kuzyk (1979)

Table 20.  (contd.)
Target organ  Types of effects                       References
or organ
Respiratory   i)   irritation coughing               Assouly (1951); Belomyttseva & Karimova (1963);
system                                               Belomyttseva (1965); Wallis et al. (1970);
                                                     Andreasik et al. (1979)
              ii)  functional disorders              Belomyttseva & Karimova (1963); Bashirov (1969);
                                                     Wallis et al. (1970)

Circulatory   i)   functional changes:               Belomyttseva & Karimova (1963); Belomyttseva
system           - cardiac involvement               (1967); Winkelmann (1960); Bashirov (1969);
                 - vascular involvement              Paggiaro et al. (1974); Andreasik et al. (1979)
              ii)  haematological or chemical        Monarca & Divito (1961); Todd (1962); Belomyttseva
                   changes                           (1967); Radionov et al. (1967); Long et al.
                                                     (1969); Paggiaro et al. (1974); Andreasik et al.
              iii) subjective symptoms               Radionov et al. (1967); Bashirov (1969); Andreasik
                                                     et al. (1979)

Liver         functional abnormalities               Belomyttseva & Karimova (1963); Belomyttseva
                                                     (1967); Bashirov (1969); Andreasik et al. (1979)

Kidney        functional abnormalities               Monarca & Divito (1961); Foissac-Gegoux et al.
                                                     (1962); Belomyttseva (1967); Bashirov (1969);
                                                     Paggiaro et al. (1974); Andreasik et al. (1979)

Skin          i)   irritation or allergic reactions  Belomyttseva (1967); Radionov et al. (1967);
                                                     Dennis (1976); Kuzyk (1979)
              ii)  desquamation                      Foissac-Gegoux et al. (1962)
              iii) chloracne                         Londońo (1966)

Reproductive  functional abnormalities (women)       Elina et al. (1975)
system        decreased libido (men)                 Andreasik et al. (1979)
              impotence                              Espir et al. (1970)
    The observations of Apffel (1959a) and Seabury (1963) on 
patients treated with 2,4-D suggest that the acute no-observed-
adverse-effect level for biological effects in human beings may be 
as high as 36 mg of purified 2,4-D/kg body weight, or its 
equivalent in alkali or amine salts or esters.  The lack of 
subjective or clinical effects in studies in which volunteers 
ingested low doses (5 mg/kg body weight) of purified 2,4-D also 
supports the idea that a dose of a few mg/kg body weight is 
unlikely to be toxic (Khanna & Kohli, 1977; Sauerhoff et al., 
1977).  However, it is less certain whether this is true also of 
the less pure commercial 2,4-D products.  From the point of view of 
occupational and bystander safety, it is reassuring that no reports 
were found of fatal poisonings following dermal exposure or 
inhalation, though temporary unconsciousness and other severe acute 
effects have been attributed to massive combined dermal and 
inhalation exposures to 2,4-D herbicides. 

    Most poisonings with 2,4-D herbicides involved formulations 
containing more than one toxic ingredient, including solvents, 
surfactants, and other additives.  The symptoms and clinical signs 
therefore tended to vary with different products. 

8.1.1.  Neurotoxic effects of 2,4-D and related compounds

    Some of the case reports cited below on poisonings with, and 
occupational overexposures to, herbicides indicate that 2,4-D and 
other chlorophenoxy compounds may affect both the central and 
peripheral nervous systems.  Effects on the central nervous system

    In addition to subjective symptoms of the central nervous 
system, impaired coordination, impaired responses to external 
stimuli, unconsciousness, coma, and death have been observed in 
human beings mainly after absorption of lethal or nearly lethal 
doses of 2,4-D.  The acute effects on the central nervous system 
seem to resemble those produced by alcohol, sedative drugs, or 
aromatic chlorinated hydrocarbons rather than those produced by 
organophosphate or carbamate neurological poisons (Geldmacher-Von 
Mallinckrodt & Lautenbach, 1966; Prescott et al., 1979).  Acute 
cerebral demyelination occurred in a suicide who ingested a 
solution of 2,4-D in kerosene (Dudley & Thapar, 1972).  Severe 
degeneration of brain ganglion cells was observed in another 
suicide who drank a herbicide product containing 2,4-D in the form 
of water-soluble dimethylamine salt (Nielsen et al., 1965).  It is 
therefore possible that lethal doses of chlorophenoxy compounds may 
cause structural as well as functional damage to the brain. 

    Craniocerebral and peripheral functional nerve damage was noted 
by Bezuglyi et al. (1979) in a group of women occupationally 
overexposed to 2,4-D herbicides and other pesticides.  Electro-
encephalographic (EEG) abnormalities were observed in tractor 
drivers spraying herbicides containing 2,4-D, MCPA, or mecoprop 
(Kontek et al., 1973), in "individuals exposed to" chlorophenoxy 
herbicides, including 2,4-D and MCPA (Bielski & Madra, 1976) and in 

workers packaging 2,4-D sodium salt (Andreasik et al., 1979).  On 
the other hand, a case of neuropathy with EEG abnormalities and 
flaccid quadriplegia, originally attributed to occupational 
overexposure to MCPA, was diagnosed as being of viral origin 
(Nayrac et al., 1958), and therefore some of the neurological 
damage attributed to 2,4-D, may have been caused by viruses.  There 
is some evidence that 2,4-D herbicides may affect the sensory 
system, as Andreasik et al. (1979) and Assouly (1951) reported 
intolerance to certain odours, hypersensitivity to noise, and other 
sensory abnormalities in workers producing or packaging 2,4-D 
herbicides, while Fetisov (1966) reported hyposmia and other 
sensory deficiencies in similarly-exposed workers.  Effects on the peripheral nervous system

    "Peripheral neuropathy" and reduced peripheral nerve conduction 
velocities have been reported in workers producing 2,4-D and 
2,4,5-T (Poland et al., 1971; Singer et al., 1982).  More than one 
dozen other studies of persons overexposed to chlorophenoxy 
herbicides also indicated detrimental effects of 2,4-D products on 
the peripheral nervous system (Goldstein et al., 1959; Goldstein & 
Brown, 1960; Foissac-Gegoux et al., 1962; Todd, 1962; Berkley & 
Magee, 1963; Wallis et al., 1970; Bezuglyi et al., 1979).  Long-
lasting flaccid paraparesis or quadriparesis following skin contact 
with 2,4-D herbicides was reported by Goldstein et al. (1959) and 
Goldstein & Brown (1960).  Abnormal tendon reflexes in these or 
similar cases were reported by the same authors and by Andreasik et 
al. (1979), Berkley & Magee (1963), and Foissac-Gegoux et al. 
(1962).  Cases of sensory neuropathy attributed to the ingestion 
of, or dermal exposure to, 2,4-D herbicides have also been reported 
by Monarca & Divito (1961), Foissac-Gegoux et al. (1962), Todd 
(1962), Wallis et al. (1970), Sare (1972), and Bezuglyi et al. 
(1979).  However, no signs of peripheral neuropathy were reported 
by Apffel (1959a), Seabury (1963), Paggiaro et al. (1974), and 
Prescott et al. (1979), in similar cases of massive exposure to 
2,4-D herbicide, and in patients given relatively large amounts of 
purified 2,4-D or 2,4,5-T salts or esters as drugs.  One 
explanation for this may be great individual differences in 
susceptibility to poisoning with chlorophenoxy herbicides 
(Rosenberg, 1980), as attested by the case of a 58-year-old woman 
who "was fully conscious with no clinical evidence of toxicity" 
after ingesting enough herbicide to allegedly attain 2,4-D and 
mecoprop blood plasma concentrations of 335 and 400 mg/litre 
respectively (Prescott et al., 1979).  By comparison, Herbich & 
Machata (1963) reported that a plasma concentration of 447 mg 
2,4-D/litre caused death in a 46-year-old man. 

    Herbicide ingredients other than 2,4-D and related compounds 
might be at least partly responsible for the observed neurotoxic 
effects.  In particular, organic solvents, emulsifiers, and 
ethylene glycol present in herbicide formulations have been 
mentioned in this connection (Goldstein & Brown, 1960; Goldwater, 
1960).  Solvents such as alcohols and trichloroethylene, used in 
the manufacture of the active herbicide ingredients, might account 

for some of the abnormalities observed in workers involved in the 
production of chlorophenoxy compounds (Assouly, 1951; Bashirov, 
1969; Bashirov & Ter-Bagdasarova, 1970). 

    Some of the reported cases of central nervous system 
dysfunction or peripheral neuritis may have been merely 
coincidental to the herbicide exposure, as there are many known 
causes of neuropathy, such as nutritional and hereditary factors, 
infectious diseases, and many toxic chemicals, including alcohol 
(Freemon, 1975).  Thus, alcoholism may have been a contributory 
factor in one case of "2,4-D polyneuropathy" reported by Brandt 

    Further studies of the possible effects of 2,4-D and other 
chlorophenoxy compounds or their by-products on the human nervous 
system are desirable, including studies of behavioural effects 
measurable by recently-developed test batteries (Baker et al., 

8.1.2.  Myotoxic effects of 2,4-D

    Muscle fibrillations, myotonia, myoglobinuria, muscular 
weakness and other indications of a myotoxic effect of 2,4-D have 
been reported in patients treated with large doses of purified 
2,4-D products by Apffel (1959a) and Seabury (1963), as well as in 
cases of suicidal or accidental ingestion of 2,4-D herbicides or 
following occupational overexposure (Herbich & Machata, 1963; 
Berwick, 1970; Dudley & Thapar, 1972; Prescott et al., 1979).  In 
laboratory animals, myotonia and structural or biochemical muscle 
lesions can be reliably induced by doses in excess of about 100 mg 
2,4-D/kg body weight.  In human beings, the threshold dose for 
gross myotoxic effects certainly exceeds 5 mg/kg body weight per 
day, and may be above 36 mg/kg body weight per day (Seabury, 1963; 
Khanna & Kohli, 1977; Sauerhoff et al., 1977). 

8.1.3.  Cardiopathies and cardiovascular effects

    Myocardial dystrophy, myocarditis, cardiac arrhythmias or 
fibrillations, a slowed heart rate, or electrocardiographic (ECG) 
changes were observed in human beings who ingested herbicides 
containing 2,4-D (Duric et al., 1979) or 2,4-D and mecoprop 
(Prescott et al., 1979), and also after occupational overexposure 
to chlorophenoxy herbicides (Belomyttseva, 1965; Khibin et al., 
1968; Zakharov et al., 1968; Paggiaro et al., 1974; Kaskevich & 
Sobolova, 1978; Andreasik et al., 1979; Prescott et al., 1979).  
However, in other cases of acute poisoning with 2,4-D herbicides, 
the ECG was essentially normal (Berwick, 1970; Monarca & Divito, 

    Thus, further studies are desirable to determine the threshold 
2,4-D doses at which electrophysiological cardiac abnormalities can 
be observed, and to determine whether they result from a direct 
effect on the nerve conducting system of the heart, or secondarily 
from a toxic action on the myocardium. 

    It has been suggested that allergic reactions and an increased 
sensitivity may be involved in 2,4-D-related cardiac arrhythmias 
(Winkelmann, 1960; Rea, 1978). 

    Both hypertension and hypotension have been reported following 
exposure to high doses of 2,4-D (Apffel, 1959a; Kaskevich & 
Sobolieva, 1978; Bezugly et al., 1979), but no conclusions could be 
drawn from these studies. 

8.1.4.  Haematological effects

    Monarca & Divito (196l), Todd (1962), Radionov et al. (1967), 
Bashirov (1969), Bashirov & Ter-Bagdarasova (1970), Brandt (1971), 
Andreasik et al. (1979), and Bezuglyi et al. (1979) observed 
haematological changes such as mild anaemia, bone marrow 
depression, mono- or lymphocytosis or eosinophilia, changes in 
erythrocyte volume or size, or methaemoglobinaemia following 
ingestion of, or overexposure to 2,4-D.  However, these changes may 
have been due to other causes, as Apffel (1959a) did not observe 
either haematological changes or effects on haematopoiesis in 
patients given 0.1 - 0.3 g of purified 2,4-D per day as an 
anticancer drug. 

8.1.5.  Blood chemistry effects

    Hyperglycaemia, hypercholesterolaemia, elevated levels of blood 
urea, transaminase (SGOT, SGPT), and creatine phosphokinase (CPK), 
or altered blood albumin, globulin, or phospholipid levels 
following acute poisoning with, or occupational overexposure to 
2,4-D were reported by Bashirov (1969), Bashirov & Ter-Bagdarasova 
(1970), Berwick (1970), Lukoshkina et al. (1970), Brandt (1971), 
Bezuglyi et al. (1979), Duric et al. (1979) and Prescott et al. 
(1979).  However, Bashirov (1969) reported hypoglycaemia (< 700 
mg/litre) and abnormally slow return to normal values in glucose 
tolerance tests in about one-third of a group of workers producing 
2,4-D.  Increased activity of erythrocytic glycolytic enzymes was 
found in Polish workers packaging 2,4-D sodium salt (Andreasik et 
al., 1979).  In one case of intentional 2,4-D poisoning, there was 
hyperglycaemia (De Larrard & Barbaste, 1969), while in some cases 
of 2,4-D overexposure, blood glucose abnormalities were not 
observed (Goldstein et al., 1959).  Apffel (1959a) never observed 
hyperglycaemia in his patients, on the contrary, daily doses of 
1 - 1.25 g 2,4-D led to hypoglycaemia.  Thus, under some 
circumstances, high doses of 2,4-D apparently can affect glucose 
metabolism, and produce hypo- or hyperglycaemia. Gamble (1975) 
proposed that 2,4-D might inhibit certain APT-dependent enzymes and 
thus affect lipid metabolism. 

8.1.6.  Pulmonary effects

    Pulmonary emphysema, oedema, hyperaemia and haemorrhages were 
found in cases of fatal poisonings due to 2,4-D herbicide ingestion 
(Herbich & Machata, 1963; Geldmacher-Von Mallinckrodt & Lautenbach, 
1966; Dudley & Thapar, 1972).  It is not clear whether the acute 

pulmonary effects were caused by the 2,4-D preparations or by the 
solvents such as kerosene or fuel oil.  However, it is unlikely 
that the pulmonary emphysema was caused by acute exposure to 2,4-D. 

    Dyspnoea or respiratory tract irritation were occasionally 
reported following occupational overexposure of 2,4-D production 
workers or herbicide sprayers (Assouly, 1951; Belomyttseva, 1964; 
Bashirov, 1969; Bezuglyi et al., 1979). 

8.1.7.  Hepatotoxic effects

    Liver necrosis or fatty liver cell changes were observed in 2 
fatal cases following 2,4-D herbicide ingestion (Geldmacher-Von 
Mallindkrodt & Lautenbach, 1966; Dudley & Thapar, 1972).  In 
several non-fatal 2,4-D poisonings, no biochemical evidence of 
liver damage was noted, and neither Apffel (1959a) nor Seabury 
(1963) reported indications of liver damage in patients treated 
with up to 2.5 g/day of purified 2,4-D, salts, or esters.  
Hyperbilirubinaemia, elevated urobilinogen levels, or liver 
enlargement were reported in workers occupationally exposed both to 
2,4-D herbicides and to other chemicals (Belomyttesva, 1964, 1965; 
Bashirov, 1969; Bashirov & Ter-Bagdasarova, 1970; Kaskevich & 
Sobolova, 1978; Andreasik et al., 1979). 

8.1.8.  Nephrotoxic effects

    Degeneration of, or fatty changes in kidney tubules, or 
proteinuria, increased blood urea levels, and other indications of 
a nephrotoxic effects were observed in cases of fatal or nearly 
fatal herbicide ingestion (Goldstein et al., 1959; Curry, 1962; 
Geldmacher-Von Mallinckrodt & Lautenbach, 1966; Brandt, 1971; 
Dudley & Thapar, 1972; Duric et al., 1979).  Impaired renal 
function was reported in occupationally-exposed persons by Bashirov 
(1969), Bashirov & Ter-Bagdasarova (1970), Paggiaro et al. (1974), 
and by Andreasik et al. (1979).  On the other hand, neither Apffel 
(1959a) nor Seabury (1963) reported any evidence of kidney damage 
in their patients, some of whom received in excess of 2 g of pure 
2,4-D per day. 

8.1.9.  Effects on the digestive tract

    Vomiting, diarrhoea, nausea, and other indications of toxic 
effects on the digestive tract were observed by Apffel (1959a) in 
patients injected intramuscularly with large doses (up to 2.5 g) of 
purified 2,4-D products. 

    The same effects have also been noted after ingestion of large 
doses of 2,4-D herbicides, or after combined inhalation and dermal 
overexposure (Goldstein et al., 1959; Monarca & Divito, 1961; 
Nielsen et al., 1965; Tsapko, 1966; Radionov et al., 1967; Paggiaro 
et al., 1974; Dennis, 1976; Kuzyk, 1979; Prescott et al., 1979).  
However, no gastrointestinal symptoms were reported by volunteers 
who ingested a single dose of 5 mg pure 2,4-D/kg body weight 
(Khanna & Kohli, 1977; Sauerhoff et al., 1977).  Thus, an intake of 
more than 300 mg 2,4-D per adult appears to be required to induce 
acute toxic effects on the gastrointestinal tract. 

8.1.10.  Effects on endocrine organs

    Andreasik et al. (1979) found an impaired iodine uptake by the 
thyroid, and decreased thyroxine, thyroxine clearance, and 
thyroxine iodine values in workers packaging 2,4-D sodium salt.  
Since these workers were exposed to a variety of chemicals, these 
results need confirmation. 

8.1.11.  Irritative and allergenic effects 

    Chronic tonsillitis and paranasal sinusitis were reported in 
workers packaging 2,4-D sodium salt (Andreasik et al., 1979). 

    Acute eye or skin irritation, as well as skin reactions of an 
allergic type, including anaphylactoid purpura (allergic angiitis) 
and contact eczema have been reported in agricultural and forestry 
workers following occupational exposure to 2,4-D herbicides 
(Winkelmann, 1960; Radionov et al., 1967; Balo-Banga et al., 1973; 
Jung & Wolf, 1977; Kuzyk, 1979). Jung & Wolf (1977) found that 
exposure to the vapour of a 2,4-D/2,4,5-T formulation in diesel oil 
(SELEST 100) caused an acute allergic reaction in the skin of 
sensitized herbicide applicators, and that the allergic reactions 
were caused by the mixture of 2,4-D/2,4,5-T esters and not by the 
diesel oil. 

8.2.  Epidemiological Studies of the Chronic Effects of 2,4-D

    Much concern has been raised about the phenoxy herbicides, 
including 2,4-D, especially in relation to birth defects and cancer 
in human beings. 

    Several episodes have also been reported in which defined 
populations were exposed to mixtures of 2,4-D and 2,4,5-T, in which 
the 2,4,5-T was contaminated with various amounts of 2,3,7,8-
tetrachlorodibenzodioxin (2,3,7,8-TCDD) (Bleiberg et al., 1964; 
Huff et al., 1980).  It is now generally accepted that chloracne 
and porphyria cutanea tarda observed in these studies were caused 
by exposure to 2,3,7,8-TCDD and not by exposure to 2,4,5-T or 2,4-D 
(Kimbrough, 1980). 

    The following sections concentrate on epidemiological studies 
or other related studies on human beings in which actual or 
potential exposures to 2,4-D products alone or to mixtures of 2,4-D 
with other chlorphenoxy herbicides were demonstrated. 

8.2.1.  Reproductive, fetotoxic, and teratogenic effects

    Although effects on reproduction have been demonstrated in 
animals with 2,4,5-T, 2,4-D and 2,3,7,8-TCDD, all of the attempts 
made to determine whether human beings suffer similar effects have 
been frustrated by the poor design of the studies, inadequate 
determination of exposure, or inadequate information about the 
background incidence of spontaneous abortions and other abnormal 
reproductive outcomes, by inadequate evaluation of confounding 
variables, by inadequate assessment of exposure, and by mixed 

exposures (Aldred et al., 1978; Lee, 1978; Field & Kerr, 1979; 
Brogan et al., 1980; Hanify, 1980; Carmelli et al., 1981).  For 
these reasons they are not discussed in detail in this report. 

    Conclusive evidence of reproductive effects caused by 2,4-D in 
populations that might be exposed to chlorophenoxy herbicides is 
unlikely to be obtained from new epidemiological studies on 
indirectly-exposed populations living in, or adjacent to, areas in 
which phenoxy herbicides are used.  Doses of 2,4-D absorbed by 
bystanders are far below those expected to be toxic, as shown by 
occupational exposure studies with 2,4-D and 2,4,5-T herbicides 
(section 5).  Any effects induced by such small amounts would 
probably be obscured by more potent confounding factors (Janerich, 
1973; Karkinen-Jääskelainen & Saxén, 1974; Saxén et al., 1974; 
Elwood & Rogers, 1975; Granroth et al., 1977, 1978; James, 1977; 
Holmberg, 1979; Lappe, 1979; Schacter et al., 1979). 

    Additional studies on female workers occupationally exposed to 
significantly higher levels of 2,4-D than bystanders would be 
useful to clarify some of the uncertainties raised by past studies, 
if sufficiently large cohorts could be identified. 

8.3.  Studies on Mutagenic Effects in Workers Exposed to 2,4-D

    Lymphocytes from ten workers exposed to 2,4-D esters during the 
manufacture of 2,4-D herbicides, or from 15 workers packaging 2,4-D 
sodium salt, did not show any chromosome abnormalities (Johnson, 
1971; Andreasik et al., 1979).  Chromosome or chromatid 
abnormalities in lymphoctyes from some pesticide sprayers applying 
a variety of agricultural chemicals, including in some cases 2,4-D, 
were observed by Yoder et al. (1973) and Crossen et al. (1978).  
Högstedt et al. (1980) did not observe any significant increases in 
chromosome abnormalities in workers exposed to 2,4-D and other 

    The induction of SCEs among workers occupationally exposed to 
the phenoxy herbicides 2,4-D and MCPA has been recently studied.  
The subjects used only 2,4-D and MCPA or mixtures of the two for 
spraying, and the exposure levels were estimated by determining the 
urinary 2,4-D and MCPA excretion by the workers.  No dose-related 
differences in the frequencies of SCEs could be found either in 
relation to the exposure level or to the length of the exposure 
(Linnainmaa, 1983). 

    Although some studies suggest that occupational exposure to 
2,4-D may result in chromosome abnormalities, the results are 
conflicting.  Moreover, the possiblity of mixed exposure and other 
confounding variables cannot be excluded in the studies with 
positive results. 

8.4.  Carcinogenic effects

8.4.1.  Epidemiological studies

    In two case-control studies of soft-tissue sarcoma (Hardell & 
Sundström, 1979; Eriksson et al., 1981) and one of lymphoma 
(Hardell et al., 1981), exposure to phenoxyacetic acids (mainly 
2,4,5-T, 2,4-D, and MCPA) was associated with approximately 5-fold 
increases in the risk of soft-tissue sarcomas.  Exposure to 2,4-D, 
either with or without MCPA exposure, also increased relative 
risks.  In the study of malignant lymphomas, 7 cases and 1 control 
were apparently exposed to 2,4-D only (relative risk, 19.6; 95% 
confidence interval, 4.3 - 89.8). 

    In a different case-control study with a small number of cases 
and controls, no increased risk was observed (Smith et al., 1982). 

    A follow-up was also carried out on 348 railroad workers 
exposed for less than 45 days during the period 1957 - 72 to the 
herbicides 2,4-D, 2,4,5-T, atrazine, mecoprop, dichloropropionic 
acid, and amitrole (Axelson & Sundell, 1974).  The authors found a 
significant increase in cancer mortality and morbidity among 
workers exposed to amitrole. 

    Axelson et al. (1980) reported a further follow-up of these 
workers, up to October, 1978, accumulating 5541 person-years.  The 
herbicide exposure of the workers was analysed in terms of exposure 
to either amitrole, or phenoxy acids, or to a combination of the 
two.  A 10-year lapse period from the first day of exposure was 
used as the induction latency.  They found 15 cases of cancer 
versus 6.87 expected (relative risk, 2.2).  In the cohort with 
combined exposure to amitrole and phenoxy acids, 6 cases were 
observed versus 1.78 expected (relative risk, 3.4); in the group 
exposed to amitrole alone, 3 tumours were observed versus 1.95 
expected (relative risk, 1.5); and 6 cancers were observed versus 
3.14 expected (relative risk, 1.9) in the phenoxy acid-exposed 
group.  All cancers, as well as cancers of the stomach, occurred in 
statistically-significant excesses in the cohort as a whole.  In 
the groups exposed to amitrol plus phenoxy acids, there was a 
significant excess of all cancers.  In the group exposed only to 
phenoxy acids, stomach cancer occurred in significant excess (2 
observed, 0.33 expected; relative risk, 6.1).  No soft-tissue 
sarcomas were identified, but the statistical power of this study 
to detect an excess of a rare cancer was limited. 

    Högstedt & Westerlund (1980) conducted a restrospective 
mortality study on 142 forestry workers exposed to phenoxy 
pesticides and 244 unexposed forestry workers, comparing their 
mortality experience with national statistics.  Work supervisors, 
who were more highly exposed to phenoxy herbicides than the others, 
had a significantly elevated tumour mortality (5 observed, 1.4 
expected).  No particular tumour type predominated, and no soft-
tissue sarcomas were observed, though the authors noted that the 
study had limited statistical power and was inconclusive, because 
of the relatively short follow-up period. 

    Riihimäki et al. (1982) reported on a prospective cohort study 
of 2,4-D and 2,4,5-T spray personnel which was in progress.  
Because of the small number of deaths and the brief follow-up 
period, no conclusions can so far be drawn from this study. 

    Follow-up studies on cohorts of pesticide sprayers, farmers, 
and agricultural workers occupationally exposed to a variety of 
chemicals, in some cases including phenoxy herbicides, have been 
reviewed by IARC (1983). 

    Follow-up studies on groups of industrial workers exposed to 
chlorophenols, 2,4,5-T, or other chlorophenoxy compounds, and to 
2,3,7,8-TCDD or other dioxins, during the manufacture of 
chlorophenoxy herbicides, have recently been reviewed by Huff et 
al. (1980) and IARC (1983). 

8.4.2.  Evidence on the carcinogenicity of 2,4-D

    The available studies suggest that an association exists 
between mixed exposure to phenoxy herbicides, chlorinated phenols, 
and chlorinated dibenzodioxins, and an increased incidence of soft 
tissue sarcomas and malignant lymphomas.  It is not clear, at 
present, whether these findings represent true associations, and 
further studies are in progress (Muir & Wagner, 1981) to clarify 
this point.  Since many of the tumour cases had been exposed to 
combinations of phenoxy herbicides and their contaminants as well 
as other chemicals, it is not known whether exposure to 2,4-D is 
specifically associated with the development of soft tissue 

8.5.  Treatment of Poisoning in Human Beings

    Successfully treated cases of 2,4-D poisoning indicate that 
forced alkaline diuresis is helpful in reducing the level of 2,4-D 
in the blood and tissues (Young & Haley, 1977; Prescott et al., 
1979).  Heart and kidney damage should be anticipated and 
counteracted in cases of severe poisoning (Duric et al., 1979). 

    In cases of acute poisoning due to 2,4-D, the nearest Poison 
Control Centre should be contacted for additional information on 
symptoms and recommended treatment. 


9.1.  General Considerations

    In areas of 2,4-D herbicide production, handling, or use, the 
highest exposure will be incurred by those who are directly 
involved in these processes, followed by bystanders indirectly 
exposed to 2,4-D vapour, dust, or droplets, or to contaminated 
vegetation, soil, or water.  In these two groups, exposure will 
usually be via the skin.  The general population in 2,4-D-use areas 
would be exposed to a lesser extent, mainly through food containing 
2,4-D residues and to a lesser extent through 2,4-D residues in 
water.  The contribution from air is negligible.  As far as the 
general population is concerned, 2,4-D intake from any source, is 

9.2.  Estimated Intake of 2,4-D by the Population in a 2,4-D-use Area

    The total contribution from air, food, and water is estimated 
to be 0.03 - 2 µg/kg body weight per day (Table 13). 

9.2.1.  Intake by bystanders

    Given the limited data available and the many uncertainties 
involved, an adequate estimate of 2,4-D intake by bystanders is not 
possible at this time, but it should generally be less than that 
for occupationally-exposed persons. 

9.2.2.  Occupational intake

    Workers using 2,4-D may, on average, absorb about 0.1 mg 
2,4-D/kg body weight per day.  However, this level may be exceeded 
if good occupational hygiene is not practiced (section 5.2).  
Simple precautions against excessive exposure can reduce the amount 
of 2,4-D uptake. 

9.3.  Safety Factors

9.3.1.  Definitions

    For the present assessment, the safety factor is defined as the 
integer obtained by dividing the overall no-observed-adverse-effect 
level for a known adverse effect of 2,4-D (determined from all 
available information on human beings or animals) by the daily 
exposure value (absorbed dose of 2,4-D) for the various exposed 

9.3.2.  Determination of safety factors  Acute poisoning

    Based on clinical studies in which 2,4-D was injected into 
patients as a drug, the no-observed-adverse-effect level for signs 
and symptoms of acute 2,4-D poisoning in children and adults 
appears to be at or near 36 mg/kg body weight (section 8.1).  Based 

on the available studies of the amounts of 2,4-D absorbed by 
occupationally-exposed person, bystanders, and populations in 
2,4-D-use areas, the safety factors for acute 2,4-D poisoning are 
likely to be: 

(a)  much greater than 1000 for the general population in 2,4-D-use 

(b)  at least 360 for occupationally-exposed spraying crews.

    The margin of safety for persons with excessive occupational 
exposures would be smaller.  Chronic toxicity

    Dose-effect relationships for the chronic toxic effects of 
2,4-D or 2,4-D derivatives are available only from animal studies.  
The no-observed-adverse effect levels for certain chronic toxic 
effects of 2,4-D in animals have not been firmly established, and 
for this reason safety factors cannot be established (section 
7.2.1) for all of the chronic effects of 2,4-D.  Embryotoxic, fetotoxic, and teratogenic effects

    The no-observed-adverse-effect level for embryotoxic, 
fetotoxic, or teratogenic effects of 2,4-D in mammals appears to 
lie at 10 mg/kg body weight per day (section  Assuming 
that the same is true for human beings, then the corresponding 
safety factors for the various exposed groups are: 

(a)  much greater than 1000 for the general population in 2,4-D-use 

(b)  100 for occupationally-exposed spraying crews using 
     precautions against excessive exposure.  Mutagenic effects

    The available information was inadequate for an assessment of 
the mutagenic potential of 2,4-D in mammals.  Carcinogenic effects

    Available animal bioassays and epidemiological studies are 
inadequate for an assessment of the carcinogenic potential of 2,4-D 
or of its derivatives. 

9.4.  Evaluation of Health Risks from 2,4-D Exposure

    From the data available at present, the Task Group assumes that 
a possible health risk will exist, when the safety factor is less 
than 100. 

9.5.  Recommendations on Exposure

    Results of recent exposure and occupational health studies 
suggest that excessive exposure to 2,4-D can be avoided by fairly 
simple measures of occupational hygiene, such as those recommended 
in two pertinent publications of the International Labour Office 
(ILO, 1977, 1979).  Laundering procedures for 2,4-D-contaminated 
clothing have been published by Easley et al. (1983), and these 
should be considered. 


ABO-KHATWA, N. & HOLLINGWORTH, R.M.  (1974)  Pesticidal chemicals 
affecting some energy linked functions of rat mitochondria  in 
 vitro.  Bull. environ. Contam. Toxicol., 12(4): 446-454. 

AHMED, F.E., HART, R.W., & LEWIS, N.J.  (1977)  Pesticide-induced 
RNA damage and its repair in cultured human cells.   Mutat. Res., 
42: 161-174. 

AHMED, F.E., LEWIS, N.J., & HART, R.W.  (1977b)  Pesticide-induced 
ouabain resistant mutants in Chinese hamster V79 cells.  Chem.-biol. 
 Interact., 19: 369-374.

AKESSON, N.B. & YATES, W.E.  (196l)  Drift residues on alfalfa hay.  
A progress report of investigations of pesticide drift from 
aircraft applications.  Calif. Agric., 15: 4-7.

ALABASTER, J.S.  (1969)  Survival of fish in 164 herbicides, 
insecticides, fungicides, wetting agents and miscellaneous 
substances.   Int. Pest Control, 11(2): 29-35. 

W., RAPER, C., ROUCH, G., & SINN, H.J.  (1978)   Report of the 
 Consultative Council on Congenital Abnormalities in the Yarram 
 District. Alleged relationship of congenital abnormalities to the 
 use of the herbicides 2,4-D and 2,4,5-T.  State of Victoria, 
Australia, Ministry of Health, viii + 55 pp (Document PB 338). 

ALTOM, J.D. & STRITZKE, J.F.  (1973)  Degradation of dicamba, 
picloram and familiar phenoxy herbicides in soils.  Weed Sci., 21: 

ANDERSEN, K.J., LEIGHTY, E.G., & TAKAHASHI, M.  (1972)  Evaluation 
of herbicides for possible mutagenic properties.   J. agric. food 
 Chem., 20(3): 649-656. 

ANDREASIK, Z., KOLON, S., & SMOLIK, R.  (1979)  Health status 
evaluation in workers packaging the herbicide "Pielik" 
(cholorophenol).   Arh. Hig. Rad. Toksikol., 30 (Suppl.): 599-602. 

ANDRUSHAITIS G.P.  (1972)  [The effect of pesticides on the 
environment.]   Latvi. PSR Zinatnu Akad. Vest., 4:(297) 44-49 (in 
Russian, Health & Welfare Canada Translation No. 2441). 

ANTONENKO, T.A.  (1977)  [Experimental data from a study of the 
permeability of the placental barrier to the herbicide 2,4-D and 
its passage with the mother's milk during feeding.]   Gig. Aspekt. 
 Okhr. Zdor. Naseleniya (Saratov).  In: Saratov, Saratov Institute 
for Oral Hygiene, pp. 177-178 (in Russian, Health & Welfare Canada 
Translation No. 2370). 

APFFEL, C.A.  (1959a)  Action cytostatique de certaines auxines, 
compte rendu préliminaire.   Presse med., 67(6): 207-209. 

ARJMAND, M., HAMILTON, R.H., & MUMMA, R.O.  (1978)  Separation of 
amino acid conjugates of 2,4-dichlorophenoxyacetic acid by high-
pressure liquid chromatography employing ion-pair techniques.  
 J. agric. food Chem., 26: 971-973. 

ARKHIPOV, G.N. & KOZLOVA, I.N.  (1974)  [A study of the 
carcinogenic potential of a herbicide: 2,4-D amine salt.]   Vopr. 
 Pit., 5: 83-84 (in Russian). 

ASSOULY, M.  (1951)  Désherbants sélectifs et substances de 
croissance aperēu technique. Effet pathologiques sur l'homme au 
cours de la fabrication de l'ester du 2,4-D.   Arch. Mal. prof. Hyg. 
 Toxicol. Ind., 12(1): 26-30. 

AVERITT, W.K.  (1967)  An evaluation of the persistence of 2,4-D 
amine in surface waters in the state of Louisiana.   Proc. South. 
 Weed Sci. Soc., 20: 342-347. 

AXELSON, O. & SUNDELL, L.  (1974)  Herbicide exposure, mortality 
and tumor incidence.  An epidemiological investigation on Swedish 
railroad workers.   Scand. J. Work Environ. Health, 11:21-28. 

& KLING, H.  (1980)  Herbicide exposure and tumor mortality: An 
updated epidemiological investigation on Swedish railroad workers. 
 Scand. J. Work Environ. Health, 6: 73-79. 

BACHE, C.A., HARDEE, D.D., HOLLAND, R.F., & LISK, D.J.  (1964a)  
Absence of phenoxyacid herbicide residues in the milk of dairy cows 
at high feeding levels.   J. dairy Sci., 47(3): 298-299. 

(1960)  Potential anticancer agents. I.  Non-classical 
antimetabolites. II.  Some factors in the design of exo-alkylating 
enzyme inhibitors, particularly of lactic dehydrogenase.   J. med. 
 pharm. Chem., 2(6): 633-657. 

& BERKEY, C.S.  (1983)  Monitoring neurotoxins in industry: 
Development of a neuro-behavioral test battery.  J. occup. Med., 
25(2): 125-130. 

BAKER, P.G., HOODLESS, R.A., & TYLER, J.F.C.  (1981)  A review of 
methods for the determination of polychlorodibenzo-p-dioxins and 
polychlorodibenzofurans in phenoxyalkanoic acid herbicides.  
 Pestic. Sci., 12: 294-304. 

(1973)  Effect of 2,4-D on semiconservative and DNA repair 
synthesis.  (Case report: bullous dermatitis after exposure to 
2,4-D).   Ber. Oesterr. Studienges Atomenerg. (Forschungszentrum 
 Seibersdorf), 2218: 1-7. 

BAMESBERGER, W.L. & ADAMS, D.F.  (1966)  An atmospheric survey for 
aerosol and gaseous 2,4-D components.   Adv. Chem. Ser., 60: 

BARTLEY, T.R. & HATTRUP, A.R.  (1970)  2,4-D contamination and 
persistence in irrigation water.   Proc. West. Soc. Weed Sci., 
23: 10-33. 

BASHIROV, A.A.  (1969)  [The health of workers involved in the 
production of amine and butyl 2,4-D herbicides.]   Vrach. Delo, 
10: 92-95 (in Russian, Health & Welfare Canada Translation No. 

BASHIROV, A.A. & TER-BAGDASAROVA, I.K.  (1970)  [The state of the 
cardiovascular system in workers engaged in the production of amine 
salt herbicides and 2,4-dichlorophenoxyacetic acid butyl ester.]  
 Azerb. Med. Zh., 47 (12): 44-48 (in Russian). 

Development and evaluation of simplified approaches to residue 
analysis.   Pure appl. Chem., 53: 1039-1049. 

BEAVEN, F.G., RAWLS, C.K., & BECKET, G.E.  (1962)  Field 
observations upon estuarine animals exposed to 2,4-D.   Proc. 
 northeast. Weed Contr. Conf., 16: 449-458. 

BELOMYTTSEVA, L.A.  (1964)  [Toxic effects of the herbicide 2,4-D 
sodium on the lungs.]   Sb. Nauchn. Tr. Bashk. Gos. Med. Inst., 
16(2): 135-141 (in Russian). 

BELOMYTTSEVA, L.A.  (1965)  [In:  Contributions to the 3rd All-Union 
 Scientific Conference on the Problems of Hygiene and Toxicology 
 related to the Use of Chemicals in the National Economy, Kiev,] 
p. 380 (in Russian). 

BELOMYTTSEVA, L.A.  (1967)  The toxic effect of the sodium salt of 
2,4-dichlorophenoxyacetic acid. UFA 1967. 

BELOMYTTSEVA, L.A. & KARIMOVA, A.K.  (1963)  In:  [Proceedings of 
 the UFA Scientific Research Institute of Hygiene and Occupational 
 Diseases, Vol. 2.] (in Russian). 

BERKLEY, M.C. & MAGEE, K.R.  (1963)  Neuropathy following exposure 
to a dimethylamine salt of 2,4-D.  Arch. internal. Med., 111: 

BERWICK, P.  (1970)  2,4-dichlorophenoxyacetic acid poisoning in 
man.  J. Am. Med. Assoc., 214(6): 1114-1117. 

ILINA, V.I., & GORSKAJA, I.I.  (1979)  [Clinical manifestations of 
long-term sequels of acute poisoning with 2,4-D.]  Gig. Truda Prof. 
 Zabol., 3: 47-48 (in Russian). 

BIELSKI, J. & MADRA, B.  (1976)  [Acute poisoning with pesticides.] 
 Pol. Tyg. Lek., 31(46): 1971-1973 (in Polish, Health & Welfare 
Canada Translation No. 2245). 

BJERKE, E.L., HERMAN, J.L., MILLER, P.W., & WETTERS, J.H.  (1972)  
Residue study of phenoxy herbicides in milk and cream.  J. agric. 
 food Chem., 20: 963-967. 

BJORKLUND, N.E. & ERNE, K.  (1966)  Toxicological studies of 
phenoxyacetic herbicides in animals.  Acta vet. scand., 7: 364-390. 

BJORN, M.D. & NORTHEN, H.T.  (1948)  Effects of 2,4-dichloro- 
phenoxyacetic acid on chicks.  Science, 108: 479-480. 

BLEIBERG, J., WALLEN, M., & BRODKIN, R.  (1964)  Industrially 
acquired porphyria.  Arch. Derm., 89: 793-797. 

BODAI, J., TAMAS, L., & VEGH, A.  (1974)  [Reproductive 
consequences of Dikonirt toxicosis in cattle.]   Magy. Allatorv. 
 Lapja, 29(5): 319-322 (in Hungarian, Health & Welfare Canada 
Translation No. 2238). 

BODEM, R., PREISS, D., & KUHN, E.  (1971)  [On the delay of the 
relaxation of the guinea pig papillary muscle by 2,4-dichloro- 
phenoxy-acetic acid (2,4-D).]   Klin. Wochenschr., 49(1): 227-228 
(in German). 

(1969)  [The effects of chlorophenoxyacetic acid derivatives 
(herbicides) on animals and human beings.  (A literature review).]  
 Farmakol. Toksikol., 32 (6): 747-751 (in Russian, Health & Welfare 
Canada Translation No. 2031). 

BOLLAG, J.M., HELLINGS, C.S., & ALEXANDER, M.  (1968)  2,4-D 
metabolism.  Enzymatic hydroxylation of chlorinated phenols. 
 J. agric. food Chem., 16: 826-828. 

BONGSO, T.A. & BASRUR, P.K.  (1973)   In vitro response of bovine 
cells to 2,4-dichlorophenoxy acetic acid.  In vitro, 8: 416-417. 

BONTOYAN, W.R.  (1977)  Report on pesticide formulations.  J. Assoc. 
 Off. Agric. Chem., 60: 324-327. 

BOVAL, B. & SMITH, J.M.  (1973)  Photodecomposition of 2,4- 
dichlorophenoxyacetic acid.   Chem. Eng. Sci., 28: 1661-1675. 

BOVEY, R.W.  (1980a)  Residues and fate of phenoxy herbicides in 
the environment.  In: Bovey, R.W. & Young, A.L., ed.   The science 
 of 2,4,5-T and associated phenoxy herbicides, New York, Chichester, 
Brisbane, Toronto, John Wiley & Sons, pp. 301-356. 

BOVEY, R.W.  (1980b)  Human risk with phenoxy herbicides in the 
environment.  In: Bovey, R.W. & Young, A.L., ed.   The science of 
 2,4,5-T and associated phenoxy herbicides, New York, Chichester, 
Brisbane, Toronto, John Wiley & Sons, pp. 425-433. 

BOVEY, R.W. & YOUNG, A.L., ed.  (1980)   The science of 2,4,5-T and 
 associated phenoxy herbicides, New York, Chichester, Brisbane, 
Toronto, John Willey & Sons, 462 pp. 

Comparative induction of aryl hydrocarbon hydroxylase activity 
 in vitro by analoques of dibenzo- p-dioxin.  Food cosmet. Toxicol., 
18: 627-635. 

BRANDT, M.R.  (1971)  [Herbatox poisoning. A short survey and a 
report of a case.]  Ugeskrift Laeger, 133(11): 500-503 (in Danish, 
Health & Welfare Canada Translation No. 2147. 

BRETAG, L.H. & CAPUTO, C.  (1978)  The nature of the antimyotonic 
action of 2,4-D on the soleus muscle of the rat.   Proc. Aust. 
 Physiol. Pharmacol. Soc., 9(2): 150 pp. 

BRISTOL, D.W., COOK, L.W., KOTERBA, M.T., & NELSON, D.C.  (1982)  
Determination of free and hydrolyzable residues of 2,4-
dichlorophenoxyacetic acid and 2,4-dichlorophenol in potatoes.  
 J. agric. food Chem., 30: 137-144. 

BRODY, I.A.  (1973)  Myotonia induced by monocarboxylic aromatic 
acids: A possible mechanism.   Arch. Neurol., 28: 243-246. 

BRODY, T.M.  (1952)  Effect of certain plant growth substances on 
oxidative phosphorylation in rat liver mitochondria.   Proc. Soc. 
 Exp. Bio. Med., 80: 533-536. 

BROGAN, W.F., BROGAN, C.E., & DADD, J.T.  (1980)  Herbicides and 
cleft lip and palate.   Lancet, 2: 597. 

BUCHER, N.L.R.  (1946)  Effects of 2,4-dichlorophenoxyacetic acid 
on experimental animals.   Proc. Soc. Exp. Biol. Med., 63: 204-205. 

BURCAR, P.J., WERSHAW, R.L., GOLDBERG, M.C., & KHAN, L.  (1966)  
Gas chromatographic study of the behaviour of the isooctyl ester 
of 2,4-D under field conditions in North Park, Colorado.   Anal. 
 Instrum., 4: 215-224. 

BURTON, J.A., GARDINER, T.H., & SCHANKER, L.S.  (1974)  Absorption 
of herbicides from the rat lung.   Arch. environ. Health, 29: 31-33. 

BUSLOVICH, S.Y.  (1963)  [The effect of the chlorinated derivatives 
of phenoxyacetic acid.]   Zdrav. Beloruss., 9: 41-45 (in Russian, 
Health & Welfare Canada Translation No. 2315). 

BUSLOVICH, S.Y. & KOLDOBSKAYA, F.D.  (1972)  [Activity of 
hexokinase in skeletal muscles of albino rats in experimental 
myotonia.]   Vopr. Med. Khim., 18(4): 403-406 (in Russian). 

BUSLOVICH, S.Y & MILCHINA, M.G.  (1976)  [The dynamics of 2,4-D 
amine decomposition in soil.]   Gig. i Sanit., 5: 109-110 
(in Russian). 

BUSLOVICH, S.Y., VOINOVA, I.V., & MILCHINA, M.G.  (1973)  [The 
distribution of chlorinated phenoxy acid herbicides in albino 
rats.]   Gig. Tr. Prof. Zabol, 17(3): 171-173 (in Russian, Health & 
Welfare Canada Translation No. 2237). 

[Embryotoxic effects of herbicides: Chlorinated phenoxy acids.]  
 Zdrav. Beloruss., 10: 83-84 (in Russian). 

A.I.  (1982)  [The role of mixed-function oxidases in the 
detoxication of some herbicides: Chlorinated derivatives of 
phenoxyacids.]  Gig. i Sanit., 10: 76-77 (in Russian). 

BUTLER, P.A.  (1965)  Effects of herbicides on estuarine fauna.  
 Proc. South. Weed Sci. Soc., 18: 576-580. 

MILLEMANN, R.E.  (1979)  Toxicity of the herbicides 2,4-D, DEF, 
propanil, and trifluralin to the Dungeness crab,  Cancer magister.  
 Arch. environ. contam. Toxicol., 8: 383-396. 

CANADA, HEALTH & WELFARE  (1980)  Pesticides.  In:   Guidelines for 
 Canadian drinking water quality, 1978.  Supporting documentation,  
Ottawa, Supply and Services, Canada, pp. 457-488. 

CARL, M.  (1979)  Internal laboratory quality control in the 
routine determination of chlorinated pesticide residues.   Adv. 
 pestic. Sci., 3:660-663. 

CARMELLI, D., HOFHERR, L., TOMSIC, J., & MORGAN, R.W.  (1981)   A 
 case-control study of the relationship between exposure to 2,4-D 
 and spontaneous abortions in humans, Menlo Park, California, SRI 
International (Final Report). 

CARTER, E.P.  (1960)  Volatility of ester forms of hormone type 
herbicides III.   J. Assoc. Off. Anal. Chem., 43: 367-370. 
CHANG, H., RIP, J.W., & CHERRY, J.H.  (1974)  Effects of 
phenoxyacetic acids on rat liver tissues.   J. agric. food Chem., 
22(1): 62-65. 

CHAU, A.S.Y. & THOMSON, K.  (1978)  Investigation of the integrity 
of seven herbicidal acids in water samples.   J. Assoc. Off. Anal. 
 Chem., 61: 1481-1485. 

CHAU, A.S.Y., AFGHAN, B.K., & ROBINSON, J.W.  (1982)   Analysis of 
pesticides in water.  Volume II.   Chlorine- and phosphorus-
 containing pesticides. Boca Raton (Florida), CRC Press Inc., 
pp. 238. 

D.C., KEYES, D.G., & SCHWETZ, B.A.  (1981)  2,4-D (2,4-
dichlorophenoxy) acetic acid: results of a 13-week feeding study in 
CDF Fisher 344 rats.   Proc. Annu. Meet. Can. Fed. Biol. Soc., 
24: 233. 

CHOI, K.L., QUE HEE, S.S., & SUTHERLAND, R.G.  (1976)  2,4-D levels 
in the South Saskatchewan River in 1973 as determined by a GLC 
method.   J. environ. Sci. Health, Part B, 11: 175-183. 

CHOW, C., MONTGOMERY, M.L., & YU, T.C.  (1971)  Methodology and 
analysis for residues of MCP and 2,4,5-T in wheat.   Bull. environ. 
 Contam. Toxicol., 18: 361-365. 

FARR, F.M.  (1975)  Residues of chlorophenoxy acid herbicides and 
their phenolic metabolites in sheep and cattle.   J. agric. food 
 Chem., 23(3): 573-578.

COCHRANE, W.P.  (1981)  Chemical derivatization in pesticide 
analysis.  In: Frei, R.W. & Lawrence, J.F., ed.  Chemical 
 derivatization in analytical chemistry, I: Chromatography, New 
York, Plenum Press, pp. 1-97. 

COCHRANE, W.P. & RUSSELL, J.B.  (1975)  Residues in wheat and soil 
treated with the mixed butyl esters of 2,4-D.   Can. J. plant Sci., 
55: 323-325. 

COCHRANE, W.P., SINGH, J., MILES, W., & WAKEFORD, B.  (1981)  
Determination of chlorinated dibenzo- p-dioxin contaminants in 
2,4-D products by gas chromatography - mass spectrometric 
techniques.   J. Chromatogr., 217: 289-299. 

COCHRANE, W.P., LANOUETTE, M., & SINGH, J.  (1982)  High pressure 
liquid chromatographic determination of impurity phenols in 
technical 2,4-D acid and 2,4-dichlorophenol.   J. Assoc. Off. Anal. 
 Chem., in press. 

COGGON, D. & ACHESON, E.D.  (1982)  Do phenoxy herbicides cause 
cancer in man?   Lancet, 1: 1057-1059. 

(1978)  Analytical determination of  N-nitroso compounds in 
pesticides by the United States Environmental Protection Agency.  
In: Walker, E.A., Castegnaro, M., Criciute, L., & Lyle, R.E., ed. 
 Environmental Aspects of N-nitroso compounds, Lyons,  IARC 
 Scientific Publications, 19: 333-342. 

(1970)   CIPAC Handbook, Vol. I, Analysis of technical and 
 formulated pesticides, Harpenden, England, CIPAC, pp. 241-273. 

COMMISSION OF EUROPEAN COMMUNITIES  (1981)   Criteria (dose/effect 
 relationships) for organochlorine pesticides. Oxford, New York, 
Toronto, Sydney, Paris, Frankfurt, Pergamon Press, pp. 223-240. 

CONNICK, W.J., Jr & SIMONEAUX, J.M.  (1982)  Determination of (2,4-
dichlorophenoxy) acetic acid and of 2,6-dichlorobenzo-nitrile in 
water by high performance liquid chromatography.   J. agric. food 
 Chem., 30: 258-260. 

COOKE, A.S.  (1972)  The effects of DDT, dieldrin and 2,4-D on 
amphibian spawn and tadpoles.   Environ. Pollut., 3: 51-68. 

COPE, O.B., WOOD, E.M., & WALLEN, G.H.  (1970)  Some chronic 
effects of 2,4-D on the bluegill  (Lepomis macrochirus).  Trans. Am. 
 Fish. Soc., 99(1): 1-12. 

CORNELIUSSEN, P.E.  (1970)  Pesticide residues in total diet 
samples (V).   Pestic. monit. J., 4(3): 89-105. 

CORNELIUSSEN, P.E.  (1972)  Pesticide residues in total diet 
samples (VI).   Pestic. monit. J., 5(4): 313-330. 

COURTNEY, K.D.  (1977)  Prenatal effects of herbicides:  Evaluation 
by the prenatal development index.   Arch. environ. Contamin. 
 Toxicol., 6: 33-46. 

COUTSELINIS, A., KENTARCHOV, R., & BOUKIS, D.  (1977) Concentration 
levels of 2,4-D and 2,4,5-T in forensic material.   Forensic Sci.,
1: 203-204. 

CRAFTS, A.S.  (1960)  Evidence for hydrolysis of esters of 2,4-D 
during absorption by plants.   Weeds, 8: 19-25. 

CRIPPS, R.E. & ROBERTS, T.  (1978)  Microbial degradation of 
herbicides.  In:  Hill, I.R. & Wright, S.J.L., ed.:   Pesticide 
 microbiology - Microbial aspects of pesticide behaviour in the 
 environment, London, New York, San Francisco, Academic Press, 
pp. 669-730. 

CROSBY, D.G. & TUTASS, H.O.  (1966)  Photodecomposition of 2,4-
dichlorophenoxyacetic acid.  J. agric. Food Chem., 14: 596. 

CROSBY, D.G. & WONG, A.S.  (1973)  Photodecomposition of 2,4,5-
trichlorophenoxyacetic acid (2,4,5-T) in water.  J. agric. Food 
 Chem., 21(6): 1052-1054. 

CROSSEN, P.E., MORGAN, W.F., HORAN, J.J., & STEWART, J.  (1978)  
Cytogenetic studies of pesticide and herbicide sprayers.   New 
 Zealand med. J., 88(619): 192-195. 

CRUMMET, W.P. & STEHL, R.H.  (1973)  Determination of chlorinated 
dibenzo- p-dioxins and dibenzofurans in various materials.   Environ. 
 Health Perspect., 5: 15-25. 

CURRIE, L.A.  (1968)  Limits of qualitative detection and 
quantitative determination.   Anal. Chem., 40: 586-593. 

CURRY, A.S.  (1962)  Twenty-one uncommon cases of poisoning.   Br. 
 med. J., 1: 687-689. 

DANON, J.M., KARPATI, G., CARPENTER, S., & WOLFE, L.S.  (1976)  
Experimental myotonic myopathy.   Neurology, 26: 384. 

(1981)  Mass fragmentographic determination of 2,4-D and 2,4,DP 
trace levels in biosamples using intramolecular deuterated interval 
standards.  Med. Fac. Landbouww. Rijksuniv. Gent, 46(1): 305-316. 

DELARRARD, J. & BARBASTE, M.  (1969)  Intoxication suicidaire 
mortelle agro-chimique de l'hormone désherbante 2,4-D.  Arch. Mal. 
 prof. Med. Trav. Secur. soc., 30(7-8): 434. 

DENNIS, C.A.R.  (1976)  Health effects of 2,4-D.  In: National 
Research Council of Canada Associate Committee on Scientific 
Criteria for Environmental Quality, ed.   Phenoxy herbicides: their 
 effects on environmental quality, Ottawa, NRCC Publications 
Service, p.333. 

Influence of 2,4-dichlorophenoxyacetate and of dantrolene sodium on 
the target phenomenon in tenotomized rat gastrocnemius muscle.  
 Acta neuropathol., 46: 167-168. 

DESI, I. & SOS, J.  (1962a)  Central nervous injury by a chemical 
herbicide.   Acta med. Acad. Sci. Hung., 18: 429-433. 

DESI, I. & SOS, J.  (1962b)  [The effect of 2,4-dichloro- 
phenoxyacetic acid and triorthocresyl phosphate on the function of 
the upper central nervous system (bioelectric activity and 
conditioned reflexes).]   Gig. i Sanit., 12: 38-46  (in Russian, 
Health & Welfare Canada Translation No. 2183). 

DESI, I., SOS, J., & NIKOLITS, I.  (1962a)  New evidence concerning 
the nervous site of action of a chemical herbicide causing 
professional intoxication.   Pathophysiologica (Budapest), 22: 

DESI, I., SOS, J., OLASZ, J., SULE, F., & MARKUS, V.  (1962b)  
Nervous system effects of a chemical herbicide.   Arch. environ. 
 Health, 4: 95-102. 

DEWITT, J.B., CRABTREE, D.G., FINLEY, R.B., & GEORGE, J.L.  (1962)  
Effects on wildlife. pp. 4-52.  In:  Effects of pesticides on fish 
 and wildlife:  A review of investigations during 1960. Washington, 
DC, US Dept. of the Interior (Fish and Wildlife Circ. No. 143). 

DRAPER, W.M. & STREET, J.C.  (1982)  Applicator exposure to 2,4-D, 
dicamba, and a dicamba isomer.  J. environ. Sci. Health, B17(4): 

DRILL, V.A. & HIRATZKA, T.  (1953)  Toxicity of 2,4-D and 2,4,5-T, 
a report on their acute and chronic toxicity in dogs.   Arch. ind. 
 Hyg. occup. Med., 7: 61-67. 

DUDLEY, A.W. & THAPAR, N.T.  (1972)  Fatal human ingestion of 
2,4-D, a common herbicide.   Arch. Pathol., 94: 270-275. 

DUGGAN, R.E. & CORNELIUSSEN, P.E.  (1972)  Dietary intake of 
pesticide chemicals in the United States (III), June 1968 - April 
1970.   Pestic. monit. J., 5(4): 331-341.

R.C.  (1971)  Pesticide residue levels in foods in the United 
States from July 1, 1963 to June 30, 1969.   Pestic. monit. J., 
5(2): 73-80. 

DUNACHIE, J.F. & FLETCHER, W.W.  (1967)  Effect of some herbicides 
on the hatching rate of hens' eggs.   Nature (Lond.), 215: 

DUNACHIE, J.F. & FLETCHER, W.W.  (1970)  The toxicity of certain 
herbicides to hens' eggs assessed by the egg injection technique.  
 Ann. app. Biol., 66: 515-520. 

DURIC, V., STOJANOVIC, V., & IGIC, B.  (1979)  [Presentation of 
patients with pesticide poisoning.]   Med. Pregl., 32(3/4): 129-133.  
(In Serbo-Croatian, Health & Welfare Canada Translation No. 2382.) 

DUX, E., TOTH, I., DUX, L., & JOO, F.  (1978)  The localization of 
calcium by X-ray microanalysis in myopathic muscle fibers.  
 Histochemistry, 56: 239-244. 

DZHAPAROV, I.R. & TSILIKOV, V.V.  (1969)  [The effect of the sodium 
salt of 2,4-D and carbothione on the content of glycogen in the 
liver and the blood sugar level in rats.]   Farmakol. Tsentr. 
 Kholinolitikov  Drugikh Neirotropnykh Sredstv., p. 180 (in 

EASLEY, C.B., LAUGHLIN, J.M., GOLD, R.E., & TUPY, D.R.  (1983)  
Laundering procedures for removal of 2,4-dichloro-phenoxyacetic 
acid ester and amine herbicides from contaminated fabrics.  Arch. 
 Environ. Contam. Toxicol., 12: 71-76. 

EBERSTEIN, A. & GOODGOLD, J.  (1979)  Experimental myotonia induced 
in denervated muscles by 2,4-D.   Muscle Nerve, 2: 364-368. 

ELO, H. & YLITALO, P.  (1977)  Substantial increase in the levels 
of chlorophenoxyacetic acids in the CNS of rats as a result of 
severe intoxication.   Acta pharmacol. toxicol., 41: 280-284. 

ELO, H. & YLITALO, P.  (1979)  Distribution of 2-methyl-4- 
chlorophenoxyacetic acid and 2,4-dichlorophenoxyacetic acid in male 
rats:  evidence for the involvement of the central nervous system 
in their toxicity.   Toxicol. appl. Pharmacol., 51: 439-446. 

ELWOOD, J.M. & ROGERS, J.R.  (1975)  The incidence of congenital 
abnormalities in British Columbia, Alberta, Manitoba and New 
Brunswick, 1966-1969.   Can. J. public Health, 66: 471-475. 

(1972)  Detection of chemical mutagens by the dominant lethal assay 
in the mouse.   Toxicol. appl. Pharmacol., 23: 288-325. 

ERICKSON, L.C., BRANNAMAN, B.L., & COGGINS, C.W. Jr.  (1963)  
Residues in stored lemons treated with various formulations of 
2,4-D.   J. agric. food Chem., 11: 437-440. 

(1981)  Soft-tissue sarcomas and exposure to chemical substances: a 
case-referent study.   Br. J. ind. Med., 38: 27-33. 

ERNE, K.  (1966a)  Distribution and elimination of chlorinated 
phenoxyacetic acids in animals.   Acta vet. Scand., 7: 240-256. 

ERNE, K.  (1966b)  Studies on the animal metabolism of 
phenoxyacetic herbicides.   Acta vet. Scand., 7: 264-271. 

ERNE, K.  (1974)  Weed-killers and wildlife.  In:   Proceedings of 
 the XI International Congress on Game Biology, Stockholm, 1973. 
pp. 415-422 (National Swedish Environment Protection Board 
Publications No. 13E). 

ERNE, K.  (1975)  Phenoxy herbicide residues in Swedish fish and 
wildlife.  In:  Coulston, F., Korte, F., Klein, W., & Rosenblum, 
I., ed.   Pesticides:  Environmental quality and safety, Stuttgart, 
George Thieme Publishers, Suppl. Vol. III.,  pp. 192-195. 

ERNE, K.  (1980)  [Further studies of phenoxy herbicide residues in 
woodland berries and mushrooms, 1973-1979.]   Vr Föda, 32(5):  
285-292 (in Swedish). 

ERNE, K. & RUTQVIST, L.  (1979)  [Pesticide residues in feedstuffs 
in Sweden.]   Nord. Veterinaermed., 31: 263-274 (in Swedish). 

ERNE, K. & SPERBER, I.  (1974)  Renal tubular transfer of 
phenoxyacetic acids in the chicken.   Acta pharmacol. toxicol., 35: 

ERNE, K. & VON HAARTMAN, U.  (1973)  [Phenoxy acid residues in 
forest berries and mushrooms.]   Vr Föda, 25: 146-153 (in Swedish). 

EVANS, W.C., SMITH, B.S.W., FERNLEY, H.M., & DAVIES, J.I.  (1971)  
Bacterial metabolism of 2,4-dichlorophenoxyacetate.  Biochem. J., 
122: 543-551. 

(1948)  Experimental myotonia and repetitive phenomena:  The 
veratrinic effects of 2,4-D acetate in the rat.   Am. J. Physiol., 
155: 69-77. 

FABACHER, D.L. & CHAMBERS, H.  (1974)  Resistance to herbicides in 
insecticide-resistant mosquitofish,  Gambusia affinis.  Environ. 
 Lett., 7(1): 15-20. 

FAO  (1981)   Pesticide residues in food:  1980 evaluations. Rome, 
FAO, pp. 109-110 (Plant Production and Protection Paper 26 Suppl.) 

FAO/WHO  (1971)  2,4-D.  In:  1970 Evaluations of some pesticide 
 residues in food, Rome, FAO/WHO, pp. 59-86 (FAO/AGP/1970/M/ 12/1, 
WHO Food Additive Series, 71, 42). 

FAO/WHO  (1972)  1971 evaluations of some pesticide residues in 
food: 2,4-D.   WHO Pesticide Residues Series, 1: 83-97. 

FAO/WHO  (1973)   Pesticide residues in food. Report of the 1972 
Joint FAO/WHO meeting, Geneva, (WHO Techn. Rep. Series No. 525). 

FARWELL, S.O., BOWES, F.W., & ADAMS, D.F.  (1976a)  Determination 
of chlorophenoxy herbicides in air by gas chromatography/mass 
spectrometry:  selective ion monitoring.  Anal. Chem., 48: 420-426. 

FARWELL, S.O., ROBINSON, E., POWELL, W.J., & ADAMS, D.F.  (1976b)  
Survey of airborne 2,4-D in south central Washington.   J. Air 
 Pollut. Control Assoc., 26: 224-230. 

FAUST, S.D. & ALY, O.M.  (1963)  Some effects of 2,4-D and 2,4-DCP 
on drinking water quality.   Proc. Northeast. Weed Contr. Conf., 17:

FAUST, S.D. & SUFFET, I.H.  (1966)  Recovery, separation, and 
identification of organic pesticides from natural and potable 
waters.   Residue Rev., 15: 44-116. 

FEDOROVA, L.M. & BELOVA, R.S.  (1974)  [Inclusion of 2,4-
dichlorophenoxyacetic acid in organs of animals:  Paths and 
dynamics of its excretion.]  Gig. i Sanit., 39(2): 105-107  
(in Russian, US NTC Translation No. 76-10918-05J). 

FELDMAN, R.J. & MAIBACH, H.I.  (1974)  Percutaneous penetration of 
some pesticides and herbicides in man.   Toxicol. appl. Pharmacol., 
28: 126-132. 

FETISOV, M.I.  (1966)  Occupational hygiene in the application of 
herbicides of the 2,4-D group.   Hyg. Sanit., 31(7-9): 383-386. 

FEUNG, C.S., HAMILTON, R.H., & WITHAM, F.H.  (1971)  Metabolism of 
2,4-dichlorophenoxyacetic acid by soybean cotyledon callus tissue 
cultures.   J. agric. food Chem., 19: 474-479. 

FEUNG, C.S., HAMILTON, R.H., WITHAM, F.H., & MUMMA, R.O.  (1972)  
The relative amounts and identification of some 2,4-
dichlorophenoxyacetic acid metabolites isolated from soybean 
cotyledon callus cultures.   J. agric. food Chem., 50: 80-86. 

FEUNG, C.S., HAMILTON, R.H., & MUMMA, R.O.  (1973b)  Metabolism of 
2,4-dichlorophenoxyacetic acid.  V. Identification of metabolites 
in soybean callus tissue cultures.   J. agric. food Chem., 21: 

FEUNG, C.S., HAMILTON, R.H., & MUMMA, R.O.  (1975)  Metabolism of 
2,4-dichlorophenoxyacetic acid.  VII. Comparison of metabolites 
from five species of plant callus tissue cultures.   J. agric. food 
 Chem., 23: 373-376. 

FEUNG, C.S., LOERCH, S.L., HAMILTON, R.H., & MUMMA, R.O.  (1978)  
Comparative metabolic fate of 2,4-dichlorophenoxy acetic acid in 
plants and plant tissue culture.  J. Agric. Food Chem., 26: 

FIELD, B. & KERR, C.  (1979)  Herbicide use and incidence of 
neural tube defects.   Lancet, 1: 1341-1342.

(1963-1969)   Investigations on pesticide residues.  pp. 83.

FLEEKER, J.R. & STEEN, R.  (1971)  Hydroxylation of 2,4-D in 
several weed species.   Weed Sci., 19: 507-510.

FLORSHEIM, W.H. & VELCOFF, S.M.  (1962)  Some effects of 
2,4-dichlorophenoxyacetic acid on thyroid function in the 
rat:  Effects on iodine accumulation.   Endocrinology, 71(1): 

FLORSHEIM, W.H., VELCOFF, S.M., & WILLIAMS, A.D.  (1963)  Some 
effects of 2,4-D on thyroid function in the rat:  Effects on 
peripheral thyroxine.   Endocrinology, 72: 327-333.

Polynevrite aprčs usage d'un desherbant: l'acide 2,4-D.  Lille Med., 
7(10): 1049-1051.

FOLMAR, L.C.  (1976)  Overt avoidance reaction of rainbow trout fry 
to nine herbicides.   Bull. environ. Contam. Toxicol., 15(5): 

FOLMAR, L.C.  (1979)   Effects of short term field applications of 
 acrolein and 2,4-D (DMA) on flavor of the flesh of rainbow trout,  
124 pp.

FOSTER, R.K. & McKERCHER, R.B.  (1973)  Extraction of 14C-labelled 
chlorophenoxyacetic acids from soil.   Can. J. soil Sci., 53: 

FRANK, P.A.  (1972)  Herbicidal residues in aquatic environments.  
In: Faust, S.D., ed.   Fate of organic pesticides in the aquatic 
 environment.  Washington, DC, American Chemical Society, 
pp. 135-148 (Advances in Chemistry Series, No. III).

FRANK, P.A. & COMES, R.D.  (1967)  Herbicidal residues in pond 
water and hydrosoil.   Weeds, 15(3): 210-213.

FRANK, P.A., DEMINT, R.J., & COMES, R.D.  (1970)  Herbicides in 
irrigation water following canal-bank treatment for weed control.  
 Weed Sci., 18(6): 687-692.

FRANK, R. & SIRONS, G.J.  (1980)  Chlorophenoxy and chlorobenzoic 
acid herbicides; their use in eleven agricultural waterbeds and 
their loss to stream waters in southern Ontario, Canada, 1975-1977.  
 Sci. total Environ., 15: 149-167.

FRANK, R., SIRONS, G.J., & RIPLEY, B.D.  (1979)  Herbicide 
contamination and decontamination of well waters in Ontario, 
Canada, 1969-1978.   Pestic. monit. J., 13(3): 120-127.

FRANK, R., SIRONS, G.J., CAMPBELL, R.A., & MEWETT, D.  (1982)  
Residues of 2,4-D, dichlorprop, and picloram in wild berries from 
treated rights-of-way and conifer release sites in Ontario, 
1979-81.  Can. J. Plant Sci., 63: 196-209.

K.  (1982)  Effect of various factors on exposure of workers 
involved in the aerial application of herbicides.   Am. Conf. of 
 Govern. Ind. Hygienists, Transactions, 43: 97-117.

FREEMON, F.R.  (1975)  Causes of polyneuropathy.   Acta neurol. 
 Scand., 51(Suppl. 59): 5-43.

KOVTUNOVA, N.Y.  (1977)  [Residual content of chlorophenoxyacetic 
acids in the environment and human body.]  Gig. i Sanit., 6: 101-103 
(in Russian).

GAMBLE, W.  (1975)  Mechanism of action of hypolipidemic and 
herbicidal aryloxy acids.   J. theor. Biol., 54: 181-190.

GAVRILOVA, L.I.  (1965)  Experimental substantiation of the 
permissible concentration of 2,4-dichlorophenoxy-gamma-butyric (DB) 
acid in water bodies.   Hyg. Sanit., 29(1): 11-16.

fatal poisonings (suicides) with chlorinated phenoxyacetic acids 
(2,4-D and MCPA).]   Arch. Toxicol., 21: 261-278 (in German).

GLUCK, S.J. & MELCHER, R.G.  (1980)  Concentration and 
determination of the propylene glycol butyl ether esters of 
2,4-dichlorophenoxyacetic acid (PGBE 2,4-D) in air.  Am. Hyg. Ass. 
 J., 41(12): 932-934.

GOLDSTEIN, N.P. & BROWN, J.R.  (1960)  Peripheral neuropathy.  
 J. Am. Med. Assoc., 173: 171.

GOLDSTEIN, N.P., JONES, P.H., & BROWN, J.R.  (1959)  Peripheral 
neuropathy after exposure to an ester of dichlorophenoxyacetic 
acid.   J. Am. Med. Assoc., 171: 1306-1309.

GOLDWATER, L.J.  (1960)  Peripheral neuropathy.   J. Am. Med.  
 Assoc., 173(1): 171.

GORSHKOV, A.I.  (1972)  Hygienic evaluation of chlorocholine 
chloride (Preparation CCC) and its combination with 2,4-D amine 
salt.   Hyg. Sanit., 36(10-12): 208-211.

GOWEN, J.A., WIERSMA, G.B., & TAI, H.  (1976)  Mercury and 2,4-D 
levels in wheat and soils from sixteen states, 1969.  Pestic. Monit. 
 J., 10(3): 111-113.

GRAFF, G.L.A., GUENING, C., & VANDERKELEN, B.  (1972)  Influence de 
l'acide 2,4-dichlorophénoxyacéticque (2,4-D), un agent myotonisant, 
sur le métabolisme des phosphates acidosolubles des muscle 
squelettiques du rat.   C. R. Soc. Biol. (Paris), 166(II): 

GRANROTH, G., HAKAMA, M., & SAXEN, L.  (1977)  Defects of the 
central nervous system in Finland: I.  Variations in time and 
space, sex distribution, and parental age.   Br. J. prev. soc. 
 Med., 31: 164-170.

GRANROTH, G., HAAPAKOSKI, J., & SAXEN, L.  (1978)  Defects of the 
central nervous system in Finland: V.  Multivariate analysis of 
risk indicators.   Int. J. Epidemiol., 7(4): 301-308.

GRANT, W.  (1976)  2,4-D. In: Hart, R.W., Kraybill, H.F., & 
DeSerres, F.J., ed.:  A rational evaluation of pesticidal vs 
 mutagenic/carcinogenic action. Bethesda, Maryland, National 
Institute of Health (Publication No. (NIH) 78-1306 U.S. Department 
of Health, Education & Welfare, Public Health Service).

S.D.  (1983)  Peroxisome proliferation in primary cultures of rat 
hepatocytes.  Toxicol. appl. Pharmacol., 67: 15-25

GREEN, S. & MORELAND, F.S.  (1975)  Cytogenic evaluation of 
several dioxins in the rat.   Toxicol. appl. Pharmacol., 33: 161.

GRIBANOV, O.I.  (1968)  Pollution of an open water source at 
Shortandy Railroad Station by the herbicide 2,4-D butyl ester.  
 Hyg. Sanit., 32: 267-268.

GRIGSBY, B.H. & FARWELL, E.D.  (1950)  Some effects of herbicides 
on pasture and on grazing livestock.   Mich. Agric. Exp. St. Bull.,  
32(3): 378-385.

GROLLEAU, G., DE LAVAUR, E., SIOU, G., & FROUX, Y.  (1974)  Effects 
of 2,4-D on the reproduction of quail and partridge after the 
application of the product by spraying on eggs.  Ann. Zool. Ecol. 
 anim., 6(2): 313-331.

GROVER, R.  (1976)  Relative volatilities of ester and amine forms 
of 2,4-D.   Weed Sci., 24: 26-28.

GROVER, R. & KERR, L.A.  (1981)  Evaluation of polyurethane foam as 
a trapping medium for herbicide vapour in air monitoring and worker 
inhalation studies.   J. environ. Sci. Health, B 16(1): 59-66.

GROVER, R. & SMITH, A.E.  (1974)  Adsorption studies with the acid 
and dimethylamine forms of 2,4-D and dicamba.   Can. J. Soil Sci., 
54: 179-186.

GROVER, R., MAYBANK, J., & YOSHIDA, K.  (1972)  Droplet and vapour 
drift from butyl ester and dimethylamine salt of 2,4-D.   Weed Sci., 
20:  320-324.

(1976)  Residues of 2,4-D in air samples from Saskatchewan 
1966-1975.   J. environ. Sci. Health, B 11(4): 331-347.

GRUNOW, W. & BOHME, C.  (1974)  [On the metabolism of 2,4,5-T and 
2,4-D in rats and mice.]   Arch. Toxicol., 32: 217-225 (in German).

GUARDIGLI, A., CHOW, W., & LEFAR, M.S.  (1971)  Determination of 
some acidic herbicides by thin layer chromatography.   J. agric. 
 food Chem., 19: 1181-1182.

GUARINO, A.M. & ARNOLD, S.T.  (1979)  Xenobiotic transport 
mechanisms and pharmacokinetics in the dogfish shark.  In: Khan, 
M.A.Q., Lech, J.J., & Menn, J.J., ed.   Pesticide and xenobiotic 
 metabolism in aquatic organisms. Washington, DC, American Chemical 
Society, pp. 250-258.

GUMMER, W.D.  (1980)  Pesticide monitoring in the prairies of 
western Canada.   Environ. Sci. Res., 16: 345-372.

GUNTHER, F.A.  (1962)  Instrumentation in pesticide residue 
determination. In: Metcalf, R.L., ed.   Advances in Pest Control 
 Research, 5,  New York, Interscience Publishers, pp. 191-319.

GUSEVA, E.N.  (1956)  [On the pharmacology of 2,4-dichloro- 
phenoxyacetic acid.]   Farmakol. Toksikol. (Mosc.), 19(4): 
41-44 (in Russian).

GUTENMANN, W.H. & LISK, D.J.  (1965)  Conversion of 4-(2,4-DB) 
herbicide to 2,4-D by bluegills.   NY Fish Game J., 12(1): 108-111.

GUTENMANN, W.H., HARDEE, D.D., HOLLAND, R.F., & LISK, D.J.  (1963)  
Disappearance of 4(2,4-dichlorophenoxy-butyric) acid herbicide in 
the dairy cow.   J. dairy Sci., 46: 991-992.

GYRD-HANSEN, N. & DALGAARD-MIKKELSEN, S.  (1974)  The effects of 
phenoxy herbicides on the hatchability of eggs and the viability of 
the chicks.   Acta pharmacol. toxicol., 35: 300-308.

HACQUE, R., DEAGEN, J., & SCHMEDDING, D.  (1975)  Binding of 
2,4-dichloro- and 2,4,5-trichlorophenoxyacetic acid to bovine serum 
albumin.  A proton magnetic resonance study.   J. agric. food Chem., 
23: 763-766.

HALLIOP, J., TOCHMAN, A., & LATALSKI, M.  (1980)  [Ultrastructural 
investigations and myeloperoxidase determinations in rat 
neutrophils in acute poisoning with 2,4-dichlorophenoxyacetic 
acid.]   Acta haematol. Pol., 11(4): 249-257 (in Polish).

HALTER, M.  (1980)  2,4-D in the aquatic environment  In: Shearer, 
R., & Halter, M., ed.  Literature reviews of four selected 
 herbicides: 2,4-D dichlobenil, diquat & endothall, Seattle 
Municipality of Metropolital Seattle, January 1980, pp. 89-182.

HANIFY, J.A., METCALF, P., NOBBS, C.L., & WORSLEY, K.J.  (1980) 
Congenital malformations in the newborn in Northland: 1966-1977.  
 New Zealand med. J., 92: 245-248.

HANSEN, D.J., MATTHEWS, E., NALL, S.L., & DUMAS, D.P.  (1972)  
Avoidance of pesticides by untrained mosquito fish,  Gambusa 
 affinis.  Bull. environ. Contam. Toxicol., 8(1): 46-51.

HANSEN, D.J., SCHIMMEL, S.C., & KELTNER, J.M.  (1973)  Avoidance of 
pesticides by grass shrimp  (Palaeomonetes pugio).  Bull. environ. 
 Contam. Toxicol., 9(3): 129-133.

(1971)  Chronic toxicity of 2,4-dichlorophenoxyacetic acid in rats 
and dogs.   Toxicol. appl. Pharmacol., 20: 122-129.

HARDELL, L. & SANDSTRÖM, A.  (1979)  Case-control study: soft 
tissue sarcomas and exposure to phenoxyacetic acids or 
chlorophenols.   Br. J. Cancer, 39: 711.

Malignant lymphoma and exposure to chemicals, especially organic 
solvents, chlorophenols, and phenoxy acids: a case-control study. 
 Br. J. Cancer, 43: 169-176.

HARRISON, J.W.E. & REES, E.W.  (1946)  2,4-D toxicity - I.  
Toxicity towards certain species of fish.   Am. J. Pharm., 118: 

HASS, J.R., FRIESEN, M.D., & HOFFMAN, M.K.  (1981)  Recent mass 
spectrometric techniques for the analysis of environmental 
contaminants.  In:  McKinney, J. D., ed.  Environ. Health Chem.,  
Ann Arbor, Arbor Sciences, pp. 219-243.

HATCH, T.F. & GROSS, P.  (1964)   Pulmonary desposition and 
 retention of inhaled aerosols. New York, London, Academic Press, 
XIV + 192 pp (American Industrial Hygiene Association Monograph 
Series on Industrial Hygiene).

HAYES, W.J.  (1982)  2,4-D.  In:  Pesticides studied in man. 
Baltimore & London, Williams & Wilkins.

HEENE, R.  (1966)  [Histochemical proof of phosphorylase inhibition 
by 2,4-D in the skeletal muscles and liver of the rat.]  
 Naturwissenschaften, 53: 308 (in German).

HEENE, R.  (1967)  [Inhibition of glycogen-forming enzymes by 
2,4-D.]   Histochemie, 8: 45-53 (in German).

HEENE, R.  (1968)  Histochemical and morphological findings in 
experimental 2,4-D myopathy in warmblooded animals.  Acta 
 neuropathol., 10: 166-169.

HEENE, R.  (1975)  Experimental myopathies and muscular dystrophy.  
Studies in the formal pathogenesis of the myopathy of 2,4-D 
acetate.   Schriftenr. Neurol. Ser., 16: 1-97.

HENSHAW, B., QUE HEE, S.S., SUTHERLAND, R.F., & LEE, C.D.  (1975)  
Gas-liquid chromatography and gas-liquid chromatography combined 
with mass spectrometry of a butyl ester formulation of 2,4-
dichlorophenoxy-acetic acid.   J. Chromatogr., 106: 33-39.

HERBICH, J. & MACHATA, G.  (1963).  [Poisoning with 
2,4-dichlorophenoxy-acetic acid (2,4-D).]   Beitr. gerichtl. Med., 
22: 133-139 (in German).

HILBIG, V., LUCAS, K., & SEBEK, V.  (1976a)  [Studies to determine 
the toxic effects of derivatives of 2,4-dichloro- and 2,4,5-
trichlorophenoxyacetic acid (2,4-D and 2,4,5-T) on incubated eggs 
of pheasants, quails, and chickens.  First Report.]   Anz. 
 Schaedling-sk. D. Pflanzenschutz Umweltschutz, 49: 21-25 (in 

HILBIG, V., LUCAS, K., SEBEK, V., & MUNCHOW, H.  (1976b)  [Studies 
to determine the toxic effects of derivatives of 2,4-dichloro- and 
2,4,5-trichlorophenoxyacetic acid (2,4-D and 2,4,5-T) on incubated 
eggs of pheasants, quails, and chickens.  Second report.]   Anz. 
 Schaedlingsk. D. Pflanzenschutz Umweltschutz, 49: 65-68 (in 

HILL, E.V. & CARLISLE, H.  (1947)  Toxicity of 2,4-D for 
experimental animals.   J. ind. Hyg. Toxicol., 29(2): 85-95.

HILTIBRAN, R.C.  (1967)  Effects of some herbicides on fertilized 
fish eggs and fry.   Trans. Am. Fish. Soc., 96(4): 414-416.

HOFMANN, W.W., ALSTON, W., & ROWE, G.  (1966)  A study of 
individual neuro-muscular junctions in myotonia. 
 Electroencephalogr. clin.  Neuro-physiol., 21: 521-537.

HOGSTEDT, C. & WESTERLUND, B.  (1980)  Cohort studies of cause of 
death of forest workers with and without exposure to phenoxy 
preparations.  Läkartidninger, 77(19): 1828-1831.

Cytogenetic study of pesticides in agricultural work.  Hered., 
92: 177-178.

HOLCOMBE, G.W., FIANDT, J.T., & PHIPPS, G.L.  (1980)  Effects of pH 
increases and sodium chloride additions on the acute toxicity of 
2,4-dichlorophenol to the fathead minnow.   Water Res., 14(8): 

HOLMBERG, P.C.  (1979)  Central nervous system defects in children 
born to mothers exposed to organic solvents during pregnancy. 
 Lancet, 2: 177-179.

HOOPER, F.N.  (1958)  The effect of applications of pelleted 2,4-D 
upon the bottom fauna of Kemt Lake, Oakland County, Michigan.  Proc. 
 Ann. Meet. North Centr. Weed Control Conf., 41.

HORNER, J., QUE HEE, S.S., & SUTHERLAND, R.G.  (1974)  
Esterification of (2,4-dichlorophenoxy) acetic acid - a 
quantitative comparison of esterification techniques  Anal. Chem., 
46: 110-112.

HUCKINS, J.N., STALLING, D.C., & SMITH, W.A.  (1978)  Foam-charcoal 
chromatography for the analysis of polychlorinated dibenzodioxins 
in Herbicide Orange.   J. Assoc. Anal. Chem., 61: 32-38.

HUFF, J.E., MOORE, J.A., SARACCI, R., & TOMATIS, L.  (1980)  Long 
term hazards of polychlorinated dibenzodioxins and polychlorinated 
dibenzofurans.   Environ. Health Persp., 36: 221-240.

HUGHES, J.S. & DAVIS, J.T.  (1963)  Variations in toxicity to 
bluegill sunfish of phenoxy herbicides.  Weeds, 11(1): 50-53.

HUNT, L.M., GILBERT, B.N., & PALMER, J.S.  (1970)  Effects of a 
herbicide, 2-ethylhexyl ester of 2,4-D on magnesium: calcium ratios 
and blood urea nitrogen levels in sheep and cattle.  Bull. environ. 
 Contam. Toxicol., 5(1): 54-60.

IARC  (1977)  2,4-D and esters. In:  Some fumigants, the herbicides 
 2,4-D and 2,4,5-T, chlorinated dibenzodioxins, and miscellaneous 
 industrial chemicals. Lyons, International Agency for Research on 
Cancer, pp. 111-138 (IARC monograph on the evaluation of the 
carcinogenic risk of chemicals to man Vol. 15).

IARC  (1982)   Chemicals, industrial processes and industries 
 associated with cancer in humans. Lyons, International Agency for 
Research on Cancer, p. 101 (IARC Monographs of 1-29, Supplement 4).

IARC  (1983)   Miscellaneous pesticides, Lyons, International 
Agency for Research on Cancer, Vol. 30.

ILO  (1977)   Safe use of pesticides, Geneva, International 
Labour Office (Occupational Safety and Health Series, No. 38).

ILO  (1979)   Guide to health and hygiene in agricultural work, 
Geneva, International Labour Organisation, pp. 309.

(1977)  [Taste of flavour changes in woodland berries after 
herbicide spraying.]   Vr Föda, 29(6): 1-16 (in Swedish).

& GART, J.J.  (1969)  Bioassay of pesticides and industrial 
chemicals for tumorigenicity in mice: A preliminary note.   J. Natl 
 Cancer Inst., 42: 1101-1114.

IYER, V., WHITING, M., & FENICHEL, G.  (1976)  Neural influence in 
experimental myotonia.   Neurology, 26: 384.

JACKSON, J.W. & THOMAS, T.C.  (1978)  A simple and inexpensive 
method for sampling 2,4-D and 2,4,5-T herbicides in air.  J. Air 
 Pollution Control Assoc., 28(11): 1145-1147.

JAMES, M.O.  (1979)  Dispositon of 2,4-D, 2,4,5-T, DDA and 
phenylacetic acid in the spiny lobster  (Palinurus argus).  
 Pharmacologist, 21(3): 251.

JAMES, W.H.  (1977)  Clomiphene, acencephaly, and spina bifida.  
 Lancet, 1: 603.

JANERICH, D.T.  (1973)  Epidemic waves in the prevalence of 
anencephally and spina bifida in New York State.   Teratology, 8: 

JENSEN, D.J. & GLAS, R.D.  (1981)  Analysis for residues of acidic 
herbicides. In: Moye, H.A., ed.  Analysis of pesticide residues,  
New York, Chichester, Brisbane, Toronto, John Wiley & Sons, pp. 

JENSSEN, D. & RENBERG, L.  (1976)  Distribution and cytogenetic 
test of 2,4-D and 2,4,5-T phenoxyacetic acids in mouse blood 
tissues.   Chem. biol. Interactions, 14: 291-299.

JOHNSON, J.E.  (1971)  The public health implications of widespread 
use of the phenoxy herbicides and picloram.   Bioscience, 27(17): 

JOHNSON, E.R., YU, T.C., & MONTGOMERY, M.L.  (1977)  Trapping and 
analysis of atmospheric residues of 2,4-D.   Bull. environ. Contam. 
 Toxicol., 17: 369-372.

JOHNSON, R.D. & MANSKE, D.D.  (1976)  Pesticide residues in total 
diet samples (IX)  Pestic. Monit. J., 9(4): 157-168.

JOHNSON, R.D., MANSKE, D.D., NEW, D.H., & PODREBARAC, D.S.  (1979)  
Pesticides and other chemical residues in infant and toddler total 
diet samples - (I) - August 1974 - July 1975.   Pestic. monit. J., 
13(3): 87-98.

JOHNSON, R.D., MANSKE, D.D., NEW, D.H., & PODREBARAC, D.S.  (1981a)  
Pesticide, heavy metal and other chemical residues in infant and 
total diet samples - (II) - August 1975 - July 1976.   Pestic. 
 monit. J., 15(1): 39-53.

JOHNSON, R.D., MANSKE, D.D., & PODREBARAC, D.S.  (1981b)  
Pesticide, heavy metal, and other chemical residues in adult total 
diet samples (XII) - August 1975 - July 1976.   Pestic. monit. J., 
15(1): 54-69.

JUNG, H.D. & WOLF, F.  (1977)  [Contact eczemas due to forestry use 
of the herbicide SELEST100.]   Dtsch. Gesundheit., 32(31): 1464-1467 
(in German).

JUZWIAK, I., JUZWIAK, J., SUCHOWIAK, J., & ORDA, E.  (1973)  [A 
study of the extent of the pesticide threat to the health of 
agricultural employees in Olesnicki Country.]   Pol. Tyg. Lek., 
28(11): 419-422  (in Polish, Health & Welfare Canada Translation 
No. 2157).

KAISER, H.  (1973)  Guiding concepts relating to trace analysis. 
 Pure appl. Chem., 34: 35-61.

KARKINEN-JAASKELAINEN, M. & SAXEN, L.  (1974)  Maternal influenza, 
drug consumption, and congential defects of the central nervous 
system.   Am. J. Obstet. Gynecol., 118(6): 815-818.

KASKEVICH, L.M. & SOBOLOVA, L. P.  (1978)  [A case of acute 
poisoning with herbicide 2,4-D (late after effects).]   Gig. Tr. 
 Prof. Zabol., 22 (10): 49-50 (in Russian, US National 
Translations Center, Translation No. 79-11916-06T).

KAS'JANENKO, A. G. & KOROLEVA, N. S.  (1979)  [An evaluation of the 
genetic danger of pesticides.]   Izv. Akad. Nauk SSSR Ser. Biol., 
3: 401-409 (in Russian).

KATEMAN, G. & PIJPERS, F.W.  (1981)   Quality Control in analytical 
 chemistry, New York, John Wiley & Sons, 276 pp.

MAY, D.R.  (1972)  Effects on fresh water fish.   J. Water Pollut. 
 Control Fed., 44(6): 122-1250.

KAY, J.H., PALAZZOLO, B.S., & CALANDRA, J.C.  (1965)  Subacute 
dermal toxicity of 2,4-D.   Arch. environ. Health, 11: 648-651.

KENIGSBERG, Y.E.  (1968)  [Model myotonia in rats induced by 
means of the diethylamine salt of 2,4-dichlorophenoxyacetic acid.]  
 Dok. Akad. Nauk Beloruss. SSR, 12(5): 473-475 (in Russian, Health & 
Welfare Canada Translation No. 2440).

(1970)  Residues in sorghum treated with the isooctyl ester of 
2,4-D.   Pestic. monit. J., 4(3): 111-113.

KHALATKAR, A.S. & BHARGAVA, Y.R.  (1982)  2,4-dichlorophenoxy- 
acetic acid. A new environmental mutagen.  Mutat. Res., 103: 

KHANNA, S. & FANG, S.  (1966)  Metabolism of C14-labelled 
2,4-dichlorophenoxyacetic acid in rats.  J. agric. Food Chem., 
14: 500-503.

KHANNA, R.N. & KOHLI, J.D.  (1977)  Metabolism of chlorophenoxy 
herbicides in man.  In:  Zaidi, S. H., ed.  Proceedings of the 
 International Symposium on Industrial Toxicology, Lucknow, India, 
 November 1975, Lucknow, Industrial Toxicology Research Centre, 
pp. 590-599.

KHERA, K.S. & McKINLEY, W.P.  (1972)  Pre- and postnatal studies on 
2,4,5-T, 2,4-D and their derivatives in rats.   Toxicol. appl. 
 Pharmacol., 22: 14-28.

KHERA, K.S. & RUDDICK, J.A.  (1973)  Polychlorodibenzo- p-dioxins. 
Perinateal effects and the dominant lethal test in Wistar rats. In: 
Blair, E.H., ed.  Chlorodioxins - origin and fate. Washington, DC, 
American Chemical Society, pp. 70-84 (Advances in Chemistry Series 
No. 120).

KHIBIN, L.S., TAITSEL', L.A., & SLATOV, I.V.  (1968)  [On the 
clinical aspects of acute poisoning with Dicotex 40.]   Gig. Tr. 
 Prof. Zabol., 3: 52-53 (in Russian, Health & Welfare Canada 
Translation No. 2240).

KIMBROUGH, R.D., ed.  (1980)   Halogenated biphenyls, terphenyls, 
 naphthalenes, debenzodioxins and related products. Amsterdam, 
New York, Oxford, Elsevier, North Holland Biomedical Press.

KING, J.E. & PENFOUND, W.T.  (1946)  Effects of two of the new 
formagenic herbicides on bream and largemouth bass.   Ecology, 
27(4): 327-374.

KING, C.T.G., HORIGAN, E.A., & WILK, A.L.  (1971)  Screening of the 
herbicides 2,4,5-T and 2,4-D for cleft palate.   Teratology, 4(2): 

KLEKOWSKI, R.Z. & ZVIRGZDS, J.  (1971)  [The influence of herbicide 
2,4-D Na on respiration and survival of  Simocephalus vetulus O.F. 
 Muller (Cladocera).]  Pol. Arch. Hydrobiol., 18(4): 393-400 (in 

Residues in the forage and milk from cows grazing forage treated 
with esters of 2,4-D.   Weeds, 14: 164-167.

KNUTSON, J.C. & POLAND, A.  (1980)  Keratinization of mouse 
teratoma cell line xB produced by 2,3,7,8-tetrachlorodibenzo- p-
dioxin: an  in vitro model of toxicity.  Cell, 22: 27-36.

KOCIBA, R.J. & SCHWETZ, B.A.  (1982)  A review of the toxicity of 
2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) with a comparison to the 
toxicity of other chlorinated dioxin isomers.  Assoc. Food Drug 
 Offic. Q. Bull., 46(3): 168-188.

SIRCAR, K.P.  (1974)  Absorption and excretion of 2,4-
dichlorophenoxyacetic acid in man.   Xenobiotica, 4(2): 97-100.

KOLBERG, J., HELCELAND, K., & JONSEN, J.  (1973)  Binding of 
2,4-dichloro and 2,4,5-trichlorophenoxyacetic acid to bovine serum 
albumin.   Acta pharmacol. toxicol., 33(5-6): 470-475.

[Control of occupational exposure to phenoxyacids (2,4-D and 
2,4-5-T).]   Arbete och Hälsa, 17: 3-26 (in Swedish).

KOLMODIN-HEDMAN, B. & ERNE, K.  (1980)  Estimation of occupational 
exposure to phenoxy acids (2,4-D and 2,4,5-T).   Arch. Toxicol., 
(Suppl. 4): 318-321.

KOLMODIN-HEDMAN, B., ERNE, K., & AKERBLOM, M.  (1980)  Field 
application of phenoxy acid herbicides.  In: Tordoir, W.F. & 
Van Heemstra, E.A.H., ed.  Field workers exposure during pesticide 
 application. New York, Elsevier Scientific Publishing Co., pp.73-77 
(Studies in Environmental Science, Vol. 7).

KONSTANTINOVA, T.K.  (1970)   Toxicology and some problems of the 
 embryotropic action of the butyl ester of 2,4-D. In: Vygodchikov, 
 G.V., ed. Proceedings of a Conference on Problems on Hygiene and 
 Toxicology of Pesticides, USSR, 1967, Moscow, Meditsina, pp. 

[Embryotropic effects of the products from the decomposition of 
herbicides based on 2,4-dichlorophenoxyacetic acid.]  Gig. i Sanit., 
11: 102-105 (in Russian, US National Translation Centre, 
Translation No. 78-14230-06F.)

KONTEK, M., MARCINKOWSKA, B., & PIETRASZEK, Z.  (1973)  [Electro-
encephalographic investigations in farm workers exposed to 
derivatives of arylakanocarboxylic acids.]   Pol. Tyg. Lek., 
28(25): 937-939 (in Polish, Health & Welfare Canada 
Translation No. 2215).

KOPISCHKE, E.D.  (1972)  The effect of 2,4-D and diesel fuel on egg 
hatchability.   J. Wildl. Manage., 36(4): 1353-1356.

KORTE, C. & JALAL, S.M.  (1982)  2,4-D-induced clastogenicity and 
elevated rates of sister chromatid exchanges in cultural human 
lymphocytes.  J. Hered., 73: 224-226.

KOSCHIER, F.J., GIRAD, P., & HONG, S.K.  (1978)  Transport of 
2,4-dichlorophenoxyacetate by rat renal cortical slides.   Toxicol. 
 appl. Pharmacol., 45: 883-894.

KOSCHIER, F.J. & PRITCHARD, J.B.  (1979)  Excretion of 
2,4-dichlorophenoxyacetate (2,4-D) by the dogfish shark  (Squalus 
 acanthias).  Pharmacologist, 21(3):184.

(1974)  [A toxicological evaluation of the new herbicide 3-nitro-4-
oxybenzyl ether of (2,4-dichlorophenoxy) acetic acid (NK-2).]  
 Zh. eksp. klin. Med., 14(3): 14-18 (in Russian, Health & Welfare 
Canada Translation No. 2436).

KRAMER, D. & SCHMALAND, G.  (1974)  [Plant protection agent 
residues in water: Problems in water management as a consequence of 
biocide applications.]   Wasserwirtsch. Wassertech., 24(5): 161-167 
(in German).

KUHN, E. & STEIN, W.  (1964)  [Experimental myotonia with 2,4-D in 
the rat.]   Klin. Wochenschr., 42: 1215-1216 (in German).

KUHN, E. & STEIN, W.  (1965)  [Model myotonia after 2,4-
dichlorophenoxyacetate (2,4-D) in the rat.   In vitro and  in vivo 
studies on the effects of 2,4-D on the energy metabolism of 
muscle.]   Klin. Wochenschr., 43: 673-677 (in German).

KUHN, E. & STEIN, W.  (1966) [Model myotonia with 2,4-
dichlorophenoxyacetate (2,4-D).]   Klin. Wochenschr., 44: 700-702 
(in German).

KUZMINSKAJA, U.A. & BERSAN, L.V.  (1975)  [The effects of the 
sodium salt of dichlorophenoxyacetic acid on the glycolysis, 
ATPase, and transketolase activity of erythrocytes.]   Farmakol. 
 Toksikol., 38(1): 102-104 (in Russian).

KUZYK, A.  (1979)   A report on a survey of the Alberta farming 
 community respecting the use of pesticides, Edmonton, Alberta 
Department of the Environment, Pollution Control Division.

LAPPE, M.  (1979)  HLA homozygosity and neural-tube defects.  
 Lancet, 1: 1342.

LASKOWSKI, M.B. & DETTBARN, W.D.  (1977)  The pharmacology of 
experimental myopathies.   Ann. Rev. Pharmacol. Toxicol., 17:  

LAVY, T.L. ROETH, F.W., & FENSTER, C.R.  (1973)  Degradation of 
2,4-D and atrazine at three soil depths in the field.   J. Environ. 
 Qual., 2(1): 132-137.

LAVY, T.L., WALSTAD, J.D., FLYNN, R.R., & MATTICE, J.D.  (1982)  
(2,4-dichlorophenoxy) acetic acid exposure received by aerial 
applications crew during forest spray operations.   J. agric. food 
 Chem., 30: 373-381.

LEE, B.  (1978)  Herbicides under suspicion in Australia.   New 
 Sci., 80(1125): 159.

LENG, M.  (1972)  Residues in milk and meat and safety to livestock 
from the use of phenoxy herbicides in pasture and rangeland.   Down 
 Earth, 28(1): 12-20.

LENG, M.  (1977)  Comparative metabolism of phenoxy herbicides in 
animals.  In: Ivie, G.W. & Dorough, H.W., ed.  Fate of pesticides in 
 large animals, New York, San Francisco, London, Academic Press, 
pp. 53-76.

LENG, M.L.  (1979)  Comparative toxicology of various chlorinated 
dioxins as related to chemical structure. In: Bontoyan, W.R., ed. 
 Collaborative International Pesticides Analytical Council 
 Proceedings Symposium Series I, Cambridge, Heffers Printers Ltd., 
pp. 141-169.

LENG, M.L., LAVY, R.L., RAMSEY, J.C., & BRAUN, W.H.  (1982)  
Review of the studies with 2,4,5-T in humans including applicators 
under field conditions, pp. 133-156. In: Plimmer, J.R., ed.:  
 Pesticide residues and exposure. Washington, DC, American Chemical 
Society, (ACS Symposium Series 182). 

LHOSTE, J. & ROTH, P.  (1946)  [The effect of aqueous sodium 
2,4,-dichlorophenoxyacetate on the development of eggs of  Rana 
 temporaria L.]   C.R. Soc. Biol. Paris, 140: 272-274.

LIBICH, S., TO, J.C., WANG, K. Y., & WATSON, D. A.  (1981)   A 
 study to assess the occupational exposure to 2,4-D herbicides,  
Toronto, Safety Services Department, Health and Safety Division. 
pp. 16 (Ontario Hydro. Report SSD-81-1).

LINDQUIST, N.G. & ULLBERG, S.  (1971)  Distribution of the 
herbicides 2,4,5-T and 2,4-D in pregnant mice.  Accumulation in the 
yolk sac epithelium.   Experientia (Basel), 27: 1439-1441.

LINNAINMAA, K.  (1983a)  Non-mutagenicity of phenoxyacid herbicides 
2,4-D and MCPA. In: Keith, L.H., Choudhary, G., & Rappe, C., ed.: 
 Chlorinated dioxins and dibenzofurans in the total environment.  
Ann Arbor, Ann Arbor Sci. Publ. Inc., Vol. 1.

LINNAINMAA, K.  (1983b)  Induction of sister chromatid exchanges by 
the peroxisome proliferators 2,4-D, MCPA, and clofibrate  in vivo 
and  in vitro. Carcinogenesis, accepted for publication.

LIPSCOMB, G.Q.  (1968)  Pesticide residues in prepared baby foods 
in the United States.   Pestic. monit. J., 2(32):104-108.

D.G.  (1963)  Elimination of 2,4-D in the urine of steers fed 4 
(2,4-DB) or 2,4-D.   J. dairy Sci., 46: 1434-1435.

LIU, L.C. & CIBES-VIADE, H.R.  (1973)  Adsorption of fluometuron, 
prometryne, Sencor and 2,4-D by soils.   Univ. Puerto Rico, J. 
 Agric., 57: 286-293.

LOKKE, H.  (1975)  Analysis of free and bound chlorophenoxy-acids 
in cereals.   Bull. environ. Contam. Toxicol., 13: 730-736.

N.V.  (1973)  [Toxicological characteristics of 2,4-D derivatives.]  
 Veterinariya, 5: 107-109 (in Russian, Health & Welfare Canada 
Translation No. 2173).

LONDONO, F.  (1966)  [Occupational acne.  Five cases caused by 
herbicide.]   Med. cutanea, 3: 225-232 (in Spanish).

H.E., FALABALLA, F., BONDERMANN, D.P., & CHOI, U.Y.  (1969)  The 
epidemiology of pesticides in a rural area.   J. Am. Ind. Hyg. 
 Assoc., 20(3): 298-304.

LOOS, M.A.  (1969)  Phenoxyalkanoic acids.  In: Kearney, P.C. & 
Kaufman, D.D., ed.  Degradation of herbicides, New York, Marcel 
Dekker, pp. 1-49.

LOOS, M.A.  (1975)  Phenoxyalkanoic acids. In: Kearney, P.C. & 
Kaufman, D.D., ed.  Herbicides: Chemistry, degradation and mode of 
 action, New York, Marcel Dekker, pp. 1-128.

LOPEZ, M.R.  (1961)  [Action of 2,4-dichlorophenoxyacetic acid and 
its sodium salt on the spermatozoa of the frog.]   Biol. R. Soc. 
 Esp. Hist. Nat., 59: 219-226 (in Spanish).

LUCKWILL, L.C. & LLOYD-JONES, C.P.  (1960a)  Metabolism of plant 
growth-regulators.  I. 2,4-dichlorophenoxyacetic acid in leaves of 
red- and blackcurrant.   Ann. appl. Biol., 48: 613-625.

LUCKWILL, L.C. & LLOYD-JONES, C.P.  (1960b)  Metabolism of plant 
growth-regulators.  II. Decarboxylation of 2,4-dichloro- 
phenoxyacetic acid in leaves of apple and strawberry.   Ann. appl. 
 Biol., 48: 626-636.

Study of certain aspects of lipid-protein-carbohydrate metabolism 
in workers engaged in 2,4-D production.   Trud. Azerbaid. Nauchno-
 Issled. Instituta Gig. prof. Zabol., No.5: 146-149.

LUTZ-OSTERTAG, Y. & LUTZ, H.  (1970)  Action néfaste de l'herbicide 
2,4-D sur le développement embryonaire et la fécondité du gibier ą 
plumes.   C.R. Acad. Sci. Paris, Ser. D., 271(25): 2418-2421.

LUTZ-OSTERTAG, Y. & LUTZ, H.  (1974)  Sexualité et les pesticides.  
 Ann. Biol. anim. (Paris), 13(3-4): 173-185.

MAAS, W. & KERSSEN, M.C.  (1973)  Drift studies in ULV and 
conventional applications.  Agric. Aviation, 15: 41-50.

MACKENTHUN, K.M. & KEUP L.E. (1972)  Freshwater macroinvertebrates.  
 J. Water Pollut. Control Fed., 44(6): 1137-1150.

MACLEAN, G.J. & DAVIDSON, J.H.  (1970)  Diagnosis of disorders in 
pastured livestock.   Down Earth, 25(4): 12-16.

MAGNUSSON, J., RAMEL, C., & ERIKSSON, A.  (1977)  Mutagenic effects 
of chlorinated phenoxyacetic acids in  Drosophila melanogaster.  
 Hereditas, 85: 121-123.

MAIER-BODE, H. (1971)   [Herbicides and their residues.], Stuttgart, 
FRG, Verlag Eugen Ulmer,  479 pp. (in German).

MANSKE, D.D. & CORNELIUSSEN, P.E.  (1974)  Pesticide residues in 
total diet samples (VII).  Pesticide Mont. J., 8(2): 110-124.

MANSKE, D.D. & CORNELIUSSEN, P.E.  (1974)  Pesticide residues in 
total diet samples (VIII).  Pesticide Mont. J., 9(2): 94-105.

MANSKE, D.D. & JOHNSON, R.D.  (1975)  Pesticide residues in total 
diet samples VII.  Pestic. Monit. J., 9(2): 94-105.

MARTH, P.C. & MITCHELL, J.W.  (1949)  Comparative volatility of 
various forms of 2,4-D.   Bot. Gaz., 110: 632-636.

MARTYNOV, Y.E.  (1970)  The effect of 2,4-d compounds on wild warm 
blooded animals.   Lesn. Khoz., 6: 57-59 (in Russian, Health & 
Welfare Canada Translation No. 2186).

MASON, R.W.  (1975)  Binding of some phenoxyalkanoic acids to 
bovine serum albumin  in vitro. Pharmacology, 13: 177-186.

MATSUNAKA, S.  (1972)  Metabolism of pesticides in higher plants.  
In:  Matsumura, F., Boush, G.M., & Mitsato, T., ed.   Environmental 
 toxicology of pesticides, New York, Academic Press, pp. 341-365.

MAYBANK, J. & YOSHIDA, K.  (1969)  Delineation of herbicide-drift 
hazards on the Canadian prairies.   Trans. Am. Soc. Agric. Eng., 
12(6): 759-762.

MAYBANK, J., YOSHIDA, K., & GROVER, R.  (1978)  Spray drift from 
agricultural pesticide applications.   J. Air Poll. Control Assoc., 
28: 1009-1014.

MAZAREAN, H.H., DUX, L., & GUBA, F.  (1979a)  Changes of metabolism 
during experimentally induced myotonia of rats. I. Alterations in 
lactate and malate dehydrogenase isoenzyme activities.   Biochem. 
 Med., 22: 350-358.

MAZAREAN, H.H., DUX, L., & GUBA, F.  (1979b)  Changes of metabolism 
during experimentally induced myotonia of rats. II. Alterations in 
creatinine kinase and acid phosphatase activities: a possible 
mechanism in the development of muscle damage.   Biochem. Med., 
22: 359-364.

MCARDLE, F.J., MARETZKI, A.N., WILEY, R.C., & MODREY, M.G.  (1961)  
Influence of herbicides on flavor of processed fruits and 
vegetables.   J. agric. food Chem., 9: 228-230.

The comparative toxicity of chlorinated dibenzo- p-dioxins in mice 
and guniea pigs.  Toxicol. appl. Pharmacol., 44: 335-356.

MCLENNAN, M.W.  (1974)  2,4-D toxicity in diary cattle.   Aust. 
 vet. J., 50: 578.

MEEHAN, W.R., NORRIS, L.R., & SEARS, H.S.  (1974)  Toxicity of 
various formulations of 2,4-D to salmonids in Southeast Alaska.  
 J. Fish. Res. Board Can., 31(4): 480-485.

MELNIKOV, M.N.  (1971)  Chemistry of pesticides.   Res. Rev., 
36: 165-166.

MIERZWA, S. & WITEK, S.  (1977)  Gas-liquid chromatographic 
method with electroncapture detection for the determination of 
residues of some phenoxyacetic acid herbicides in water as their 
2,2,2-trichloroethyl esters.   J. Chromatogr., 136: 105-111.

Toxicologie des phytohormones.   Rec. Méd. Vet., 146: 345-357.

MITCHELL, J.W., HODGSON, R.E., & GAETJENS, C.F.  (1946)  Tolerance 
of farm animals to feed containing 2,4-dichloro-phenoxyacetic acid.  
 J. anim. Sci., 5(1): 226-232.

MONARCA, G. & DIVITO, G. (1961)  [On acute poisoning by a herbicide 
(2,4-dichlorophenoxyacetic acid).]   Folia med. (Naples), 44(6): 
480-485 (in Italian, Health & Welfare Canada Translation No. 2234).

MONTGOMERY, M.L., CHANG, U.L., & FREED, V.H.  (1971)  Comparative 
metabolism of 2,4-D by bean and corn plants.   J. agric. food Chem., 
19: 1219-1221.

MOREALE, A. & VAN BLADEL, R.  (1980)  Behaviour of 2,4-D in Belgian 
soils.   J. environ. Qual., 9: 627-633.

SHIRASU, Y.  (1983)  Further mutagenicity studies on pesticides in 
microbial reversion assay systems.  Mutat. Res., 116: 185-216.

MORRE, D.J. & ROGERS, B.J.  (1960)  The fate of long chain esters 
of 2,4-D in plants.   Weeds, 8: 436-447.

MORTON, H.L., ROBINSON, E.D., & MEYER, R.T.  (1967)  Persistence of 
2,4-D, 2,4,5-T, and dicamba in range forage grasses.   Weeds, 
15: 268-271.

MOUNT, D.I. & STEPHAN, C.E.  (1967)  A method for establishing 
acceptable toxicant limits for fish - malathion and the butoxy-
ethane ester of 2,4-D.   Trans. Am. Fish. Soc., 96(2): 185-193.

MUIR, C.S. & WAGNER, G.  (1982)   Directory of on-going research in 
 cancer epidemiology 1982, Lyons, International Agency for Research 
on Cancer, (IARC Scientific publications No. 46) pp. 86 (Abstract 
No. 227), 432(1146) 460(1221).

LALLUKKA, R.  (1978)  Phenoxy herbicide residues in cowberries, 
mushrooms and the twigs of forest plants.   Ann. Agric. Fenn., 
17: 23-31.

MUNRO, H.E.  (1972)  Determination of 2,4-dichloro-phenoxyacetic 
acid and 2,4,5-trichlorophenoxyacetic acid in tomato plants and 
other commercial crops by microcoulometric gas chromatography.  
 Pestic. Sci., 3: 371-377.

MURTHY, M.S.S.  (1979)  Induction of gene conversion in diploid 
yeast by chemicals:  Correlation with mutagenic action and its 
relevance in genotoxicity screening.   Mutat. Res., 64: 1-17.

S.N.  (1982)  Agricultural applicators' exposure to 2,4-
dichlorophenoxyacetic acid. In: Plimmer, J.R., ed.  Pesticide 
 residues and exposure, Washington, DC, American Chemical Society, 
pp. 119-132 (ACS Symposium Series 182).

 Polychlorinated dibenzo- p-dioxins: Criteria for their effects on 
 man and his environment, Ottawa, NRCC Publications Service, NRCC 
Publication No. 18574, 251 pp.

 herbicides. Their effects on environmental quality, Ottawa, NRCC 
Publications Service, NRCC publication no. 16075, 437 pp.

(1958)  Polyradiculonévrite subaciguė chez deux agriculteurs: 
intoxication par des produits anti-parasitaires.  Lille Med., 
3(3): 161-164.

NESBITT, H.J. & WATSON, J.R.  (1980a)  Degradation of the 
herbicide 2,4-D in river water. I.  Description of the study 
area, and survey of rate determining factors.   Water Res., 
14(12): 1683-1688.

NESBITT, H.J. & WATSON, J.R.  (1980b)  Degradation of the 
herbicide 2,4-D in river water. II.  The role of suspended 
sediment, nutrients, and water temperature.   Water Res., 
14(12): 1689-1694.

NIELSEN, N.O.  (1968)  Teratogenic effects of hyperthermia in 
chicken embryo. Preliminary report.   Teratology, 1: 102-107.

NIELSEN, K., KAEMPE, B., & JENSEN-HOLM, J.  (1965)  Fatal 
poisoning in man by 2,4-D: Determination of the agent in 
forensic materials.   Acta pharmacol. toxicol., 22: 224-234.

NIKANDROV, V.N.  (1974).  [The activity of malate dehydrogenase in 
some organs and tissues of albino rats after administration of the 
amine salt of 2,4-D,]   Vesti Akad. Navuk Belaruskai SSR (Ser. 
 Biol.) 1: 126-127 (in Belorussian).

NISHIUCHI, Y. & YOSHIDA, K.  (1974)  [Toxicity of new agricultural 
chemicals to tadpoles.]   Bull. agric. Chem. Insp. St., 14: 66-68 
(in Japanese).

NORSTROM, A., RAPPE, C., LINDAHL, R., & BUSTER, H.R.  (1979)  
Analysis of some older Scandinavian formulations of 2,4-D and 
2,4,5-T for contents of chlorinated dibenzo- p-dioxins and 
dibenzofurans.   Scand. J. Work Environ. Health, 5: 375-378.

OLSON, B.A., SNEATH, T.C., & JAIN, N.C.  (1978)  Rapid, simple 
procedures for the simultaneous gas chromatographic analysis 
of four chlorophenoxy herbicides in water and soil samples.  
 J. agric. food Chem., 26: 640-643.

ORBERG, J.  (1980a)  Observations on the 2,4-dichlorophenoxy- 
acetic acid (2,4-D) excretion in the goat.   Acta pharmacol. 
 toxicol., 46: 78-80.

ORBERG, J.  (1980b)  Effects of low protein consumption on the 
renal clearance of 2,4-dichlorophenoxyacetic acid (2,4-D) in goats.  
 Acta pharmacol. toxicol., 46: 138-140.

OSADCHUK, M., SALAHUB, E., & ROBINSON, P.  (1977)  Isolation of 
chlorophenoxy herbicides on columns of glass beads.   J. Assoc. Off. 
 Anal. Chem., 60: 1327-1327.

OSTERLOH, J., LOTTI, M., & POND, S.M.  (1983)  Toxicologic studies 
in a fatal overdose of 2,4-D, MCPP, and chlorpyrifos.  J. anal. 
 Toxicol., 7: 125-129.

OU, L.T., ROTHWELL, D.F., WHEELER, W.B., & DAVIDSON, J.M.  (1978)  
The effect of high 2,4-D concentrations on degradation and carbon 
dioxide evolution in soils.   J. environmental Qual., 7(2): 241-246.

PADEROVA, V.P.  (1975)  [Some hygienic problems of using 2,4-D 
herbicides.]   Gig. i Sanit., 40(9): 96-97 (in Russian).

PAGGIARO, P.L., MARTINO, E., & MARIOTTI, S.  (1974)  [On a case of 
poisoning by 2,4-dichlorophenoxyacetic acid.]   Med. lav., 65(3-4): 
128-135 (in Italian, Health & Welfare Canada Translation No. 2200).

PALMER, J.S.  (1972)  Toxicity of 45 organic herbicides to cattle, 
sheep, and chickens.  In:  Production Research Report, Washington, 
DC, Agricultural Research Service, pp. 1-38.

PALMER, J.S. & RADELEFF, R.D.  (1969)  The toxicity of some 
organic herbicides to cattle, sheep, and chickens.  In:  Production 
 Research Report, Washington, DC, Agriculture Research Service, 
pp. 1-26.

PAL'MOVA, I.V. & GALUZOVA, L.V. (1963)  [Maximum permissible 
concentration of sodium salt and butyl ester formulations of 
2,4-D in water.]   Gig. i Sanit., 28(7): 11-13 (in Russian, 
Health & Welfare Canada Translation No. 2717).

PEMBERTON, J.M.  (1979)  Pesticide degrading plasmids:  a 
biological answer to environmental pollution by phenoxyherbicides.  
 Ambio, 8: 202-205.

PHILLEO, W.W. & FANG, S.C.  (1967)  Effects of 2,4-D on metabolism.  
 J. agric. food Chem., 15(2): 256-260.

(1975)  Clofibrate-induced muscle damage in patients with chronic 
renal failure.  Lancet, 2: 1279-1282.

PILINSKAJA, M.A.  (1974)  [Cytogenetic effect of the herbicide 
2,4-D on human and animal chromosomes.]  Tsitol. Genet., 8(3): 
202-206 (in Russian).

POCCHIARI, F., SILANO, V., & ZAMPIER, A.  (1979)  Human health 
effects from accidental release of tetrachlorodibenzo- p-dioxin 
(TCDD) at Seveso, Italy.   Ann. NY Acad. Sci., 320: 311-320.

PODOLAK, M.  (1979)  [Effect of paraquat and 2,4-dichloro- 
phenoxyacetic acid (2,4-D) on oxidative phosphorylation and 
respiration of brain mitochondria in the rat.]   Bromatol. Chem. 
 Toksykol., 12(2): 147-152 (In Polish).

POLAND, A. & GLOVER, E.  (1973)  2,3,7,8-Tetrachlorodibenzo- p- 
dioxin: a potent inducer of S-aminolevulinic acid synthetase. 
 Sci., 179: 476.

POLAND, A. & GLOVER, E.  (1973)  Chlorinated dibenzo- p-dioxins: 
potent inducers of -aminolevulinic acid synthetase and aryl 
hydrocarbon hydroxylase.  Molec. Pharmacol., 9: 736-747.

POLAND, A. GLOVER, E.  (1976)  Sterospecific, high affinity 
binding of 2,3,7,8-tetrachlorodibenzo -p-dioxin by hepatic cytosol. 
 J. Biol. Chem., 251(16): 4936-4946.

POLAND, A. & KENDE, A.  (1976)  2,3,7,8-tetra-chlorodibenzo- p-
dioxin environmental contaminant and molecular probe.  Fed. Proc., 
35: 2404-2411.

POLAND, A., SMITH, D., METTER, G., & POSSICK, P.  (1971)  A health 
survey of workers in a 2,4-D and 2,4,5-T plant.   Arch. environ. 
 Health, 22: 316-327.

PRAVDA, O.  (1973)  [On the influence of herbicides on some fresh-
water animals.]   Hydrobiologia, 42(1): 97-142 (in German).

PREISS, D. & ROSSNER, J.A.  (1971)  [Effect of 2,4-
dichlorophenoxyacetic on the transverse tubular system of the 
mycardium.]   Naturwissenschaften, 11: 576-577 (in German).

PRESCOTT, I.F., PARK, J., & DARRIEN, I.  (1979)  Treatment of 
severe 2,4-D and mecoprop intoxication with alkaline diuresis.  
 Br. J. clin. Pharmacol., 7: 111-116.

PRITCHARD, J.B. & JAMES, M.O.  (1979)  Determinants of the renal 
handling of 2,4-dichlorophenoxyacetic acid by winter flounder.  
 J. Pharmacol. exp. Therap., 208(2): 280-286.

PRITCHARD, J.B. & MILLER, D.S.  (1980)  Teleost kidney in 
evaluation of xenobiotic toxicity and elimination.   Fed. Proc., 
39(14): 3207-3212.

& NEAL, S.B.  (1981)  Chemically-induced unscheduled DNA synthesis 
in primary rat hepatocyte cultures: A comparison with bacterial 
mutagenicity using 218 compounds.  Environ. Mutagen., 3: 11-32.

A review of the use of 2,4-D for Eurasian water milfoil control in 
the Okanagan Lakes, 1976-1980.   Inf. Bull., aquatic Plant Manage. 
 Program, 10: 1-10.

QUE HEE, S.S. & SUTHERLAND, R.G.  (1974)  Purity of reagent grade 
 p- and  o-chlorophenoxyacetic acids and its biological implications.  
 J. agric. food Chem., 22: 726-727.

QUE HEE, S.S. & SUTHERLAND, R.G.  (1975)  A specific gas-liquid 
chromatographic method for analysis of some amine salts of 2,4-
dichlorophenoxyacetic acid.   J. agric. food hem., 23: 1007-1008.

QUE HEE, S.S. & SUTHERLAND, R.G.  (1981)   The phenoxyalkanoic 
 herbicides, Vol. I.  Chemistry, analysis and environmental 
 pollution, Boca Raton, CRC Press, Inc., 321 pp.

The toxic properties of the herbicide 2,4-D.   Hyg. Sanit., 
32(4-6): 116-118.

RAMEL, C.  (1978)  Chlorinated phenoxy acids and their dioxins. 
Mode of action, health risks, and environmental effects.  Ecol. 
 Bull. (Stockholm), 27: 302.

RAOUL, Y. & MARNAY, O.  (1948)  [Effect of 3-indolacetic acid 
2,4-dichlorophenoxyacetic acid on the growing rat.]   C. R. Acad. 
 Sci. (Paris), 226: 1043-1045.

RAPPE, C. & BUSER, H.R.  (1981)  Occupational exposure to 
polychlorinated dioxins and dibenzofurans.  In: Choudhary, G., 
 Chemical hazards in the workplace:  Measurement and control,  
Washington, DC, American Chemical Society, pp. 319-342  (ACS 
Symposium Series No. 149).

RASMUSON, B. & SVAHLIN, H.  (1978)  Mutagenicity tests of 
2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic 
acid in genetically stable and unstable strains of  Drosophila 
 melanogaster.  Ecol. Bull. (Stockholm), 27: 190-192.

RAWLS, C.K.  (1965)  Field tests of herbicide toxicity to 
certain estuarine animals.   Chesapeake Sci., 6(3): 150-161.

REA, W.J.  (1978)  Environmentally triggered cardiac disease.  
 Ann. Allergy, 40(4): 243-251.

REDDY, J.K., AZARNOFF, D.L., & HIGNITE, E.E.  (1980)  
Hypolipidaemic hepatic peroxisome proliferators form a novel 
class of chemical carcinogens.  Nature (Lond.), 283: 397-398.

C.M.  (1982a)  Induction by ciprofibrate of hepatic peroxisome 
proliferation in rats, pigeons, chickens, cats and rhesus monkeys. 
 Fed. Proc., 41: 1741.

REDDY, J.K., LALWANI, N.D., REDDY, M.K., & QURESHI, S.A.  (1982b)  
Excessive accumulation of autofluorescent lipofuscin in the liver 
during hepatocarcinogenesis by methyl clofenapate and other 
hypolipidaemic peroxisome proliferators.  Cancer Res., 42: 259-266.

REHWOLDT, R.E., KELLEY, E., & MAHONEY, M.  (1977)  Investigations 
into the acute toxicity and some chronic effects of selected 
herbicides and pesticides on several fresh water fish species.  
 Bull. environ. Contam. Toxicol., 18(3): 361-365.

RENBERG, L.  (1974)  Ion exchange technique for the determination 
of chlorinated phenols and phenoxy acids in organic tissue, soil 
and water.   Anal. Chem., 46: 459-461.

RIIHIMAKI, V., ASP, S., & HERNBERG, S.  (1982)  Mortality of 
chlorinated phenoxyacid herbicide 2,4-D and 2,4,5-T applicators in 
Finland.  First report of an ongoing prospective follow-up study.  
 Scand. J. Work Environ. Health, 8: 37-42.

RIVERS, J.B., YAUGER, W.L., Jr., & KLEMMER, H.W.  (1970)  
Simultaneous gas chromatographic determination of 2,4-D and 
dicamba in human blood and urine.   J. Chromatogr., 50: 334-337.

ROBINSON, E. & FOX, L.L.  (1978)  2,4-D herbicides in central 
Washington.   J. Air Poll. Control Assoc., 28: 1015-1020.

ROBSON, T.O.  (1966)  Some studies of the persistence of 2,4-D in 
natural surface waters in Britain.   Proc. Br. Weed Control Conf., 
2: 594-597.

ROSENBERG, J.  (1980)   2,4-Dichlorophenoxyacetic acid (2,4-D) 
 - Evaluation of human health hazards, Berkeley, California, 
Hazard Alert System, Epidemiological Studies Laboratory, 64 pp.

(1977)   N-nitroso compound impurities in herbicide formulations.  
 J. agric. food Chem.,  25: 1416-1418.

ROWE, V.K. & HYMAS, T.A.  (1954)  Summary of toxicological 
information on 2,4-D and 2,4,5-T type herbicides and an evaluation 
of the hazards to livestock associated with their use.   Am. J. vet. 
 Res., 15: 622-629.

RUDIGER, K.D., MEERBACH, W., OSSKE, G., & FISCHER, W.  (1972)  [On 
the experimental 2,4-dichlorophenoxyacetate myopathy.]   Zentralbl. 
 allg. Pathol.,  115: 145-152 (in German).

SADYKOV, R.E., RABOCHEV, V.K., & STROKOV, Y.N.  (1972)  [The 
effect of butyl 2,4-D treatment of pastures on the reproductive 
functions of sheep.]   Zhivodnovodstvo, 34(1): 73-74 (in Russian).

SANDERS, H.O.  (1970a)  Pesticide toxicities to tadpoles of the 
western chorus frog,  Pseudacris triseriata and Fowler's toad,  Burfo 
 woodhousii fowleri.  Copeia, 2: 246-251.

SANDERS, H.O.  (1970b)  Toxicities of some herbicides to six 
species of freshwater crustaceans.   J. Water Pollut. Control Fed., 
42(8): 1554-1550.

SARE, W.M.  (1972)  The weedicide 2,4-D as a cause of headaches and 
diplopia.   New Z. med. J., 75(478): 173-174.

SAUERHOFF, M.W., BRAUN, W.H., BLAU, G.E., & LEBEAU, J.E.  (1976)  
The fate of 2,4-dichlorophenoxyacetic acid (2,4-D) following oral 
administration to man.   Toxicol. appl. Pharmacol., 37(1): 136-137.

SAUERHOFF, M.W., BRAUN, W.H., BLAU, G.E., & GEHRING, P.J.  (1977)  
The fate of 2,4-dichlorophenoxyacetic acid (2,4-D) following oral 
administration to man.   Toxicology, 8: 3-11.

SAXEN, L., KLEMETTI, A., & HARO, A.S.  (1974)  A matched-pair 
register for studies of selected congenital defects.   Am. J. 
 Epidemiol., 100(3): 297-306.

SCHACTER, B., GYVES, M., MUIR, A., & TASIN, M.  (1979)  HLA-A, B 
compatibility in parents of offspring with neural-tube defects or 
couples experiencing involuntary fetal wastage.   Lancet, 1: 796-797.

SCHILLER, K.  (1964)  [Effects on the fertility of rats produced by 
substances with special effects in potato cultivation. 1st 
communication:  Growth hormones and weed control agents 2,4-D and 
MCPA.]  Landbauforsch. Völkenrode, 14(2): 111-114 (in German).

SCHILLINGER, J.E.  (1960)  [Hygienic evaluation of agricultural 
products cultivated with the use of herbicides.]   J. Hyg. 
 Epidemiol. Microbiol. Immunol., 4: 243-252 (in German).

SCHNEIDER, B.A.  (1979)  Toxicological evaluation of pesticides by 
the EPA Chemical and Biological Investigations Branch Laboratories 
(1966-77).  In:   Toxicology handbook, mammalian and aquatic data.  
 Book 1: Toxicology data.  Report for 1966-67, Beltsville, Md., US, 
Environmental Protection Agency.

SCHULTZ, D.P. & HARMAN, P.D.  (1974)  Residues of 2,4-D in pond 
waters, mud, and fish, 1971.   Pestic. monit. J., 8(3): 173-179.

SCHULTZ, D.P. & WHITNEY, E.W.  (1974)  Monitoring 2,4-D residues at 
Loxahatchee National Wildlife Refuge.   Pestic. monit. J., 7(3/4): 

SCHUPHAN, W.  (1963)  [Impaired health due to plant protection 
agents.]   Der Landarzt, 39: 1217-1222 (in German).

SCHUPHAN, W.  (1965)  [Plant protection problems reflected in 
quality testing.]   Anz. Schädlingsk. D. Pflanzenschutz. 
 Umweltschutz, 38(7): 97-104 (in German).

SCHUPHAN, W.  (1969)  [Pesticides: Usefulness and possible harm.]  
 Zentralbl. Bakteriol., 210: 240-258 (in German).

SCHWETZ, B.A., SPARSCHU, G.L., & GEHRING, P.J.  (1971)  The effect 
of 2,4-D and esters of 2,4-D on rat embryonal, foetal and neonatal 
growth and development.   Food cosmet. Toxicol., 9: 801-817.

P.J., EMERSON, J.L., & GERBIG, C.G.  (1973)  Toxicology of 
chlorinated dibenzo- p-dioxins.  Environ. Health Perspect., Exp. 
Issue 5: 87-99.

SEABURY, J.H.  (1963)  Toxicity of 2,4-dichlorophenoxyacetic acid 
for man and dog.   Arch. environ. Health, 7: 202-209.

SEILER, D.  (1971)  The ATPase of the sarcolemma of skeletal 
muscle in experimental myotonia.   Experientia (Basel), 27: 

SEILER, J.P.  (1978)  The genetic toxicology of phenoxy acids 
other than 2,4,5-T.   Mutat. Res., 55: 197-226.

SENCZUK, W. & POGORZELSKA, H.  (1975)  [Urinary excretion of 
2,4-dichlorophenoxyacetic acid.]   Rocz. Panstw. Zakl. Hig., 
26(2): 217-222 (in Polish, Health & Welfare Canada Translation 
No. 2451).

SENCZUK, W. & POGORZELSKA, H.  (1981)  [Chemical structure and 
toxodynamic properties of phenoxycarboxylic acid derivatives, II.  
Methods of determining derivatives of phenoxyacetic and 
phenoxypropionic  acids in blood and urine.]   Rocz. Panstw. Zakl. 
 Hig., 32: 339-344 (in Polish).

SENCZUK, W. & POGORZELSKA, H.  (1981)  [Chemical structure and 
toxicodynamic properties of derivatives of phenoxyacetic and 
phenoxypropionic acid, III.  The pattern of absorption into the 
bloodstream and measurements of urinary excretion of phenoxyacetic 
and phenoxypropionic acid.]  Roczn. Panstw. Zak. Hig., 32(5-6): 
419-426 (in Polish).

SENCZUK, W., POGORZELSKA, H., & DEBSKA, M.  (1980)  [Absorption of 
2,4-dichlorophenoxyacetic acid through the skin.]  Roczn. Panstw. 
 Zak. Hig., 31(6): 611-614 (in Polish).

SENGES, J. & RDEL, R.  (1972)  Experimental myotonia in mammalian 
skeletal muscle:  changes in contractile properties.   Pflueger. 
 Arch., 331: 315-323.

SHAFIK, M.T., SULLIVAN, H.C., & ENOS, H.F.  (1971)  A method for 
determination of low levels of exposure to 2,4-D and 2,4,5-T.  
 Int. J. environ. anal. Chem., 1: 23-33.

SHEARER, R.W.  (1980)  Public health effects of the aquatic use of 
herbicides:  2,4-D dichlobenil, endothall and diquat.  In: Shearer, 
R.W. & Halter, M., ed.  Literature reviews of four selected 
 herbicides: 2,4-D dichlorbenil, diquat & endothall, Municipality of 
Washington, US, Metropolitan Seattle, pp. 1-76.

SHEARER, R. & HALTER, M.  (1980)   Literature reviews of four 
 selected herbicides: 2,4-D, dichlobenil, diquat, and endothall.  
Municipality of Washington, US, Metropolitan Seattle.

SHILLINGER, U.Y.I. & NAUMOVA, L.P.  (1957)  [Hygienic evaluation of 
a harvest in connection with the treatment of crops with the 
herbicide 2,4-D.]   Gig. i Sanit., 7: 33-38 (in Russian).

SHIM, J.C. & SELF, L.S.  (1973).  Toxicity of agricultural 
chemicals to larvivorous fish in Korean rice fields.   Trop. Med., 
15(3): 123-130.

(1981).  Triclopyr, glyphosate and phenoxyherbicide residues in 
cowberries, bilberries and lichen.   Bull. Environ. Contam Toxicol., 
27: 731-737.

SIMPSON, G.R.  (1982a)  Pesticide exposure - New South Wales 
Services. In:  Education and safe handling in pesticide application, 
 studies in environmental science, 18: 209-214.  Amsterdam, 
Oxford, New York, Elsevier Scientific Publishing Co.

SITTIG, M. ed.,  (1980)   Pesticide manufacturing and toxic 
 materials control encyclopedia.  Park Ridge, NJ, USA, Noyes Data 
Corp., pp. 229-234.

SKELLY, N.E., STEVENS, T.S., & MAPES, D.A.  (1977)  Isomer-specific 
assay of ester and salt formulations of 2,4-dichlorophenoxyacetic 
acid by automated high pressure liquid chromatography.   J. Assoc. 
 Off. Anal. Chem., 60: 868-872.

SMALS, A.G.H., BEEX, L.A.V.M., & KLOPPENBORG, P.W.C.  (1977) 
Clofibrate-induced muscle damage with myoglobinuria and 
cardiomyopathy.   N. Engl. J. Med., 296: 942.

SMITH, A.E.  (1972)  The hydrolysis of 2,4-dichlorophenoxy-acetate 
esters to 2,4-dichlorophenoxyacetic acid in Saskatchewan soils.  
 Weed Res., 12: 364-372.

SMITH, A.E.  (1976a)  The hydrolysis of herbicidal phenoxy-alkanoic 
esters to phenoxyalkanoic acids in Saskatchewan soils.   Weed Res., 
16: 19-22.

SMITH, A.E.  (1976b)  Method for the determination of 
2,4-dichlorophenoxyacetic acid in urine.   J. Chromatogr, 171: 

SMITH, A.H., FISHER, D.O., PEARCE, N., & CHAPMAN, C.J.  (1982)  
Congenital defects and miscarriages among New Zealand 2,4,5-T 
sprayers.   Arch. environ. Health, 37(4): 197-200.

SMITH, G.E. & ISOM, B.G.  (1967)  Investigation of effects of 
large-scale applications of 2,4-D on aquatic fauna and water 
quality.   Pestic. monitoring J., 1(3): 16-21.

Effect of external application of pesticides to the fertile egg on 
hatching success and early chick performance. 1. Pre-incubation 
spraying with DDT and commercial mixtures of 2,4-D: picloram, and 
2,4-D: 2,4,5-T.   Bull. environ. Contam. Toxicol., 11(1) 33-38.

SOMERS, J., MORAN, E.T., & REINHART, B.S.  (1974b)  Effect of 
external application of pesticides to the fertile egg on 
hatching success and early chick performance.  2.  Commercial 
herbicide mixtures of 2,4-D with pioloram or 2,4,5-T using the 
pheasant.   Bull. environ. Contam. Toxicol., 11(4): 339-342.

SOMERS, J.D., MORAN, E.T., & REINHART, B.S.  (1974c)  Effect of 
external application of pesticides to the fertile egg on hatching 
success and early chick performance. 3. Consequences of combining 
2,4-D with picloram and extremes in contamination.  Bull. environ. 
 Contam. Toxicol., 11(4): 511-516.

SOS, J. & KERTAI, P.  (1958)  Effect of dichlorophenoxyacetic acid 
upon the I131-uptake of the thyroid.  Acta physiol. Acad. Sci. 
 Hung., 14: 367-369.

SPITTLER, H.  (1976) [Experiments on the influence of herbicides on 
the embryonic development of  Phasianus colchicus (L.) and  Coturni 
 coturnix japonica (L.).]  Z. Jagdwiss., 22: 197-201 (in German).

STANLEY, C. W., BARNEY, J. E., HELTON, M. R., & YOBS, A.  (1971)  
Measurement of atmospheric levels of pesticides.   Environ. Sci. 
 Technol., 5(5): 430-435.

STANOSZ, S.  (1969)  [The effects of sodium salt of 2,4-
dichlorophenoxy-acetic acid on cell respiration in the parenchymal 
organs of rats.]   Med. Prac., 20(6): 600-605 (in Polish).

STEIN, W. & KUHN, E.  (1968)  [Model myotonia after 2,4-
dichlorophenoxyacetate (2,4-D).  Isolated rat diaphragm preparation 
as simple experimental object.]   Klin. Wochenschr., 46: 328-330 
(in German).

STEVENS, L. J., COLLIER, C. W., & WOODHAM, D. W.  (1970)  
Monitoring pesticides in soils from areas of regular, limited, and 
no pesticide use.   Pestic. Monit. J., 4(3): 145-164.

STEVENS, T.S.A., SKELLY, N.E., & GRORUD, R.B.  (1978)  Isomer-
specific assay of ester and salt formulations of 2,4-
dichlorophenoxyacetic acid by high pressure liquid chromatography:  
Collaborative study.   J. Assoc. Off. Anal. Chem., 61: 1163-1165.

STEWART, D.K.R. & GAUL, S.O.  (1977)  Persistence of 2,4-D, 
2,4,5-T, and dicamba in a dykeland soil.   Bull. environ. Contam. 
 Toxicol., 18(2): 210-218.

STRACH, S. & BOHOSIEWICZ, M.  (1964) [Studies of the toxicity for 
pigs of the weed-killer "Pielik."]   Med. weter, 20(11): 662-666 
(in Polish, Health & Welfare Canada Translation No. 2467).

STUPNIKOV, A.A.  (1959)  In:  [Collected works of the Leningrad 
 Veterinary Sciences Research Institute.]  No. 8: 289 (in Russian).

SUDAK, F.N. & CLAFF, C.L.  (1960)  Survival of  Uca pugnax in sand, 
water, and vegetation contaminated with 2,4-dichloro-phenoxyacetic 
acid.   Proc. Northeast. Weed Control Conf., 14: 508-510.

SUDAK, F.N., CLAFF, C.L., & CANTOR, M.  (1966)  Body temperature 
regulation in rats treated with 2,4-dichloro-phenoxyacetic acid.  
 Arch. int. Pharmacodyn. Ther., 160(2): 253-264. 

SUFFET, I.H.  (1973a)  The p-value approach to quantitative liquid-
liquid extraction of pesticides and herbicides from water. 2.  
Selection of water: solvent ratios and number of extractions.  
 J. agric. food Chem., 21: 288-294. 

SUFFET, I.H.  (1973b)  The p-value approach to quantitative liquid-
liquid extraction of pesticides and herbicides from water. 3.  
Liquid-liquid extraction of phenoxy acid herbicides from water.  
 J. agric. food Chem., 21: 591-598.

SUNDSTROM, G., JENSEN, S., JANSSON, B., & ERNE, K.  (1979)  
Chlorinated phenoxyacetic acid derivatives and tetrachlorodibenzo- p-
dioxin in foliage after application of 2,4,5-trichlorophenoxyacetic 
acid esters.   Arch. environ. Contam. Toxicol., 8: 441-448.

SZOCS, J., MOLNAR, V., BALOGH, E., AJTAY, M., & FULOP, I. (1970)  
[Experimental data on the toxic effects of 2,4-D (Diclordon) 
herbicide.]   Rev. Med. (Tirgu-Mures, Rom.), 16: 91-93 (in 

(1981a) [Results of analysis for deriving exposure time limits in 
the industrial hygiene monitoring of people working at agrochemical 
centres who are exposed to pesticides.]   Z. gesamte Hyg. Grenzgeb., 
27(3): 173-177 (in German).

(1981b)  [Determination of toxic concentrations at places of work 
and patterns of distribution of pesticide exposure of people 
working at agrochemical centres subdivided by substance groups.]  
 Z. gesamte Hyg. Grenzgeb., 27(3): 177-180 (in German).

THIESS, A.M., FRENTZEL-BEYME, R., & LINK, R.  (1982)  Mortality 
study of persons exposed to dioxin in a trichlorophenol-process 
accident that occurred in the BASF AG on November 17, 1953. 
 Am. J.ind. Med., 3: 179-189.

THOMAS, F.W., LOUGHMAN, B.C., & POWELL, R.G.  (1964a)  Metabolic 
fate of some chlorinated phenoxyacetic acids in the stem tissue of 
 Avena sativa.  Nature (Lond.), 204: 286.

THOMAS, F.W., LOUGHMAN, B.C., & POWELL, R.G.  (1964b)  Metabolic 
fate of 2,4-dichlorophenoxyacetic acid in the stem tissue of 
 Phaseolus vulgaris.  Nature (Lond.), 204: 884-885.

THOMSSEN, C.  (1958)  [Contribution to the question of possible 
poisoning of domestic animals through growth hormone-based weed 
control agents.]   Arch. exp. Veterinaermed., 12: 216-221 (in 

TODD, R.L.  (1962)  A case of 2,4-D intoxication.   J. Iowa Med. 
 Soc., 52: 663-664.

TSAPKO, V.P.  (1966)  The herbicide 2,4-D as a health hazard in 
agriculture.   Hyg. Sanit., 9: 449-450.

TSILIKOV, V.V.  (1969)  [Effect of the sodium salt of 2,4-D, 
trichlorometaphos, nicotine, and arecoline on thyroid function.]  
In: Denisenko, P.P., ed.  Farmakol. Tsent. Kholinolitikov Drugikh 
 Neirootropnykh Sredstv., pp. 181-185 (in Russian, Health & Welfare 
Canada Translation No. 2447).

TUINSTRA, L.G.M., ROOS, A.H., & BRONSGEEST, J.M.  (1976)  
Suggestions for a sensitive multi-detection high-performance 
liquid chromatography method for several phenoxy-acid herbicides.  
 Meded. Fac. Landbouwwet. Rijksuniv. Gent, 41: 1443-1448.

TULP, M.T.M. & HUTZINGER, O.  (1978)  Rat metabolism of 
polychlorinated dibenzo- p-dioxins.  Chemosphere, 7(9): 761-768.

(1980)   Teratology and postnatal studies in rats on propylene 
 glycol butyl ether and isooctyl esters of 2,4-dichloro- 
 phenoxyacetic acid, Washington, US Environmental Protection 
Agency (60/12-80).

US EPA  (1976)   National interim primary drinking water 
 regulations, Washington, DC, US Environmental Protection Agency.

US EPA  (1980a)  Environmental Protection Agency Review and 
Conclusions Concerning Potential Health Effects of the Herbicide 
2,4-D, April 1980,   Chem. Regul. Rep., 4(5): 134-136.

US EPA  (1982)  Tetrachlorodibenzo- p-dioxin; re-evaluation of 
disposal prohibition.  Fed. Reg., 47(2): 103.

US NATIONAL CANCER INSTITUTE  (1979)   Bioassay of 2,7-
 dichlorodibenzo-p-dioxin (DCDD) for possible carcinogenicity.  
Springfield, Virginia, National Technical Information Service 
Document PB 290570 (Report No. NCI-CG-TR 123).

(1981)   Review of literature on herbicide, including phenoxy 
 herbicides and associated dioxins. Volume I. Analysis of 
 literature.  Volume II.  Annotated bibliography, Washington, DC, 
US Veterans' Administration, 397 pp.

VACHKOVA-PETROVA, R.  (1978)  [Mutagenic activity of pesticides.]  
 Hig. Zdraveopaz., 21(5): 496-506 (in Bulgarian).

VAINIO, H., NICKELS, J., & LINNAINMAA, K.  (1982)  Phenoxy acid 
herbicides cause peroxisome proliferation in Chinese hamsters. 
 Scand. J. Work. Environ. Health, 8: 70-73.

MARNIEMI, J., & PELTONEN, P.  (1983)  Hypolipidemia and peroxisome 
proliferation induced by phenoxyacetic acid herbicides in rats. 
 Biochem. Pharmacol., (in press).

VAN DYK, L.P. & VISWESWARIAH, K.  (1975)  Pesticides in air: 
sampling methods.  Res. Rev., 55: 91-134.

VAN PETECHEM, C.R. & HEYNDRICKX, A.M.  (1975)  Beta oxidation of 
chlorophenoxybutyric acid herbicides in guinea pigs.   Bull. 
 environ. Contam. Toxicol., 14(5): 632-640.

VARDIA, H.K. & DURVE, V.S.  (1981)  Bioassay study on some fresh 
water fishes exposed to 2,4-dichlorophenoxyacetic acid.   Acta 
 hydrochim. hydrobiol., 9(2): 219-223.

VENKAIAH, B. & PATWARDHAN, M.V.  (1978)  Inhibition of 
mitochondrial energy transfer reactions by phenoxy acids.   Indian 
 J. Biochem. Biophys., 15(3): 219-221.

VINOKUROVA, M.K.  (1960)  [On the toxicity of a herbicide: The 
octyl ester of 2,4-dichlorophenoxyacetic acid.]   Gig. i Sanit., 
12: 31-34 (in Russian, Health & Welfare Canada Translation No. 

VOGEL, E. & CHANDLER, J.L.R.  (1974)  Mutagenicity testing of 
cyclamate and some pesticides in  Drosophila melanogaster.  
 Experientia (Basel), 30(6): 621-623.

WALLIS, W.E., VAN POZNAK, A., & PLUM, F.  (1970)  Generalized 
muscular stiffness, fasciculations, and myokymia of peripheral 
nerve origin.   Arch. Neurol., 22: 430-439.

(1981)  Pesticides:  Mutagenic and carcinogenic potential.  
In: Bandal, S.K., Marco, G.J., Golberg, L., & Leng, M.L., 
ed.,   The pesticide chemist and modern toxicology. Washington, 
DC, American Chemical Society (ACS Symposium Series 160).

WAY, J.M.  (1969)  Toxicity of hazards to man, domestic 
animals and wildlife from some commonly used auxin herbicides.  
 Res. Rev., 26: 37-62.

WEINMANN, W.  (1957)  [Investigations of the influence of a 
treatment of tomato plants with growth substances on the 
nutritional and physiological value of the fruits.  Offspring 
mortality in albino rats.]   Qual. Plant. Mater. Veg., 2(4): 
342-349 (in German).

WHITEHEAD, C.C. & PETTIGREW, R.J.  (1972)  The subacute 
toxicity of 2,4-dichlorophenoxyacetic acid and 2,4,5- 
trichlorophenoxyacetic acid to chicks.   Toxicol. appl. 
 Pharmacol., 21:348.

(1973)  The effects of a 2,4-D application on the biota and water 
quality in Currituck Sound, North Carolina.   Hyacinth Control J., 
11: 13-17.

WHO  (1976)   Pesticide residues in food. Report of the 1975 
 Joint FAO/WHO meeting (WHO Tech. Report Series, 592).

WHO/FAO  (1972)   1971 Evaluations of some pesticide residues in 
 food.  Geneva, World Health Organisation (WHO Pesticide Residue 
Series No. 1).

WHO/FAO  (1976)   1975 Evaluations of some pesticide residues in 
 food.  Geneva, World Health Organisation (WHO Pesticide Residues 
Series No. 5).

WHO/IARC  (1980)  Walker, E.A., Castegnaro, M., Griciute, L., 
Börzsönyi, M., & Davis, W., ed.:  N-Nitroso compounds: Analysis, 
 formation and occurrence. Lyons, International Agency for 
Research on Cancer, 841 pp (IARC Scientific Publications No. 31).

WHO/IARC  (1982)  Bartsch, H., Castegnaro, M., O'Neill, I.K., 
Okada, M., & Davis, W., ed.:  N-Nitroso compounds: Occurrence 
 and biological effects. Lyons, International Agency for Research 
on Cancer, 755 pp (IARC Scientific Publications No. 41).

WIERSMA, G.B., TAI, H., & SAND, P.F.  (1972)  Pesticide residue 
levels in soils, F.Y. 1969 - National soils monitoring program.  
 Pestic. monit. J., 6(3): 194-228.

WIERZBICKA, M.  (1974a)  Haemolymph concentration in Cyclopoida 
copepodids during active and resting stage and the effect of 
2,4-D sodium salt.   Pol. Arch. Hydrobiol., 21(2): 269-273.

WIERZBICKA, M.  (1974b)  Influence of 2,4-D sodium salt on the 
survival of some  Copepodia species.   Pol. Arch. Hydrobiol., 
21(2): 275-282.

WINKELMANN, R.K.  (1960)  Diagnosis and treatment of allergic 
angiitis  (anaphylactoid purpura).  Postgrad. Med., 27: 437-444.

WOJTALIK, T.A., HALL, T.F., & HILL, L.O.  (1971).  Monitoring 
ecological conditions associated with wide-scale applications 
of DMA-2,4-D to aquatic environmental.   Pestic. monit. J., 
4(4): 184-203.

(1971)  An improved gas chromatographic method for the analysis of 
2,4-D free acid in soil.   J. agric. food Chem., 19: 186-188.

YIP, G.  (1975)  Analysis for herbicides and metabolites.   J. 
 Chromatogr. Sci., 13: 225-230.

YODER, J., WATSON, M., & BENSON, W.  (1973)  Lymphocyte chromosome 
analysis of agriculture workers during extensive occupational 
exposure to pesticides.   Mutat. Res., 21: 335-340.

YOUNG, A.L., ARNOLD, E.L., & WACHINSKI, A.M.  (1974)  Field 
studies in soil persistence and movement of 2,4-D, 2,4,5-T and 
TCDD.   Weed Sci. Soc. Am., (Abstract No. 226).

(1978)   The toxicology, environmental fate, and human risk of 
 Herbicide Orange and its associated dioxin. Springfield, Va., 
USA,  US Air Force Occupational & Environmental Health 
Laboratory (Technical Report No. TR-78-92, US National 
Technical Information Service.)

YOUNG, F. & HALEY, T.J.  (1977)  Pharmacokinetic study of a 
patient introduced with 2,4-dichlorophenoxyacetic acid and 
2-methoxy-3,6-di-chlorobenzoic acid.   Clin. Toxicol., 11(5) 

(1968)  [The clinical picture and prophylaxis of "Dikotex" 
poisoning.]   Zdrav. Beloruss., 9: 7-21 (in Russian, Health & 
Welfare Canada Translation No. 2367).

ZETTERBERG, G.  (1977)  Experimental results of phenoxy acids 
on microorganisms. In: Ramel, C., ed.  Chlorinated phenoxy acids 
 and their dioxins: Mode of action, health risks and environmental 
 effects. Ecol. Bull.  (Stockholm), 27.

RYTTMAN, H.  (1977)  The influence of pH on the effects of 2,4-D on 
 Saccharomyces cerevisiae and  Salmonella typhimurium.  Mutat. Res., 
42(1): 3-18.

ZHITENEVA, L.D. & CHESNOKOVA, T.V.  (1973)  [Alteration of the 
morphological composition of the blood in white amur larvae under 
the effect of herbicides.]   Eksp. vod. toksikol., 4: 56-67 
(in Russian).

ZIELENSKI, W.L., Jr & FISHBEIN, L.  (1967)  Gas chromatographic 
measurement of disappearance rates of 2,4-D and 2,4,5-T acids and 
2,4-D esters in mice.   J. agric food Chem., 15(5): 841-844.

ZIEM, G. & MAY, G.  (1983)  Tetrachlorodibenzodioxin.  Br. J. ind. 
 Med., 40: 116.

    See Also:
       Toxicological Abbreviations