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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY


    ENVIRONMENTAL HEALTH CRITERIA 39





    PARAQUAT AND DIQUAT







    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


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CONTENTS

ENVIRONMENTAL HEALTH CRITERIA FOR PARAQUAT AND DIQUAT

 PARAQUAT

1. SUMMARY AND RECOMMENDATIONS

    1.1. Summary
         1.1.1. General properties
         1.1.2. Environmental distribution and
                transformation - environmental effects
         1.1.3. Kinetics and metabolism
         1.1.4. Effects on experimental animals
         1.1.5. Effects on man
    1.2. Recommendations
         1.2.1. General
         1.2.2. Prevention and treatment
         1.2.3. Experimental work

2. IDENTITY, PROPERTIES AND ANALYTICAL METHODS

    2.1. Identity
    2.2. Physical and chemical properties
    2.3. Analytical methods

3. SOURCES IN THE ENVIRONMENT

    3.1. Introduction
         3.1.1. Industrial technology
         3.1.2. Impurities
    3.2. Production and use
    3.3. Mechanism of the herbicidal effect

4. ENVIRONMENTAL DISTRIBUTION AND TRANSPORTATION

    4.1. Photochemical degradation
         4.1.1. Photochemical degradation on plant
                surfaces
         4.1.2. Photochemical degradation of paraquat on
                soil and other mineral surfaces
    4.2. Microbial degradation
    4.3. Environmental adsorption and transformation
         4.3.1. Soil
         4.3.2. Water
         4.3.3. Air
         4.3.4. Plants
         4.3.5. Animals

5. BIOLOGICAL ACTIVITY OF RESIDUES

    5.1. Soil organisms
    5.2. Effect of residues on crop yields
    5.3. Effects on fish and aquatic organisms
    5.4. Effects on birds

6. KINETICS AND METABOLISM

    6.1. Animal studies
         6.1.1. Absorption
                6.1.1.1  Oral absorption
                6.1.1.2  Pulmonary absorption
                6.1.1.3  Dermal absorption
         6.1.2. Distribution
         6.1.3. Metabolic transformation and excretion
    6.2. Observations on human beings
         6.2.1. Observations on paraquat poisoning after
                ingestion: non-fatal cases
         6.2.2. Observations on paraquat poisoning after
                ingestion: fatal cases
         6.2.3. Significance of paraquat concentrations in
                cases of paraquat poisoning
    6.3. Biochemical mechanisms

7. EFFECTS ON ANIMALS

    7.1. Effects on experimental animals
         7.1.1. Respiratory system
                7.1.1.1  Pathomorphological lung studies
                7.1.1.2  Species differences in lung injury
                7.1.1.3  Functional lung studies
         7.1.2. Renal system
         7.1.3. Gastrointestinal tract and liver
         7.1.4. Skin and eyes
         7.1.5. Other systems
         7.1.6. Effects on reproduction, embryotoxicity, and teratogenicity
                7.1.6.1  Effects on reproduction
                7.1.6.2  Embryotoxicity and teratogenicity
         7.1.7. Mutagenicity
         7.1.8. Carcinogenicity
    7.2. Effects on farm animals
    7.3. Dose-effect of paraquat
    7.4. Methods for decreasing paraquat toxicity
    7.5. Relation between age, sex, and toxicity

8. EFFECTS ON MAN

    8.1. Accidental and suicidal poisoning
         8.1.1. Case reports
         8.1.2. Distribution of cases of paraquat poisoning
         8.1.3. Route of entry
         8.1.4. Formulations
         8.1.5. Dose

         8.1.6. Clinical and pathomorphological data
                relating to fatal paraquat poisoning
                8.1.6.1  Respiratory system
                8.1.6.2  Renal system
                8.1.6.3  Gastrointestinal system, the
                         liver, and the pancreas
                8.1.6.4  Cardiovascular system
                8.1.6.5  Central nervous system
                8.1.6.6  Adrenal glands
                8.1.6.7  Pregnancy
         8.1.7. Recovery from paraquat poisoning
    8.2. Occupational exposure
         8.2.1. Epidemiological studies and case reports
                8.2.1.1  Spraying personnel
                8.2.1.2  Formulation workers
         8.2.2. Cases of occupational poisoning and local caustic effects
                8.2.2.1  Oral ingestion
                8.2.2.2  Dermal absorption
                8.2.2.3  Local skin and nail effects
                8.2.2.4  Ocular damage
                8.2.2.5  Inhalation
    8.3. Use of marijuana contaminated by paraquat
    8.4. Guidelines for the treatment of paraquat poisoning

9. EVALUATION OF RISKS FOR HUMAN HEALTH AND EFFECTS ON THE ENVIRONMENT

    9.1. Exposure
    9.2. Poisoning by paraquat
         9.2.1. Suicidal ingestion
         9.2.2. Accidental poisoning
         9.2.3. Occupational poisoning
    9.3. Occupational exposure
    9.4. Effects
         9.4.1. Paraquat toxicity in animals
         9.4.2. Paraquat determination in biological fluids and tissues
    9.5. Earlier evaluations by international bodies
    9.6. Conclusions

REFERENCES

 DIQUAT

1. SUMMARY AND RECOMMENDATIONS

    1.1. Summary
         1.1.1. General properties
         1.1.2. Environmental distribution and
                transformation - environmental effects
         1.1.3. Kinetics and metabolism
         1.1.4. Effects on animals
         1.1.5. Effects on man
    1.2. Recommendations
         1.2.1. General
         1.2.2. Prevention and treatment
         1.2.3. Experimental work

2. PROPERTIES AND ANALYTICAL METHODS

    2.1. Physical and chemical properties
    2.2. Analytical procedures

3. SOURCES IN THE ENVIRONMENT

    3.1. Production and uses

4. ENVIRONMENTAL DISTRIBUTION, LEVELS, AND EXPOSURE

    4.1. Photochemical and microbial degradation of diquat
         4.1.1. Photochemical degradation
         4.1.2. Microbial degradation
    4.2. Diquat adsorption, residue levels, and
         exposure in soil
         4.2.1. Diquat adsorption on soil particles
         4.2.2. Residue levels of diquat in soils
         4.2.3. Effect of residual diquat on soil biological activity,
                and on plants and crop yields
    4.3. Diquat transformation, residue levels, and
         effects on aquatic organisms and crops
         4.3.1. Transformation and residue levels of diquat in water
         4.3.2. Effects of residual diquat on aquatic
                organisms and crops
    4.4. Diquat exposure and residue levels in plants and animals
         4.4.1. Plants
         4.4.2. Animals
    4.5. Diquat levels in air and exposure of workers

5. KINETICS AND METABOLISM

    5.1. Animal studies
         5.1.1. Absorption
         5.1.2. Distribution
         5.1.3. Metabolic transformation and excretion
    5.2. Observations on man

6. EFFECTS ON ANIMALS

    6.1. Effects on experimental animals
         6.1.1. Gastrointestinal system and liver
         6.1.2. Renal system
         6.1.3. Eyes and skin
         6.1.4. Respiratory system
         6.1.5. Nervous system
         6.1.6. Effects on reproduction, embryotoxicity, and teratogenicity
                6.1.6.1  Effects on reproduction
                6.1.6.2  Embryotoxicity and teratogenicity
         6.1.7. Mutagencity
         6.1.8. Carcinogenicity
    6.2. Effects on farm animals
    6.3. Dose-effect of diquat

7. EFFECTS ON MAN

    7.1. Case reports
    7.2. Effects on agricultural operators
    7.3. First aid and medical treatment

8. EVALUATION OF RISKS FOR HUMAN HEALTH AND EFFECTS ON THE ENVIRONMENT

    8.1. Exposure
         8.1.1. Relative contributions of soil, water, air, and food
                sources to total diquat uptake
         8.1.2. General population exposure
         8.1.3. Occupational exposure
    8.2. Effects
         8.2.1. Diquat toxicity in animals
    8.3. Earlier evaluations of diquat by international bodies
    8.4. Conclusions

REFERENCES

NOTE TO READERS OF THE CRITERIA DOCUMENTS

    While every effort has been made to present information in the 
criteria documents as accurately as possible without unduly 
delaying their publication, mistakes might have occurred and are 
likely to occur in the future.  In the interest of all users of the 
environmental health criteria documents, readers are kindly 
requested to communicate any errors found to the Manager of the 
International Programme on Chemical Safety, World Health 
Organization, Geneva, Switzerland, in order that they may be 
included in corrigenda, which will appear in subsequent volumes. 

    In addition, experts in any particular field dealt 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. 


                         *     *     *


    A detailed data profile and a legal file can be obtained from 
the International Register of Potentially Toxic Chemicals, Palais 
des Nations, 1211 Geneva 10, Switzerland (Telephone no. 988400 - 
985850). 


TASK GROUP MEETING ON ENVIRONMENTAL HEALTH CRITERIA FOR
PARAQUAT AND DIQUAT

 Members

Dr D.A. Akintonwa, Department of Biochemistry, College of
   Medical Sciences, University of Calabar, Calabar, Nigeria

Dr A. Bainova, Institute of Hygiene and Occupational Health,
   Medical Academy, Sofia, Bulgaria  (Rapporteur)

Dr J. Bus, Chemical Industry Institute of Toxicology, Research
   Triangle Park, North Carolina, USA

Dr R. Davies, Pialba, Queensland, Australia  (Chairman)

Dr G.R. FitzGerald, Ardkeen Hospital, Waterford, Ireland

Dr S.K. Kashyap, National Institute of Occupational Health
   (Indian Council of Medical Research), Meghaninagar,
   Ahmedabad, India

Dr L.L. Smith, ICI Central Toxicology Laboratory, Alderley
   Park, Macclesfield, Cheshire, England

 Representatives of Other Organizations

Dr M.A. Arellano-Parra, Latin-American Association of Poison
   Control Centres

Mme M.Th. van der Venne, Commission of the European
   Communities, Health and Safety Directorate, Luxembourg

 Observer

Mr G. Willis, International Group of National Associations of
   Agrochemical Manufacturers (GIFAP)

 Secretariat

Dr J. Cabral, International Agency for Research on Cancer,
   Lyons, France

Dr M. Gilbert, International Register for Potentially Toxic
   Chemicals, United Nations Environment Programme, Geneva,
   Switzerland

Dr K.W. Jager, Division of Environmental Health, International
   Programme on Chemical Safety, World Health Organization,
   Geneva, Switzerland  (Secretary)

Ms A. Sundén, Internation Register for Potentially Toxic
   Chemicals, United Nations Environment Programme, Geneva,
   Switzerland

 Secretariat (contd.)

Dr M. Vandekar, Division of Vector Biology and Control,
   Pesticides Development and Safe Use, World Health
   Organization, Geneva, Switzerland

Dr C. Xintaras, Division of Noncommunicable Diseases, Office
   of Occupational Health, World Health Organization, Geneva,
   Switzerland

ENVIRONMENTAL HEALTH CRITERIA FOR PARAQUAT AND DIQUAT

    Following the recommendations of the United Nations Conference 
on the Human Environment held in Stockholm in 1972, and in response 
to a number of World Health 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, 
3 July 1973), a programme on the integrated assessment of the 
health effects of environmental pollution was initiated in 1973.  
The programme, known as the WHO Environmental Health Criteria 
Programme, has been implemented with the support of the Environment 
Fund of the United Nations Environment Programme.  In 1980, the 
Environmental Health Criteria Programme was incorporated into the 
International Programme on Chemical Safety (IPCS).  The result of 
the Environmental Health Criteria Programme is a series of criteria 
documents. 

    A WHO Task Group on Environmental Health Criteria for Paraquat 
and Diquat was held in Geneva from 5 - 10 December 1983.  
Dr M. Mercier opened the meeting on behalf of the Director-General.  
The Task Group reviewed and revised the draft criteria document and 
made an evaluation of the health risks of exposure to paraquat and 
diquat. 

    The draft documents were prepared by Dr A. Bainova of Bulgaria. 

    The efforts of all who helped in the preparation and 
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 
Institute of Environmental Health Sciences, Research Triangle Park, 
North Carolina, USA - a WHO Collaborating Centre for Environmental 
Health Effects. 


PARAQUAT

1.  SUMMARY AND RECOMMENDATIONS

1.1.  Summary

1.1.1.  General properties

    Paraquat (1,1'dimethyl, 4,4'bipyridyl) is a non selective 
contact herbicide.  It is produced in several countries including 
China, Province of Taiwan, Italy, Japan, the United Kingdom, and 
the USA, and it is used world-wide in approximately 130 countries.  
If not manufactured under strictly controlled conditions, it can 
contain impurities that are more toxic than the parent compound.  
It is almost exclusively used as a dichloride salt and is usually 
formulated to contain surfactant wetters. 

    Both its herbicidal and toxicological properties are dependent 
on the ability of the parent cation to undergo a single electron 
addition to form a free radical which reacts with molecular oxygen 
to reform the cation and concomitantly produce a superoxide anion.  
This oxygen radical may directly or indirectly cause cell death. 

    Paraquat can be detected because of its ability to form a 
radical.  Numerous analytical procedures are available. 

1.1.2.  Environmental distribution and transformation -
environmental effects

    Paraquat deposits on plant surfaces undergo photochemical 
degradation to compounds that have a lower order of toxicity than 
the parent compound. 

    On reaching the soil, paraquat becomes rapidly and strongly 
adsorbed to the clay minerals present.  This process inactivates 
the herbicidal activity of the compound.  While free paraquat is 
degraded by a range of soil microorganisms, degradation of 
strongly-adsorbed paraquat is relatively slow.  In long-term field 
studies, degradation rates were 5 - 10% per year.  Strongly-bound 
paraquat has no adverse effects on soil microfauna or soil 
microbial processes. 

    Paraquat residues disappear rapidly from water by adsorption on 
aquatic weeds and by strong adsorption to the bottom mud.  The 
toxicity of paraquat for fish is low, and the compound is not 
cumulative.  Normal applications of paraquat for aquatic weed 
control are not harmful to aquatic organisms.  However, care should 
be taken when applying paraquat to water containing heavy weed 
growth to treat only a part of the growth, since oxygen consumed by 
subsequent weed decay may decrease dissolved oxygen levels to an 
extent that may be dangerous for fish.  Treated water should not be 
used for overhead irrigation for 10 days following treatment. 

    Paraquat is not volatile and following spraying the 
concentrations of airborne paraquat have been shown to be very low.  
Under normal working conditions, the exposure of workers in 
spraying and harvesting operations remains far below present TLVs 
and the exposure of passers-by or of persons living downwind of 
such operations is lower still. 

    Normal paraquat usage has been shown not to have any harmful 
effects on birds. 

    Finite paraquat residues are to be expected only when a crop is 
sprayed directly.  Cattle allowed to graze on pasture 4 h after 
spraying at normal application rates did not suffer any toxic 
effects.  Consequent residues in products of animal origin are very 
low. 

1.1.3.  Kinetics and metabolism

    Although toxic amounts of paraquat may be absorbed after oral 
ingestion, the greater part of the ingested paraquat is eliminated 
unchanged in the faeces.  Paraquat can also be absorbed through the 
skin, particularly if it is damaged.  The mechanisms of the toxic 
effects of paraquat are largely the result of a metabolically 
catalyzed single-electron reduction-oxidation reaction, resulting 
in depletion of cellular NADPH and the generation of potentially 
toxic forms of oxygen such as the superoxide radical. 

    Absorbed paraquat is distributed via the bloodstream to 
practically all organs and tissues of the body, but no prolonged 
storage takes place in any tissue.  The lung selectively 
accumulates paraquat from the plasma by an energy-dependent 
process.  Consequently, this organ contains higher concentrations 
than other tissues.  Since the removal of absorbed paraquat occurs 
mainly via the kidneys, an early onset of renal failure following 
uptake of toxic doses will have a marked effect on paraquat 
elimination and distribution and on its accumulation in the lung. 

1.1.4.  Effects on experimental animals

    A characteristic dose-related lung injury can be induced in the 
rat, mouse, dog and monkey, but not in the rabbit, guinea-pig and 
hamster.  The pulmonary toxicity is characterized by initial 
development of pulmonary oedema and damage to the alveolar 
epithelium, which may progress to fibrosis.  Exposure to high doses 
of paraquat may also cause less severe toxicity to other organs, 
primarily the liver and kidney.  Minor toxic effects have been 
noted only at high doses in the nervous, cardiovascular, blood, 
adrenal and male reproductive systems. 

    Paraquat has not been found to be teratogenic or carcinogenic 
in long-term studies on rats and mice.   In vitro mutagenicity 
studies have been inconclusive although generally suggestive of 
weak potential activity, while  in vivo studies were negative. 

1.1.5.  Effects on man

    Occupational exposure to paraquat does not pose a health risk 
if the recommendations for use are followed and there is adherence 
to safe working practices.  This has been shown in several studies 
evaluating the potential risk either short- or long-term.  However, 
nail damage, epistaxis, and delayed skin damage have been described 
and may generally be taken as an indication that work practices 
should be reviewed. 

    In the small number of reported cases of paraquat poisoning 
allegedly resulting from occupational exposure, the cause can be 
identified as one or a combination of a number of factors, viz 
contamination of the skin with concentrated products, use of 
inadequately diluted solutions, use of faulty equipment, misuse of 
equipment (e.g., blowing blocked spray jets) or failure to take 
action in the event of contamination of skin or clothing.  Eye and 
skin damage can follow splashes with the concentrate. 

    A large number of cases of suicidal or accidental poisoning 
from paraquat has been reported.  With the exception of a few 
unusual cases in which the liquid concentrate was improperly used 
to treat body lice, poisoning has followed its ingestion or, in a 
few cases, ingestion of the granular formulation. 

    Two types of fatal poisoning can be distinguished:  acute 
fulminant poisoning leading to death within a few days, and a more 
protracted form that may last for several weeks, resulting in fatal 
pulmonary fibrosis.  Depending on the severity of the poisoning, 
there may be involvement of kidneys, liver, and other organs.  
Extensive damage to the oropharynx and the oesophagus are usually 
seen in cases of ingestion of liquid concentrate. 

    After ingestion, speed is imperative in commencing emergency 
treatment and it should be noted that this can take place before 
arrival of the patient at hospital. 

    The response to treatment of paraquat poisoning is very 
disappointing and the mortality rate remains high.  In less severe 
cases, without lung damage, recovery has always been complete. 

    The possibility of recovery clearly depends on the dose of 
paraquat taken and the time interval between ingestion and the 
commencement of emergency treatment. 

1.2.  Recommendations

1.2.1.  General

    Where practical and reasonable, the availability and use of the 
20% liquid product should be limited to  bona fide agriculturalists, 
horticulturalists, and professional users who work with trained 
personnel, properly maintained equipment, and adequate supervision. 

    Every effort should be made to prevent the practice of 
decanting or rebottling of the product into improperly labelled 
containers. 

    Further research should be carried out in order to achieve a 
safer commercial product and a reduced incidence of fatalities. 

    National Registers of cases of poisoning should be maintained 
for all classes of chemicals - including paraquat.  The information 
so obtained should be made available to International bodies such 
as WHO. 

1.2.2.  Prevention and treatment

    Attention should be drawn to the fact that persons with skin 
lesions (either pre-existing or following contamination with 
paraquat) should not be permitted to take any part in spraying 
procedures until the skin condition has resolved. 

    It must be stressed that treatment of persons with paraquat 
poisoning should be instituted as early as possible.  The likelihood 
of recovery from a fatal dose is greatest when therapy begins 
within 5 - 6 h of poisoning. 

1.2.3.  Experimental work

    Further research should be undertaken on the mechanism of 
retention of paraquat in, amongst others, the lung and also on the 
concomitant damage caused at the molecular level. 

    Information was presented to the Task Group showing that 
saturation of the cation exchange capacity of soils is not observed 
under field conditions.  This indicates that residual phytotoxicity 
from directly available paraquat is unlikely.  It is recommended 
that such information be published. 

    Existing mutagenicity and carcinogenicity studies, although 
generally suggesting that paraquat is unlikely to produce genotoxic 
effects in man, require more detailed information. 

    The group has been informed that new long-term toxicity and 
carcinogenicity assays have been completed recently and recommends 
that the results be made available in the public literature. 

2.  IDENTITY, PROPERTIES AND ANALYTICAL METHODS

2.1.  Identity

    Paraquat is a non-selective contact bipyridylium herbicide.  
The term has been applied to 2 technical products:  1,1'-dimethyl-
4,4'-bipyridylium dichloride (C12H14N2Cl2) or 1,1'-dimethyl-4,4'-
bipyridylium dimethylsulfate (C12H14N2[CH3SO4]2). 

2.2.  Physical and Chemical Properties

    Pure paraquat salts are white and the technical products 
yellow.  They are crystalline, odourless, hygroscopic powders with 
a relative molecular mass of 257.2 for paraquat dichloride and 
408.5 for paraquat dimethylsulfate.  The relative molecular mass of 
the paraquat ion is 186.2 (Summers, 1980).  Some of the other 
physical properties of paraquat dichloride, the salt most used for 
herbicide formulations, are listed in Table 1. 

Table 1.  Physical properties of paraquata
-------------------------------------------------------------------
Specific gravity at 20 °C                 1.240 - 1.260

Melting point                             175 - 180 °C

Boiling point                             approximately 300 °C
                                          with decomposition

Solubility in water at 20 °C              700 g/litre

pH of liquid formulation                  6.5 - 7.5

Vapour pressure                           not measurable
-------------------------------------------------------------------
a From:  Worthing (1979).

    Paraquat is slightly soluble in alcohol and practically 
insoluble in organic solvents (Haley, 1979).  The chemical 
structure of paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) 
is: 

Chemical Structure

    Paraquat is non-explosive and non-flammable in aqueous 
formulations.  It is corrosive to metals and incompatible with 
alkylarylsulfonate wetting agents.  It is stable in acid or neutral 
solutions but is readily hydrolysed by alkali. 

    Paraquat readily undergoes a single-electron reduction to the 
cation radical.  The redox potential for this reaction is 446 mv.  
This chemical property led to its use as a redox indicator dye 
(methyl viologen) as early as 1933 (Summers, 1980). 

2.3.  Analytical Methods

    The analytical methods for paraquat determination have been 
reviewed by Haley (1979) and Summers (1980).  Current procedures in 
common use are listed in Table 2.  Spectrophotometric 
determinations involve the reaction of paraquat with 1% aqueous 
sodium dithionite in 0.1 N sodium hydroxide.  The absorbance of the 
resulting blue cation measured at 600 nm can be used as a measure 
of the paraquat concentration.  Diquat does not interfere because 
its radical cation is green in colour.  For residue level 
determinations (e.g., sub mg/kg levels) the higher intensity  
absorption at 396 nm for the paraquat radical and the 379 nm for 
the diquat radical are more commonly used.  Calderbank & Yuen 
(1965) developed a column chromatographic spectrophotometric method 
that was successfully applied for soil, biological tissues, and 
food.  The sensitivity was 0.01 mg/kg.  Gas chromatographic and 
high-pressure liquid chromatographic analyses were used 
satisfactorily.  High-pressure liquid chromatography with 
ultraviolet detection was proposed by Pryde & Darby (1975) for 
determining the paraquat content of urine with a sensitivity of 100 
µg/litre. 

    A comparison of thin-layer chromatography with the 
spectrophotometric methods for determining paraquat in human 
tissues showed that the former method gave less favourable results, 
because of the presence of large amounts of interfering substances 
from the tissues (Tsunenari et al., 1975; Haley, 1979).  
Spectrophotometric determination of paraquat, after alkaline 
reduction with sodium dithionite, has been published (Leary, 1978) 
for soil, and plant and biological tissues, the sensitivity limit 
being 0.01 mg/kg when a 50 g sample was used. 

    In a comparison of colorimetric, gas-liquid chromatographic   
techniques and radioimmunoassay (Levitt, 1979; Stewart et al.,    
1979), it was shown that the latter was a rapid method with       
satisfactory sensitivity for determining paraquat in serum, urine,
and organ tissues from poisoned patients.  The variation in       
detection limits in paraquat determinations in soil, water, and   
plant and animal material is related to the size of the sample    
obtained, its purity, and the extraction of the paraquat ion from 
the material tested.                                              

(a)  Soil                                                          
                                                                   
    Analytical methods include spectrophotometry (Calderbank & 
Yuen, 1965; Leary, 1978) and gas chromatography (Khan, 1974; Payne 
et al., 1974).                                                     


Table 2.  Analytical methods for paraquat
----------------------------------------------------------------------------------------
Matrix              Analytical procedure     Detection       Reference
                                             limitsa 
----------------------------------------------------------------------------------------
Soil                spectrophotometry        0.01 mg/kg      Calderbank & Yuen (1965)
                    spectrophotometry        -               Leary (1978)
                    spectrophotometry        0.5 mg/kg       Pope & Benner (1974)
                    gas chromatography       0.01 mg/kg      Khan (1974)
                    gas chromatography       0.01 mg/kg      Payne et al. (1974)

Water               spectrophotometry        0.01 mg/litre   Calderbank & Yuen (1965)
                    gas chromatography       0.01 mg/litre   Soderquist & Crosby (1972)
                    gas chromatography       0.01 mg/litre   Khan (1974)
                    gas chromatography       0.01 mg/litre   Payne et al. (1974)
                    gas chromatography       10 mg/litre     Ukai et al. (1977)
                    spectrophotometry        -               Pope & Benner (1974)

Air                 spectrophotometry        0.01 mg/m3      Calderbank & Yuen (1965)
                    gas chromatography       0.5 ng/m3       Seiber & Woodrow (1981)

Biological tissues  spectrophotometry        0.01 µg/ml      Calderbank & Yuen (1965)
                    spectrophotometry        0.01 µg/ml      Berry & Grove (1971)
                    spectrophotometry        0.01 µg/ml      Beyer (1970)
                    gas chromatography       0.03 µg/ml      van Dijk et al. (1977)
                    gas chromatography/mass  0.025 µg/ml     Draffon et al. (1977)
                    spectrophotometry
                    radioimmuno assay        0.12 µg/ml      Levitt (1979)
                    radioimmuno assay        0.10 µg/ml      Proudfoot et al. (1979)

Plants              spectrophotometry        0.01 mg/kg      Calderbank & Yuen (1965)
                    spectrophotometry        0.01 - 1 mg/kg  Dickes (1979)
                    gas chromatography       0.01 - 1 mg/kg  Paschal et al. (1979)
                    gas chromatography       -               Harrington (1979)
----------------------------------------------------------------------------------------
a  The figures refer to the detection limits in the assay solutions.

                                                                  
(b)  Water

    The concentration of paraquat in water has been determined by 
treating the lesser duckweed  (Lemna minor) with the test sample 
and comparing the time taken to produce chlorosis with known 
concentrations.  This procedure has been used to determine 
herbicide residues in ponds and streams with a sensitivity of 0.075 
mg/litre.  Determination of chlorosis in  Phaseolus vulgaris or 
 Lemna polyrhiza was classified as more sensitive than the chemical 
analyses (Haley, 1979). 

    A change in cell-membrane permeability, as indicated by the 
leakage of electrolytes from treated fronds of  Lemna minor, was 
used by O'Brien & Prendeville (1978) to detect paraquat in water.  
The minimum detectable concentrations ranged from 1.8 - 1.7 µg of 
paraquat cation/ml, after 3 h of treatment, to 180 and 17 ng/ml 
after 72 h of exposure to light. 

    Ukai et al. (1977) found a gas chromatographic method suitable 
for paraquat determination with a sensitivity of 10 - 90 µg/ml 
water, using 4-anisidine as the internal standard.  Pope & Benner 
(1974) have also used a spectrophotometric method. 

(c)  Air-working environment

    Sprayed or dusted, paraquat is absorbed on filter/sorbent 
systems.  The absorbed paraquat is dissolved and determined 
spectrophotometrically using one of the classical methods 
(Calderbank & Yuen, 1965; Staiff et al., 1975; Anderson et al., 
1981).  Carlstrom (1971) applied a colorimetric method for 
analysing paraquat formulations.  Seiber & Woodrow (1981) developed 
a nitrogen-selective gas chromatographic method for paraquat 
determination in airborne particulate matter. 

(d)  Plants

    The method of Calderbank & Yuen (1965) is considered to be the 
best procedure for determining paraquat in crops, treated plants, 
and food.  The limit of the spectrophotometric analysis ranged from 
0.01 - 0.1 mg/kg, depending on the crop.  A gas chromatographic 
method for paraquat residues in food was suggested by Dickes 
(1979).  A procedure based on gas-liquid chromatography (Paschal et 
al., 1979) provided linear working curves over a paraquat 
concentration range of 0 - 20 µg/g, determined by extraction from 
1 g samples of sunflower seeds.  The method has been proposed for 
herbicide analyses in plant materials.  A vapour-phase 
chromatographic technique, used for determining paraquat in wood 
(Harrington, 1979), is based on the liberation of methyl chloride 
after pyrolysis. 

(e)  Biological material

    A spectrophotometric method, applied for determining paraquat 
residues in milk (ICI, 1972), had a detection limit of 0.01 
mg/litre sample.  Analyses of the plasma (serum) and urine of 

subjects poisoned by paraquat are important for diagnosis and 
prognosis.  Tompsett (1970) described a method for analysing 
biological samples from patients suffering from accidental oral 
intoxication.  Paraquat extracted from human blood, urine, and 
faeces was separated on a strong acid cation-exchange resin (Beyer, 
1970), reacted with sodium dithionite, and determined 
spectrophotmetrically at 391 nm.  The method had a sensitivity of 
0.01 µg ion/ml in a 250 ml aliquot of urine.  A similar procedure, 
published by Pickova (1978), for estimating paraquat levels in the 
urine of patients had a sensitivity of 30 µg in a sample of 50 - 
500 ml.  Gas chromatographic methods were successfully used (Dijk, 
van et al., 1977; Draffon et al., 1977). 

    A radioimmunoassay using 3H-labelled paraquat was found to
be a sensitive method for analysing plasma, urine, and biological 
tissues (ICI, 1979).  Antibodies to paraquat were prepared in 
rabbits and tested for sensitivity by a charcoal separation 
technique (Levitt, 1979).  The results showed that the antibodies 
were specific for the herbicide.  A comparison of radioimmunoassay 
and gas liquid chromatographic techniques (Levitt, 1979; Proudfoot 
et al., 1979) showed the high sensitivity of this method.  The 
total assay time was no more than 30 min.  A series of 50 serum 
specimens from persons poisoned with paraquat were tested by 
radioimmunoassay and colorimetric analysis (Stewart et al., 1979); 
the results from both methods corresponded closely. 

    Tsunenari et al. (1975) used 7 analytical methods for 
determining paraquat with a view to diagnosing accidental, 
suicidal, or homicidal poisoning.  Colorimetry, with dithionite 
thin-layer chromatography, was used for the qualitative assay of 
paraquat in biological tissues, while ion-exchange resin column 
chromatography, with colorimetry or gas chromatography, was used 
for the quantitative assay.  Tsunenari et al. (1981) also studied 
the influence of putrefaction on paraquat determinations in autopsy 
materials.  Detection was possible, even in tissues in advanced 
stages of decomposition. 

3.  SOURCES IN THE ENVIRONMENT

3.1.  Introduction

3.1.1.  Industrial technology

    Paraquat does not occur naturally.  It was originally 
synthesized by Weidel & Russo as reported in 1882 (Summers, 1980).  
Its herbicidal properties were discovered only in 1955.  The 
compound is produced by coupling pyridine in the presence of sodium 
in anhydrous ammonia and quaternizing the 4,4'-bipyridyl with 
methyl chloride (Fig. 1). 

FIGURE 1

    When bipyridyl is refluxed with methyl iodide, the iodide salt 
is obtained.  Haley (1979) and Summers (1980) thoroughly reviewed 
the published methods for paraquat synthesis, and for the 
separation and purification of bipyridylium salts.  The yields 
obtainable vary from 20% to 96% of pure product. 

    The first commercial paraquat formulation approved for 
agricultural use was Gramoxone(R). 

3.1.2.  Impurities

    Aqueous solutions of paraquat used as herbicides must
correspond to the FAO Specification Code 56/13/S/6 (FAO, 1973).  
This requires a description of the active ingredient in the 
formulation, of the impurities, of the physical and chemical 
properties, and of the methods for determining the components.  
The only impurity permitted in paraquat is free 4,4'-bipyridyl 
at a maximum level of 0.25% of the paraquat content. 

3.2.  Production and Use

    Paraquat is produced in several countries, including China, 
Province of Taiwan, Italy, the United Kingdom, and the USA.  
Formulations of the active ingredients (mainly paraquat dichloride) 
are used in more than 130 countries world-wide.  Paraquat 
dimethylphosphate is used in the USSR.  Since its introduction for 
agricultural use in 1962, paraquat has been widely used for weed 
control and as a dessicant.  In many countries, paraquat is 
formulated locally, only the technical active ingredient being 
imported.  Records of world production of paraquat are not 
available. 

    Technical paraquat dichloride has been formulated in liquid 
concentrates or granules.  Water-soluble granules containing 
paraquat (25 g/kg) and diquat (25 g/kg) are used for weed control 
in private gardens.  Paraquat is sold under a variety of trade 
names which are summarized in Table 3. 

    Gramoxone(R) is a dark aqueous solution containing a paraquat 
dichloride concentration of 200 ± 10 g/litre.  Its specific gravity 
at 20 °C is 1.1 and the crystallization point is -5 °C to 10 °C.  
It is not flammable and, in its original polyethylene containers, 
is stable for a long time under normal atmospheric conditions.  The 
formulation is incompatible with anionic surface active agents and 
decomposes in ultraviolet radiation.  Gramoxone(R) rapidly 
corrodes aluminium; zinc, iron, and tinplate are more resistant. 

    Paraquat is a total contact herbicide used to control broad-
leaved and grassy weeds.  It should be sprayed when the weeds are 
young and less than 30 cm high.  It kills all green tissues, but 
does not harm the mature bark.  Paraquat is used for plantation 
crops (banana, cocoa-palm, coffee, oil-palm, rubber, etc.) and for 
citrus fruits, apples, plums, vines, and tea.  On certain crops 
(potato, pineapple, sugar-cane, sunflower), it is used as a 
dessicant; it is also used as a cotton defoliant.  It is applied 
around the trees in orchards and between the rows of crops. 

    Uncropped land on industrial sites, railways, roadsides, etc. 
can be cleared of weeds by applying paraquat at higher 
concentrations. 

    Gramoxone S(R) is largely applied for aquatic weed control. 

    Application rates usually range from 250 g - 1500 g/ha (1.1 -  
7.1 1itre of Gramoxone(R), but, for grass and stubble clearing, up 
to 2200 g of the herbicide are used per ha.  The working dilutions 
vary from 1 - 5 g per litre paraquat in water.  It is applied by 
ground sprayers (not mist-blowers) in 200 - 500 litres solution/ha. 

3.3.  Mechanism of the Herbicidal Effect           
                                                                   
    The herbicidal activity of paraquat is dependent on the parent 
molecule undergoing a single-electron redox cycling reaction.      
Paraquat is reduced to the paraquat radical, which, in the presence
of molecular oxygen, is immediately reoxidized forming the parent  
molecule and superoxide radicals (O2-) (Conning et al., 1969).  As
early as 1960, Mees had shown that oxygen was necessary for the    
herbicidal activity of paraquat, suggesting the importance of the  
redox cycling and O2- formation in mediating toxicity.  Paraquat 
was not toxic to plant leaves incubated under anaerobic conditions, 
despite the continuation of photosynthetic reactions capable of 
forming paraquat radicals.  Exposure of the anaerobic incubates to 
air, however, resulted in immediate onset of toxicity.  Dodge 
(1971) subsequently confirmed that isolated plant chloroplasts 
could form the paraquat radical under anaerobic conditions.  The 
possibility that O2- generation may be an essential component of 
the herbicidal activity was further supported in a study by 

Youngman & Dodge (1979).  These investigators observed that the 
phytotoxicity of paraquat in plant cotyledons was decreased by a 
copper chelate of D-penicillamine.  The chelate possessed activity 
similar to the enzyme superoxide dismutase (EC 1.15.1.1) 
(Lengfelder & Elstner, 1978), an enzyme that detoxifies O2- 
(McCord & Fridovich, 1969).                                       

    The generation of O2- may lead to many potentially 
cytotoxic reactions, including the membrane-damaging process of 
lipid peroxidation (Bus & Gibson, 1979).  When plant leaves were 
incubated with paraquat, there was rapid stimulation of the 
formation of malondialdehyde, which is an indicator of lipid 
peroxidation (Dodge, 1971). 


Table 3.  Paraquat trade namesa
--------------------------------------------------------------------------------------------------------
Products                        Countries                                 Paraquat content (W/V for       
                                                                          liquids, W/W for solids)
--------------------------------------------------------------------------------------------------------
Dextrone X                      United Kingdom                            20%
Dexuron                         United Kingdom                            10%, also contains diuron
Duanti                          Germany, Federal Republic of              2.5%, also contains diquat
Dukatalon                       Israel                                    9%, also contains diquat
Esgram                          United Kingdom                            20%
Frankol Prompt                  Germany, Federal Republic of              10%, also contains diuron
Gramazin                        Italy                                     10%, also contains simazine
Gramixel                        Germany, Federal Republic of              10%, also contains diuron
Gramanol                        United Kingdom, Ireland,                  14%, also contains monolinuron
                                Belgium, Greece, Middle East
Gramoxone                       worldwide                                 20%
Gramoxone S                     worldwide                                 20%
Gramoxone W                     discontinued                              20%
Gramoxone ZU                    The Netherlands, Belgium                  20%
Gramuron                        Africa, Italy                             10%, also contains diuron
Katalon                         Israel                                    20%
Ortho Paraquat CL               USA                                       24.6% (2 lb/US gal)
Ortho Spot Weed & Grass Killer  USA                                       0.2% (Solid Stream Aerosol)
Orvar                           United Kingdom                            5%
Paracol                         Malaysia, Indonesia, Philippines          10%, also contains diquat
                                Chile, Peru
Paradi                          Australia                                 10%, also contains diquat
Pathclear                       United Kingdom, New Zealand               2.5%, also contains diquat,
                                                                          3 aminotriazole and simazine
Preeglone                       Denmark, Norway                           2.5%, also contains diquat
Preeglone                       Belgium, France, Spain                    12%, also contains diquat
Preeglone Extra                 New Zealand                               9%, also contains diquat
Priglone                        France, Switzerland                       12%, also contains diquat
Seythe                          United Kingdom                            20%
Spray Seed                      Australia                                 10%, also contains diquat
Terraklene                      United Kingdom, Ireland, Denmark,         10%, also contains simazine
                                France, Switzerland
Tota-Col                        Wide range of countries                   10%, also contains diuron
Tryquat                         Australia                                 10%, also contains diquat
Weedol                          The Netherlands, Ireland, United Kingdom  2.5%, also contains diquat
Weedrite                        Canada                                    2.5%
Weedrite Aerosol                Canada                                    0.44%
--------------------------------------------------------------------------------------------------------
a  From: Fletcher (1975).

4.  ENVIRONMENTAL DISTRIBUTION AND TRANSPORTATION

4.1.  Photochemical Degradation

4.1.1.  Photochemical degradation on plant surfaces

    In agricultural practice, much of the paraquat sprayed is 
initially deposited on plant surfaces.  Slade (1965, 1966) applied 
paraquat dichloride droplets to maize, tomato, and broad-bean 
plants.  Determinations carried out at intervals of 100 days showed 
that degradation was caused by photochemical decomposition on the 
leaf surfaces but not by metabolism.  Degradation products isolated 
from plants sprayed with 14C-paraquat dichloride included 4-
carboxyl-1-methyl-14C-pyridylium chloride and methylamine-14C-
hydrochloride.  No 14C02 was detected as a photochemical 
decomposition product.  The photochemical degradation of paraquat 
dichloride continued after the plants were dead (Fig. 2).  Paraquat 
photodegradation products were not translocated from the dessicated 
leaves of the plants, nor were they found in the crops (cereals and 
fruits), when weeds were treated with paraquat during 3 - 4 
successive seasons (Calderbank, 1966). 

FIGURE 2

    The rate of decomposition was related to the intensity of UV 
radiation between 285 and 310 mµ present in daylight.  In strong 
sunlight, about 2/3 of the applied herbicide decomposed within a 
3-week period.  Vegetation directly sprayed with paraquat (1.12 
kg/ha) was analysed at intervals up to 4 months.  The residues 
varied from 5 - 200 mg/kg.  The 4-carboxyl-1-methylpyridynium 
chloride ranged from 0.02 - 5 mg/kg (about 7% of the paraquat 
residues determined on dry leaves).  The toxicity of 4-carboxyl-1-
methylpyridylium for mammals was low, the acute oral LD50 in rats 
being more than 5000 mg/kg body weight (FAO/WHO, 1971). 

    The degradation product from the photochemical destruction of 
paraquat dimethylsulfate was  N-methyl-isonicotinic acid 
methylsulfate (Fig. 3). 

    A 90-day feeding test (Broadhurst et al., 1966) on rats 
revealed that levels of 20 000 - 5000 mg/kg of the  N-methyl-
isonicotinic acid methylsulfate were not toxic. 

FIGURE 3

4.1.2.  Photochemical degradation of paraquat on soil and other 
mineral surfaces

    Slade (1966) showed that there was a breakdown, similar to that 
on plant surfaces, if spots of paraquat on silica gel were exposed 
to direct sunlight.  When 14C-paraquat dichloride was sprayed on 
the bare soil surface of a field during a hot sunny period, traces 
of 4-carboxy-1-methylpyridynium chloride were detected in the top 
inch of soil for the first few weeks afterwards (Calderbank & 
Slade, 1976).  Radioassay showed that the total soil residue did 
not markedly decrease during a 6 - 18 month period, so that, in 
agricultural practice, UV degradation of herbicide reaching the 
soil should be regarded as insignificant. 

    The principal intermediates of photochemical paraquat 
degradation on plants or soil surfaces are of low toxicity.  
They decompose easily and are not expected to produce adverse 
environmental effects. 

4.2.  Microbial Degradation

    Microbial paraquat degradation has been thoroughly reviewed by 
Haley (1979).  Baldwin et al. (1966) identified many soil 
microorganisms capable of degrading paraquat.  The herbicide was 
decomposed by  Corynebacterium fascians, Clostridium pasteurianum, 
and  Lipomyces starkeyi.  Several other microorganisms were found to 
degrade paraquat (Smith et al., 1976; Tchipilska, 1980) but 
 Lipomyces starkeyi proved to be the most active (Burns & Audus, 
1970).  Burns & Audus (1970) concluded that microbiological 
degradation was possible only for a short time following the 
application of paraquat to soil.  Once adsorbed on to clay 
materials, the paraquat was inaccessible to microorganisms.  
Microbial degradation of paraquat in the field is therefore 
relatively slow. 

    Studies of 4-carboxyl-1-methylpyridylium chloride in soil have 
demonstrated that the radiolabelled product readily decomposes to 
form several chemical substances, including carbon dioxide.  No 
significant residues of the compound have been determined in plants 
as a result of uptake from the soil.  Wright & Cain (1970) isolated 
 Achromobacter D from the soil; this utilized the 4-carboxyl-1-
methylpyridylium chloride and the methylamine originating from 
the N-methyl group of the molecule.  The NADH and the oxygen 
requirement indicated the possibility of direct oxidative 
fission of a partly reduced ring to form dialdehyde, which was 
then hydrolysed to formate, methylamine, and succinic dialdehyde.  
The end-products of the microbial ring degradation were formate, 
succinate, and carbon dioxide. 

4.3.  Environmental Adsorption and Transformation

4.3.1.  Soil

    The property of paraquat that is most important in nullifying 
its impact on the environment is its rapid and complete binding to 
clay soils.  Desorption of the herbicide from soil particles, for 
the purpose of chemical analysis, requires destruction of the 
mineral particles by refluxing with strong sulfuric acid.  The 
strong adsorption to clay has been attributed to the flat and 
highly polarizable nature of the paraquat ion (Coats et al., 1966; 
Knight & Denny, 1970).  Weber et al. (1965) reported that the 
adsorption appeared to be one of ion exchange and was very rapid, 
the rate of adsorption depending on the rate at which the paraquat 
ion contacted the adsorbing particles. 

    In highly organic soils, the weaker adsorption sites of soil 
organic matter delay the redistribution of paraquat without 
inactivating it herbicidally.  In this connection, Khan (1980) 
reported tests showing a remarkable affinity of humic substances in 
the soil for the paraquat ion.  These humic substances enhance the 
degradation of pesticides via non-biological pathways. 

    It has been demonstrated that on soil containing 98% organic 
matter, the herbicidal effects of 1.12 and 2.24 kg of paraquat/ha 
persisted for 16 - 29 days, but such soils are not widespread 
naturally.  Burns & Audus (1970) studied the migration of paraquat 
from soil organic matter to clay mineral particles.  The transfer 
of the paraquat from the organic to the inorganic fraction, through 
a membrane, was 90% complete within 6 h.  The remaining 10% took 
about 2 days to be transferred.  No paraquat was detected in the 
organic fraction after 4 days.  At high paraquat concentrations 
(more than 20 mg/kg in equilibrium solution), the total adsorption 
capacity was greater than normal in soils with high organic 
content, as opposed to those with low organic content. 

    Mithyanta & Perur (1975) studied samples of 4 different soils 
treated with paraquat in different experimental schemes.  After 24 
h, the soils were extracted with a water solution of ammonium 
chloride.  The percentages of paraquat, extractable with water, 
ranged from 4.8 - 66.9%, depending on the type of soil and the 
conditions.  Data on the persistence of paraquat in the soil have 
also been compiled by Coats et al. (1966), Knight & Tomlinson 
(1967), Knight & Denny (1970), and Burns & Audus (1970). 

    As summarised in section 4.2, free paraquat is degraded by a 
range of microorganisms, but degradation of strongly adsorbed 
paraquat is relatively slow.  In plot studies, degradation was very 
slow or non-detectable (Riley et al. 1976).  However, in long-term 
field studies, degradation rates were 5 - 10% per year.  This is 
greater than the rate required to prevent saturation of the 
deactivation capacity of soils. 

    In a long-term trial on a loamy soil, plots were treated with 
0, 90, 198, and 720 kg paraquat/ha, which was incorporated to a 
depth of 15 cm.  These rates were equivalent to 0, 50, 110, 400% of 
the soils strong absorption capacity (Gowman et al., 1980; 
Wilkinson, 1980; Riley, 1981).  Over the 7 years, paraquat residues 
declined by 5% per year (sig  P = 0.05) on the 90 kg/ha plots and 
by 7% per year (sig  P = 0.01 on the 198 and 720 kg/ha plots.  The 
rate of decline on the 198 and 720 kg/ha plots was significantly 
greater ( P = 0.01) than on the 90 kg/ha plots. 

    In another long-term trial on a sandy loam, plots were treated 
annually with 4.4 kg/ha for 12 years (Hance et al, 1980).  The rate 
of loss of paraquat soil residues was about 10% per year and the 
soil residues tended to plateau when the rate of application 
equalled the rate of degradation.  Data for the last 4 years (total 
16 years) has confirmed the early results (Hance, unpublished 
data). 

    Some paraquat could be recovered from its tightly bound form by 
chemical destruction of the soil from field plots, several years 
after application.  The limit of paraquat adsorption, at which 
further treatment would result in phytotoxic activity, was 
considered to be important.  Strong adsorption capacity was defined 
as the measure of paraquat that can be adsorbed by the soil without 
entailing phytotoxic effects, and this capacity was determined in 
several kinds of soil with various clay and organic contents 
(Knight & Tomlinson, 1967).  Mechanical analyses, pH, and organic 
matter content were also determined.  Independently of the soils 
studied, it was found that, by applying 1 kg/ha per year, it would 
take from 30 - 1440 years to saturate the top 15 cm of soil at 
strong adsorption sites.  The conditions of study precluded any 
form of paraquat degradation or metabolism in the soil.  Riley et 
al. (1976) reviewed the hazard of continuous application of 0.1 - 
2 kg paraquat ion/ha, assuming soil contamination by 10 - 100% of 
the amount applied.  Bound paraquat soil residues were not adsorbed 
by living organisms.  Paraquat residues did not induce any effects 
on microarthropods or microorganisms.  Continued application of 
the herbicide in different soils has been investigated by Pestemer 
et al. (1979).  The ED50 valuesa for phytotoxic action on lettuce 
ranged from 0.01 mg/litre paraquat solution in agar-agar to 98 - 
1930 mg/litre in different soils, depending on their constituents, 
and 31 - 57.6 mg paraquat residues/kg have been determined in the 
soil samples.  There is evidence (Hance et al., 1980) that 
strongly-bound paraquat residues were degraded in soil by microbial 
activity at a rate of 5 - 10% per annum.  A correlation was reported 
between the paraquat residues, the number of treatments, doses, and 
depth of soil sampling. 

-------------------------------------------------------------------
a ED50 = median effective dose.

    Although, as mentioned, adsorption on clay is important, 
extremely sandy soils can adsorb and inactivate significant 
quantities of the herbicide, as illustrated by studies on a South 
African vineyard soil that contained only 1% clay (Riley et al., 
1976).  Over an 8-year period, more than 20 applications (total 
15.6 kg paraquat/ha) resulted in saturation of about 20% of the 
soil-paraquat-strong-adsorption capacity in the top 2.5 cm.  The 
paraquat residues were not phytotoxic in the field or in greenhouse 
tests on different plants.  No paraquat residues were detected 
(<0.05, <0.03, <0.03 mg/kg) in leaves, grapes, and twigs, 
respectively. 

    Very low concentrations of free paraquat would be detected 
easily by their phytotoxicity.  Five trials at 4 sites were 
conducted by Newman & Wilkinson (1971).  In 4 of the trials, single 
applications of paraquat at 112 kg/ha were made at sites subjected 
to normal agricultural practice.  At this unrealistic, extremely 
high rate, short-duration residual phytotoxicity was observed.  On 
undisturbed plots of mineral soils, seedlings did not appear for 
several months; on organic soils, the time lag was even longer.  
After cultivation, there was no further indication of 
phytotoxicity.  In the 5th trial, a total of 565 kg/ha was applied 
in 5 doses over 4 1/2 years. The plot then remained undisturbed, 
apart from periodic cultivation of the top 20 mm to prepare a 
seedbed.  It was at this site that phytotoxicity to ryegrass 
seedlings was detected, and free paraquat was determined in the 
surface soil using the  Lemna minor bioassay.  Phytotoxicity was 
confined to the surface layer of the soil.  The free paraquat that 
had leached out of the top 2.5 cm had been adsorbed in the deeper 
soil layers, and this was confirmed by the absence of residual 
phytotoxicity when the site was more deeply cultivated. 

    However, the extreme situations seen in high-dosage trials are 
not encountered in practice and only serve to show the possible 
consequences for the environment of a gross overdose of the 
herbicide.  Thus, when paraquat is used in normal application 
doses, no adverse environmental effects can be expected. 

    Accidental spillage is probably the most likely cause of high 
levels of residual paraquat.  The 200 g of paraquat contained in 1 
litre of Gramoxone(R) would be completely inactivated by the 
addition of 10 kg of bentonite, for inactivation can be effected 
either by cultivation and mixing other soil with the contaminated 
layer or by adding clay minerals.  Simulated spills of paraquat 
have also been treated with sodium borohydride or alkali (Staiff et 
al., 1981); within 1 day the paraquat in the soil had been 
effectively degraded. 

4.3.2.  Water

    The ecological effects of paraquat in water have been 
studied in relation to its use as an aquatic herbicide at a 
normal concentration of 1 mg/litre (Newman & Way, 1966; Grzenda et 
al., 1966).  Following this use, the concentration present in water 
decreased to about half of the initial 1 mg/litre level within 

36 h, and, in less than 2 weeks, the concentration was below 
0.01 mg/litre.  Weed-sample analysis, 4 days after paraquat 
application, showed a residue of approximately 25 mg/kg, suggesting 
that absorption by the weed was mainly responsible for paraquat 
removal.  Mud-residue analysis 5 1/2 months after treatment showed 
that 36% of the applied paraquat remained in the mud, and 70% of 
that was found in the top 2.5 cm.  In the mud, paraquat had been 
adsorbed on to the mineral material.  Since bottom mud often has 
organic components, the residues may be more accessible to 
bacterial degradation.  Compared to other products, paraquat 
appears to be the herbicide of choice for future use in water 
supplies because of its rapid disappearance from water (6 - 14 days 
after treatment) (Grzenda et al., 1966).  The residues were not 
desorbed from the bottom sediments, and mud taken from the bottom 
of a paraquat-treated lake carrying inactivated residues, showed no 
toxic effects on barley seedlings that germinated on it (Way et 
al., 1971). 

    Wauchope (1979) discussed the fate of pesticides in water 
draining from fields after rain.  For most formulations, a total 
loss of 1.5%, or less, of the amount applied was the rule, except 
when severe rainfall occurred within 1 - 2 months following 
treatment.  Nearly all the pesticides examined were lost by runoff; 
only those binding strongly to clay particles, such as paraquat, 
were carried off in the sediment phase of runoff.  The lack of 
paraquat runoff loss has also been discussed by Smith et al. 
(1978). 

    Grover et al. (1980) compared the efficiency of various 
herbicidal treatments for weed control in a series of irrigation 
ditches.  At the relatively low dose of 2.2 kg/ha, paraquat 
resulted in aquatic weed suppression from 1973 to 1976, and this 
made for satisfactory water flow without environmental 
contamination.  Water that contains small amounts of paraquat 
residues loses them rapidly on contact with soil, the adsorption 
process being irreversible (Knight & Tomlinson, 1967; Calderbank, 
1972).  Thus treated water may be used quite safely for channel 
irrigation, if an interval of 10 days is observed between treatment 
of the water and its use, because the paraquat will be unavailable 
to the plant roots.  Caution should, however, be exercised in 
prolonged crop irrigation until the residue is well below 0.1 
mg/litre, although phytotoxic damage is unlikely at even 0.5 mg 
paraquat/litre (Calderbank, 1972). 

    Coats et al. (1966) treated 0.1 ha experimental ponds with 
paraquat to obtain a concentration of 0.4 mg/litre.  The soil in 
one of the ponds was stirred twice after 24 h.  Analysis of the 
water over  several weeks revealed a decrease from 0.4 mg/litre to 
0.01 mg/litre after several weeks, but when the soil of the pond 
was stirred, the paraquat concentration fell from 0.75 mg/litre 
to <0.01 mg/litre after 8 - 12 days.  In static water experiments, 
the concentration of 0.5 - 1 mg/litre fell rapidly to about 0.1 
mg/litre within 4 - 7 days of treatment in 4 trials performed by 
Calderbank (1972).  These reductions in the paraquat concentration 

were due to its rapid adsorption and concentration in aquatic 
plants. Decaying weeds transported it to the bottom mud (Table 4) 
where it was not released back into the water (Way et al., 1971). 

    Earnest (1971) treated a pond with paraquat at an initial 
concentration of 1.14 mg/litre.  No residues were detected in the 
water after 16 days (limit of detection 0.01 mg/litre); in the mud 
the concentration was 1.13 mg/kg after 3 h and 3.25 mg/kg after 99 
days.  These data were confirmed by Grover et al. (1980). 

    Grover et al. (1980) studied irrigation water from ditches.  
Three days after treatment with 2.2 kg paraquat/ha, the 
concentrations in the water used to flood the treated ditches were 
less than 0.01 mg/litre, and paraquat residues in the ditch water 
ranged from 0.002 - 0.034 mg/litre in samples taken 3 - 5 days 
after foliar applications. 

Table 4.  Residues of paraquat in water, weed, and bottom muda
-------------------------------------------------------------------
                            Days after treatment
-------------------------------------------------------------------
                            1      4      16    32    175   420
-------------------------------------------------------------------
Trial 1   water (mg/litre)  0.31   0.12   ND
          weed (mg/kg)      13.70  25.80  21.0  0.55
          mud (mg/kg)       3.70   -      -     -     57.1  20.1

Trial 2   water (mg/litre)  0.37   ND     ND    ND    -     -
          weed (mg/kg)      25.50  40.0   37.8  27.8  -     -
          mud (mg/kg)       ND     0.97   0.23  0.32  6.6   0.96
-------------------------------------------------------------------
a  From: Way et al. (1971).
ND - not detectable.

4.3.3.  Air

    Paraquat is not volatile.  Dry deposits of 14C-paraquat 
chloride exposed at room temperature showed no measurable loss in 
64 days (Coats et al., 1966).  Exposure to paraquat in the air is 
not important in spraying and harvesting operations; the skin is 
the principal route of occupational exposure (Chester & Woollen, 
1982; Staiff et al., 1975). 

    Air concentrations of paraquat were measured on summer days by 
Makovskii (1972) using the method of Calderbank & Yuen (1965).  
About 1 - 1.3 kg paraquat/ha had been applied as a herbicide or 
desiccant in 0.25 - 0.35% water solutions.  The paraquat aerosol 
concentrations varied according to spraying method and work-place 
(Table 5).  Using the same analytical method, Staiff et al. (1975) 
examined 35 sites after paraquat application with tractor-mounted 
field sprayers or hand-pressure garden dispensers.  The working 
solutions contained 0.15% paraquat for field use, and 0.44% for 
garden use.  The respiratory exposure of field and garden operators 
was below the limit of detection (<0.001 mg paraquat/h). 

    Mature cotton fields (Seiber & Woodrow, 1981) were sprayed with 
paraquat, the dose being 0.94 kg/ha.  The air paraquat 
concentrations measured downwind decreased regularly from the 
extrapolated interval-average values of 4.31 and 10.7 µg/m3 1 
metre downwind of the 2 fields to <50 ng/m3 at 400 metres away in 
the same direction.  Forty-five percent of the aerosol particles 
had diameters ranging from 0.01 to 4 µm.  The remaining 55% had a 
median diameter of 12 µm.  Downwind samples taken 2 - 4 h after 
spraying contained 1 - 10% of the amount dispersed, but, after 
5 - 7 h, no paraquat was detectable in the air. 

Table 5.  Paraquat total airborne concentrations (mg/m3) in 
working areasa
-------------------------------------------------------------------
Place of                               Number of  Mean 
sampling                               samples    concentrations
                                                  ± SE
-------------------------------------------------------------------
Working area   sprayer loading         28         0.13 ± 0.03
               tractor cabin           16         0.37 ± 0.07
               (in direction of wind)
               tractor cabin           16         0.55 ± 0.01
               (against the wind)                 
               manual spraying         16         0.18 ± 0.04

Treated field  after 5 min             16         0.05 ± 0.01
               after 10 min            32         < 0.01
               after 20 min            16         0

Distance from  200 m                   8          0.08 ± 0.01
treated field  400 m                   8          0.04 ± 0.01
-------------------------------------------------------------------
a  From:  Makovskii (1972).

    A study of Malaysian plantation workers, occupationally exposed 
to paraquat, revealed a mean total airborne exposure of 0.97 mg/m3 
for spray operators.  This exposure is less than present TLVs 
(Chester & Woollen, 1982).  Wojeck et al. (1983) reported that 
after spraying paraquat in fields of tomatoes and citrus, the total 
airborne exposure ranged from 0 - 0.070 mg/h.  It was less than 
0.1% of the total body exposure (12.16 - 168.59 mg/h) in all 
trials. 

    During mechanical harvesting of cotton dessicated by paraquat, 
the maximum levels in airborne dust were found to be 1245 ng/m3 
outside the cabin of the tractor and 516 ng/m3 inside the open 
cabin.  With the cabin door closed, the concentration was only 13.7 
ng/m3.  The trapped particulate matter consisted of dessicated 
plant material and soil dust.  A cascade impactor analysis 
established that 57% of the paraquat had a median particle diameter 
of 4 µm, 23%, 12 µm, and 11%, 3 µm.  Cotton harvesting generated 
parti- culate concentrations in the field comparable to those 
immediately downwind of the field during spraying.  Bearing in mind 
the highest paraquat air concentration in the harvest-time air 
(0.0012 mg/m3), a harvester operator's maximum exposure through 
inhalation was calculated to be 0.01 mg/8 h/day (Seiber & Woodrow, 
1981). 

    Bulgaria has established a maximum allowable concentration 
(MAC) of 0.01 mg paraquat/m3 (1972), the Federal Republic of Germany 
0.1 mg/m3 (1982), Hungary 0.02 mg/m3 (1978), and the USA a TLV of 
0.1 mg/m3 (1982). 

4.3.4.  Plants

    Paraquat residues on plants have been reviewed several times by 
the Joint Meeting on Pesticide Residues (JMPR) (FAO/WHO, 1971, 
1973, 1983).  The residues found after paraquat was used as a 
desiccant are summarized in Tables 6 and 7 (Calderbank, 1968). 

Table 6.  Paraquat residues (mg/kg) in cotton 10 days after 
dessication at 0.55 kg/haa
-------------------------------------------------------------------
Fraction analysed                                    Paraquat found
-------------------------------------------------------------------
Cotton as picked, including trash and balls          2.00

Ginned seed                                          0.18

Mechanically reginned seed                           0.08

Acid-delinated seed                                  0.05

Lint cotton                                          3.00

Trash                                                3.70

Hulls                                                0.13

Crude oil                                            ND

Meal                                                 0.02
-------------------------------------------------------------------
a  From:  Calderbank (1968).

    Coats et al. (1966) reported that 14C-paraquat applied to wheat 
as a 1% solution was translocated in the plants, including the 
roots.  Slade (1966) studied the degradation of 14C-paraquat 
dichloride and its photochemical degradation products in plants.  
Maximum loss occurred in tomato, broad-bean, and maize when the 
paraquat remained on the leaf surfaces during sunny days. 

    In potatoes treated with paraquat as a desiccant, Makovskii 
(1972) found a residue of 0.05 mg/kg, and there was no change after 
the potatoes had been boiled.  No residues (limit of detection 0.01 
mg/kg) were found in fruits (apples, citrus fruits, plums, pears), 
tea, and cereals.  In tests on sunflower seeds treated with 0.25 or 
0.5 kg paraquat/ha, residues of up to 0.9 mg/kg were found in the 
whole seed, up to 1.2 mg/kg in sunflower meal, and no residue in 
the oil (Anonymous, 1979).  Therefore, the use of sunflower meal in 
the diet of hens, dairy cattle, and other livestock would not 
result in paraquat levels exceeding current standards. 

Table 7.  Paraquat residues (mg/kg) in food crops 3 - 21 days
after dessicationa
-------------------------------------------------------------------
Crop                          Rate of application   Paraquat found
                              (lb/acre)
-------------------------------------------------------------------
Barley                        0.50 - 1.00           3 - 10

Wheat                         0.50 - 1.00           1 - 2.5

Maize                         0.50 - 1.20           ND - 0.2

Rice (with husk)              0.15 - 0.54           0.7 - 22

Rice (de-husked or polished)  0.15 - 0.54           ND - 0.2

Peas, beans, sunflower seed   0.35 - 1.20           ND - 0.2

Sorghum seed                  0.25 - 1.00           0.1 - 0.4

Cotton (as picked)            0.50 - 1.00           2 - 3

Potatoes                      0.50 - 1.50           0.02 - 0.13

Onions                        0.50 - 2.00           ND - 0.05

Sugar cane juice              0.50 - 2.00           ND

Seed oils (sunflower, rape,   up to 1.20            ND
 sesame, cotton)
-------------------------------------------------------------------
a  From:  Calderbank (1968).

    Seiber et al. (1979) determined the paraquat residues in 
treated cotton (the foliage and bolls of the live plant, the lint 
and seed of harvested cotton, the gin waste and the lint and 
non-lint components).  Gin waste residues were surveyed during 
5 months of open storage.  The paraquat dose had been 0.21 and 
2.0 kg/ha.  The results obtained are summarized in Table 8.  The 
minimal degradation of paraquat in the plants studied was confirmed 
by Hills et al. (1981). 

    Significant paraquat residues are to be expected only when a 
crop is directly sprayed. 

    After spraying fields of marijuana with paraquat for the 
purpose of eradication, residues of paraquat were detected in 
marijuana (Smith, 1978; Patrick, 1980).  Of the 54 samples 
collected in 1976, 7.4% were positive and of 46 samples collected 
in 1977, 19.6% were positive. 

Table 8.  Paraquat residues (mg/kg) in cotton plantsa
-------------------------------------------------------------------
Material                Days after   Leaves  Lint   Non-lint  Seeds
                        treatment
-------------------------------------------------------------------
Standing cotton plants  2            13.1    22.10            0.06
                        6            8.2     3.80             0.06

Harvested seed cotton   18                   7.15             0.25
 stored in field        49                   4.85             0.18

Gin waste               49                   2.7    9.3
                        119                  5.3    10.1
                        171                  5.8    9.7
-------------------------------------------------------------------
a From:  Seiber et al. (1979).
 
4.3.5.  Animals

    The effects and fate of 14C-paraquat orally-administered to 
cattle at 8 mg/kg body weight were studied by Stevens & Walley 
(1966).  Seven days after this single dose, 0.03 - 0.08 g/litre had 
been excreted in the milk and 2.4 g/litre in the urine of the cows.  
The total paraquat excretion in the milk was only 0.01% of the 
ingested dose.  In cows given daily oral doses of 8 mg paraquat/kg 
for 3 weeks, residues of less than 0.01 mg/litre were detected in 
the milk (FAO/WHO, 1977).  Cattle did not suffer any toxic effects 
over a 4-week period when turned loose on pasture immediately after 
it had been sprayed with 1.12 kg paraquat/ha (Calderbank et al. 
1968).  During the first 2 weeks of grazing on the dried herbage, 
it was estimated that the cattle ingested approximately half of 
their acute oral LD50 (36 - 54 mg/kg body weight) every day. 
Paraquat levels in the herbage ranged from about 400 mg/kg 1 day 
after spraying, to about 200 mg/kg 14 days after treatment; 
14 - 35 days after spraying the levels were 135 -214 mg/kg.  The 
4-carboxyl-1-methylpyridylium chloride content during the trial 
period was 5.1 - 3.4 mg/kg.  By the 4th week of the study, paraquat 
levels in the urine were 0.01 - 0.19 mg/litre and in the faeces, 
0.9 - 42 mg/kg.  Only on the first day after spraying were paraquat 
residues (0.02 mg/litre) found in the milk of 2 cows; no residues 
were found (< 0.005 mg/litre) thereafter.  The only organs of a 
slaughtered animal that contained paraquat were the kidney 
(0.03 mg/kg) and the stomach (0.05 mg/kg). 

    The fate of paraquat in large animals is addressed far more 
completely in the Evaluations of the 1976 Joint Meeting on 
Pesticide Residues (JMPR) (FAO/WHO, 1977). 

    Rabbits were fed with lucerne treated with normal-use levels of 
paraquat (Lavaur et al., 1979).  Immediately after spraying, the 
paraquat residues were 272 mg/kg (dry weight of lucerne).  After 
24 h and 48 h, they were 114 mg/kg and 62 mg/kg, respectively.  No 
systemic toxicity symptoms or gastrointestinal damage were observed 
in the treated rabbits. 

    When hens were given paraquat at 40 mg/litre in their drinking-
water for 14 days, the amount of paraquat found in the eggs rose to 
0.1 mg/kg, but fell to less than 0.005 mg/kg, 6 days after 
cessation of treatment (Fletcher, 1967).  Eggs from hens eating 
grain containing paraquat at a concentration of 10 mg/kg contained 
residues below 0.025 mg/kg. 

5.  BIOLOGICAL ACTIVITY OF RESIDUES

5.1.  Soil Organisms

    Haley (1979) reviewed the effects of paraquat on soil 
microorganisms and fungi, while Tu & Bollen (1968), Curry (1970), 
Radaelli & Martelli (1971), Roslycky (1977), and Smith et al. 
(1981a) studied the effects of paraquat on the size and composition 
of the microbial soil populations, total microbial respiration in 
the soil, the rate of organic matter degradation, and the number of 
soil microorganisms.  None of these authors found any adverse 
ecological effects from normal and excessive (up to 32 times the 
normal dose) paraquat treatment, although in some cases 
nitrification was temporarily suppressed or activated, and some 
bimodal microbiological effects were observed with intermediate 
herbicide concentrations (Tu & Bollen, 1968; Tchipilska, 1980). 

    At normal doses, paraquat had no adverse effect on 
endomycorrhiza formation and function (Smith et al., 1981a), on 
total populations of bacteria, actynomyces, fungi (Roslycky, 1977; 
Haley, 1979; Tchipilska, 1980; Smith et al., 1981a), or on 24 
different species of soil fauna taken from 2 plots at a depth of 
3.8 cm (Curry, 1970). 

    Curry (1970), and Riley et al. (1976) made extensive 
studies of the effects of normal and high doses of paraquat on 
microarthropod and earthworm populations at sites at different 
stages of cultivation.  The herbicide was neither harmful nor 
repellant to earthworms, nor was there any evidence of a toxic 
effect or of paraquat accumulation in any species examined.  When 
the residues in the top 2.5 cm of soil reached 20 mg/kg, the 
highest concentration determined in  Allolbophora caliginosa, living 
near the surface, was 3.2 mg/kg (live weight).  Worms from highly-
dosed plots eliminated paraquat residues within 36 h, when placed 
in clean soil. 

5.2.  Effects of Residues on Crop Yields

    The absence of adverse effects from residual paraquat on the 
growth and yield of crops grown in paraquat-treated soils has been 
demonstrated by Knight & Tomlinson (1967), Damanakis et al. (1970), 
Newman & Wilkinson (1971), and Riley et al. (1976).  It is known 
that the paraquat-inactivation capacity of soils varies widely.  
Paraquat has been tested on soils of low adsorption capacity, it 
has been used repeatedly on the same soil (section 4.3.1) and has 
been tested at extremely high concentrations.  The absence of any 
reports or observations of long-term phytotoxic effects confirms 
the data obtained in greenhouse and laboratory studies. 

5.3.  Effects on Fish and Aquatic Organisms

    Despite variation in LC50s for fish (67 - 110 mg/litre after 
24 h, 38 - 62 mg/litre after 48 h, more than 25 - 32 mg/litre after 
96 h), the herbicide has proved to have a wide margin of safety for 
warm- and cold-water fish species (Calderbank, 1972).  The toxicity 

of paraquat for fish varies with the species, the size of the 
fish, and the softness or hardness of the water.  A large number 
of aquatic species have shown a 100% survival at 96 mg/litre over 
96 h, though the decreased oxygen concentration following decay of 
weeds, may be dangerous in extreme situations.  Rainbow trout 
tolerated 1 mg paraquat/litre water in prolonged toxicity tests 
and only a 30% mortality was recorded after 16 days of repeated 
exposure (Calderbank & Slade, 1976).  At the end of the test, 0.54 
mg paraquat/kg was found in the rainbow trout.  In a 7-day exposure 
test at 1 mg paraquat/litre, the herbicide was detected in the gut 
(0.41 mg/kg) and liver (0.35 mg/kg), but not in the meat of the 
fish (< 0.025 mg/kg).  Water snails collected from 2 ditches, 
12 weeks after treatment of the waters with 1 mg/litre were found 
to contain 0.43 mg herbicide/kg.  Fish (major carp fingerlings) 
exposed to paraquat in the presence of weeds were more susceptible 
than those in weed-free environments (Singh & Yadav, 1978), owing 
to the changed oxygen content of the water.  Where there is heavy 
weed growth, the oxygen taken up by weed decay may dangerously 
reduce the oxygen available for aquatic organisms.  To avoid this, 
as far as possible, paraquat should be applied before weed growth 
becomes dense and only to one part of the water-course or lake at 
a time (FAO/WHO, 1973). 

5.4.  Effects on Birds

    Paraquat is less toxic for birds than for mammals.  The acute 
oral LD50 for the hen is 262 - 380 mg/kg body weight (Table 11).  
The acute oral and 24-h percutaneous (applied to feet) LD50 for 
mallards are 200 and 600 mg/kg body weight, respectively (Hudson et 
al., 1979).  For duck, pheasants, and quail, LC50 values of 
paraquat when mixed in the diet are 1000 mg/kg of food or more 
(Summers, 1980); residues on sprayed vegetation would not therefore 
be expected to present a hazard for birds. 

    When paraquat was sprayed directly on to pheasants' eggs before 
incubation, treatment rates up to 2 kg paraquat/ha did not have any 
effect on egg hatchability or on the birds' reproductive organs 
(Newman & Edwards, 1980).  In a similar study with Japanese quail 
eggs, sprays containing paraquat levels of up to 3 kg/ha did not 
have any effect on hatchability or development of reproductive 
organs (Edwards et al., 1979).  Thus, normal spray rates should not 
induce any adverse effects, even if paraquat is sprayed directly on 
eggs. 

    Bird populations have been monitored in detail, over a 5-year 
period, on a farm in the United Kingdom where paraquat use was much 
higher than normal; the average application to the whole arable 
area was 0.6 kg/ha per year.  The paraquat was applied beneath 
hedgerows and along fence lines.  The farm maintained an excellent 
wild bird population (40 species), including ground-nesting birds 
(Edwards, 1979).  Most species were at a similar or greater density 
than the national average in the United Kingdom. 

    The Ministry of Agriculture, Fisheries, and Food in the United 
Kingdom has carried out detailed investigations on mammalian and 
avian deaths that could have been caused by pesticides.  For the 
period 1971 - 81, the normal use of pesticide was not found to have 
caused any significant adverse effects on mammals and birds (MAFF, 
1980a, 1981).  The Ministry concluded, "It is widely believed that 
the use and misuse of paraquat is responsible for a considerable 
number of wildlife casualties.  There is no evidence from the 
investigations to support this allegation...." (MAFF, 1980b). 

6.  KINETICS AND METABOLISM

6.1.  Animal Studies

6.1.1.  Absorption

6.1.1.1.  Oral absorption

    Daniel & Gage (1966) studied the absorption of 14C-paraquat 
following oral and subcutaneous single-dose administration to rats.  
About 76 - 90% of the oral doses were found in the faeces, and 
11 - 20% in the urine; most of the subcutaneous dose (73 - 88%) 
was found in the urine and only 2 - 14.2% in the faeces.  This, 
together with the absence of marked biliary excretion, was evidence 
that paraquat was poorly absorbed from the gut.  This low rate of 
absorption was confirmed by Litchfield et al. (1973) and Conning et 
al. (1969).  Rats, guinea-pigs, and monkeys orally administered 
LD50 doses of 14C-paraquat had low peak serum concentrations 
(2.1 - 4.8 mg/litre) (Murray & Gibson, 1974).  The radioactivity 
levels reached a maximum 30 - 60 min after administration and then 
remained relatively constant for 32 h.  A dose of 126 mg/kg body 
weight resulted in a rat serum level of 4.8 - 4.7 mg/litre. 

    In fasting dogs, low oral doses of paraquat were rapidly but 
incompletely absorbed, the peak plasma concentration being attained 
75 min after dosing (Bennett et al., 1976).  After an oral dose of 
0.12 mg/kg body weight, 46 - 66% was absorbed in 6 h.  For doses of 
2 - 5 mg/kg, only 22 - 38% and 25 - 28% of the dose was absorbed, 
respectively.  Dose-dependent data from dogs and whole-body 
autoradiography suggest that absorption is facilitated in the small 
intestine.  Some non-ionic surfactants (0.001%) increased 14C-
paraquat transport through isolated gastric mucosa models, but 
histological evaluation suggested that this was due to damage of 
the epithelial cell membranes (Walters et al., 1981). 

6.1.1.2.  Pulmonary absorption

    Absorption of paraquat following instillation and inhalation in 
the lung has been described in several studies (Gage, 1968a; 
Kimbrough & Gaines, 1970; Seidenfeld et al., 1978; Popenoe, 1979).  
The uptake of 14C-paraquat after an intratracheal injection of 
1.86 nmol/lung was investigated in the isolated perfused rat lung 
by Charles et al. (1978).  The efflux of 14C-paraquat was diphasic 
with a rapid phase half-life of 2.65 min and a slow phase half-life 
of 356 min.  It was suggested that the slow phase represented a 
storage pool, possibly responsible for the pulmonary toxicity of 
paraquat.  Various doses of 3H-paraquat (10-5 - 10-12 g) in 0.1 ml 
saline were introduced directly into the left bronchus of rats 
(Wyatt et al., 1981).  Fifteen min after instilling 10-8 of 3H-
paraquat, 90% of the ion could be accounted for in the tissues and 
urine, 50% being present in the lung.  With doses at or greater 
than 10-5 g, pathological changes were seen in the lung, similar to 
those seen after systemic poisoning.  Zavala & Rhodes (1978) 
reported that the lung of the rabbit was highly sensitive to 
paraquat intrabronchial instillation in doses ranging from 

0.1 g - 1 pg; moderately sensitive to intraveneously administered 
paraquat (25 mg/kg body weight); resistant to the herbicide when 
given intraperitoneally or subcutaneously (25 mg/kg body weight). 

6.1.1.3.  Dermal absorption

    Paraquat absorption through animal and human skin has been 
studied using an  in vitro technique (Walker et al., 1983).  Human 
skin was shown to be impermeable to paraquat, having a very low 
permeability constant of 0.73.  Furthermore, human skin was found 
to be at least 40 times less permeable than animal skins tested 
(including rat, rabbit, and guinea-pig). There are no  in vivo 
studies on the rate of absorption of paraquat through the skin.  
However, observations of dose-related dermal toxicity in 
experimental animals and human percutaneous poisoning have provided 
some qualitative information concerning the dermal absorption of 
paraquat (further discussed in section 8.2.2.2). 

6.1.2.  Distribution

    Since the most characteristic feature of paraquat toxicity is 
lung damage, it is important to stress the high concentrations and 
retention of paraquat in the lung tissues, relative to other 
tissues, following oral, intravenous, intraperitoneal, 
subcutaneous, and intrabronchial routes of administration in rats, 
guinea-pigs, and monkeys (Sharp et al., 1972; Ilett et al., 1974; 
Murray & Gibson, 1974; Kurisaki & Sato, 1979; Waddell & Marlowe, 
1980).  An association between paraquat concentrations in the lung 
and degree of toxicity or lung injury has been reported (Sharp et 
al., 1972; Ilett et al., 1974; Waddell & Marlowe, 1980; Wyatt et 
al., 1981).  Some of their data are summarized in Tables 9 and 10. 
Table 9.  Paraquat distribution in tissues
---------------------------------------------------------------------------
Route of entry      Dose       Species  Time after  Tissue  Concentration
                                        treatment
---------------------------------------------------------------------------
1. Intrabronchial   10 ng      rat      60 min      plasma  0.0092 µg/litre
                                                    lung    5.2 ng
                                                    kidney  0.052 ng
                                                    liver   -
                                                    heart   -
                                                    brain   -


2. Intravenous      20 mg/kg   rat      24 h        plasma  0.7 mg/litre
                                                    lung    8.0 mg/kg
                                                    kidney  1.45 mg/kg
                                                    liver   0.48 µg/g
                                                    heart   0.75 mg/kg
                                                    brain   -
---------------------------------------------------------------------------

Table 9.  (contd.)
---------------------------------------------------------------------------
Route of entry      Dose       Species  Time after  Tissue  Concentration
                                        treatment
---------------------------------------------------------------------------
3. Intravenous      20 mg/kg   rat      24 h        plasma  ND
                                                    lung    11.36 µm/kg
                                                    kidney  1.93 µmol/kg
                                                    liver   0.90 µmol/kg
                                                    heart   1.13 µmol/kg
                                                    brain   0.87 µmol/kg


                    20 mg/kg   rabbit   24 h        plasma  0.28 µmol/litre
                                                    lung    7.9 nm/g
                                                    kidney  5.25 µmol/kg
                                                    liver   1.59 µmol/kg
                                                    heart   1.52 µmol/kg
                                                    brain   0.49 µmol/kg
                                                            
4. Intraperitoneal  15 mg/kg   rat      24 h        plasma  0.32 µmol/litre
                                                    lung    26.28 µm/kg
                                                    kidney  10.4 µmol/kg
                                                    liver   5.04 µmol/kg
                                                    heart   4.59 nmol/g
                                                    brain   1.22 µmol/kg

5. Oral             126 mg/kg  rat      16 h        plasma  0.90 mg/litre
                                                    lung    5.0 mg/kg
                                                    kidney  7.00 mg/kg
                                                    liver   2.1 mg/kg
                                                    heart   2.7 mg/kg
                                                    brain   -

                    22 mg/kg   guinea-  16 h        plasma  0.03 mg/litre
                               pig                  lung    1.29 mg/kg
                                                    kidney  1.99 mg/kg
                                                    liver   0.08 mg/kg
                                                    heart   0.31 mg/kg
                                                    brain   -
---------------------------------------------------------------------------
1.  From:  Wyatt et al. (1981).
2.  From:  Sharp et al. (1972).
3.  From:  Ilett et al. (1974).
4.  From:  Maling et al. (1978).
5.  From:  Murray & Gibson (1974).

Table 10.  Paraquat distribution in tissues (in mg/kg (mean) tissue)
----------------------------------------------------------------------------
Route of Entry  Dose     Species  Time    Lung  Kidney  Liver  Heart  Plasma
                (mg/kg            after
                body              dosing
                weight)
----------------------------------------------------------------------------
1. Oral         126      rat      1 h     3.3   27.5    2.0    1.8    4.7
                                  4 h     3.7   4.5     4.4    0.9    0.8
                                  32 h    13.6  9.4     5.7    2.8    1.1
                                  64 h    1.7   1.0     7.7    0.2    0.1

2. Intravenous  20       rat      1 h     9.0   25.0    5.0    -      6.0
                                  4 h     8.0   6.0     2.0    -      0.3
                                  24 h    6.0   1.0     0.4    -      0.07
                                  2 days  4.0   0.8     0.3    -      0.05
----------------------------------------------------------------------------
1.  From:  Murray & Gibson (1974).
2.  From:  Sharp et al. (1972).
    Toxic doses of paraquat were administered orally and iv to rats 
(Sharp et al., 1972).  Paraquat concentrations in the whole blood 
were the same as those in the plasma.  The distribution of the 
herbicide in various tissues was then followed for 10 - 18 days.  
The lung had the greatest retention and consequently contained the 
highest concentration 4 h after dosing.  Four to 10 days after 
dosing, the paraquat concentration in the lung was 30 - 80 times 
higher than that in the plasma.  The high lung-tissue 
concentrations of paraquat were confirmed by Ilett et al. (1974) 
for rats and rabbits after iv injection of 20 mg 14C-paraquat/kg 
body weight.  Although the herbicide showed a selective 
localization in rabbit lung, the concentration decreased far more 
rapidly in rabbit lung than in rat lung.  The rabbit did not show 
any histological or biochemical signs of lung damage, and no 
evidence of covalent binding of paraquat in lung tissue was found 
by Ilett et al. (1974).  After thorough washing of tissue 
precipitate with dilute trichloroacetic acid, only insignificant 
amounts of 14C-paraquat were detected in protein from the brain, 
heart, kidney, liver, lung, and plasma. 

    Autoradiographic studies using 14C-paraquat have been carried 
out on mice and rats (Litchfield et al., 1973).  Paraquat was 
observed in nearly all organs 10 min after intravenous injection of 
20 mg/kg body weight.  Waddell & Marlowe (1980) obtained similar 
autoradiographic results in mice, after intravenous injection of 
288 - 338 µg 3H-paraquat dichloride/kg body weight.  Cellular 
resolution autoradiography showed that paraquat was confined almost 
entirely to cells having the distribution of alveolar Type II 
cells.  These cells are known to be susceptible to the toxicity of 
paraquat (Kimbrough & Gaines, 1970).  Waddell & Marlowe (1980) 
suggested that it was unlikely that the radioactivity was bound to 
cellular constituents. 

    No paraquat was detected in rat kidney, brain, liver, or lung 
when paraquat was administered in the diet at a concentration of 
50 mg/kg for a period of 8 weeks.  At 120 mg/kg, it was found in 
low concentrations in the lung, kidney, gastrointestinal system, 
and brain (Litchfield et al., 1973).  At 250 mg/kg, it was detected 
in the tissues within 2 weeks.  No sex differences or any clear 
pattern of accumulation were noted throughout the 8-week study.  
Within 1 week of return to a normal diet, no paraquat was detected 
in any tissue examined.  Histological changes were observed in all 
lungs of animals fed paraquat at 250 mg/kg diet. 

    Rose et al. (1974a) demonstrated an energy-dependent 
accumulation of paraquat in slices of rat lung that obeyed 
saturation kinetics.  The same investigators also examined the 
ability of paraquat to accumulate in tissue slices from other 
organs  in vitro (Rose & Smith, 1977).  The herbicide in brain, 
adrenal gland, and kidney slices accumulated; however, the uptake 
was less than 10% of that observed in the lung slices.  The authors 
established the uptake of paraquat by the lung in various species 
(rat, rabbit, dog, monkey, man).  The human lung accumulated 
paraquat as strongly as that of the rat and there was a 
relationship between the concentration of paraquat in the different 
lung areas and the development of microscopic lung lesions.  It has 
been demonstrated that the rate of paraquat efflux from lung tissue 
is less than its rate of accumulation in the lung slices (Smith et 
al., 1981).  Efflux from lung slices, prepared from rats dosed iv 
with the herbicide, was found to be biphasic.  There was a fast 
component (half-life 20 min), followed by a first-order slow 
component characterized by a half-life of 17 h.  The half-life  in 
 vitro was similar to that seen  in vivo following iv 
administration to rats. 

6.1.3.  Metabolic transformation and excretion

    Paraquat participates to a considerable extent in cyclic 
reduction-oxidation reactions.  After undergoing a single electron 
reduction in tissues, the resultant free radical is readily 
oxidized by molecular oxygen to the parent compound (section 6.3).  
This leads to an overall excretion of essentially unchanged 
paraquat in the urine after oral administration to rats (Murray & 
Gibson, 1974). 

    Daniel & Gage (1966) reported that paraquat was metabolized by 
gut microflora following oral dosing of rats.  This observation was 
not confirmed in subsequent studies (Murray & Gibson, 1974) and was 
later attributed to a problem with the method (FAO/WHO, 1977). 

    Urinary concentrations of paraquat following oral 
administration are relatively low (Daniel & Gage, 1966:  Murray & 
Gibson, 1974; Sharp et al., 1972; Maling et al., 1978) and are thus 
used to estimate its elimination from the body. 

    Sharp et al. (1972) reported a biphasic elimination of paraquat 
from the plasma of rats after iv injection.  The initial rapid 
phase had a 20 - 30 min half-life, and the slower phase a half-life 

of 56 h.  Murray & Gibson (1974) also showed prolonged paraquat 
elimination after oral administration to rats, guinea-pigs, and 
monkeys.  The urinary and faecal routes were equally important in 
all species studied.  The faecal content was due mainly to 
elimination of unabsorbed paraquat.  Prolonged elimination of 
paraquat in all animals tested indicated retention of the herbicide 
in the body. 

    Following iv administration to rats, about 75 - 79% of the dose 
was excreted in the urine within 6 h (Maling et al., 1978).  The 
plasma disappearance of an iv dose of paraquat of 5 mg/kg was 
fitted to a 3-compartment model.  Total body clearance was 
estimated to be 8.39 ± 0.54 ml/kg per min (Maling et al., 1978).  
The relatively high concentration of paraquat in the duodenal and 
jejunal walls suggested biliary secretion of the herbicide, and the 
authors' hypothesis was supported by the observation of radio-
activity in the intestines of mice in whole-body autoradiographic 
studies (Waddell & Marlowe, 1980). 

    Since absorbed paraquat is mainly removed via the kidneys, the 
early onset of renal failure will have a marked effect on paraquat 
elimination and distribution, including accumulation in the lung.  
Hawksworth et al. (1981) used the dog as a model to evaluate the 
influence of paraquat-induced renal failure on the kinetics of 
paraquat elimination.  After iv injection of a trace dose of 14C-
paraquat (30 - 50 µg/kg body weight) in dogs, the kinetics of 
distribution was described by a 3-compartment model.  To obtain a 
good fit of the curve, it was necessary to sample the central 
(plasma) compartment for at least 24 h after dosing.  Simulation of 
paraquat levels in the peripheral compartments suggested the 
existence of a compartment with rapid uptake and removal (kidney) 
and another with slow uptake (lung).  The renal clearance of 
paraquat approximated total body clearance indicating that paraquat 
elimination occurs through renal excretion.  The urinary excretion 
rate of an iv dose was rapid, approximately 80 - 90% of the dose 
being eliminated during the first 6 h.  Intravenous injection of a 
large toxic dose of paraquat (20 mg/kg body weight), however, 
brought about a marked decrease in renal clearance, from 73 ml/min 
to 18 ml/min after 2 1/2 h and 2 ml/min after 6 h.  This data 
suggested that damaged renal tubules could contribute to paraquat 
accumulation in the lung. 

6.2.  Observations on Human Beings

6.2.1.  Observations on paraquat poisoning after ingestion:
non-fatal cases

    Tompsett (1970) reported a case of ingestion of 45 g of Weedol 
(2.5% paraquat).  On hospital admission, the gastric aspirate 
contained 0.215 g paraquat/litre and the urine 0.148 g/litre.  
After 2 - 4 h, paraquat concentrations dropped to 5.1 mg/litre in 
the urine and 0.4 mg/litre in the serum but, 16 - 24 h after 
admission, the urinary level was 0.95 mg/litre, while no paraquat 
was detectable in the serum.  Paraquat was also detected in the 

urine for up to 15 days after poisoning, while at the same time 
serum concentrations were below the detectable limits in chemical 
analysis (Fletcher, 1975). 

    The cumulative elimination of paraquat in the faeces and urine 
of a patient was followed for 7 days by van Dijk et al. (1975).  
Faecal elimination increased from 340 mg the first day to 530 mg 
after 7 days, while cumulative urinary excretion reached 60 mg the 
lst day and increased to 75 mg after 7 days.  It was calculated 
that only 87 mg of paraquat had been absorbed from a total 
ingestion of about 637 mg, determined in the urine, dialysate, and 
faeces.  In this patient, less than 14% of the ingested paraquat 
was absorbed through the gastrointestinal system. 

6.2.2.  Observations on paraquat poisoning after ingestion:  
fatal cases

    It is well established that paraquat lung disease resulting in 
death is usually preceded or accompanied by renal insufficiency.  
This contributes to the retention of paraquat in body tissues.  
Nevertheless, Fairshter et al. (1979) detected only small 
concentrations (below 0.09 mg/kg) of paraquat in several organs of 
patients who died 3 weeks after ingestion. 

    The detection of 27 mg paraquat/litre in the bile of a woman 
after autopsy suggested that some faecal paraquat might be 
attributable to biliary excretion (Dijk et al., 1975). 

6.2.3.  Significance of paraquat concentrations in cases of
paraquat poisoning

    Not only oral ingestion, but also dermal absorption of paraquat 
after occupational overexposure, resulted in measurable urinary 
levels of paraquat.  The determination of paraquat in urine and 
serum is an important biological exposure test for the diagnosis 
and the prognosis in cases of human poisoning. 

    Wright et al. (1978) followed the urinary excretion of paraquat 
in 16 patients (7 of whom died).  The total amount of paraquat 
excreted ranged from 0.6 mg to 386 mg.  The excretion rate 
decreased rapidly during the 48 h following ingestion, though less 
rapidly in the patients who eventually died.  All patients 
excreting 1 mg of paraquat or more per hour, for 8 h or more after 
ingestion, died. 

    Plasma-paraquat concentrations were measured by gas 
chromatography, radioimmunoassay, and colorimetric methods in 79 
patients with paraquat poisoning (Proudfoot & Stewart, 1979).  At 
any given time after ingestion (within a limit of 35 h), plasma 
concentrations were significantly higher in the patients who died 
(Fig. 4).  Patients whose plasma concentrations were not higher 
than 2.0, 0.6, 0.3, 0.16, and 0.10 mg paraquat/litre at 
respectively, 4 h, 6 h, 10 h, 16 h, and 24 h after the poisoning, 
were likely to survive.  When plasma levels exceeded 0.3 mg/litre 

15 h after ingestion, a fatal outcome could be expected, despite 
treatment.  These conclusions were supported by the studies 
performed on 28 patients by Bismuth et al. (1982). 

FIGURE 4

6.3.  Biochemical Mechanisms

    The mechanism of the toxic action of paraquat has been
extensively investigated.  Several reviews or monographs have
summarized the biochemical mechanism of paraquat toxicity in
plants (Calderbank, 1968), bacteria (Fridovich & Hassan,
1979), and animals (Bus et al., 1976; Autor, 1977; Smith et
al., 1979; Bus & Gibson, in press).

    Paraquat has long been known to participate in cyclic 
reduction-oxidation reactions in biological systems.  The compound 
readily undergoes a single electron reduction in tissues, forming a 
free radical.  In an aerobic environment, however, a free radical 
is immediately oxidized by molecular oxygen, generating the 
superoxide radical (O2-).  The reoxidized paraquat is capable of 
accepting another electron and continuing the electron transfer 
reactions in a catalytic manner (Fig. 5).  Research into the 
mechanism of paraquat toxicity has identified at least 2 partially 
toxic consequences of the redox cycling reaction:  a) generation of 
O2-, and b) oxidation of cellular NADPH, which is the major source 

of reducing equivalence for the intracellular reduction of 
paraquat.  Generation of O2- can lead to the formation of more 
toxic forms of reduced oxygen, hydrogen peroxide (H2O2) and 
hydroxyl radicals (OH-).  Hydroxyl radicals have been implicated in 
the initiation of the membrane-damaging by lipid peroxidation, 
depolymerization of hyaluronic acid, inactivation of proteins and 
damage to DNA (Hassan & Fridovich, 1980).  Depletion of NADPH, on 
the other hand, may disrupt important NADPH-requiring biochemical 
processes such as fatty acid synthesis (Smith et al., 1979). 

FIGURE 5

    The importance of molecular oxygen and the potential role of O2- 
generation in mediating have been implicated in studies on plants 
(section 3.3), bacteria, and in  in vitro and  in vivo mammalian 
systems.  In cultures of  Escherichia coli, Hassan & Fridovich 
(1977, 1978, 1979) demonstrated that paraquat stimulated cyanide-
resistant respiration, which could be almost entirely accounted for 
by an NADPH-dependent formation of O2-.  The possibility that 
formation of O2- might be responsible for the toxicity of paraquat 
in bacteria was supported by observations that bacteria containing 
elevated activities of superoxide dismutase, an enzyme that 
detoxifies O2-, were resistant to paraquat toxicity (Hassan & 
Fridovich, 1977, 1978; Moody & Hassan, 1982). 

     In vitro studies on preparations of lung and liver from various 
animal species have supported the hypothesis that paraquat redox 
cycling and associated O2- and H2O2 generation also occur in 
mammalian systems (Gage, 1968b; Ilett et al., 1974; Montgomery, 
1976, 1977; Steffen & Netter, 1979; Talcott et al., 1979).  Bus et 
al. (1974) reported that the single electron reduction of paraquat 
in mammalian systems was catalysed by microsomal cytochrome P-450 
reductase and NADPH.  The observation that the  in vivo toxicity of 
paraquat in animals is markedly potentiated by exposure to elevated 
oxygen tensions further supported the potential role for molecular 
oxygen in mediating toxicity (Fisher et al., 1973b; Autor, 1974; 
Bus & Gibson, l975; Witschi et al., 1977; Kehrer et al., 1979; 
Keeling et al., 1981). 

    The results of  in vivo studies conducted by Bus et al. (1974) 
suggested that stimulation of lipid peroxidation, which was 
dependent on paraquat redox cycling and associated O2- generation, 
might be an important toxic mechanism in mammalian systems.  
Consistent with this hypothesis, animals fed diets deficient in 
selenium or vitamin E, in order to diminish cellular antioxidant 

defences, were significantly more sensitive to paraquat toxicity 
than control animals (Bus et al., 1975; Omaye et al., 1978).  In 
contrast to these studies, a number of studies have shown that 
paraquat inhibited  in vitro microsomal lipid peroxidation (Ilett 
et al., 1974; Montgomery & Niewoehner, 1979; Steffen & Netter, 
1979; Kornburst & Mavis, 1980).  Subsequent studies have indicated, 
however, that paraquat would stimulate microsomal lipid 
peroxidation when an adequate supply of electrons (NADPH) and  in 
 vitro oxygen tensions were maintained (Trush et al., 1981, 1982). 

    Despite the evidence described above, the hypothesis that lipid 
peroxidation is the underlying toxic mechanism functioning  in vivo 
has not been conclusively demonstrated.  Direct quantification of
paraquat-induced lipid peroxidation damage  in vivo by analysis of 
tissue malondialdehyde levels or ethane exhalation, both markers of 
peroxidation injury, has been largely unsuccessful (Reddy et al., 
1977; Shu et al., 1979; Steffen et al., 1980).  Furthermore, 
attempts to counteract paraquat toxicity by administration of 
various antioxidants have also been unsuccessful (Fairshter, 1981). 

    Superoxide radicals generated in paraquat redox cycling may 
induce biochemical changes other than the initiation of 
peroxidation reactions.  Ross et al. (1979) demonstrated that 
paraquat increased DNA strand breaks in cultured mouse 
lymphoblasts.  Paraquat was also reported to induce a superoxide-
dependent stimulation of guanylate cyclase (EC 4.6.1.2) activity in 
rat liver (Viseley et al., 1979) and guinea-pig lung (Giri & 
Krishna, 1980).  These investigators postulated that increased 
cyclic GMP might stimulate the pulmonary fibroproliferative changes 
characteristic of paraquat toxicity (section 7.1.1.1).  In other 
studies, paraquat has also been found to increase collagen 
synthesis in rat lung (Hollinger & Chvapel, 1977; Greenberg et al., 
1978; Thompson & Patrick, 1978; Hussain & Bhatnagar, 1979). 

    Redox cycling of paraquat has also been proposed to lead to 
increased oxidation of cellular NADPH (Brigelius et al., 1981; 
Keeling et al., 1982).  The activity of pentose shunt enzymes in 
the lung rapidly increased in rats administered paraquat, which 
suggested an increased demand for NADPH (Fisher et al., 1975; Rose 
et al., 1976).  The observation that paraquat decreased fatty-acid 
synthesis in lung slices (Smith et al., 1979) further supported 
this hypothesis, since fatty acid synthesis requires NADPH.  Direct 
analysis of NADPH in the lung has confirmed that paraquat treatment 
decreased the NADPH content in rat lung (Witschi et al., 1977; 
Smith et al., 1979).  These observations led Smith et al. (1979) to 
propose that oxidation of NADPH might not only interrupt vital 
physiological processes, such as fatty-acid synthesis, but also 
render tissues more susceptible to lipid peroxidation by decreasing 
the equivalents (NADPH) necessary for the function of the 
antioxidant enzyme glutathione peroxidase (EC 1.11.1.9) (Fig. 6). 

FIGURE 6

7.  EFFECTS ON ANIMALS

7.1.  Effects on Experimental Animals

7.1.1.  Respiratory system

    Toxicity studies in rats, mice, dogs, and monkeys (Clark et 
al., 1966; Kimbrough & Gaines, 1970; Murray & Gibson, 1972; 
Makovskii, 1972; Kelly et al., 1978) demonstrated that paraquat had 
a specific effect on the lung (Table 11).  Administration by every 
route of entry tested whether parenteral (Fisher et al., 1973a; 
Robertson, 1973; Hunsdorfer & Rose, 1980), oral (Clark et al., 
1966; Bainova, 1969a; Kimbrough, 1974; Tsutsui et al., 1976; 
Dikshith et al., 1979), dermal (Howe & Wright, 1965; Bainova, 
1969b; McElligott, 1972), or inhalatory (Gage, 1968b; Bainova, 
1971; Makovskii, 1972; Seidenfeld et al., 1978) resulted in 
irreversible changes in the lung. 

    Clark et al. (1966) reported that, in rats, in the earlier 
stages after a single toxic oral dose of paraquat, breathing was 
gasping or deep and fast, but some days after a single or repeated 
toxic doses, the respiration became increasingly laboured, and the 
hairs around the mouth and nares were soiled with a brownish 
liquid.  The extensive alveolar oedema observed in severe 
intoxication was responsible for the development of hypoxia, 
cyanosis, and dyspnoea.  The progressive development of pulmonary 
fibrosis was accompanied by difficulty in breathing, gasping, and 
hyperpnoea (Smith et al., 1973). 

    Exposure of rats to high concentrations of respirable paraquat 
aerosols was accompanied by shallow respiration.  Within 2 - 3 h, 
the test animals became dyspnoeic, cyanotic, and inactive, and 
there were signs of local eye and nose irritation (Gage, 1968a). 

7.1.1.1.  Pathomorphological lung studies

    Macroscopic examination of the lungs revealed that lesions and 
their severity were dependent on the dose of paraquat and the time 
between exposure and sacrifice (or death).  The wet weight of the 
lung increased after a single treatment, owing to oedema and 
haemorrhage.  The pathogenesis of the paraquat lung lesion has been 
well characterized, and has been reviewed by Smith & Heath (1976).  
The acute pulmonary toxicity of paraquat in animals has been 
described as occurring in two phases (Smith & Heath, 1976).  In the 
initial "destructive" phase, alveolar epithelial cells were 
extensively damaged and their subsequent disintegration often 
resulted in a completely denuded alveolar basement membrane. 


Table 11.  Effects on experimental animals of repeated oral, dermal, or inhalation exposure to paraquat
---------------------------------------------------------------------------------------------------------
Species  Dosage               Duration      Effects obtained                         Reference
---------------------------------------------------------------------------------------------------------
Rat      diet - 125 mg/kg     2 years       no toxic effects                         Howe & Wright (1965)

Dog      diet - 50 mg/kg                    no toxic effects

Rat      diet - 0.25 mg/kg    27 days       death; histological changes in the lung  Clark et al. (1966)

Rat      diet - 300, 400,     90 days       cumulative toxic effects; chronicity     Kimbrough & Gaines
         500, 600, 700 mg/kg                factor (Hayes) 5.2; histological         (1970)
                                            changes in the lung

Rat      oral - 4, 9, 25      30 days       inhibition of ChE activity, increasing   Bainova (1969, 1975)
         mg/kg body weight                  GPT activity in the serum; biochemical 
         per day                            and histological changes in the lung, 
                                            kidney, liver

Rat      oral - 1.3, 2.6      4 1/2 months  increased GPT and G-6-P-isomease         Bainova (1969, 1975)
         mg/kg body weight                  activities in the serum; biochemical 
         per day                            and histological changes in lung, 
                                            kidney, liver

Rat      oral - 3.3, 1.3,     1 year        the higher doses were toxic for both     Makovskii (1972)
         0.13 mg/kg body                    species tested; no-observed-adverse-
         weight per day                     effect levels:
Guinea-  oral - 1.0, 0.4,                   for rat 0.13, guinea-pig 0.04 mg/kg 
pig      0.04 mg/kg body                    body weight per day
         weight per day

Rat      diet - 20 - 30       30 days       histological and electron-optical lung   Kimbrough (1974)
         mg/kg body weight                  changes
         per day

Mouse    diet - 25, 50, 70    80 weeks      death; dose-dependent clinical and       FAO/WHO (1973)
         mg/kg                              histological changes in the lung, 
                                            liver, kidney, and other organs tested

Rat      oral - 25, 50,       1 - 5 days    body weight loss; increased serum LDH,   Tsutsui et al. 
         100 mg/kg body                     GOT activity; no haematological          (1976)
         weight per day                     changes; histological changes in the 
                                            lung, kidney, liver, myocardium
---------------------------------------------------------------------------------------------------------

Table 11.  (contd.)
---------------------------------------------------------------------------------------------------------
Species  Dosage               Duration      Effects obtained                         Reference
---------------------------------------------------------------------------------------------------------
Rat      drinking-water -     2 years       mortality increased; histological        Bainova & Vulcheva
         1.3, 2.6 mg/litre                  changes in the lung, but only minimal    (1977)
                                            at the lowest level

Rabbit   dermal - 2.8, 4.5,   20 days       skin irritation; mortality and toxic     Clark et al. (1966)
         7, 14 mg/kg body                   effects at 7 & 14 mg/kg/day. LD50 
         weight per day                     mg/kg/day; no-observed-adverse-effect 
                                            level 2.8 mg/kg/day

Rat      dermal - 2, 5, 15,   21 days       skin irritation; mortality and toxic     Bainova (1969a)
         30, 45 mg/kg body                  effects at 5 - 45 mg/kg/day; 
         weight per day                     histological changes in the lung, 
                                            kidney, liver, myocardium; LD50
                                            15 mg/kg/day; no-observed-adverse-
                                            effect level 2 mg/kg/day

Rabbit   dermal - from 1.56   20 days       skin irritation; mortality and toxic     McElligott (1972)
         - 50 mg/kg per day                 effects at 3.13 - 192 mg/kg/day; LD50  
         (with occlusion)                   4.5 mg/kg/day with occlusion and 24 
         from 2.4 - 192 mg/kg               mg/kg/day without occlusion; No-
         body weight per day                observed-adverse-effect levels: 1.56 
         (without occlusion)                and 2.4 mg/kg/day with and without 
                                            occlusion

Rat      inhalationa -        4 days        at higher concentrations (0.40 & 0.75    Gage (1968)
         0.75 mg/m3                         mg/m3) histological changes in the 
         0.4, 0.1, 0.06 mg/m3 15 days       lung; no-observed-adverse-effect levels
         0.003 mg/m3          60 days       from 0.003 - 0.06 mg/m3 6 h  daily; 
         6 h daily                          TLV - 0.1 mg/m3 paraquat aerosol


Rat      inhalationa -        4 1/2 months  biochemical, histochemical, and          Bainova et al. 
         1.1, 0.05 mg/m3                    histological changes in the lung at      (1972)
         6 h daily                          1.1 mg/m3 no-observed-adverse-effect  
                                            level below 0.05 mg/m3 paraquat aerosol
---------------------------------------------------------------------------------------------------------

Table 11.  (contd.)
---------------------------------------------------------------------------------------------------------
Species  Dosage               Duration      Effects obtained                         Reference
---------------------------------------------------------------------------------------------------------
Rabbit   inhalationa -        3 months      no clinical, functional and              Seidenfeld et al.
         10 mg paraquat in                  histological changes in the lung; no     (1978)
         100 ml water for the               toxic effects
         aerosol  2 h daily
---------------------------------------------------------------------------------------------------------
a  Respirable paraquat aerosol.
    Pulmonary oedema was also a characteristic of the destructive 
phase, and was frequently of sufficient severity to result in the 
death of the animals.  Animals surviving the initial destructive 
phase, which occurred in the first 1 - 4 days after acute paraquat 
overexposure, progressed to what has been termed the 
"proliferative" phase.  In this phase, the lung was infiltrated 
with profibroblastic cells that rapidly differentiated into 
fibroblasts which, in some cases, progressed to fibrosis.  The 
histopathological outcome of the second phase may be influenced by 
the treatment regimen, however.  Administration of repeated low 
doses of paraquat, which less severely damaged the alveolar 
epithelial cells, could also induce a hyperplasia of the Type II 
cells.  This response may represent an attempt by the lung to 
repair the damaged epithelium. 

    Following a single high dose of paraquat to animals, the 
earliest ultrastructural changes were observed in the Type I 
alveolar epithelial cells, approximately 4 - 6 h after treatment, 
and were usually characterized by cellular and mitochondrial 
swelling, increased numbers of mitochondria, and the appearance of 
dark granules in the cytoplasm.  When a high dose (approximately 
LD50 or greater) was given, the lesions in the Type I cells often 
progressed to the point of complete cellular disintegration leaving 
areas of exposed basement membrane (Kimbrough & Gaines, 1970; Smith 
et al., 1973; Smith & Heath, 1974; Vijeyaratnam & Corrin, 1971; 
Klika et al., 1980). 

    In contrast to the effects on Type I pneumocytes, however, the 
capillary endothelial cells were remarkably resistant to the toxic 
effects of paraquat (Sykes et al., 1977). 

    Ultrastructural lesions in the alveolar Type II pneumocytes 
were also observed shortly after single dose paraquat exposure, 
although, generally, these lesions were not apparent until after 
the first lesions were seen in the Type I cells (Kimbrough & 
Gaines, 1970).  Swollen mitochondria and damage to the lamellar 
bodies usually occurred between 8 and 24 h after a high dose of 
paraquat (Robertson, 1973; Robertson et al., 1976).  Progressive 
deterioration of the Type II cells continued, resulting in 
completely denuded alveolar basement membranes and debris-filled 
alveolar spaces (Vijeyaratnam & Corrin, 1971).  Infiltration and 
proliferation of fibroblasts may produce fibrosis that obliterates 
the alveolar structure (Smith & Heath 1974). 

    Vijeyaratnam & Corrin (1971) observed that less severely 
affected parts of the lung appeared to undergo epithelial 
regeneration, 7 - 14 days after a single dose of paraquat. 
Electron microscopic examination revealed the alveoli to be 
lined with cuboidal epithelial cells that closely resembled 
Type II pneumocytes except for a general lack of lamellar bodies.  
Similar phenomena have also been noted by other investigators who 
administered paraquat in the diet (Kimbrough & Linder, 1973) or as 
repetitive intraperitoneal administrations (Smith et al., 1974).  
Thus, in animals where the paraquat dose was sufficient to kill 
only the Type I pneumocytes, the surviving Type II cells repaired 

the damaged epithelium by proliferating and subsequently 
differentiating into Type I epithelial cells.  Inhaled paraquat in 
aerosol produced initial necrosis and sloughing of the epithelia 
and type 2 pneumocyte hyperplasia, fibroblast proliferation, and 
increased synthesis of collagen in mice (Popenoe, 1979). 

    Histochemical alterations have been noted in rats exposed 
through inhalation to 1.9 and 1.1 mg/m3 paraquat respirable 
aerosol, 6 h/day, 6 days/week, for 4 1/2 months.  The histoenzyme 
activity of NAD lactate dehydrogenase-diaphorase, beta-
glucuronidase (EC 3.2.1.31), and acid phosphatase (EC 3.1.3.2) was 
enhanced in the epithelial cells and in areas of pneumonitis 
(Bainova et al., 1972).  The changes were concentration-related, 
although the activity of succinate dehydrogenase (EC 1.3.99.1) and 
aspartate esterase appeared to be less pronounced in comparison 
with the controls (Bainova et al., 1972). 

7.1.1.2.  Species differences in lung injury

    Butler & Kleinerman (1971) injected rabbits intraperitoneally 
with total doses of from 2 - 100 mg/kg body weight.  Thymus atrophy 
was observed, but most lungs showed only occasional and small 
histological deviations that were poorly correlated with the 
clinical signs of paraquat intoxication. The study confirmed the 
resistance of the rabbit to paraquat-induced lung lesions (Clark et 
al., 1966), and no evidence of any kind of pulmonary disease was 
found; nor could significant lung injury be established in rabbits 
after 30 days ingestion of 11 mg paraquat/kg in distilled water 
(Dikshith et al., 1979).  However, some animals showed pulmonary 
fibrosis and emphysema, and a few changes were present in all 
parenchymatous organs (Mehani, 1972; Zavale & Rhodes, 1978; 
Dikshith et al., 1979).  The rabbit also proved to be less 
sensitive, than the rat, after inhalation exposure (Gage 1968a; 
Seidenfeld et al., 1978). 

    According to Murray & Gibson (1972), and Hundsdorfer & Rose 
(1980), guinea-pigs treated orally or sc did not develop the same 
type of progressive pulmonary fibrosis as paraquat-intoxicated 
rats.  In hamsters, a single administration did not induce lung 
damage, but prolonged exposure resulted in lung fibrosis (Butler, 
1975). 

    In conclusion, for lung toxicity studies, a characteristic 
dose-related pulmonary fibrosis can be induced in the rat, mouse, 
dog, and monkey (Murray & Gibson, 1972) but not in the rabbit, 
guinea-pig, or hamster. 

7.1.1.3.  Lung function studies

    Rabbits exposed to an aerosol of 200 mg paraquat in 100 ml 
distilled water (Seidenfeld et al., 1978) survived more than 3 
exposures but showed significantly reduced arterial oxygen tension 
and an increased alveolar arterial O2 gradient; specific compliance 
decreased and functional residual capacity and breathing frequency 
increased.  Lam et al. (1980) administered paraquat at 27 mg/kg 

body weight ip to rats and 0.5 mg/kg body weight intratracheally.  
After 12 h, decreases were observed in total lung capacity, 
functional residual capacity, vital capacity, residual volume, and 
alveolar volume.  These deviations persisted for 72 h.  Oral 
administration of paraquat at doses ranging from 1 mg/kg body 
weight - 13.5 mg/kg body weight to rats resulted in functional lung 
changes after 24 h. 

    Thus clinical, functional, and pathomorphological studies after 
single and repeated exposure demonstrated that the spectrum of 
paraquat lung disease depended on the magnitude of the dose and the 
manner of administration (Seidenfeld et al., 1978; Restuccia et 
al., 1974). 

7.1.2.  Renal system

    In paraquat toxicity, kidney damage often precedes signs of 
respiratory distress (Clark et al., 1966; Butler & Kleinerman, 
1971; Murray & Gibson, 1972) (Table 11).  Paraquat is excreted 
mainly via the urine and the concentrations of the herbicide in the 
kidneys are relatively high (section 6.1). Gross pathological and 
histological examinations of paraquat-poisoned rats, guinea-pigs, 
rabbits, and dogs revealed vacuolation of the convoluted renal 
tubules and proximal tubular necrosis (Bainova, 1969a; Murray & 
Gibson, 1972; Tsutsui et al., 1976).  The degeneration of the 
proximal tubular cells has also been confirmed by electron-optical 
studies (Fowler & Brooks, 1971; Marek et al., 1981). 

    Paraquat is actively secreted by the kidney base transport 
system.  The nephrotoxicity caused by paraquat is pronounced and 
appears to be restricted to the proximal nephron (Ecker et al., 
1975: Gibson & Cagen, 1977; Lock & Ishmael, 1979; Purser & Rose, 
1979). 

7.1.3.  Gastrointestinal tract and liver

    The clinical signs of acute and chronic oral poisoning 
(Kimbrough & Gaines, 1970; Murray & Gibson, 1972; Bainova, 1969a) 
or of ip injection (Butler & Kleinerman, 1971) include transient 
diarrhoea and body weight loss, decreased food intake, and 
dehydration.  Some of the animals vomited soon after paraquat 
administration.  Residual skin contamination after dermal toxicity 
studies on rabbits (McElligott, 1972) caused severe tongue 
ulceration and an unwillingness to eat.  The adverse irritant 
effects were minimized by continued restraint after skin 
decontamination of the treated rabbits. 

    There have been several reports of liver damage following 
exposure to high doses of paraquat (Clark et al., 1966; Bainova, 
1969a; Murray & Gibson, 1972; Tsutsui et al., 1976; Gibson & Cagen, 
1977, Cagen et al., 1976).  Centrilobular necrosis of hepatocytes 
with proliferation of the Kupfer cells and bile canals have been 
described. 

    In general, liver damage in experimental animals has not been 
severe compared with lung and kidney damage.  Serum enzyme 
activities (SGOT, SGPT, LAP) only increased when large amounts of 
paraquat were given (Giri et al., 1979). 

7.1.4.  Skin and eyes

    The herbicide can provoke local irritation of the skin and 
eyes.  Clark et al. (1966) found skin irritation in rabbits only 
when paraquat was applied beneath occlusive dressings in aqueous 
solutions (total dose 1.56, 5.0, and 6.25 mg ion/kg body weight).  
In mice and rats, the application of 5 - 20 g paraquat/litre 
solutions in single and 21-day repeated dermal toxicity tests 
provoked dose-related toxic dermatitis with erythema, oedema, 
desquamation, and necrosis (Bainova, 1969b).  Doses from 1.56 to 50 
mg/kg, in repeated 20-day studies using the occlusive technique 
(McElligott, 1972) resulted in local erythema and scab formation.  
The histological changes consisted of parakeratosis and occasional 
intra-epidermal pustules.  A delayed skin irritant action of the 
herbicide was reported by Fodri et al. (1977) in guinea-pig 
studies. 

    No skin sensitization was observed in studies on guinea-pigs 
when paraquat was applied (Bainova, 1969b; Fodri et al., 1977). 

    The instillation of dilutions of paraquat (up to 500 g/litre) 
in rabbit eye induced inflammation within 24 h and this continued 
for 96 h (Clark et al., 1966).  Sinow & Wei (1973) introduced 62.5, 
125, 250, 500, and 1000 paraquat/litre into the rabbit eye.  
Concentrations of 62.5 and 125 g/litre caused severe conjunctival 
reactions; higher levels (250 - 500 g/litre) provoked iritis and 
pannus, while at the 500 g/litre concentration there was corneal 
opacification, iritis, and conjunctivitis.  All rabbits receiving 
0.2 ml of paraquat at 1000 g/litre in 1 eye or 0.2 ml of a 
concentration of 500 g/litre in both eyes died within 6 days of 
application (Sinow & Wei, 1973). 

    Both conjunctival and dermal application of different 
concentrations induced systemic toxicity (Sinow & Wei, 1973; Clark 
et al., 1966; Bainova, 1969b; Kimbrough & Gaines, 1970; Makovskii, 
1972; McElligott, 1972), lung, kidney, and liver damage, and death. 

7.1.5.  Other systems

    No specific functional, histological, or biochemical effects of 
paraquat have been reported in other systems that have been 
examined; this is of prime importance in an evaluation of its 
toxicity.  When lethal doses of paraquat are given to rats, 
symptoms consistent with neurological disturbances have been 
observed.  These include decreased motor activity, lack of 
coordination, ataxia and dragging of the hind limbs (Smith et al., 
1973).  Also associated with near lethal or lethal doses are damage 
to the myocardium (Tsutsui et al., 1974), haemolytic anaemia 
(Bainova, 1969a), increased haemosiderin in the spleen (Bainova et 
al., 1972) and increased concentrations of plasma corticosteroids 
(Rose et al., 1974b). 

7.1.6.  Effects on reproduction, embryotoxicity, and teratogenicity

7.1.6.1.  Effects on reproduction

    Some histological changes in the testes have been reported in a 
few paraquat toxicity studies.  Butler & Kleinerman (1971) found 
multinuclear giant cells in rabbit testicular tubules.  When 
paraquat was orally administered at 4 mg/kg body weight to male 
rats for 60 days and the testes were examined, there were no 
significant deviations in the spermatozoa count or motility, nor 
were there any biochemical changes in the several enzymes of testes 
homogenates.  The histoenzyme activity of lactate dehydrogenase, 
succinate dehydrogenase, DPN-diaphorase, alkaline phosphatase, and 
acid phosphatase in the treated animals did not differ from that of 
the controls, nor did quantitative and qualitative histological 
examination of the testicular tubule cells reveal any abnormality. 

    A 3-generation reproduction study has been carried out on rats 
treated with paraquat ion at 100 mg/kg diet (FAO/WHO, 1973).  There 
were no significant abnormalities in fertility, fecundity, and 
neonatal morbidity or mortality, nor were there any signs of 
gonadotoxicity or structural or functional lesions.  Pulmonary 
function in the treated offspring was normal. 

    Clegg (1979) has reviewed animal reproduction and 
carcinogenicity studies conducted in relation to the safe use of 
pesticides. 

7.1.6.2.  Embryotoxicity and teratogenicity

    Oral or ip administration of high doses of paraquat to mice and 
rats on various days of gestation produced significant maternal 
toxicity, evidenced by increased mortality rates (Bainova & 
Vulcheva, 1974; Bus et al., 1975).  Examination of the fetuses from 
the higher-dose groups revealed a reduction in fetal body weights, 
delayed ossification of the sternabrae, and increased resorption 
rate in mice, as a result of the maternal intoxication.  The 
minimal embryotoxic effect seemed due in part to difficulty in 
crossing the placenta, reflected by low concentrations of paraquat 
in the embryo relative to maternal tissues (Bus et al., 1975).  The 
absence of a specific embryotoxic action of paraquat has also been 
observed and reported in other studies on rats (Khera et al., 1968; 
Luty et al., 1978), mice (Selypes et al., 1980), and rabbits 
(FAO/WHO, 1973). 

    In a perinatal toxicity study, Bus & Gibson (1975) administered 
paraquat at 50 or 100 mg/litre in the drinking-water to pregnant 
mice beginning on day 8 of gestation, with continued treatment of 
the litters up to 42 days after birth.  Paraquat treatment did not 
alter postnatal growth rate, although the mortality rate in the 100 
mg/litre-treated mice increased to 33% during the first 7 days 
after birth.  It was also noted that paraquat at 100 mg/litre 
significantly increased the sensitivity of the pups to oxygen 
toxicity on days 1, 28, and 42 after birth. 

7.1.7.  Mutagenicity

    Paraquat has been found to have minimal to no genotoxic 
activity when evaluated in a variety of  in vitro and  in vivo test 
systems.  In studies producing weakly positive results (Moody & 
Hassan, 1982; Parry 1977, 1973; Tweats, 1975; Benigni et al., 1979; 
Bignami & Grebelli, 1979), which were limited to  in vitro studies, 
paraquat genotoxicity was accompanied by high cytotoxicity.  These 
results are best explained by Moody & Hassan (1982), who showed 
that the mutagenicity of paraquat in bacterial test systems 
( Salmonella typhimurium TA 98 and TA 100) was mediated by the 
formation of superoxide.  However, other investigators (Andersen et 
al., 1972; Levin et al., 1982) did not find mutagenic activity in 
bacterial test systems.  Furthermore, paraquat was not mutagenic 
when evaluated in human leukocytes and in  in vivo cytogenetic 
tests on mouse bone marrow (Selypes & Paldy, 1978) and dominant 
lethal tests on mice (Pasi et al., 1974; Anderson et al., 1976). 

7.1.8.  Carcinogenicity

    A carcinogenicity study was performed on mice at dietary levels 
of 25, 50, and 75 mg/kg per day for 80 weeks (FAO/WHO, 1973).  
There were reduced weight gains among the animals receiving 
paraquat, but deaths during the study were associated with 
respiratory disease.  Clinical and histopathological examination 
determined that paraquat was not tumorigenic in mice. 

    A 2-year exposure of rats to 1.3 and 2.6 mg/litre, daily, in 
the drinking-water provoked histopathological changes in the lung, 
liver, kidney, and myocardium.  The lung lesions were dose-related; 
inflammation, atelectasis, reactive proliferation of the 
epithelium, pulmonary fibrosis, and pulmonary adenomatosis were 
noted, but no sign of tumour growth or atypism (Bainova & Vulcheva, 
1977).  Nor was any increased tumour incidence reported in rats in 
a 2-year study with a maximum dietary level of 250 mg/kg diet (12.5 
mg/kg body weight per day) (FAO/WHO, 1971). 

    Bainova & Vulcheva (1977) did not discover any indication of 
tumorigenicity in a 2-year study on rats receiving paraquat at 1.3 
or 2.6 mg/litre in their drinking-water (Table 11). 

    While testing the carcinogenicity of urethane in mice, Bojan et 
al. (1978) also attempted to evaluate the influence of paraquat on 
urethane-induced lung tumorigenesis.  It is felt that the results 
of this study are not of relevance for the assessment of the 
carcinogenic potential of paraquat. 

7.2.  Effects on Farm Animals

    The effects of paraquat on farm animals has been discussed in 
section 4.3.5.  The LD50 doses have been established for hen, 
turkey, cow, and sheep (Howe & Wright, 1965; Clark et al., 1966; 
Smalley, 1973).  Massive doses resulted in convulsions, 
neurological symptoms, and death due to respiratory failure. 

    Domestic animals may ingest paraquat by feeding on a sprayed 
area, as a result of spray drifting on to their pasture, by 
drinking water contaminated with paraquat used as an aquatic 
herbicide, or by feeding on a crop sprayed with paraquat as a 
dessicant.  Sheep and calves were given paraquat at concentrations 
of up to 20 mg/litre drinking-water for 1 month without any obvious 
ill effects (Howe & Wright, 1965; Calderbank, 1972), and a cow 
dosed with 2/3 of the LD50 of 14C-paraquat gave milk containing 
less than 0.1 mg/litre.  Field tests demonstrated that cattle did 
not suffer any toxic effects when turned loose on pasture after it 
had been sprayed with paraquat at 0.45 kg/ha.  The same trial 
showed that horses had local lesions of the mouth and increased 
mucous secretion after grazing on newly-sprayed pasture (Calderbank 
et al., 1968).  The hazard to stock feeding on such pasture depends 
on the density of the pasture, the dose of the herbicide, and the 
length of time that has elapsed since its application. 

    Paraquat was fed to cattle at levels in herbage of 200 - 400 
mg/kg for 1 month without any apparent ill effects, and no residues 
could be detected in the meat and milk (Calderbank et al., 1968). 

    However, all domestic animals should be kept far from freshly-
sprayed areas, and when crops are treated with paraquat, due 
attention should be paid to the accepted maximum residue limits. 

7.3.  Dose-Effect of Paraquat

    The acute LD50 values for paraquat in various species are given 
in Tables 12 and 13.  The acute toxicity studies of paraquat salts 
(dichloride, dimethylsulfate, dimethylphosphate) have not shown 
any significant differences in the acute oral and ip LD50 in rats 
(Clark et al., 1966; Makovskii, 1972). 

    There were no significant differences in the oral LD50 values 
obtained for the same species from different laboratories, but the 
acute oral LD50 values among the species examined varied. 

    The effects of repeated paraquat exposure are summarized in 
Table 11.  Paraquat was administered, orally and in the diet, to 
rats, mice, guinea-pigs, and dogs.  The guinea-pigs appeared to be 
very sensitive (Makovskii, 1972).  According to Kimbrough & Gaines 
(1970), Makovskii (1972), and Bainova (1975), the herbicide has a 
moderate cumulative toxicity.  The joint FAO/WHO meeting (1976) 
decided on a no-observed-adverse-effect level of 1.5 mg/kg body 
weight per day in the rat and 1.25 mg/kg body weight per day in the 
dog.  As can be seen from Table 11, effects at lower levels have 
been observed in other studies. 

    Guinea-pigs, monkeys, cattle, and human subjects are more 
sensitive, while rats and birds are less sensitive to paraquat 
through the gastrointestinal route. 

Table 12.  Paraquat LD50 (mg/kg body weight) and LC50
(mg/m3) in various species
-------------------------------------------------------------------
Species/Sex     Oral        Dermal         Inhalation LC50
                LD50        LD50           respirable
                                           paraquat aerosol
-------------------------------------------------------------------
Rat             200a                       1c
Rat (F)         100e        90e            10f
Rat (M)         110e        80e            10f
Rat             126i        350g           6g

Mouse                       62d

Rabbit                      500a
Rabbit                      236b
Rabbit                      240h

Guinea-pig      40 - 80a
Guinea-pig (M)  30b
Guinea-pig      22i
Guinea-pig      42g         319g           4g

Monkey          50i

Cat             40 - 50a
Cat (F)         35b

Hen             300 - 380a
Hen             262b

Turkey          250 - 280j  approximately
                            375j

Cow             50 - 75a

Sheep           50 - 75a
-------------------------------------------------------------------
a  Howe & Wright (1965).
b  Clark et al. (1966).
c  Gage (1968).
d  Bainova (1971).
e  Kimbrough & Gaines (1970).
f  Bainova & Vulcheva (1972).
g  Makovskii (1972).
h  McElligott (1972).
i  Murray & Gibson (1972).
j  Smalley (1973).

Table 13.  Paraquat LD50 (mg/kg body weight) after parenteral 
treatment
-------------------------------------------------------------------
Species/Sex     Subcutaneous      Intraperitoneal       Intravenous
-------------------------------------------------------------------
Rat (F)                           19a

Rat             22b

Mouse                             30e                   50d

Guinea-pig (F)                    3a

Guinea-pig      5b

Turkey                            100c                  20c
-------------------------------------------------------------------
a  Clark et al. (1966).         d  Ecker et al. (1975).
b  Makovskii (1972).            e  Bus et al. (1975).
c  Smalley (1973).                                  

7.4.  Methods for Decreasing Paraquat Toxicity

    These have been studied in connection with requirements in the 
case of paraquat poisoning in man.  Clark (1971) showed the 
efficacy of Bentonite and Fuller's earth in binding orally 
administered paraquat and preventing its absorption from the 
gastrointestinal tract.  Staiff et al. (1973) reported the high 
adsorption capacity of Amerlite.  Smith et al. (1974) found 
considerably reduced plasma-paraquat levels after the combined 
treatment of rats with purgatives and bentonite suspension; these 
rats survived a dose that normally killed 90 - 100% of the animals.  
The absorption capacities of six absorbent materials were tested by 
Okonek et al. (1982) who demonstrated that activated charcoal was 
the most successful in absorbing ingested paraquat in rats. 

    Another way of decreasing paraquat absorption is to introduce 
an emetic in the concentrated formulations.  Kawai et al. (1980) 
examined the protection this provided in fasting and non-fasting 
male and female dogs that were given paraquat containing an emetic.  
The amount of paraquat eliminated by vomiting was 61 - 86% of the 
orally-administered dose.  In the group given paraquat only, the 
blood level averaged 44 mg/litre; in the group given paraquat and 
emetic, it was 0.26 mg/litre. 

7.5.  Relation Between Age, Sex, and Toxicity

    There is no evidence that paraquat is more toxic to either sex 
of adult experimental animals (section 7.3)  Young rats were more 
resistant than older rats, and some authors have paralleled this 
resistance with that of young rats to oxygen toxicity.  Smith & 
Rose (1977b) found a more than 40% increase in cumulative mortality 
in 180 g rats compared with 50 g rats, after oral dosing with 
paraquat at 680 µmol/kg body weight.  According to Smith & Rose 
(1977b), the difference in renal function between young and mature 
rats accounted for the difference in paraquat toxicity. 

8.  EFFECTS ON MAN

8.1.  Accidental and Suicidal Poisoning

8.1.1.  Case reports

    The first fatalities from acute paraquat poisoning occurred in 
1964 and were reported in 1966 (Bullivant, 1966).  By 1977, 600 
deaths had been reported following accidental or intentional 
ingestion of paraquat.  The number of accidental cases of poisoning 
is small relative to instances of suicide.  Because of different 
requirements or practices for notification or reporting of cases of 
poisoning in the many countries in which paraquat is used, the 
magnitude of the problem is difficult, if not impossible, to 
determine.  Some representative reports on acute paraquat poisoning 
are summarised in Table 14. 

    The earlier cases of paraquat intoxication were mostly 
accidental (Fennelly et al., 1968; Matthew et al., 1968; Masterson 
& Roche, 1970; Malone et al., 1971).  These cases seemed to have 
resulted mainly from the habit of decanting the liquid formulations 
into small unmarked or incorrectly labelled containers such as 
beer, wine, or soft-drink bottles. 

    An increased ratio of suicidal to accidental poisoning has been 
noted in recent years (Fletcher, 1975; Carson & Carson, 1976; 
Fitzgerald et al., 1978a; Bramley & Hart, 1983).  This change from 
accidental to suicidal poisoning was also reflected in the enhanced 
percentage of fatal cases, shorter survival times, and 
significantly higher tissue and body fluid levels (Connolly et al., 
1975; McGeown, 1975; Park et al., 1975; Carson & Carson, 1976; 
Howard, 1979a; Sugaya et al., 1980; Bismuth et al., 1982). 

    While the vast majority of poisoning cases are due to 
swallowing, a small number of fatal cases of accidental paraquat 
poisoning via the skin have been reported when liquid concentrates 
(200 g/litre) have been applied in order to kill body lice (Ongom 
et al., 1974; Binns, 1976).  A few other fatal and non-fatal cases 
have been reported following skin-contamination (McDonagh & Martin, 
1970; Kimura et al., 1980). 


Table 14.  Case report data on accidental and suicidal acute paraquat poisoning
-------------------------------------------------------------------------------
Number of cases      Fatal     Non-fatal  Fatality  Reference
-------------------------------------------------------------------------------
19                   12        7          63%       Malone et al. (1971)

24   3 accidental    10        14         42%       Connolly et al. (1975)
     19 suicidal
     2 homicidal

25   10 accidental   17        8          68%       McGeown (1975)

31   7 accidental    18        13         58%       Park et al. (1975)
     21 suicidal
     3 homicidal

33   7 accidental    26        7          79%       Carson & Carson (1976)
     19 suicidal

16                   7         9          44%       Wright et al. (1978)

136  77 suicidal     92        44         68%       Fitzgerald et al. (1978)

10                   10        0          100%      Natori et al. (1979)

188                  69        119        37%       Higginbottom et al. (1979)

79                   28        51         35%       Proudfoot et al. (1979)

68   68 suicidal     41        27         66%       Howard (1979)

6    6 suicidal      5         1          83%       Sugaya et al. (1980)

28   12 suicidal     17        11         61%       Bismuth et al. (1982)

262  95% deliberate  94 (36%)  168 (64%)  36%       Bramley & Hart (1983)
     intent
-------------------------------------------------------------------------------
8.1.2.  Distribution of cases of paraquat poisoning

    Cases of acute paraquat poisoning have been reported in: 
Bulgaria (Mircev, 1976), Denmark (Pederson et al.,1981), England, 
Ireland, Scotland, and the Netherlands (Fletcher, 1975), the 
Federal Republic of Germany (Grundies et al., 1971; Hofman & 
Frohberg, 1972; Fletcher, 1975; Fischer & Kahler, 1979), France 
(Faure et al., 1973; Gervais et al., 1975; Bismuth et al., 1982; 
Efthymiou, 1983), Hungary (Farago et al., 1981), Poland (Firlik, 
1978), Switzerland (Schlatter, 1976), the USA (Kimbrough, 1974; 
Dearden et al., 1978; Stephens et a1., 1981), and in Yugoslavia 
(Vucinovic, 1978). Recently, a number of cases of paraquat 
poisoning, mainly suicidal, have also been reported in Japan 
(Takahashi et al., 1978; Natori et al., 1979; Tomura et al., 1979; 
Kimura et al., 1980; Matsumoto et al., 1981).  No attempt has been 
made to make this list exhaustive, in fact the distribution is 
worldwide. 

8.1.3.  Route of entry

    By far the most frequent route of poisoning has been ingestion.  
An unusual case of subcutaneous injection of 1 ml paraquat by a 
mentally disturbed farmer was reported in Israel (Almog & Tal, 
1967).  Cases of dermal poisoning have been mentioned in section 
8.1.1.  There is no evidence of fatal poisoning as a result of 
inhalation. 

8.1.4.  Formulations

    Paraquat trade names are listed in Table 3.  Concentrated 
liquid formulations have been responsible for most (and more 
severe) poisonings than granular forms, which contain less paraquat 
(McGeown, 1975; Park et al., 1975; Fitzgerald & Barnville, 1978; 
Wright et al., 1978; Higginbottom et al., 1979; Howard, 1979a). 

8.1.5.  Dose

    The minimum lethal dose of paraquat is stated to be about 35 
mg/kg body weight for human beings (Pederson et al., 1981; Bismuth 
et al., 1982). 

    Symptoms of poisoning depend on the dose absorbed.  It is 
difficult to estimate the dose absorbed from case histories since 
in many cases the patients spat out part of the paraquat 
concentrate or vomited profusely after swallowing the herbicide.  
Some patients have survived after apparently ingesting 50 - 100 ml 
Gramoxone(R) (10 - 20 g paraquat), whereas some died after taking 
as little as 2 sachets of Weedol (2.5 g paraquat) (Table 15). 

    Howard (1979) demonstrated the relationship between the dose of 
paraquat ingested, the time elapsing between ingestion and 
institution of treatment, and the ultimate outcome in 68 cases of 
intentional paraquat poisoning. 

8.1.6.  Clinical and pathomorphological data relating to fatal 
paraquat poisoning

    Cases of fatal poisoning can be sub-divided into cases of:

    (a) acute fulminant poisoning from a massive dose leading
        to generalized systemic poisoning and death from a
        combination of acute pulmonary oedema, oliguria,
        hepatocellular and adrenal failure and biochemical
        disturbances (death usually occurs within 1 - 4 days);

    (b) less overwhelming poisoning with slower onset of
        organ failure and death from pulmonary oedema,
        mediastinitis, and complications of therapy (McGeown,
        1975; Fitzgerald et al., 1978a); and

    (c) late pulmonary fibrosis (death ensuing 4 days to
        several weeks later).


Table 15.  Recovery from paraquat poisoning involving lung dysfunction
---------------------------------------------------------------------------------------------------------
Dose of paraquat  Major organ       Notes                                                 Reference
ingested          damage
---------------------------------------------------------------------------------------------------------
50 ml             kidney, liver,    vomiting; pains in stomach; changes in urine          Grundies et al. 
                  lung              and serum                                             (1971)

15 ml approx.     lung              nausea; buccal lesions; chest X-ray: poor             Lloyd (1969)
                                    aeration at lung bases

10 ml approx.     kidney, lung      oliguria; changed renal function; basal rales;        Fisher et al. 
                                    chest X-ray: small bilateral, pleural effusions;      (1971)
                                    limited atelectasis; functional lung change

not specified     kidney, liver,    oliguria; serum, and urine changes; minimal           Fennelly et al. 
                  lung              deviations in the respiratory function                (1971)

30 ml approx.     kidney, liver     nausea; oliguria; ECG changes; chest X-ray:           Galloway & 
                  myocardium, lung  increased vascular markings                           Petrie (1972)

granular          kidney, liver,    14 cases with mild oral, renal, lung, and liver       Fitzgerald & 
paraquat          lung              impairment                                            Barniville 
                                                                                          (1978)

50 ml             kidney, liver,    vomiting; diarrhoea; abdominal pain; serum and urine  Rose (1980)
                  lung              changes; dyspnoea, decreased forced vital capacity;
                                    chest X-ray: extensive perivascular changes
---------------------------------------------------------------------------------------------------------
8.1.6.1.  Respiratory system

(a)  Clinical data

    Soon after ingestion, there is oropharyngeal pain and swelling, 
followed within a few days by exudation, ulceration, and mucosal 
sloughing, sometimes with pseudomembrane formation, which on 
occasion leads to total sloughing of the oropharynx and oesophagus 
(Malone et al., 1971).  In severe poisoning, pulmonary oedema 
rapidly ensues with clinical and functional deterioration until 
death.  Less intense, but ultimately fatal, poisoning causes 
progressive pulmonary fibrosis over days or several weeks, with 
gradually increasing dyspnoea and hypoxaemic pulmonary failure.  
Pulmonary oedema may occur from fluid overload in oliguric 
patients.  Mediasteinitis and pneumothorax are occasionally seen 
(Dearden et al., 1978; Kimura et al., 1980). 

    Pulmonary function tests reflect the underlying pathology, with 
hypoxaemia, reduction in lung volume, high alveolar-arterial 
gradient, and impaired gas transfer (Cooke et al., 1973, 
Higginbottom et al., 1979).  Chest radiographs may show bilateral 
pulmonary oedema, coalescing consolidations, and later, sequential 
changes of pulmonary fibrosis (Davidson & McPherson, 1972). 

(b)  Pathology

    At autopsy, the lungs do not collapse properly and the pleural 
cavity contains a small amount of fluid.  In cases of lung 
fibrosis, the lungs are heavy, firm, dark purple, and rubbery.  
Consolidation and decreased aeration are found predominantly at the 
bases.  Emphysema and atelectasis are often found. 

    Histological studies following lung biopsy and necropsy show 
pulmonary oedema, haemorrhages, and atelectasis due to pulmonary 
infiltrates, loss of alveolar epithelial cells and, at a later 
stage, interstitial and intra-alveolar fibrosis (Smith & Heath, 
1976). 

    During the first 7 days of paraquat poisoning in man, loss of 
alveolar epithelial cells has been seen with alterations in, or 
detachment of, the type I and II cells, proliferation of 
fibroblasts and polymorphous cells, loss of surfactant secretion, 
and thickening of the alveolar septa by interstitial fibrosis 
(Toner et al., 1970).  The later findings (2 - 3 weeks) involved 
pulmonary fibrosis and endothelial abnormalities.  Dearden et al. 
(1978) reviewed the histological and electron-microscopic findings 
in human lungs.  Capillary permeability seemed to be enhanced 
either by vesicles forming transendothelial channels or by 
disruption of endothelial cells. 

8.1.6.2.  Renal system

    Acute oliguric renal failure is common in severely poisoned 
patients.  Less severe manifestations include impaired renal 
function, which may disappear before the pulmonary fibrosis 

progresses (Beebeejaun et al., 1971; Fisher et al., 1971; Fletcher, 
1975; Natori et al., 1979; Grant et al., 1980).  Other 
manifestations include proteinuria, with hyaline casts, white and 
red blood cells.  Tubular damage is reflected in glycosuria, 
aminoaciduria, and excessive leaking of phosphorus, sodium, and 
uric acid (Vaziri et al., 1979). 

    Soft, pale, swollen kidneys with extensive tubular necrosis, 
compatible with toxic injury, are found at necropsy (Beebeejaun et 
al., 1971).  Sometimes necrosis of the proximal tubules is found 
together with extreme dilatation of the distal tubules of the 
kidney (Shuzui, 1980). 

8.1.6.3.  Gastrointestinal system, the liver, and the pancreas

    The initial symptoms after oral ingestion of paraquat are 
nausea, vomiting, upper abdominal pain, and diarrhoea. Perforation 
of the oesophagus is uncommon (Ackrill et al., 1978; Natori et al. 
1979). 

    The ingestion of large doses of paraquat has resulted in severe 
liver damage (Ward et al., 1976; Grant et al., 1980) with 
progressive metabolic acidosis (Shuzui, 1980; Sugaya et al., 1980).  
Fatty degeneration of periportal hepatocytes and sporadic cellular 
necrosis in the central region of the liver lobules have been 
described (Matsumoto et al., 1980).  Cholestasis and portal 
inflammation may occur (Matsumoto et al., 1981).  Oedematous 
degeneration or necrosis of both the intra-hepatic and extra-
hepatic bile ducts, and of the gall bladder, have also been noted 
(Mullick et al., 1981). 

    Takayama et al. (1978) noted stasis of the pancreatic duct, 
with increased serum amylase levels after severe paraquat 
poisoning. 

8.1.6.4.  Cardiovascular system

    Occasionally, toxic myocarditis after paraquat ingestion has 
been described (Bullivant, 1966; Malone et al., 1971; Copland et 
al., 1974; Grant et al., 1980). 

    Takahashi et al. (1978) found fibrinoidal necrosis of the small 
arteries in the pancreas, kidney, and liver on days 3 - 6 following 
ingestion. 

8.1.6.5.  Central nervous system

    The ingestion of very high doses of paraquat provoked anxiety, 
convulsions, ataxia, and semi-consciousness (Grant et al., 1980; 
Mukada et al., 1978).  Haemorrhagic leukoencephalopathy was 
present throughout the central nervous system, involving almost 
exclusively the white matter.  Focal haemorrhage and 
demyelinization were present at various stages together with 
haemorrhagic meningitis. 

8.1.6.6.  Adrenal glands

    Adrenal cortical necrosis may contribute to death in severe 
paraquat poisoning and the severity of the damage appears to be 
dose-related (Nagy, 1970; McGeown, 1975; Fitzgerald et al., 1977a; 
Takahashi et al., 1978). 

8.1.6.7.  Pregnancy

    A woman, who accidentally swallowed paraquat in the 28th week 
of pregnancy (Fennelly et al., 1968), died 20 days later.  Gross 
pathological examination did not reveal any abnormalities in the 
fetal organs. 

    A woman, in the 7th month of pregnancy, intentionally ingested 
about 60 ml of technical paraquat (Takeuchi et al., 1980) and 
vomited approximately half that amount.  Oliguria, jaundice, and 
cough with sputum production progressed; fetal heartbeat 
disappeared on the l3th day and the next day the dead fetus was 
delivered.  The mother died on the l7th day after poisoning.  The 
lungs of the dead fetus were filled with the debris of amniotic 
fluid; the fetus had begun intra-uterine respiration to compensate 
for the insufficient oxygen supply.  No symptoms of paraquat 
poisoning were noted in the body of the neonate. 

    A case report published by Musson & Porter (1982) concerning 
paraquat ingestion by a 20-week pregnant woman, confirmed the lack 
of teratogenic risk in human beings.  The pregnancy was allowed to 
continue after the treatment of the mother.  The infant was 
followed up to the age of 3 years and did well clinically, with 
normal laboratory tests, development, and behaviour. 

8.1.7.  Recovery from paraquat poisoning

    In the largest series reported (68 - 188 cases) (Fitzgerald et 
al., 1978a; Higginbottom et al., 1979; Howard, 1979a; Proudfoot et 
al., 1979), survival rates varied from 32% to 65% (Table 14)  
Factors determining recovery from paraquat poisoning, reviewed by 
Fletcher (1975), McGeown (1975), Fitzgerald & Barniville (1978), 
Howard (1979a), and Bismuth et al. (1982), are shown in Table 16. 

    Victims of paraquat poisoning, who escape major pulmonary 
complications, usually recover fully within a few weeks of 
ingestion.  Renal, gastrointestinal, and hepatic manifestations 
return to normal (Fisher et al., 1971; Beebeejaun et al., 1971; 
Grundies et al., 1971; Galloways & Petrie, 1972). 

    Minor pulmonary functional and radiographic abnormalities may 
be transient and are of doubtful relationship to paraquat lung 
injury.  Some patients have recovered despite major pulmonary 
abnormalities (Table 15).  Among 5 survivors, Schlatter (1976) 
reported no signs of lung residual disorders.  Fitzgerald et al., 
(1979a) followed, for at least a year, 13 survivors of paraquat 
poisoning to determine the prevalence of residual pulmonary 
disability.  Of 11 adults, 5 (all non-smokers) did not have any 

clinical, radiological, or functional evidence of pulmonary 
dysfunction; 4 others (all smokers) were considered normal on 
clinical and chest X-ray examination, but had a mild deficit in 
pulmonary function, while the remaining 2 adults were known to have 
suffered from respiratory disability before the paraquat poisoning.  
Only 1 patient showed new and persistent lung infiltrates that 
could be ascribed to permanent paraquat lung damage.  No 
abnormalities were discovered in the 2 children studied. 

Table 16.  Factors determining recovery from paraquat poisoning
-------------------------------------------------------------------------
No.  Factor            Notes
-------------------------------------------------------------------------
1.   Route of entry    Most paraquat poisonings have occurred following
                       ingestion; ingestion following a meal usually has
                       less serious consequences; skin contamination
                       with liquid concentrate formulations is dangerous;
                       poisoning through inhalation is usually benign

2.   Dose              Dose rarely known, but usually, for survivors,
                       less than 6 g paraquat, often, spat out or vomited
                       after ingestion

3.   Intention         High mortality rates established in suicidal or
                       homicidal poisoning; many more survivors reported
                       reported among cases of accidental poisoning

4.   Formulation       High mortality rate registered after ingestion of
     ingested          liquid concentrates; survivors have more often 
                       than not ingested dilute or granular formulations

5.   Time of starting  Treatment should start as soon as possible; delay
     treatment         of more than 2 - 5 h reduces chances of survival;
                       patients hospitalized several days after paraquat
                       ingestion have minimal chance of recovery

6.   Decreased         Occurs when there is vomiting, use of emetics
     gastrointestinal  stomach washout, application of adsorbents (such
     absorption        as Fuller's Earth or bentonite), single or 
                       repeated, and forced diarrhoea; such treatment
                       should be as prompt as possible; a delay of more
                       than 5 h adversely affects the safe and effective
                       elimination of paraquat; care should be taken to
                       avoid complications (aspiration of Fuller's Earth,
                       oesophagal perforation)

7.   Blood paraquat    Fig. 6 (section 6.2.3) demonstrates importance of
     concentrations    paraquat plasma concentrations for prognosis

8.   Urine paraquat    Patients excreting more than 1 mg paraquat/h, 8 h
     concentrations    or more after ingestion, unlikely to recover

9.   Renal function    Patients with severe renal damage or renal failure
                       usually die
-------------------------------------------------------------------------

Table 16.  (contd.)
-------------------------------------------------------------------------
No.  Factor            Notes
-------------------------------------------------------------------------
10.  Forced diuresis   Should not be instituted when renal damage with
                       oliguria present; caution needed during the first
                       24 h

11.  Haemodialysis     Important if forced diuresis cannot be carried out
-------------------------------------------------------------------------

8.2.  Occupational Exposure

8.2.1.  Epidemiological studies and case reports

8.2.1.1.  Spraying personnel

    Paraquat has been in agricultural use since the early 1960s and 
several surveys have been conducted on spray operators (Swan, 1969; 
Hearn & Kier, 1971; Makovskii, 1972; Staiff et al., 1975; Seiber & 
Woodrow, 1981; Howard, 1979b, 1980, 1982; Chester & Ward, 1981; 
Howard et al., 1981; Chester & Woollen, 1982; Wojeck et al., 1983).  
Some of these studies were aimed at clinically evaluating possible 
adverse effects, others at estimating inhalatory and dermal 
exposure.  Some of the latter studies have been summarised in Table 
17 from which it can be seen that: 

    (a) the main route of exposure of agricultural workers to
        paraquat is via the skin; respiratory exposure is
        negligible.

    (b) The worst case of exposure (of those examined) was
        via knapsack spraying.


Table 17.  Comparison of dermal and inhalation exposure resulting 
from various methods of application
--------------------------------------------------------------------
Method of application        Dermal exposure    Respiratory exposure
                             (mg/h)             (mg/h)
--------------------------------------------------------------------
Hand-held knapsacka          66                 (0.45 - 1.3) x 10-3
                             (12.1 - 169.8)

Vehicle mountedb             0.4                0 - 2 x 10-3
                             (0.1 - 3.4)

Aerialc -   a) Flagman       0.1 - 2.4          0 - 47 x 10-3
            b) Pilot         0.5 - 0.1          0 - 0.6 x 10-3
            c) Mixer/loader  0.18               1.3 - 1.5 x 10-3
--------------------------------------------------------------------
a  From:  Chester & Woolen (1982).
b  From:  Staiff et al. (1975).
c  From:  Chester & Ward (1981).

    In Malaysian rubber plantations, exposure is likely to be 
greater than in most other situations (Swan, 1969).  Weed control 
is required continuously for 10 months of the year, and the 
herbicide is applied by knapsack sprayers during the entire working 
day, 6 days a week.  The high temperature and humidity together 
with the light clothing of the sprayers increase the potential risk 
of dermal exposure.  In 1965, a study was carried out on a team of 
6 sprayers, and in 1967 on 4 teams, to estimate the efficacy of 
protective measures.  The operators used spray dilutions containing 
paraquat at 0.5 g/litre, for 12 weeks.  Attention was paid to 
personal hygiene.  Each man was given a thorough physical 
examination, and urine samples were taken before spraying began and 
at weekly intervals throughout the study.  Paraquat analyses were 
carried out using the method of Calderbank & Yuen (1965).  Chest 
X-rays were taken before the study started and at the end of the 
6th and 12th weeks. 

    In the course of the 2 studies, a total of 528 urine samples 
were examined.  Paraquat was found on 131 occasions, the maximum 
concentration detected being 0.32 mg/litre in the first study and 
0.15 mg/litre in the second.  Average urine levels of paraquat of 
0.04 mg/litre were found in the 1965 study, and of 0.006 mg/litre 
in the 1967 study.  After spraying ceased, these levels declined 
steadily to become undetectable within a week - with one exception.  
It was concluded that the workers were not subjected to hazardous 
levels of paraquat. 

    Both trials showed that about half of the men had suffered mild 
irritation of the skin and eyes, but had recovered rapidly with 
treatment.  Two cases of scrotal dermatitis occurred in workers 
wearing trousers that were continuously soaked by the spray 
solution.  There were also 2 cases of epistaxis.  All chest 
radiographs were normal. 

    Studies over a period of several years on 296 workers were 
performed by Hearn & Keir (1971) on a Trinidad sugar estate. This 
survey drew attention to nail damage following gross contamination 
with paraquat at 1 - 2 g/litre that ranged in severity from 
localized discoloration to nail loss.  The typical distribution of 
the lesions - affecting the index, middle, and ring fingers of the 
working hand - suggested that they had occurred through leakage 
from the knapsack sprayer, and inadequate personal hygiene.  Apart 
from 2 cases of contact dermatitis of the hands, no skin, eye, or 
nose irritation was reported, nor were there any systemic effects. 

    Similar data were obtained by Makovskii (1972), who examined 
several groups of workers spraying paraquat as a herbicide and 
dessicant in cotton fields during the hot season.  These workers 
were exposed to paraquat aerosol concentrations of 0.13 - 0.55 
mg/m3 air.  Dermal exposure was low, not more than 0.05 - 0.08 mg 
paraquat on the hands and face.  There were no complaints, nor did 
the clinical and laboratory examinations of the workers demonstrate 
any significant deviations from the matched control groups. 

    In the USA (Staiff et al., 1975), the exposure of field workers 
operating tractor-mounted spray equipment in orchards was 
determined.  About 4.6 litre paraquat liquid concentrate (291 
g/litre) was used in 935 litre water per h.  In addition, exposures 
from yard and garden applications were studied in volunteers using 
pressurized hand dispensers containing paraquat solution (4.4 
g/litre).  Dermal contamination was measured by adsorbent cellulose 
pads attached to the worker's body or clothing, and by hand-rinsing 
in water in a polyethylene bag.  Special filter pads were used in 
the filter cartridges of the respirators worn by the subjects under 
study. 

    In all, 230 dermal and respiratory exposure pads, 95 samples of 
hand-rinse water, and 130 urine samples, collected during and 
following the spray, were analysed.  This involved 35 different 
paraquat application situations.  The exposure of field workers was 
found to range from about 0.40 mg/h (dermal) to less than 0.001 
mg/h (inhalation).  As for individuals spraying the yard or garden, 
exposure ranged from 0.29 mg/h (dermal) to less than 0.001 mg/h 
(inhalation). 

    In almost all cases, dermal exposure affected the hands. The 
respiratory paraquat values were generally below the sensitivity 
level of the analytical method.  No detectable paraquat 
concentrations were found in the urine samples (lower limit 0.02 
mg/litre).  This study confirmed the general safety of paraquat 
under correct conditions of use. 

    The potential long-term hazard associated with the use of 
paraquat has also been studied.  Howard et al. (1981) studied the 
health of 27 spraymen who had been exposed to paraquat for many 
months per year for an average of 5.3 years, and compared them with 
two unexposed control groups consisting of 24 general workers and 
23 factory workers.  There were a few skin lesions resulting from 
poor spraying techniques and 1 case of eye injury.  The workers 
were given full clinical examinations and lung, liver, and kidney 
function tests were carried out.  There were no significant 
differences in all health parameters measured between the groups, 
which led the authors to suggest that the long-term use of paraquat 
was not associated with harmful effects on health. 

    A paraquat formulation (240 g/litre) diluted 300 times by 
volume with water was sprayed for 2 h on weedy ground (Kawai & 
Yoshida, 1981).  No irritation of the eyes and the skin was 
reported.  The urine of the workers who wore gauze masks contained 
1.4 - 2.7 µg paraquat, 24 h after the spraying.  The urine of 
workers who had worn a high-performance mask did not contain 
detectable levels of paraquat.  During the spraying operations, the 
concentration of paraquat aerosol was 11 - 33 µg/m3 air.  The total 
dermal exposure was about 0.22 mg.  The authors discussed the need 
for protective equipment to decrease skin contact with paraquat and 
to avoid aerosol inhalation. 

    Quantitative estimates of dermal and respiratory exposure of 26 
plantation workers in Malaysia (Chester & Woollen, 1982) have shown 
a mean dermal dose of 1.1 mg/kg body weight per h.  The highest 
individual total exposure was equivalent to 2.8 mg/kg body weight 
per h; the mean respiratory exposure was 0.24 - 0.97 µg paraquat/m3 
air.  Spray operators and carriers were exposed to an order of 1% 
or less of a TLV of 0.1 mg/m3 for respirable paraquat.  Urine 
levels of paraquat were generally below 0.05 mg/litre. 

    A study was carried out on a group of 14 spray men in Thailand 
using conventional high-volume knapsack sprayers and low-volume 
spinning disc applicators with paraquat ion concentrations of 1.5 
g/litre and 20 g/litre, respectively (Howard, 1982).  Irritation of 
unprotected skin was found, and this was severe in workers using 
high spray concentrations (caustic burns on the feet after work 
with spinning disc applicators and paraquat solution (20 g/litre)).  
Urinary paraquat levels after 14 days spraying were significantly 
higher (10.21 - 0.73 mg/litre) in unprotected men using both 
concentrations, and there was evidence that urinary levels of 
paraquat increased as the trial progressed.  No evidence of 
systemic toxicity was discovered among the spray men undergoing 
clinical and radiographic examination 1 week after spraying ended.  
The author concluded that spray concentrations in hand-held 
equipment should not exceed 5 g paraquat ion/litre. 

    After tomato spraying in the USA, the total body exposure to 
paraquat was determined to be 168.59 mg/h (Wojeck et al., 1983).  
The use of enclosed tractor cabs or a high clearance tractor 
reduced total body exposures to paraquat to 26.91 mg/h or 18.38 
mg/h, respectively.  The authors reported that the total body 
exposure of tractor spray men working in two citrus locations was 
proportional to the tank concentrations (paraquat dilutions of 1.1 
g/litre and 0.7 g/litre were applied); exposure levels of 28.50 
mg/h and 12.16 mg/h were found for workers using the higher and the 
lower concentrations, respectively.  In all situations studied, the 
respiratory exposure was consistently a small fraction (<0.1%) of 
the total body exposure.  Exposure was mainly through the skin. 

8.2.1.2.  Formulation workers

    Groups of workers exposed to formulations were examined by 
Howard (l979b).  The first group of 18 workers in England comprised 
subjects exposed to dust and liquid paraquat formulations during a 
37.5 h working week, the mean length of exposure being 5 years.  
The second group also comprised 18 males, from Malaysia, exposed to 
liquid concentrate formulations during a 42-h working week, the 
mean length of exposure being 2.3 years.  Partly protective 
clothing was worn.  However, in Malaysia, no gloves, rubber aprons, 
or goggles were used.  The medical records and the dermatological 
examinations revealed acute skin rashes, nail damage, epistaxis, 
blepharitis, and delayed wound healing in 12 - 66% of these 
workers.  Delayed caustic effects were often found among the 
Malaysian formulation workers where a lower level of safety and 
hygiene was apparent.  Clinical examination did not reveal any 
evidence of chronic contact dermatitis, hyperkeratosis, or 
eczematous lesions. 

8.2.2.  Cases of occupational poisoning and local caustic effects

    Hayes & Vaughan (1977) reviewed deaths from pesticides in the 
USA.  From 1956 - 1973, no deaths attributable to paraquat were 
registered among agricultural workers, but in 1974, 4 fatal cases 
were associated with this herbicide, although it was not clear 
whether they were accidental, suicidal, or occupational.  Conso 
(1979) reported 17 cases of skin and eye irritation, not 
accompanied by epistaxis or other signs of systemic effects, in 
paraquat-exposed workers in France.  Bismuth et al. (1983) 
discussed a few cases of paraquat poisoning due to skin 
contamination and eye irritation. 

    The available evidence indicates that, at the recommended 
dilution rates and correctly used, systemic oral, inhalation, or 
dermal effects should not be expected.  Skin and eye irritation 
have occurred only when protective measures were disregarded. 

    However, it should be emphasized that carelessness in handling 
paraquat may have serious consequences.  Fitzgerald et al. (1978a) 
summarized the clinical findings and pathological details 
concerning 13 accidents involving paraquat among agricultural 
workers, 6 of which were fatal. In 5 of these cases, swallowing was 
involved. 

8.2.2.1.  Oral ingestion

    The ingestion of paraquat may occur accidentally, if liquid 
concentrates are decanted into unlabelled containers near the 
working areas (Kawatomi et al., 1979), and dangerous ingestion can 
occur if operators suck or blow out the blocked pipes or nozzles of 
spray apparatus.  Of the 6 fatalities studied by Fitzgerald et al. 
(1978a), 3 swallowed Gramoxone(R) after sucking the outlet of a 
sprayer.  In one non-fatal case, the man had sucked out a nozzle 
containing diluted paraquat, while in another case, the man who had 
blown into the jet, to clear it, escaped with only minor signs of 
poisoning.  Dilute solution blown into the face by the wind and 
splashes of concentrate that get into the mouth probably explain 
the resultant signs in the mouth, on the tongue, and in the throat.  
Smoking with paraquat-contaminated hands has been reported to 
result in a farmer's developing oropharyngeal irritation, nausea, 
and muscular weakness (Mourin, 1967). 

8.2.2.2.  Dermal absorption

    Acute dermal paraquat poisoning has been described by 
Fitzgerald et al. (1978a).  The use of a leaking sprayer by a 
worker with severe extensive dermatitis probably resulted in fatal 
absorption of paraquat through the damaged skin.  Jaros (1978) has 
described how the use of concentrated solutions of paraquat (50 
g/litre instead of 5 g/litre), with an old leaking knapsack 
sprayer, resulted in paraquat contamination of the neck, back, and 
legs of a worker.  After 4 h of work, he complained of a burning 
sensation on the neck and scrotum.  On admission to hospital 6 days 
later, cough and respiratory difficulties were recorded.  Three 

days later the patient died of renal and respiratory failure.  This 
author has stressed the need for careful handling of paraquat.  
Jaros et al. (1978) have discussed several other cases of paraquat 
poisoning in the CSSR related to paraquat application. 

    Severe skin damage, followed by death due to respiratory 
insufficiency, occurred in a woman (Newhouse et al., 1978), 8 weeks 
after initial contact with paraquat.  The toxic dermatitis started 
with scratches on the arms and legs from the branches of fruit 
trees.  The patient had often failed to wear protective clothing or 
to shower after spraying.  During the 4 weeks preceding her first 
admission to hospital, she developed ulcers and respiratory 
complaints combined with anorexia.  Damaged and broken skin was 
thus exposed to paraquat.  A chest X-ray and needle biopsy of the 
lung revealed pulmonary lesions.  Seventeen days after discharge 
from hospital, without a specific diagnosis, she was re-admitted, 
and died 2 weeks later with progressive lung, hepatic, and renal 
dysfunction.  More recently, Levin et al. (1979) described the 
clinical and pathomorphological investigation of a patient who died 
of hypoxia after repeated dermal exposure to paraquat (28 g/litre) 
and diquat (29 g/litre) in a water-oil dilution - contrary to 
accepted practice.  The worker had used a leaking sprayer.  A 
characteristic ulcer developed at the site of paraquat contact.  
There was also lung damage.  Waight & Weather (1979) reported a 
fatal case of dermal poisoning with paraquat after prolonged 
contact with a concentrated formulation following spillage from a 
bottle in the back trouser pocket.  Wohlfahrt (1982) discussed the 
factors related to severe paraquat poisoning due to dermal 
absorption in tropical agriculture.  Three fatal incidents followed 
skin contamination; one victim used paraquat to treat scabies 
infestation, and one to treat lice.  In all cases, the skin was 
blistered and ulcerated.  The patients died of progressive 
respiratory failure, 4 - 7 days after the accidents.  However it 
has been pointed out that each of these three spraymen showed skin 
lesions much more severe than would be expected had recommended and 
customary dilutions been used and that, in one of these cases, the 
presence of mouth and throat ulceration strongly suggested that 
ingestion might also have occurred (Davies, 1982). 

8.2.2.3.  Local skin and nail effects

    Paraquat has a delayed effect on the skin.  Brief contact with 
liquid formulations, as well as repeated exposure to dilute 
solutions, produced skin irritation, desquamation, and, finally, 
necrosis at the site of contact (Ongom et al., 1974; Binns, 1976; 
Newhouse et al., 1978; Waight & Wheather, 1979; Levin et al., 1979; 
Horiuchi et al., 1980).  Harmful dermal effects have been reported 
(Howard, 1982) among spray men who worked without protective 
clothes and with naked feet.  The blistering and ulceration of the 
skin were due to excessive contact and inadequate personal hygiene.  
Horiuchi & Ando (1980) carried out patch testing on 60 patients 
with contact dermatitis due to Gramoxone(R).  In 8 patients 
(13.3%) positive allergic reactions were established.  In another 
survey with 52 persons, a positive photo-patch response was 
reported in 11 patients. 

    Nail damage has also been reported after frequent exposure to 
paraquat concentrates during the formulation of the herbicide or 
the preparation of working dilutions (Samman & Johnston, 1969; 
Howard, l979b).  Leakage from sprayers may cause nail damage only 
if there is gross contamination (Hearn & Keir, 1971).  Asymmetric 
discoloration and softening of the nail base appears together with 
an infection, that usually persists after the loss of the nail, but 
a few months after cessation of paraquat exposure, the nails 
re-grow satisfactorily. 

8.2.2.4.  Ocular damage

    A number of studies have demonstrated the hazard from splashes 
of concentrated paraquat that come into contact with the eye (Swan, 
1969; Schlatter, 1976; Howard, l979b, 1980; Deveckova & Myalik, 
1980).  Apart from irritation of the eye and blepharitis, a week 
later more serious ocular damage may occur such as destruction of 
the bulbar and tarsal conjunctiva and of the corneal epithelium 
(Cant & Lewis, 1968).  Anterior uveitis was also noted.  Joyce 
(1969) reported a case of conjunctival necrosis after paraquat had 
been splashed into the eyes during spraying in windy weather.  In a 
second case, there was progressive keratitis with gross corneal 
opacity.  Severe conjunctival injuries with keratitis and decreased 
visual acuity were reported in 3 workers by Watanabe et al. (1979) 
and in another by Okawada et al. (1980).  The eyes were washed with 
water immediately, but the damage progressed and required treatment 
for more than 3 weeks. 

8.2.2.5.  Inhalation

    The inhalation of droplets in normal paraquat spraying does not 
appear to represent a significant health hazard (Howard, 1980), and 
the effects of occupational inhalation have been limited to nose 
bleeds, and nasal and throat irritation (Swan, 1969; Howard, 
1979b).  Standard spraying equipment failed to produce significant 
levels of droplets in the respirable range of < 5-7 µm diameter, 
and chemical analyses of paraquat aerosols or particulate matter, 
sampled from working areas, have usually shown them to be well 
below the TLV.  However, there have been some reports (Malone et 
al., 1971; Mircev, 1976; Bismuth et al., 1982) of adverse effects 
as a result of inhalation exposure. 

8.3.  Use of Marijuana Contaminated by Paraquat

    In the USA, it has been found that marijuana sprayed with 
paraquat (in an attempt to destroy the plant) may become available 
for smoking by drug users.  Concentrations of paraquat in marijuana 
of up to 461 mg/kg have been reported (Liddle et al., 1980).  
Understandably, concern has been expressed that smoking this 
contaminated marijuana may be more harmful than smoking marijuana 
itself.  The available data do not justify an absolute conclusion.  
However, paraquat is known to pyrolyse at 300 °C and it has been 
established (Smith 1978) that in marijuana cigarettes contaminated 
with 1000 mg paraquat/kg (1 mg, assuming a 1 g cigarette), only 
0.26 µg of paraquat escaped pyrolysis and was available to be 
inhaled.  On this basis, the amount of paraquat inhaled by a heavy 
user of contaminated marijuana will be insufficient to cause 
injury.  In the absence of exhaustive toxicological studies, it 

cannot be stated categorically that all the pyrolysis products of 
paraquat do not damage the lung.  However, there has been no 
confirmed injury attributable to the smoking of contaminated 
marijuana. 

8.4.  Guidelines for the treatment of paraquat poisoning

    The most important measures are the immediate neutralisation of 
ingested paraquat by 15% Fuller's earth, bentonite, or activated 
charcoal and urgent removal of the poison by vomiting or, when 
possible, gastric washout.  The urgency of these measures is such 
that where transfer to hospital may involve delay of an hour or 
more, this emergency treatment may need to be given by a 
paramedical person, e.g., a nurse or a medical assistant.  The 
delay should not be more than 4 - 5 h.  Furthermore, Fuller's earth 
should be given together with a strong purgative such as magnesium 
sulfate or mannitol. 

    Admission to a hospital either directly or after emergency 
treatment elsewhere is essential. 

    Where a person has swallowed a lethal dose, the most important 
single determinant of survival is the early commencement of 
treatment. 

    Depending on local facilities, patients who reach hospital 
after the initial treatment will have further treatment aimed at 
neutralizing paraquat in the gastrointestinal tract (Fuller's 
earth, bentonite, activated charcoal) or its excretion in the 
faeces (purgatives, 10% mannitol, gut lavage).  In addition, 
attempts to remove absorbed paraquat from the circulation 
(haemoperfusion, haemodialysis) or aid its excretion by the kidney 
(forced diuresis) can be instituted. 

    In centres where facilities for analytical procedures are 
available, measurement of urinary, or ideally plasma levels of 
paraquat may give guidelines for the required intensity of 
treatment or likely prognosis. 

    Many other therapies including corticosteroids, 
immunosuppressive treatment, vitamins, beta-blocking and alkylating 
agents, alpha-tocopherol, superoxide dismutase and/or glutathione 
peroxidase (Autor, 1974, 1977) proved to be of no significant 
importance in human paraquat poisoning (Fletcher, 1975; Fairshter 
et al., 1976; Schlatter, 1976; Brown et al., 1981; Bismuth et al., 
1982).  The administration of oxygen should be avoided except where 
vital for the patient's comfort. 

    It should be noted that, as with the great majority of 
chemicals, there is no specific antidote. 

    Care must be exercised in the administration of most of these 
treatments, as the following serious complications may occur: 
perforation of the oesophagus during gastric intubation; serious 
blood chemistry disturbance when severe diarrhoea is induced; fluid 
overload during forced diuresis (McGeown, 1975). 

    Despite such an array of both simple and sophisticated 
measures, the response to therapy in paraquat poisoning is 
disappointing and the mortality rate remains high. 

    In cases of skin and eye contamination, irrigation with water 
(preferably running water) should be commenced urgently and must be 
continued uninterrupted for at least 10 min (timed by the clock).  
Eye cases should always be taken for medical treatment.  In cases 
of skin contamination by the concentrate or extensive and/or 
prolonged contamination by the diluted material (particularly where 
signs of skin irritation are present) the patient must be assessed 
at hospital for systemic poisoning. 

9.  EVALUATION OF RISKS FOR HUMAN HEALTH AND EFFECTS ON THE ENVIRONMENT

9.1.  Exposure

    Introduction

    Paraquat is a contact herbicide or dessicant that is used to 
destroy weeds in various agricultural situations.  It is used in 
the form of an aqueous spray, which means that potential human 
exposure may occur as a result of its presence in air, on plants, 
in soil, or in water. 

    Degradation of paraquat

    Photochemical degradation takes place when paraquat-treated 
plants are exposed to normal daylight and continues after the 
plants are dead (section 4.1.1).  The products formed have been 
identified and found to be of a lower order of toxicity.  
Ultraviolet degradation on soil surfaces also occurs, but 
photodecomposition of paraquat in the soil is insignificant in 
comparison with adsorption on clay particles.  Microorganisms can 
degrade free paraquat rapidly, but chemical degradation of adsorbed 
paraquat is relatively slow. 

    Soil

    Paraquat is rapidly and tightly bound to clay materials in 
soils.  The adsorbed paraquat is biologically inactive and in 
normal agricultural use no harmful metabolic or breakdown products 
are to be expected (section 4.3 and 5.1).  In multiple spray 
trials, paraquat residues in soil varied from 22 to 58 mg/kg.  
Under field conditions, the residual paraquat is slowly 
re-distributed.  Long-term field studies have shown degradation 
rates of 5 - 10% per annum, which is sufficient to prevent 
saturation of soil deactivation capacities.  At normal and high 
rates of application, no adverse effects are expected in the soil 
microflora and other soil organisms, or on crop growth (section 
4.3.1). 

    Water

    Following the use of paraquat as an aquatic herbicide at a 
normal application rate of 1 mg/litre, the concentration was found 
to decrease to about one half of the initial level within 36 h and 
to below 0.0l mg/litre in less than 2 weeks (section 4.3.2).  
Phytotoxic damage to crops irrigated with treated water is unlikely 
to occur, if an interval of 10 days is observed between treatment 
of the water and its use, because of the rapid decrease of paraquat 
residues in the water. 

    Normal application of paraquat for aquatic weed control is not 
harmful for aquatic organisms.  However, care should be taken in 
the application of paraquat to water containing heavy weed growth, 
since oxygen consumed by subsequent weed decay may decrease oxygen 
levels in the water to an extent that is dangerous for fish or 
other aquatic organisms. 

    Air

    Paraquat is not volatile so inhalation of paraquat vapour is 
not a problem, in practice.  However, droplets of paraquat solution 
can be present in the air as a consequence of aerial, knapsack, or 
tractor-mounted spraying.  Paraquat aerosol concentrations (total 
airborne) ranged up to 0.55 mg/m3 in the work situation, depending 
on the method of spraying.  The amount of respirable airborne 
paraquat was found to be insignificant under normal conditions of 
use (section 8.2.1). 

    The amount of paraquat present in airborne dust was found to 
range from 0.0004 to 0.001 mg/m3.  The binding of paraquat to the 
dust was so tight that it did not exert any toxicological effect on 
rats, when given by inhalation. 

    Food

    Examination of paraquat-treated p1ants (section 4.3.4), or of 
materials from animals fed paraquat-treated crops (section 4.3.5), 
revealed low residues, so that no hazard should be expected from 
paraquat residues in food when used as a herbicide or as a 
desiccant.  Paraquat is not subject to bioconcentration (section 5) 
and has not been found to accumulate in food chains. 

    Environmental contamination

    Exposure to paraquat from spray drift may occur in windy 
weather, though field studies suggest that the airborne paraquat 
concentration declines markedly within a few metres of the sprayed 
area (section 4.3.3).  Because of the rapid and complete binding of 
paraquat to clay particles in the soil, contamination of water 
supplies either from field runoff or percolation through soil to 
the water table is not an environmental problem (sections 4.3.1 and 
4.3.2).  Paraquat has also been shown not to have any harmful 
effects on birds (sections 5.3 and 5.4). 

9.2.  Poisoning by Paraquat

    Misuse of paraquat has led to many deaths throughout the world, 
mainly due to the swallowing of undiluted preparations. 

9.2.1.  Suicidal ingestion

    The majority of paraquat poisonings are due to swallowing 
liquid concentrates with suicidal intent and the mortality rate is 
high.  Ingestion of granular paraquat is less common and usually 
causes milder poisoning, though fatalities have occurred.  Paraquat 
has been used to commit homicide (section 8.1). 

9.2.2.  Accidental poisoning

    Poisoning by accidental swallowing is less common than 
intentional swallowing and is usually the result of storing liquid 
concentrates in inappropriate containers, particularly beer or soft 
drink bottles.  The mortality rate is lower than in suicidal cases.  
Childhood poisoning is usually accidental.  Legislation on the 
control of the sale of liquid concentrates has reduced accidental 
ingestion in some countries (section 8.1). 

    A small number of fatal cases of accidental paraquat poisoning 
via the skin have been reported following the application of liquid 
concentrates (200 g/litre) to kill body lice. 

9.2.3.  Occupational Poisoning

    Cases of severe poisoning following inappropriate behaviour or 
accidents while handling paraquat occur.  Fatal and non-fatal 
ingestion of paraquat has occurred when hand-spray operators have 
attempted to clear the spray outlet by sucking on the spraying 
nozzle or outlet pipes.  In some of the severe cases, the authors 
noted their suspicion of concealed suicidal intent.  Fatal 
poisoning by dermal soaking with dilute paraquat has been reported 
in one operator who had severe dermatitis and had been using a 
leaky sprayer (section 8.2.2). 

    Fatal systemic poisoning may result from continuous contact 
with paraquat-soaked clothing or splashes of liquid concentrate on 
the skin.  Splashes of liquid concentrate may lead to severe ocular 
and skin damage (sections 8.2.1, 8.2.2).  Spraying with 
inadequately diluted paraquat (e.g., with ultra low volume 
application) may result in similar problems. 

9.3.  Occupational Exposure

    There are several studies on paraquat exposure in normal 
agricultural use.  Occupational exposure may be oral, dermal, or by 
inhalation.  The spray aerosol and dust particles are relatively 
large and are mostly deposited in the upper respiratory tract 
(section 8.2.1). 

    The potential dermal exposure of field workers (section 8.2.1) 
is closely related to working conditions.  Workers on tractors were 
found to have a paraquat exposure of 12 - 168 mg/h while spraying 
tomatoes and citrus.  In other studies, field workers were dermally 
exposed to paraquat at approximately 0.40 mg/h, and individuals 
spraying the garden to 0.29 mg/h.  In all trials, respiratory 
exposure was not higher than 0.01 mg/h.  Urine concentrations in 
occupationally-exposed workers were often lower than 0.01 mg/litre, 
but concentrations up to 0.73 mg/litre were determined after 
improper paraquat application in tropical agriculture use. 

    Local skin effects (contact, irritative, or photoallergic 
dermatitis) delayed wound healing, and nail damage has been 
observed among formulation workers or among individuals handling 
the herbicide improperly.  Blepharitis and epistaxis may result due 
to delayed irritative action of paraquat.  Such incidents 
illustrate the need for strict personal hygiene and rigorous 
adherence to safe handling procedures. 

9.4.  Effects

9.4.1.  Paraquat toxicity in animals

    The acute lung-directed toxicity of paraquat in man has been 
confirmed in numerous studies in animals.  At high doses of 
paraquat, minor toxic effects have been noted primarily in liver 
and kidney, and in other organ systems, including nervous, 
cardiovascular, blood, adrenals and male reproductive systems.  
However, toxic effects have not been reported at low doses of 
paraquat.  Concentrated solutions of paraquat have been found to be 
irritating to both skin and eyes.  The FAO/WHO (1976) has 
determined no-observed-adverse-effect levels of 30 mg/kg diet, 
equivalent to 1.5 mg/kg body weight per day for rats and 50 mg/kg 
diet, equivalent to 1.25 mg/kg body weight per day, for dogs 
exposed to paraquat dichloride.  Additional animal studies have 
indicated that paraquat is neither teratogenic nor carcinogenic 
(sections 7.1.6 and 7.1.8).   In vitro mutagenicity studies have 
been inconclusive, though generally suggesting weak potential 
activity, while  in vivo studies have given negative results 
(section 7.1.7).  Thus, the results of animal studies suggest that 
low-level exposure to paraquat is unlikely to induce toxic effects 
in man. 

9.4.2.  Paraquat determinations in biological fluids and tissues

    Determination of paraquat levels in stomach washings, serum, 
and urine is useful for the management of poisoning (section 6.2).  
The urinary levels decline rapidly during the 24 h following 
exposure and may remain low for some weeks.  Determination of 
urinary levels of paraquat may be useful in the conduct of 
epidemiological studies. 

9.5.  Earlier Evaluations by International Bodies

    The Joint Meeting on Pesticide Residues (JMPR) has reviewed 
residues and toxicity data on paraquat on several occasions 
(FAO/WHO 1971, 1973, 1977, 1979, 1982, 1983).  In 1972, it 
estimated the acceptable daily intake (ADI) for man 0 - 0.002 mg/kg 
body weight, on the basis of no-observed-adverse-effect levels of 
1.50 mg/kg body weight per day in the rat and 1.25 mg/kg body 
weight in the dog.  Because of concern relating to lung and kidney 
toxicity, this ADI  was changed in the 1982 meeting to a temporary 
ADI of 0 - 0.001 mg paraquat dichloride/kg body weight (or 0.0007 
mg paraquat ion/kg body weight).  The no-observed-adverse-effect 
level for the rat remained, however, at 1.5 mg/kg body weight/day 
(FAO/WHO 1983). 

    The same JMPRs have recommended maximum residue levels 
(tolerances) for paraquat in food commodities of plant and animal 
origin. 

    The WHO/FAO (1978) in its series of "Data sheets on chemical 
pesticides" issued one on paraquat.  Based on a brief review of 
use, exposure, and toxicity, practical advice is given on 
labelling, safe-handling, transport, storage, disposal, 
decontamination, selection, training and medical supervision of 
workers, first aid, and medical treatment. 

    Regulatory standards established by national bodies in 12 
different countries (Argentina, Brazil, Czechcoslovakia, the 
Federal Republic of Germany, India, Japan, Kenya, Mexico, Sweden, 
the United Kingdom, the USA, and the USSR) and the EEC can be found 
in the IRPTC (International Register of Potentially Toxic 
Chemicals) Legal file (IRPTC 1983). 

9.6.  Conclusions

    On the basis of the above findings, it can be concluded that: 

    General population

    Residue levels of paraquat in food and drinking-water, 
resulting from its normal use, are unlikely to result in a health 
hazard for the general population. 

    This likely lack of hazard in normal usage of dilute paraquat 
is in strong contrast with the potential serious hazard that may 
result from handling concentrated paraquat. 

    Accidental paraquat poisoning results mainly from swallowing 
liquid concentrate that has been decanted into unlabelled bottles 
or other containers and stored inappropriately. 

    The number of suicides by means of paraquat is of great 
concern.  The total number of such suicides is unknown. 
Notwithstanding the facts that the reasons for suicide may be 
manifold and complex, and that paraquat is one among many means 
towards that goal, the prolonged and painful way of dying from 
paraquat suggests that every effort within reason should be made to 
diminish the attractiveness and availability of paraquat for this 
purpose. 

    Occupational exposure

    With reasonable work practices, including safety precautions, 
hygiene measures, and proper supervision, occupational exposure 
during manufacture, formulation, and application will not cause 
hazard.  However the undiluted concentrate must be handled with 
great care because improper work practices may result in 
contamination of eyes and skin (with possible consequent dermal 
absorption). 

    Spray concentrations should not exceed 5 g paraquat ion/litre 
in order to avoid skin damage and absorption of the herbicide 
through the skin.  Its use in hand-held ultra-low volume 
application should be discouraged. 

    Environment

    Paraquat in soil binds rapidly and tightly to clay particles 
and residual phytotoxicity from freely-available paraquat is 
unlikely.  The toxicity of the compound for birds has been shown to 
be of low significance.  Under normal conditions of use, paraquat 
shows low toxicity to aquatic organisms although resulting 
depletion of water-oxygen because of weed decay may pose a problem.  
Paraquat does not seem to represent an environmental hazard. 

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UKAI, S., HIROSE, K., & KAWASE, S.  (1977)  [Gas chromatography 
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US CONGRESSIONAL HEARING  (1979)   Health implications of 
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VALE, J.A.  (1977)  Paraquat poisoning.  Nurs. Times, 73: 
154-155.

VAZIRI, N.D., NESS, R.L., FAIRSHTER, R.D., SMITH, W.R., & 
ROSEN, S.M.  (1979)  Nephrotoxicity of paraquat in man.  Arch. 
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VESELEY, D.L., WATSON, B., & LEVEY, G.A.  (1979)  Activation 
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VIJEYARATNAM, G.S. & CORRIN, B.  (1971)  Experimental paraquat 
poisoning: a histological and electron-optical study of the 
changes in the lung.  J. Pathol., 103: 123-129.

VUCINOVIC, V.  (1978)  [Four cases of poisoning with 
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WADDELL, W.J. & MARLOWE, C.  (1980)  Tissue and cellular 
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56: 127-140.

WAIGHT, J.J.J. & WHEATHER, R.H.  (1979)  Fatal percutaneous 
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WALTERS, K.A., DUGAR, P.H., & FLORENCE, A.T.  (1981)  
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YOUNGMAN, R.J. & DODGE, A.D.  (1979)  [Mechanism of paraquat 
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marijuana.  Chest, 74: 418-420.

DIQUAT

1.  SUMMARY AND RECOMMENDATIONS

1.1.  Summary

1.1.1.  General properties

    Diquat (1,1'ethylene, 2,2'bipyridyl) is a non-selective contact 
herbicide.  It is sold primarily as a 20% w/v solution in many 
countries and is manufactured in the United Kingdom.  It is 
exclusively manufactured as a dibromide salt and is usually 
formulated to contain wetters. 

    The herbicidal property of diquat depends on its ability to 
undergo a single electron addition to form a radical that reacts 
with molecular oxygen to reform diquat and concomitantly produce a 
superoxide anion.  This oxygen radical may directly or indirectly 
cause cell death. 

    It is possible to detect the compound because of its ability to 
form a radical.  Analytical procedures are available. 

1.1.2.  Environmental distribution and transformation
environmental effects

    Diquat undergoes rapid photochemical degradation in aqueous 
solution and on surfaces.  The major degradation products produced 
in water have been identified and are of lower acute oral toxicity 
for rats than diquat itself.  The photochemical degradation of 
diquat on plants is more complex than that in water.  On diquat-
desiccated wheat and barley, diquat itself normally constitutes the 
most important single compound.  The most important photochemical 
degradation products have been identified, they are of low 
mammalian toxicity.  No other well-defined major degradation 
product is formed. 

    Ruminants excrete diquat and its photochemical products rapidly 
and very little is transferred to milk and tissues.  Consequently, 
residue levels in products of animal origin are very low.  
Ingestion of diquat and its photochemical products at higher levels 
than would be found in practice did not induce ill effects in 
ruminants. 

    Diquat reaching the soil becomes rapidly and strongly adsorbed 
to clay minerals in soil.  This process inactivates the herbicidal 
activity of diquat.  While free diquat is degraded by a range of 
soil microorganisms, degradation of strongly adsorbed diquat is 
relatively slow.  In plot studies, the rate of degradation of 
diquat in soil is very slow or non-detectable.  However, in long-
term field studies, degradation rates of the order of 5 - 10% per 
year have been shown.  This is greater than the rate required in 
normal practice to prevent saturation of the deactivation capacity 
of agricultural/horticultural soils.  Strongly-bound diquat has no 
adverse effects on soil microfauna or soil microbial processes. 

    Diquat residues disappear rapidly from water by adsorption on 
aquatic weeds and by strong adsorption on bottom mud.  Diquat is of 
low toxicity for fish and is not accumulated in them.  Normal 
applications of diquat for aquatic weed control are not harmful to 
aquatic organisms.  However, care should be taken in applying 
diquat to water containing heavy weed growth to treat only a part 
of the weed growth, since oxygen consumed by subsequent weed decay 
may decrease dissolved oxygen levels to an extent that may be 
dangerous for fish.  Treated water should not be used for overhead 
irrigation until a period of 10 days has elapsed following 
treatment. 

    Diquat is not volatile and the concentrations of airborne 
diquat during spraying have been shown to be very low. 

1.1.3.  Kinetics and metabolism

    Diquat is poorly absorbed from the intestinal tract and skin.  
Diquat monopyridone is the major metabolite of diquat in the body; 
of lesser importance is diquat dipyridone.  Both metabolites are 
considerably less toxic than diquat itself.  Depending on species 
and route of administration, less than 20% of the dose is 
metabolized.  The gastrointestinal microflora appear to be mainly 
responsible for the metabolism of diquat. 

    Compared with paraquat, accumulation of diquat in the lungs is 
far less marked, but diquat shows a certain preference for the 
kidneys.  The kidneys are the major route of excretion, but a 
considerable amount of diquat can also be excreted in the bile, 
varying with the animal species. 

1.1.4.  Effects on animals

    Diquat is less toxic than paraquat and does not give rise to 
the specific lung disease that is so typical of paraquat poisoning.  
Gastrointestinal disturbances, with vomiting, greenish diarrhoea, 
and abdominal distension from the significant accumulation of water 
in the lumen of the intestines, are typical of diquat poisoning, 
together with progressive haemoconcentration, which may progress to 
lethargy, coma, and death.  At high doses, minor toxicity has been 
noted in the liver, kidney, and the nervous and endocrine systems. 

    Diquat has induced cataracts after prolonged oral exposure 
although this effect has not been reported in man.  It is less 
irritant to the skin, mucous membranes, and the eye than paraquat, 
and is not known to be a sensitizer. 

    Diquat is not teratogenic or carcinogenic. 

     In vitro mutagenicity studies were inconclusive, though
generally suggesting only weak activity, while the results of  in 
 vivo studies have been negative.  A no-observed-adverse-effect 
level of 0.75 mg diquat ion/kg body weight per day has been 
established from long-term feeding studies on rats. 

1.1.5.  Effects on man

    Occupational exposure to diquat does not pose a health risk if 
the recommendations for use are followed and there is adherence to 
safe working practices. 

    Diquat poisoning by suicidal or accidental ingestion is much 
less common than paraquat poisoning.  It produces a similar severe 
clinical syndrome with two notable differences:  (a) diarrhoea is a 
prominent feature, and (b) pulmonary fibrosis has not been 
described. 

    Accidental cases are usually due to ingestion of decanted 
diquat. 

    The lethal dose for man appears to be approximately 6 - 12 
grams of diquat dibromide.  In agricultural workers, inflammation 
and bleeding of the nasal mucosa have been reported, as well as 
nail changes and delayed wound healing. 

1.2.  Recommendations

1.2.1.  General

    Where practical and reasonable, the availability and use of the 
20% liquid product should be limited to  bona fide agriculturalists, 
horticulturalists, and professional users who work with trained 
personnel, properly maintained equipment, and adequate supervision. 

    Every effort should be made to prevent the practice of 
decanting or rebottling of the product into containers that have 
not been properly labelled. 

1.2.2.  Prevention and treatment

    Attention should be drawn to the fact that persons with skin 
lesions (either pre-existing or following contamination with 
diquat) should not be permitted to take any part in spraying 
procedures until skin condition has resolved. 

    It must be stressed that treatment of persons with diquat 
poisoning should be instituted as early as possible.  The 
likelihood of recovery from a fatal dose is greatest when therapy 
begins within 5 - 6 h of poisoning. 

1.2.3.  Experimental work

    Results of existing mutagenicity and carcinogenicity studies 
generally suggest that diquat is unlikely to induce genotoxic 
effects in man, but more detailed information is required. 

2.  PROPERTIES AND ANALYTICAL METHODS

2.1.  Physical and Chemical Properties

    Diquat is a non-selective contact bipyridylium herbicide and 
desiccant.  The herbicide is supplied mainly as an aqueous solution 
of the dibromide (1,1'-ethylene-2,2'-bipyridylium dibromide, 
C12H12N2 Br2), with a relative molecular mass of 184.2 based on the 
cation.  The commonly available analytical standard is diquat 
dibromide monohydrate, which is an odourless, pale yellow, 
crystalline powder.  Some of the other physical properties of 
diquat dibromide are listed in Table 1.  It is slightly soluble in 
alcohol, and practically insoluble in non-polar organic solvents 
(Summers, 1980). Diquat is non-explosive and non-inflammable in 
aqueous formulations. 

Table 1.  Physical properties of diquat dibromide
--------------------------------------------------
Specific gravity at 20 °C     1.200

Melting point                 180 °C

Boiling point                 approximately 300 °C
                              with decomposition

Solubility in water at 20 °C  700 g/litre

pH of liquid formulation      6.0 - 7.0

Evaporation rate              not applicable

Vapour pressure               not measurable
--------------------------------------------------

    Diquat is stable in neutral or acid solutions but is hydrolysed 
by alkali.  It is inactivated by inert clay and by anionic 
surfactants.  Diquat dibromide has the following chemical 
structure: 

Chemical Structure

    Diquat is generally marketed as an aqueous solution of the 
dibromide salt Reglone(R) (200 g ion/1itre).  It is a dark 
reddish-brown liquid containing wetting agents that remains stable 
in the original polyethylene containers, for a long time, under 
normal atmospheric conditions. 

    Water-soluble granules containing 2.5% diquat and 2.5% paraquat 
are used in home gardens.  Diquat is sold under several different 
trade names:  Deiquat, Aquacide, Dextrone, Reglox, Weedtrim-D 
(Vanholder et al., 1981).  Fletcher (1975) listed the commercial 
forms of diquat, many of which are combinations containing paraquat 
or other herbicides. 

2.2.  Analytical Procedures

    The detection of diquat depends on its reduction to the free 
radical with sodium dithionite (Summers, 1980).  Calderbank & Yuen 
(1966) developed a column chromatographic procedure for 
colorimetric diquat determinations in food and biological tissues.  
The sensitivity of the method varied down to 0.01 mg/kg.  An 
immunological assay of diquat was published by Williams et al. 
(1976).  The minimum detectable quantity of diquat was 60 pg/ml.  
Pyl & Giebelmann (1978) proposed a thin-layer chromatographic 
method for diquat determinations with a detection threshold of 
0.5 - 1 µg diquat. 

    Soil

    Diquat residues in soil have been determined using 
spectrophotometric analysis (ICI, 1972), the detection limit being 
approximately 0.1 mg/kg, depending on the sample.  An extraction 
technique for the spectrophotometric measurement of diquat has been 
published by Leary (1978). 

    Water

    Diquat residues in water have been determined 
spectrophotometrically with a limit of detection < 0.001 -0.01 
mg/litre (ICI, 1972a).  Benecke (1977) used the inhibition of algal 
trichome movements by diquat involving photoelectric detection of 
their inhibition.  A concentration of 1 µg diquat in the test 
sample was satisfactorily detected.  A  Lemna minor bioassay was 
reported by O'Brien & Prendeville (1978) for diquat determination 
in water.  The minimum diquat concentration that could be detected 
ranged from 1.8 µg/ml after 3 h of treatment to 0.00018 µg/ml after 
72 h of treatment. 

    Plants and food

    The method of Calderbank & Yuen (1966) has been used for 
determining diquat in crops and animal tissues with detection 
limits of 0.1 mg/kg to 0.01 mg/kg, depending on the sample (ICI, 
1972b).  Leary (1978) developed a spectrophotometric procedure for 
diquat determination in crops and animal tissues (but not for whole 
blood).  The detection limit was 0.01 mg/kg when a 50 g sample was 
taken. 

    A gas-chromatographic method for determining diquat residues 
was published by King (1978).  The detection limit was 0.01 mg/kg.  
The application of gas chromatography in the analysis of food for 
diquat has been discussed by Dickes (1979). 

    Biological tissues

    The analytical method for diquat residues in milk is 
spectrophotometry (ICI, 1972a), with a detection limit of 0.01 
mg/litre.  Tompsett (1970) reported a cation exchange technique for 
colorimetric diquat determination in biological fluids and tissues 
of patients with diquat poisoning.  This technique is similar to 
those applied for paraquat determination but more time-consuming.  
A spectrophotometric procedure for diquat determination in serum, 
urine, and biological tissues has been published by Leary (1978). 

    Gas-chromatographic analysis of herbicides containing diquat 
dibromide and paraquat dichloride in forensic toxicology was 
proposed by Ukai et al. (1977).  The procedure was found to be well 
suited for assaying diquat and paraquat simultaneously at 10 - 90 
mg/litre. 

3.  SOURCES IN THE ENVIRONMENT

3.1.  Production and Uses

    Diquat is manufactured in the United Kingdom and does not occur 
naturally.  It is produced by the oxidative coupling of 2 molecules 
of pyridine over a heated Raney nickel catalyst to 2,2'-bipyridyl.  
It is then reacted with ethylene dibromide in water to give diquat. 

    Formulations of diquat dibromide are used in more than 100 
countries all over the world, mainly as a desiccant but also as a 
herbicide.  In many countries, diquat is formulated locally on the 
basis of the imported active ingredient.  Data on world production 
and uses are not available. 

    It is used to control both broad-leaved weeds among crops and 
submerged and floating weeds in water bodies, for potato haulm 
destruction, and for seed crop desiccation (rice, sunflower, etc.).  
Application rates are usually of the order of 0.56 - 0.84 kg/ha for 
potato haulm destruction, 0.42 -1.96 kg/ha for seed crop 
desiccation, pre-harvest rice desiccation, and pre-crop weed 
control (beans, beetroots, cabbages, onions, etc.), 0.42 - 1.12 
kg/ha for aquatic weed control, and 0.28 - 0.84 kg/ha for pre-plant 
weed control. Working dilutions vary between 1 and 5 g/litre water.  
It is applied by ground sprayers (not mist-blowers) in 200 - 500 
litres of the solution per hectare and in some countries aerially 
in 40 - 50 litres of solution per ha. 

    Conning et al. (1969) summarized the mechanism of the 
herbicidal effect of diquat.  Light and oxygen are required for the 
damage, which affects only the green parts of the plant.  The 
blockage of photosynthesis is due to disturbed photosynthetic 
electron transport resulting from a single-electron redox cycling 
reaction, as described for paraquat (Paraquat, section 3.3). 

<4.  ENVIRONMENTAL DISTRIBUTION, LEVELS, AND EXPOSURE 

4.1.  Photochemical and Microbial Degradation of Diquat

4.1.1.  Photochemical degradation

    In agricultural practice, most of the diquat spray is initially 
deposited on plant surfaces and part of it on the soil surface.  
According to Black et al. (1966), photochemical degradation is 
responsible for the rapid decrease in the concentration of diquat 
following the spraying of herbage.  Application of 0.284 kg/ha 
resulted in 12 - 48 mg diquat/kg dry herbage on the first day, 
2.5 - 10.9 mg/kg after 3 - 4 days, and 1.0 - 5.7 mg/kg, 7 days 
after treatment.  Photochemical degradation appears to occur more 
rapidly in the case of diquat than in the case of paraquat.  The 
light absorption maximum for diquat occurs at a longer wavelength 
(310 nm) than for paraquat (256 nm), and this partly explains the 
high rate of photochemical decomposition in the case of diquat.  
The major degradation products have been identified; they appear to 
be of low oral toxicity for rats and seem unlikely to produce 
adverse environmental effects (Black et al., 1966).  Cavell (1979) 
monitored the photochemical degradation of 14C-diquat in aqueous 
solutions aerated for 40 h.  Decomposition of diquat continued 
after the plants were dead and the degradation products were not 
translocated from the desiccated leaves of the plants.  Diquat 
photochemical degradation products (Cavell, 1979) are shown in Fig. 
1A. 

FIGURE 1A

4.1.2.  Microbial degradation

    Photochemical degradation of diquat on plants is quicker than 
microbial degradation in soil.  Microbial degradation of strongly-
bound diquat in soil is slow, but is faster in culture.  The 
degradation of diquat by soil fungi was studied by Smith et al. 
(1976).  The degradation of 14C-diquat to 14CO2 by  Aspergillus 
 niger was tested by 4 different fungal test systems.  High 
intracellular herbicidal levels and inability to grow in the 
presence of low diquat concentrations in the media characterized 
the species unable to decompose diquat.  Under laboratory 

conditions, diquat degradation by  Pseudomonas started after 3 days 
(Tchipilska, 1980).  Under field conditions, degradation started 
after 10 days, and was related to the ambient temperature, and the 
aeration and type of soil. 

    The fact that no significant hazard has been observed for 
ruminants from diquat-treated herbage, or for the general 
population from crops and water, is explained by the rapid 
photochemical degradation of diquat. 

4.2.  Diquat Adsorption, Residue Levels, and Exposure in Soil

4.2.1.  Diquat adsorption on soil particles

    Diquat binds readily to clay particles in the soil.  The rate 
of adsorption depends on the degree of contact of diquat with 
adsorbent minerals, the type of soil, and the initial herbicide 
concentrations tested.  Weber et al. (1965) studied the effects of 
temperature and exposure time on diquat adsorption by 
montmorillonite, kaolinite, charcoal, and an anionexchange resin in 
pH 6.0 phosphate buffer.  Diquat was preferably adsorbed on the 
clay particles by a process of ion exchange.  Adsorption was 
limited by the cation-exchange capacity of the test systems 
examined.  Coats et al. (1966) showed the adsorption capacity of 
kaolinite to be about 2 g/kg and that of bentonite 80 - 100 g/kg. 

    A diquat soil concentration of 0.1 mg did not produce any 
significant reduction in the dry weight of wheat grown in the soil 
(Coats et al., 1966).  The diquat appeared to be too tightly 
adsorbed to the surface and between the lattices of bentonite to be 
available to the wheat plant, at a soil treatment rate of 50 g/kg.  
Data for diquat adsorption on sandy soils (Tucker et al., 1967) 
showed that the herbicide was bound to different extents, according 
to the structure of the soil particles. 

4.2.2.  Residue levels of diquat in soils

    Makovskii (1972) reported on diquat residues in soils from 
different plots, treated every year for a period of 7 years.  There 
were 3 - 4 treatments per season, at approximately 27.5 kg 
diquat/ha.  Samples were taken at 0 - 10 cm, 10 - 20 cm, and 20 - 
30 cm depths in the soil; total diquat residues were shown to be 
about 5.4 mg/kg soil, the mean values being 3.9 mg/kg, 1.3 mg/kg, 
and 0.2 mg/kg in the respective soil layers.  No diquat residues 
were discovered in plants and citrus fruits sampled at different 
times from the treated plots.  In other studies, soil was analysed 
for diquat residues on the 1st, 8th, and 15th days after applying 
Reglone(R) at 0.8 litre/ha and 0.4 litre/ha (Tchipilska, 1980).  On 
the 1st day, residues of 0.400 mg/kg and 0.126 mg/kg were detected; 
on the 8th and l5th days residues in the treated plots were lower 
than 0.1 mg/kg. 

    As summarized in section 4.1.2, free diquat is degraded by a 
range of microorganisms.  While degradation of strongly-absorbed 
diquat is relatively slow, results of long-term field studies have 

nevertheless shown degradation rates of the order of 5 - 10% per 
year.  This is greater than the rate required to prevent saturation 
of the deactivation capacity of soils. 

    In a long-term trial on a loamy soil, plots were treated with 
0, 90, 198, and 720 kg diquat/ha, which was incorporated to a depth 
of 15 cm.  These rates were equivalent to 0, 50, 110, and 400% of 
the soils strong absorption capacity (Gowman et al., 1980; 
Wilkinson, 1980; Riley 1981).  Over the 7 years, diquat residues 
declined by 5% per year (sig  P = 0.05) on the 90 kg/ha plots and 
by 7% per year (sig  P  = 0.01) on the 198 and 720 kg/ha plots.  The 
rate of decline on the 198 and 720 kg/ha plots were significantly 
greater ( P = .01) than on the 90 kg/ha plots. 

4.2.3.  Effect of residual diquat on soil biological activity, on
plants, and crop yields

    A literature review and an extensive study of the effects of 
different concentrations of diquat on microorganisms (saprophyte 
and pathogenic microflora, and fungi) were carried out by 
Tchipilska (1980).   Staphylococcus aureus growth was inhibited 
while  Scenedesmus acutus was stimulated.  Smith et al. (1981) 
examined the effects of diquat applied at 0.5 - 32 times the 
concentration recommended in agricultural practice on vesicular 
arbuscular endophyte spore abundance in the soil and on the 
infection of wheat roots.  No measurable deviations in 
endomycorrhiza formation and function were noted at normal 
application rates.  Loss of potassium and phosphate from fungi was 
recorded at higher concentrations of diquat. 

    Coats et al. (1966) studied the uptake and translocation of 
14C-diquat from soil into wheat.  No metabolites were found in the 
plants. 

    Diquat does not appear to have any significant influence on the 
normal microbial activity that is important for soil fertility.  
Nor is there any evidence that the recommended application rates 
for diquat lead to residual effects on crop growth.  Moreover, 
tightly adsorbed diquat in soil is not reactivated into a 
biologically active form, so that, in practice, accidental spillage 
is probably the only cause of local high phytotoxic levels of 
residual herbicide. 

4.3.  Diquat Transformation, Residue Levels, and in Effects on 
Aquatic Organisms and Crops

4.3.1.  Transformation and residue levels of diquat in water

    In static water, initial diquat concentrations of 0.5 - 1.0 
mg/litre fell rapidly to 0.1 - 0.3 mg/litre after 4-7 days 
(Calderbank, 1972; Calderbank & Slade, 1976).  In field 
experiments, initial concentrations of 1.0, 0.8, and 0.5 mg/litre 
decreased to 0.03 - 0.003 mg/litre after 7 - 14 days.  This rapid 
loss of diquat from treated waters was due to rapid uptake by 
aquatic weeds.  Two weed species  (Myriophyllum spicatum and 

 Callitriche stagnalis) were immersed in water containing 1.0 mg 
diquat/litre.  The concentration of the herbicide decreased rapidly 
to 0.14 - 0.03 mg/litre during a period of 6-14 days after 
treatment.  At the end of the experiment, the residue levels in 
the weeds ranged from 6.2 - 17.4 mg/kg.  In addition to uptake 
by weeds, loss of diquat from treated waters was due to 
photodegradation at the water surface and adsorption by bottom mud.  
In field experiments carried out in 1010 m2 ponds with an initial 
concentration of diquat of 2 mg/litre water, there were no residues 
of diquat in the water after 8 days (Calderbank, 1972; Calderbank & 
Slade, 1976). 

    In pond water that had been treated with diquat at 2.5 mg/litre 
(Grzenda et al., 1966), residues of 0.01 - 0.08 mg/litre were found, 
7-9 days after applying the herbicide, and no residues could be 
determined after 14-30 days.  The authors concluded that, compared 
with other herbicides, diquat appeared to have the greatest 
potential for use in sources of potable water. 

    The data obtained from studies in ponds, large and small lakes, 
canals, and reservoirs demonstrate the fast disappearance of diquat 
from treated waters (Calderbank, 1972).  Absorption by aquatic 
weeds explains the high efficacy of the herbicide.  Decomposition 
of the dead weeds is rapid, and diquat is not released from the 
bottom mud back into the water.  Applications of paraquat and 
diquat each at a dose level of 1.1 kg/ha (Grover et al., 1980) 
proved very effective for the control of weeds in irrigation 
ditches, and the residual levels of both herbicides decreased 
rapidly. 

4.3.2.  Effects of residual diquat on aquatic organisms and crops

    The toxicity of diquat for fish varied with the species, the 
size of the fish, and the softness or hardness of the water.  The 
LC50 values range from 12 to 90 mg/litre (24 h), 6 to 44 mg/litre 
(48 h), and 4 to 36 mg/litre (96 h) (Calderbank, 1972).  Reviews of 
the effects of diquat on fish, aquatic invertebrates, 
microbiological organisms in the soil of lakes, and phytoplankton 
demonstrate that the herbicide, applied at the rates used for 
aquatic weed control, did not affect estuarine fauna, oysters, 
shrimps, water insects, or fish-food organisms (Calderbank, 1972; 
Atkinson, 1973).  At concentrations of 1 - 100 mg/litre, diquat 
appeared to be less toxic for carp fingerlings than paraquat, 
diuron, simazine, and dalapon (Singh & Yadev, 1978).  Reish et al. 
(1979) reviewed the effects of diquat on marine organisms; no 
bioaccumulation by estuarine and marine organisms was found.  The 
toxicity of diquat for fish is low, and the main risk for aquatic 
organisms and fish from its use as an aquatic weed killer is the 
decreased oxygen concentration following the decay of weeds. 

    Trout exposed to 1 mg diquat/litre for 7 days contained 
residues of 0.3 - 0.4 mg/kg in the gut, liver, and kidney, and of 
0.1 - 0.3 mg/kg in the skin and gills.  Residues were below the 
limit of detection in muscle, spleen, and heart (Calderbank, 1972).  

Trout exposed to 1 mg diquat/litre for 16 days contained residues 
of 0.5 - 0.6 mg/kg, which disappeared when the fish were returned 
to fresh water. 

    Because of irreversible adsorption, low residues in water will 
be lost on contact with soil.  The herbicide is thus unavailable to 
plant roots.  However, in overhead irrigation experiments, the use 
of water containing diquat at 0.1 - 0.5 mg/litre (Calderbank, 1972) 
resulted in diquat residues in the crops (tomato, lettuce, sugar 
beet) ranging from less than 0.01 mg/kg to 0.04 - 0.07 mg/kg.  
Thus, before using herbicide-treated waters for overhead plant 
irrigation, it is advisable to allow 10 days for the diquat aquatic 
residues to drop to acceptable levels. 

    The maximum diquat residues in water ultimately to be used for 
drinking were 0.03 - 0.01 mg/litre, at the points of entry into the 
public distribution system, 2-4 days after treatment; no residues 
were detectable on the 10th day after applying diquat as an aquatic 
herbicide.  More often than not, residue levels were below the 
detection limits of the analytical methods used. 

4.4.  Diquat Exposure and Residue Levels in Plants and Animals

4.4.1.  Plants

    Diquat is largely used as a desiccant in silage production.  At 
the recommended rates of 1.5 - 3.0 litre Reglone(R)/ha, diquat 
residues were very low (Riley & Gratton, 1974).  Following pre-
harvest desiccation of fodder crops, they ranged from below 0.05 
mg/kg to 50 mg/kg, most of the levels determined being below 25 mg 
diquat/kg (FAO/WHO, 1971, 1973).  Diquat residues in the treated 
herbage, sampled at different intervals after spraying with 0.258 - 
0.515 mg/ha, were relatively high after 1 day (12 - 65 mg/kg), but 
after 7 days had markedly decreased (1.0 - 6.5 mg/kg) (Black et 
al., 1966).  The levels of diquat found in silage during a 4-year 
trial, with application rates of 0.190, 0.258, and 0.540 mg/ha, 
varied from 1.4, 3.6, 9.3, and 13.3 to 26.8 mg/kg.  The differences 
were due to the atmospheric conditions at the time of desiccation 
and the consequent degree of photochemical degradation of the 
diquat.  For this reason, diquat residues in treated herbage should 
be expected to vary by an order of magnitude (10 times). 

    Pre-harvest desiccation of rape-seed with diquat did not result 
in any detectable residues in the extracted oil and only low 
residues (0.3 - 2 mg/kg) in the meal cake.  Rape plants were 
sprayed with 14C-diquat at 0.3 - 1.1 kg/ha, 3-14 days before 
harvesting.  There were no detectable residues of diquat or of its 
photodegradation products in the rape-seed oil when the seeds were 
harvested 7 days after desiccation, and very low diquat residues 
(0.02 - 0.003 mg/kg) were determined when the seeds were harvested 
14 days after treatment with diquat.  The diquat residues in the 
meal cake varied from 1.49 to 10.2 mg/kg, 14 days after treatment, 
a large proportion being unchanged diquat (FAO/WHO, 1973). 
Dembinski et al. (1971) reported diquat residues of 2 mg/kg in 
sunflower seeds desiccated with Reglone(R). 

    Makovskii (1972) reported the diquat residue levels in weeds 
treated with Reglone(R).  After applications of Reglone (R) at 
0.5, 1.0, and 1.3 litre/ha, the residues in dry weeds, ranged from 
34 to 74 mg/kg 1 h later; from 15 to 26 mg/kg after 1 day; from 
undetectable to 10 mg/kg after 4 days; from 2.8 to 3.5 mg/kg after 
2 weeks; from 1.9 to 2.3 mg/kg after 4 weeks; and from undetectable 
to 1.7 mg/kg after 6 weeks.  The degradation of diquat in plants 
was more rapid than the degradation of paraquat.  The residues in 
potatoes did not exceed 0.08 mg/kg, when diquat was used to destroy 
potato haulm, and levels in fruits (apples, pears, plums, citrus), 
tea, and cereals were undetectable (< 0.01 mg/kg), when diquat was 
applied as a herbicide for weed control.  Samples of potatoes 
purchased from shops (Andersson & Josefsson, 1982) were analysed 
for diquat residues.  Residues in the range of 0.004 - 0.039 mg/kg 
were found in 20 of 23 samples obtained from commercial growers. 
None of the samples contained more than the residue tolerance of 
0.1 mg/kg accepted for potatoes in Sweden. 

    Residue levels of diquat have been discussed in more detail by 
the Joint Meeting on Pesticides Residues (FAO/WHO, 1971, 1973).  
Residue levels of diquat in plants were summarized and published by 
FAO/WHO (1977a).  Some of these data are given in Table 2. 

    Data on diquat residues in desiccated wheat collected from 6 
countries showed a mean of 0.5 mg/kg (FAO, 1979). 

Table 2.  Diquat residues in plantsa
------------------------------------------------------------
Plants                      Dose of diquat  Mean value of
                            (kg/ha)         residues (mg/kg)
------------------------------------------------------------
Wheat (grain, flour)        0.6 - 1.0       0.61, 0.22
                                               
Rice (with husk, polished)  0.2 - 0.4       0.89, 0.07
                                               
Sorghum (grain)             0.4 - 0.6       0.81
                                               
Cotton (grain)              0.4 - 1.0       0.37
                                               
Potato                      0.6 - 1.0       0.03
                                               
Beans                       0.3 - 1.0       0.10
                                               
Peas                        0.3 - 1.0       0.05
                                               
Sugar beet (juice)          0.3 - 0.8       < 0.01
------------------------------------------------------------
a  From:  FAO/WHO (1977a).

4.4.2.  Animals

    Sheep and cattle fed silage containing diquat residues of up to 
13 mg/kg were studied by Black et al. (1966).  The total diquat 
excreted in the urine was 0.19 - 0.65 mg over an 8-day period.  No 
diquat residues were detected in the brain, liver, and kidney of 

sheep, or in the meat or organs of cattle fed diquat-treated silage 
for one month.  Milk collected on alternate days for 2 weeks was 
free of diquat residues (< 0.003 mg/litre). 

    Feeding trials with sunflower seed containing approximately 
0.20 mg diquat/kg were reported by Dembinski et al. (1971).  
Although the amount of diquat consumed by the cattle over 257 days 
ranged from 11.2 mg to 184.2 mg, no residues were found in any of 
the milk samples analysed.  Wethers fed ground sunflower seed 
containing approximately 0.20 mg diquat/kg for 141 days were 
estimated to have consumed a total of 14.1 mg diquat per sheep.  No 
residues were found in brain, liver, or kidney, nor were there any 
residues in the meat, lungs, and kidney of steers treated with 
diquat-desiccated sunflower forage.  In long-term feeding trials 
with silage, desiccated grass, lucerne, clover hay, barley straw, 
and sunflower seeds containing diquat residues ranging from 0.2 to 
50 mg/kg, the residues in milk and meat were determined to be less 
than 0.007 mg/litre and less than 0.0006 mg/kg, respectively 
(FAO/WHO, 1971, 1973, 1977a,b).  Calderbank (1972) reviewed the 
effects on farm animals of diquat in the drinking-water and on 
herbage; there were no adverse effects on cattle and sheep and only 
very low residue levels in milk, meat, and the organs analysed. 

    Lavaur et al. (1979) studied the effect of treated lucerne on 
rabbits.  Immediately after spraying, a concentration of 211 mg 
diquat/kg dry weight was determined in the lucerne.  After 24 h and 
48 h, diquat residues were 97 mg/kg and 25 mg/kg, respectively.  No 
signs of poisoning or gastrointestinal damage were found in the 
rabbits fed with different levels of diquat residues in the 
lucerne.  However, in some circumstances, lack of careful 
organization may result in adverse effects of diquat on animals.  
Intoxication of sheep, cattle, and swine has been reported (Schultz 
et al., 1976) after the aerial application of Reglone(R) as a 
rapeseed desiccant.  The clinical course and the causes of the 
accident stressed the need for proper diquat application by air. 

    For a more detailed discussion of the fate of diquat residues 
in exposed animals, refer to FAO/WHO (1977a,b). 

4.5.  Diquat Levels in Air and Exposure of Workers

    Experiments with 14C-diquat demonstrated that it was not 
volatile (Coats et al., 1966).  Diquat levels in air after spraying 
with aerosols were determined by Makovskii (1972), using the method 
of Calderbank & Yuen (1966).  The application rates were 1.0 - 1.3 
kg diquat/ha in working dilutions of 2.5 g and 3.3 g active 
ingredient/litre, the highest diquat concentrations being found in 
the tractor cabin when the door was open and spraying was in 
progress in the direction of the wind (Table 3).  The diquat 
concentrations in air decreased rapidly 10 - 20 min after 
completion of the treatment. 

    Wojeck et al. (1983) reported that diquat was determined in air 
samples taken near the breathing zone of workers during its 
application for aquatic weed control.  The respiratory exposure 
levels were below the limits of quantitation of the chemical 
analysis. 

    In Bulgaria and the USSR, the proposed MAC (maximum allowable 
concentration) for diquat is 0.1 mg/m3 aerosol.  The TLV for diquat 
in workroom air in the United Kingdom and the USA is 0.5 mg 
diquat/m3 (1982), a level that will not be reached under normal 
conditions of application. 

Table 3.  Total airborne diquat concentrations in the air of working areasa
---------------------------------------------------------------------------
Place of sampling                           Number of   Mean concentrations
                                            samples     (mg/m3 ± SE)
---------------------------------------------------------------------------
Working area       sprayer loading          20          0.12 ± 0.03
                   tractor cabin            8           0.56 ± 0.10
                    (in direction of wind)
                   tractor cabin            8           0.17 ± 0.04
                    (against the wind)
                   manual spraying          16          0.25 ± 0.04

Treated field      after 5 min              8           0.20 ± 0.03
                   after 10 min             24          0.06 ± 0.01
                   after 20 min             8           ND

Distance from      200 m                    8           0.09 ± 0.01
treated field      400 m                    8           ND
---------------------------------------------------------------------------
a  From:  Makovskii (1972).

5.  KINETICS AND METABOLISM

5.1.  Animal Studies

5.1.1.  Absorption

     Oral absorption

    Daniel & Gage (1966) studied the absorption of 14C-diquat 
dibromide and 14C-diquat dichloride following oral and subcutaneous 
single-dose administration to rats.  About 90 - 97% of the oral 
diquat dibromide and 84 - 90% of the diquat dichloride were found 
in the faeces and 4 - 11% of both diquat salts in the urine.  
Following subcutaneous injection of 14C-diquat (10 mg/kg body 
weight) in rats, 87% of the administered dose was excreted in the 
urine and 5% in the faeces within 4 days.  The urine contained 
mainly unchanged diquat (75% of the dose) together with diquat 
monopyridone (about 3% of the dose) and diquat dipyridone (about 6% 
of the dose) (FAO/WHO, 1978). 

    The poor absorption of diquat from the gastrointestinal tract 
was confirmed by Litchfield et al. (1973) in the rat, and by Black 
et al. (1966), Stevens & Walley (1966), and Dembinski et al. (1971) 
in farm animals. 

     Pulmonary absorption

    The uptake of 14C-diquat by perfused rat lung, following 
intratracheal injection, was examined by Charles et al. (1978) and 
Charles & Menzel (1979).  Removal of 14C-diquat from the airways 
was rapid, initially, but slowed down with time.  The results 
indicate 2 phases of absorption and removal of diquat from the 
airways in the rat. 

     Dermal absorption

    There are no data on the rate of diquat absorption through the 
skin.  Studies on the dose-related percutaneous toxicity of diquat 
suggest that it may be dermally absorbed. 

5.1.2.  Distribution

    Although paraquat and diquat have similar chemical, physical, 
and herbicidal properties, only paraquat has been shown to damage 
the lung.  According to Sharp et al. (1972), diquat concentrations 
in lung and muscle were much lower than the levels attained with 
equal 20 mg/kg body weight iv doses of paraquat.  Table 4 shows the 
distribution of both in the main internal organs. 

Table 4.  Ratio of concentration of paraquat/diquat in 
the tissues of the rata
--------------------------------------------------------
Organ             Days after intravenous administration
                        1    3    5    7    10  
--------------------------------------------------------
Lung                    8    33   12   10   20  
                                                    
Muscle                  2    13   10   7    16  
                                                    
Kidney                  0.9  0.9  0.9  0.3  0.25
                                                    
Liver                   0.4  0.7  0.7  0.5  0.2 
--------------------------------------------------------
a  From:  Sharp et al. (1972).

    Diquat concentrations were higher in the kidney and the liver 
but significantly lower in the lung (Table 4).  In addition, the 
concentrations of paraquat were 2-8 times higher than those of 
diquat in the heart, adrenal glands, spleen, stomach, ileum, 
testes, and thymus.  Plasma levels were similar for both 
bipyridylium herbicides. 

    Litchfield et al. (1973) injected 14C-diquat cation at 50 mg/kg 
body weight iv into mice.  Whole-body autoradiographs were prepared 
after 10 min, 1 h, 24 h, and 72 h.  Radioactivity was selectively 
located in the gall bladder and was also present in cartilaginous 
tissue, liver, and the gastrointestinal tract.  Low radioactivity 
was found in the brain and spinal cord.  One h after dosing, the 
amount in the urine and intestinal epithelium had increased.  After 
24 h, the excretion of diquat was virtually complete, although 
radioactivity continued to be detected in the small and large 
intestine and the bladder. 

    Litchfield et al. (1973) also determined diquat levels in 
various tissues of male and female rats fed a diet containing 
diquat dibromide monohydrate at 250 mg/kg for 2, 4, and 8 weeks.  
High levels (0.18 - 1.17 mg/kg) were found in the kidney and the 
large intestine; levels in the lung ranged from < 0.05 to 0.53 
mg/kg; those in the liver from 0.07 - 0.22 mg/kg, while levels in 
the brain, muscle, and blood were very low.  At all stages of the 
study, diquat lung levels were lower than those for paraquat, the 
average paraquat content in the lung (at a dose of 250 mg/kg diet) 
over the 8-week period being 1.7 mg/kg and the average diquat 
level, 0.2 mg/kg.  No sex differences were found.  Within 1 week of 
return to a normal diet, diquat was below the detectable limit in 
all tissues examined. 

    Rats given paraquat or diquat orally at 680 µmol/kg had high 
kidney levels of diquat throughout the 30 h period after dosing 
(Rose & Smith, 1977, 1977a).  There was no significant time-
dependent increase in diquat levels in the lung, liver, brain, 
adrenal glands, muscle, and plasma.  These results confirmed that, 
following oral dosing, the lung does not accumulate diquat.  Rose & 
Smith (1977) also incubated rat lung slices in 10-5M paraquat and 

diquat.  In contrast to paraquat, diquat did not accumulate in the 
lung slices, and the compound did not accumulate significantly in 
any tissue slices with the exception of those from the kidney.  
These observations were confirmed by Lock (1979). 

    Matsuura et al. (1978) studied the distribution of orally 
administered LD50 doses of diquat and paraquat in rats.  Two and 
24 h after dosing, there were higher concentrations of diquat in 
kidney, liver, and lung than in brain, heart, the gastrointestinal 
system, and blood.  At equitoxic doses, levels of diquat in the 
lung appeared to be lower than those of paraquat.  In a similar 
distribution study of the LD50 and 0.5 LD50 doses of diquat and 
paraquat, Kurisaki & Sato (1979) determined the tissue 
concentrations from 2 to 48 h and from 2 to 9 days after treatment.  
Distribution in the lung, heart, brain, liver, and kidney of the 
rats agreed with previously published data. 

    The results of the above studies demonstrate that diquat does 
not persist as long as paraquat in the body of the rat and that it 
does not accumulate in the lung. 

5.1.3.  Metabolic transformation and excretion

    Daniel & Gage (1966) reported that the amount of 14C-diquat 
excreted in rat bile during the 24 h following oral doses of 1.2 - 
64 mg/kg body weight represented 1.1 - 4.8% of the dose.  Small 
amounts were detected in the urine, but about 70% of the diquat was 
present in the faeces.  In other studies (FAO/WHO, 1978), the rate 
of diquat metabolism in the rat was considerably lower than 
previously reported by Daniel & Gage (1966).  The biliary, urinary, 
and faecal excretion of 14C-labelled bipyridylium herbicides was 
studied by Hughes et al. (1973) in the rat, guinea-pig, and rabbit.  
14C-diquat dichloride was injected ip at dose levels of 40 µmol/kg 
body weight in the rat, 13 µmol/kg in guinea-pig, and 14 µmol/kg in 
the rabbit.  Most of the injected diquat (82% - rat, 64% -rabbit) 
was found in the urine.  Rabbits metabolized 18% of the dose, 
guinea-pigs 5%, and rats less than 1%.  The metabolites were 
similar for the 3 species.  The rat excreted approximately 1.4% of 
the dose in the bile, the guinea-pig 4.8%, and the rabbit 2.9%. 

    Stevens & Walley (1966) treated cattle orally with 14C-diquat 
dibromide in doses of 4, 8, and 20 mg/kg body weight.  The 
radioactivity levels in the milk of the cows indicated that 0.04 - 
0.15% of the ingested dose was excreted in this way.  Very low 
levels of diquat (0.01 mg/kg) were present in muscle tissue, 2 - 8 
days after dosing.  A bull calf was dosed orally with 14C-diquat 
dibromide at 10 mg/kg.  About 2.6% of the 10 mg/kg dose was excreted 
in the urine, but the major part of the dose was excreted via the 
faeces.   In the calf, 24 h after dosing, the residues were 0.66 
mg/kg in kidney, 0.20 mg/kg in heart and skin, 0.19 mg/kg in liver, 
0.03 mg/kg in lung, testes, and serum, and 0.006 mg/kg in muscle. 

    Studies on rats dosed orally with 14C-diquat at 45 mg/kg body 
weight or subcutaneously (sc) with 10 mg/kg body weight were 
reported by FAO/WHO (1978).  Rats given the oral dose excreted 6% 
and 89% in the urine and faeces, respectively, within 4 days and 
mainly within the first 2 days.  Unchanged diquat was the major 
component in both urine (5% of the dose) and faeces (about 57% of 
the dose).  About 5% of the oral dose was excreted as diquat 
monopyridone, mainly in the faeces, while diquat dipyridone 
appeared to be the major urinary metabolite.  Following sc 
injection, rats eliminated 87% of the dose in the urine and 5% of 
the dose in the faeces within 4 days.  The urine contained 75% of 
the dose as diquat, about 3% as diquat monopyridone, and about 6% 
as diquat dipyridone.   In vitro studies have shown that the caecal 
microflora of the rat can metabolize about 10% of the diquat added 
in a 24-h incubation period, with the formation of some diquat 
monopyridone.  This observation, together with the paucity of 
metabolites following ip injection, suggests that diquat is 
metabolized by the gastrointestinal tract bacteria. 

    The oral LD50 of diquat monopyridone in the rat was more than 
4000 mg/kg body weight.  Oral administration of diquat monopyridone 
at 1000 mg/kg body weight per day for 2 weeks did not induce any 
clinical, haematological, biochemical, or histopathological 
deviations in the rat.  In other studies, no adverse effects were 
noted after sc injection of diquat monopyridone or diquat 
dipyridone in rats, but 9 animals out of a group of 10 injected 
with the equivalent dose (16 mg/kg body weight) of diquat were dead 
by the l4th day following dosing (FAO/WHO, 1978). 

5.2.  Observations on Man

    Feldman & Maibach (1974) studied the dermal penetration of 
twelve 14C-labelled insecticides and herbicides.  Diquat showed a 
very low rate of dermal absorption in man.  No other studies on the 
kinetics of diquat in volunteers have been published, but 
observations are available on accidental and suicidal ingestion 
(section 7).  Toxicological analysisk, at the time of admission, of 
the serum of a patient, who had ingested 20 ml Reglone(R), showed 
a diquat level of 0.4 mg/litre (Vanholder et al., 1981).  At 
postmortem examination on the 5th day after ingestion, 
approximately 0.20 mg diquat/kg was determined in liver, kidneys, 
muscle, and eye liquid. 

6.  EFFECTS ON ANIMALS

6.1.  Effects on Experimental Animals

6.1.1.  Gastrointestinal system and liver

    Investigation of the clinical signs of acute oral intoxication 
by diquat (Verbetskii & Pushkar, 1968; Clark & Hurst, 1970; 
Crabtree et al., 1977; Cobb & Grimshaw, 1979) have established 
gastrointestinal disturbance as the major syndrome of poisoning and 
as a cause of death.  In both rats and guinea-pigs, the clinical 
signs of acute oral poisoning (Verbetskii & Pushkar, 1968) were 
dose-dependent.  At doses greater than the LD50, signs of poisoning 
appeared after 6 - 12 h; at lower levels, the signs were less 
obvious and appeared after 1 - 2 days.  Most deaths occurred on the 
3rd - 9th day after oral administration.  The animals lost 7 - 35% 
of their initial body weight.  During the first 24 h following the 
oral dosing of rats with 900 µmol diquat/kg body weight (LD50), a 
reduction in water intake was noted (Crabtree et al., 1977).  The 
animals were subdued, showed pilo-erection and loss of appetite.  
At 24 h, they excreted mucoidal, ropy faeces of a characteristic 
greenish-yellow or grass-green colour, this colour being due to the 
reduction of diquat by intestinal bacterial metabolism.  This 
colour can be reproduced  in vitro with fresh intestinal contents 
and actively growing bacterial isolates from them (Clark & Hurst, 
1970). 

    A significant dose-dependent accumulation of water in the lumen 
of the intestines and progressive haemoconcentration were reported 
(Crabtree et al., 1977) following acute diquat intoxication in 
rats.  It was concluded that diquat had an adverse effect on water 
distribution in the body.  Rapid fluid excretion following oral 
diquat poisoning suggested a direct action on the stomach and 
intestinal mucosa.  Monkeys dosed orally with diquat ion at 100, 
200, 300, and 400 mg/kg body weight (Cobb & Grimshaw, 1979) vomited 
within 2 h and showed diarrhoea within 12 h of dosing.  The most 
severely affected became lethargic and comatose, and finally 
collapsed and died, 12 - 84 h after dosing.  An increased number of 
polymorphonuclear leukocytes as well as increased levels of serum 
urea, plasma glucose, and serum GOT and GPT activities were 
determined in monkeys that died during the study.  Histological 
examination revealed a distended gastrointestinal tract and a 
swollen caecum; the mucosa of the stomach was ulcerated and the 
small and large intestines congested.  Large areas of the stomach 
and intestines showed necrosis and exfoliation of the epithelium 
from the mucosa.  The submucosa was infiltrated with lymphocytes, 
and polymorphonuclear and mononuclear cells.  These changes were 
most severe in the intestinal villi.  The death of the monkeys was 
due to destruction of the epithelial lining of the gastrointestinal 
tract in combination with kidney damage. 

     Liver

    The liver was not severely affected in acute and repeated 
diquat poisoning of experimental animals.  High doses sometimes 
resulted in histological lesions (Verbetskii & Pushkar, 1968; 
Bainova, 1975), but signs of toxic hepatitis were not described.  
Gage (1968a) reported stimulated NADPH oxidase activity in rat 
liver microsomes  in vitro after exposure to diquat. 

6.1.2.  Renal system

    The major route of diquat elimination is through the kidneys.  
High doses of diquat provoke histological and biochemical changes 
in the kidneys, but the most severe damage occured in relation to 
renal excretion function (Lock & Ishmael, 1979). 

    Kidney damage following acute and repeated diquat poisoning was 
reported by Verbetskii & Pushkar (1968), Bainova (1969), Cobb & 
Grimshaw (1979), Lock (1979), and Lock & Ishmael (1979).  Rats, 
guinea-pigs, and monkeys were investigated after oral poisoning 
with the herbicide.  Diquat, orally administered at 680 µmol/kg to 
rats, induced a significant increase in diuresis, proteinuria, and 
glucosuria after 6-24 h.  Biochemical tests  in vitro revealed a 
decrease in  N'-methylnicotinamide, but not 4-aminohippurate, 
accumulation by renal cortical slices suggesting competition for 
the base transport system.  Stimulation of the pentose phosphate 
pathway and inhibition of fatty acid synthesis were found when 
diquat was added to renal cortical slices  in vitro.  No such 
changes were noted when the renal cortical slices were prepared 
from rats previously treated with diquat (Lock, 1979). 

    Lock (1979) also investigated the changes in several variables 
and the clearance of diquat by the rat kidney after oral 
administration of toxic doses (680 and 900 µmol/kg body weight).  
Diquat was not bound to the proteins of the rat plasma.  Active 
renal secretion was confirmed by the fact that diquat was cleared 
by the kidney at a slightly higher rate than inulin.  In rats 
treated orally with diquat at 540 µmol/kg body weight, renal 
clearance decreased after 24 h.  However, the reduction in renal 
function induced by diquat (Lock 1979) was considered to be 
secondary and due to water redistribution caused by acute 
poisoning. 

    Histopathological changes have been reported in the kidneys of 
animals poisoned with high doses of the herbicide (Verbetskii & 
Pushkar, 1968; Cobb & Grimshaw, 1979; Lock & Ishmael, 1979).  The 
renal papillae were hyperaemic, degeneration and necrosis of the 
epithelium of the proximal and distal convoluted tubules were 
noted, the epithelial cells were exfoliated, and the nuclei 
pycnotic. 

6.1.3.  Eyes and skin

     Eye irritation

    The local irritation caused by diquat is less pronounced than 
that caused by paraquat.  One drop of 20% solution gave rise to 
slight conjunctival irritation of the rabbit eye, which persisted 
for 2 days (Clark & Hurst, 1970).  A 40% diquat solution induced 
moderate conjunctival irritation. 

     Eye cataract

    Both rats and dogs fed diets containing diquat developed 
cataracts (Howe & Wright, 1965).  However, rats fed 7.5 mg 
diquat/kg diet over a life-span did not develop cataracts, while 70 
mg diquat/kg diet appeared to be the no-observed-adverse-effect 
level for dogs.  According to Clark & Hurst (1970), rats on diets 
containing 50 mg diquat/kg or more developed cataracts in the 
course of the study.  In another group fed a diet containing 1 g 
diquat/kg, eye opacities were discovered within 6 months, while a 
few animals on diets of 100 mg/kg and 50 mg/kg showed slight 
opacities at the end of the study period.  A 2-year test with a 
diet containing diquat at 10 mg/kg did not induce cataracts in 
rats. 

    Bilateral cataracts were discovered in all dogs 10 - 11 months 
following oral administration of diquat at 15 mg/kg body weight per 
day.  The dose of 5 mg/kg body weight per day induced eye opacities 
after 17 months, and doses of 1.7, 0.8, and 0.4 mg/kg body weight 
per day were ineffective after 3 - 4 years of treatment. 

    A 2-year feeding study was carried out with diquat levels of 
15, 25, and 75 mg/kg in the diet of rats.  Only the 25 and 75 mg/kg 
levels caused cataracts (FAO/WHO, 1978). 

    Pirie & Rees (1970) confirmed that rats fed diquat dibromide at 
0.5 - 0.75 g/kg in the diet developed cataracts.   In vivo  
observations showed that, invariably, the first change seen was an 
opacity in the posterior cortex, immediately under the posterior 
capsule of the lens.  The next stage was a defined nuclear cataract 
that could be seen with the naked eye.  Finally, shrinkage and 
complete opacity occurred.  This histological study revealed that 
the first posterior cortical opacity was formed from damaged 
epithelial cells.  The level of diquat in the blood of these rats 
was less than 2.2 µM.  No diquat accumulation was registered in the 
lens of these rats.  The mechanism of the specific cataractogenic 
action of diquat is not clear, although  in vitro studies 
demonstrated that reduction of diquat by the lens was enzymatically 
catalysed by glutathione reductase (EC 1.6.4.2) with NADPH as the 
source of reducing equivalents.  The loss of ascorbic acid from the 
lens and the ocular fluids of treated rats was proposed as a factor 
for maintaining the normal glutathione level in the rat lens. 

     Local skin effects

    Single diquat applications on the skin of mice (Bainova, l969a) 
and rabbits (Clark & Hurst, 1970) did not cause any local 
irritation.  Daily applications of 1% diquat solution in water to 
the skin of rats provoked slight erythema at the site of contact 
during the first 10 days, while daily applications of diquat at 20 
mg/kg body weight to the skin of rabbits caused mild erythema, 
thickening of the skin, and some scabbing (Clark & Hurst, 1970).  
Diquat has not been found to be a sensitizer (Bainova, (l969a). 

6.1.4.  Respiratory system

    The effect of diquat on the respiratory system has been studied 
after parenteral (Hawkins et al., 1979; Lam et al., 1980), oral 
(Verbetskii & Pushkar, 1968; Bainova, 1969; Bainova & Vulcheva, 
1978), intratracheal (Lam et al., 1980), and inhalation exposure 
(Gage, 1968; Bainova et al., 1972).  Unlike paraquat, no specific 
effects on the lung were reported, though difficulties in breathing 
occurred after severe acute poisoning of the animals with diquat. 

6.1.5.  Nervous system

    General depression and lethargy were most commonly seen 
following the administration of high doses of diquat to guinea-pigs 
and rats (Verbetskii & Pushkar, 1968; Clark & Hurst, 1970; Crabtree 
et al., 1977), and to monkeys (Cobb & Grimshaw, 1979). 

6.1.6.  Effects on reproduction, embryotoxicity, and teratogenicity

6.1.6.1.  Effects on reproduction

    Male rats were dosed orally with diquat dibromide at 6.5 mg/kg 
body weight per day, for 60 days, and the testes were then examined 
biochemically and histologically (Bainova & Vulcheva, 1974).  There 
were no significant changes in the sperm count, sperm motility, the 
testicular tubules, the basal cells, or in the activity of several 
enzymes. 

    A 2-generation study on rats was carried out with dietary 
levels of 125 and 500 mg diquat/kg.  The 500 mg/kg dose resulted in 
reduced body weight for F1a, F1b, F2a, and F2b, and increased 
cataracts in F1b and F2b after 91-280 days of exposure.  The 125 
mg/kg dose resulted in decreased body weight in F1b and F2b, but no 
lens opacities were noted (FAO/WHO, 1973). 

6.1.6.2.  Embryotoxicity and teratogenicity

    Diquat was reported to have induced deviations in the prenatal 
development of rats (Khera et al., 1968).  Bus et al. (1975) 
studied the fetal toxicity and teratogenicity of diquat in rats by 
administering 15 mg/kg body weight iv on days 7-21 of gestation.  
This resulted in 57% fetal resorption compared with 7.6% for 
paraquat.  The incidence of maternal deaths was essentially the 
same.  When 14C-diquat and 14C-paraquat were administered to rats, 

iv, in a dose of 15 mg/kg body weight on days 13, 16, and 21 of 
gestation, paraquat increased radioactivity in fetal lung whereas 
diquat appeared to have a stronger embryotoxic action than 
paraquat.  In the review published in 1979 by FAO/WHO, it was 
reported that diquat dibromide monohydrate, administered orally to 
pregnant rabbits at doses of 1.25, 2.5, and 5.0 mg/kg had no 
adverse effect on the fetuses.  In groups of pregnant rats kept on 
diets containing 125 and 500 mg diquat cation/kg throughout 
gestation, reduced body weight was noted only in the fetuses of 
mothers from the 500 mg/kg group.  A slightly increased incidence 
of subcutaneous haemorrhages was also noted. 

    Teratogenicity studies in mice have been reported by Selypes et 
al. (1980).  Single ip doses of diquat at 2.7 and 11 mg/kg body 
weight were injected on days 9, 10, 11, and 12 of gestation.  The 
number of dead fetuses, as well as post-implantational lethality, 
increased significantly:  average embryo weight was lower and, 
though no congenital malformations were noted, there were signs of 
skeletal retardation such as large fontanelles, wider cerebral 
sutures, flat-shaped ventral nuclei of the vertebrae, and delayed 
ossification in the sternum and phalanges.  The embryotoxic effect 
in mice of high doses of diquat was thus confirmed, but no 
chromosomal aberrations were noted in the liver cells of the 
embryos from diquat-treated female mice. 

6.1.7.  Mutagenicity

    Studies on the genotoxic potential of diquat are rather 
contradictory.  Diquat was negative in the Ames test, with and 
without metabolic activation (Anderson et al., 1972; Benigni et 
al., 1979; Levin et al., 1982).  Dominant lethal assays in mice 
performed by various authors with several doses of the herbicide 
gave negative results (Pasi et al., 1974; Pasi & Embree, 1975; 
Anderson et al., 1976).  Selypes et al. (1980) injected mice ip 
with 22 mg/kg (LD50) diquat, while another group of mice was dosed 
orally with 90 mg/kg (0.5 LD50).  After 24 and 38 h, preparations of 
bone marrow were examined for chromosome aberrations; no 
statistically significant changes were determined. 

    On the other hand, diquat was found to induce slight gene 
conversion in  Saccharomyces cerevisiae (Siebert & Lemperle, 1974).  
Ahmed et al. (1977) reported that diquat induced DNA changes in 
cultured SV-40-transformed human cells, with and without metabolic 
activation, and the induction of 8-azaguanine resistance in the 
 Salmonella typhimurium assay was positive (Benigni et al., 1979; 
Bignami & Crebelli, 1979).  Benigni et al. (1979) also found that 
diquat was positive in an  S. typhimurium repair test.  It was 
further reported by these authors that diquat induced gene 
mutations in  Aspergillus nidulans, and increased unscheduled DNA 
synthesis in human epithelial-like cells.  They commented that 
diquat may have an effect on a number of different genetic 
endpoints. 

6.1.8.  Carcinogenicity

    In 2-year feeding studies on rats (Clark & Hurst, 1970), diquat 
at levels of up to 720 mg/kg diet did not induce tumours.  The 
daily ingestion of 2 and 4 mg diquat per kg body weight in water 
for a period of 2 years did not have any significant effects on the 
health and mortality rate in rats (Bainova & Vulcheva, 1978).  Some 
histological changes related to chronic interstitial infiltration 
and pulmonary adenomatosis in the lungs were found, especially 
after the higher dose, but there were no indications of malignancy. 

6.2.  Effects on Farm Animals

    The effects of diquat on farm animals was studied in relation 
to its application as an aquatic herbicide and desiccant (Howe & 
Wright, 1965; Black et al., 1966; Stevens & Walley, 1966) (section 
4.4).  Little variation in diquat toxicity in the various animal 
species was found, but cattle appeared to be the most sensitive 
(LD50 for cattle approximately 30 mg/kg, LD50 for rat 230 mg/kg).  
Single oral doses up to 8 mg/kg produced no signs of toxicity in 
cows (Stevens & Walley, 1966), and the continuous exposure of 
animals via the forage to doses ranging from 0.2 to 330 mg/kg in 
the diet (Calderbank, 1972) did not induce any clinical or 
pathological changes in farm animals. 

    Calderbank (1972) recommended that domestic animals should not 
be allowed to enter fields newly treated with diquat, nor be given 
water recently treated with the herbicide.  When edible crops are 
treated with diquat, as desiccant, at least 4 days should elapse 
before the crops are fed to stock, and when diquat is used for 
aquatic weed control, at least 7 days should elapse before the 
treated water is used for field irrigation.  Recommended levels for 
weed control must be observed (Calderbank, 1972). 

    Sheep given doses of 1, 5, 10, and 20 mg diquat/kg per day in 
their drinking-water for 1 month and calves similarly exposed to 5 
and 20 mg diquat/kg per day did not show any adverse toxicological 
effects as evidenced by growth, food consumption, and observation. 

6.3.  Dose-Effect of Diquat

    The acute LD50 values of diquat in various species were 
published by Howe & Wright (1965) and Clark & Hurst (1970). The 
acute toxicity of diquat salts (Table 5) does not differ 
significantly and is similar for both sexes. 

    Table 6 summarizes the acute oral, dermal, and inhalation LD50 
and LC50 values of diquat in various experimental and domestic 
animals.  There are no marked species differences but cattle, 
guinea-pigs, and monkeys appear to be the most sensitive species.  
The few cases of acute diquat poisoning in man have not furnished 
sufficient data to determine the lethal dose for man. 

    The dose-effect relationship of repeated diquat exposure, from 
various studies, is summarized in Table 7.  Rats, guinea-pigs and 
dogs were subjected to ora1 and dietary administration of diquat.  
Guinea-pigs appeared to be rather sensitive (Makovskii, 1972), but 
the herbicide did not induce cumulative toxic effects (Bainova, 
1969, 1975; Makovskii, 1972), because  of its relatively rapid 
elimination from the organism and the absence of deposits in the 
tissues. 

Table 5.  LD50 (mg/kg) of diquat salts in rats
-----------------------------------------------
Diquat             Route of entry  Sex  LD50 
                                        (mg/kg)
-----------------------------------------------
Diquat dibromide   oral                 215b

Diquat dibromide   oral                 210b

Diquat dibromide   subcutaneous    F    11a

Diquat dichloride  subcutaneous    F    10a

Diquat dichloride  subcutaneous    M    11a

Diquat dibromide   subcutaneous         22b
-----------------------------------------------
a  From:  Clark & Hurst (1970).
b  From:  Makovskii (1972).

Table 6.  Diquat LD50 (mg/kg) and LC50 (mg/m3) 
in various species
----------------------------------------------
Species     Oral          Dermal   Inhalationa
            (mg/kg)       (mg/kg)  (mg/m3)
----------------------------------------------
Rat         400b          650f     35f

Rat         281c                   83h

Rat         231e

Rat         215f

Rat         130g

Mouse       170b          430d

Mouse       125e

Rabbit      190b

Rabbit      101e          > 400e

Guinea-pig  123c          400f     38f

Guinea-pig  approx. 100e

Guinea-pig  100f

Hen         400 - 800b

Hen         200 - 400e

Dog         > 200b

Dog         100 - 200e

Cow         approx. 30f

Cow         30e

Monkey      100 - 300i
----------------------------------------------
a  Respirable diquat aerosol.
b  From:  Howe & Wright (1965).
c  From:  Verbetskii & Pushkar (1968).
d  From:  Bainova (1969a).
e  From:  Clark & Hurst (1970).
f  From:  Makovskii (1972).
g  From:  Bainova (1975).
h  From:  Bainova & Vulcheva (1977).
i  From:  Cobb & Grimshaw (1979).


Table 7.  Effect of repeated oral, dermal, and inhalation exposure to diquat in experimental animals
---------------------------------------------------------------------------------------------------------
Species  Dosage                  Duration      Results obtained                          Reference
---------------------------------------------------------------------------------------------------------
Rat      87.5, 175, and 350 mg   2 years       cataract at all dietary levels            FAO/WHO (1971)
         diquat ion/kg of diet

Rat      7.2, 36, 72, 180,       2 years       no deaths; reduced growth in males at     FAO/WHO (1971)
         360, and 720 mg diquat                highest dietary level; cataract at
         ion/kg diet                           dietary levels of 36 mg diquat ion/kg
                                               diet and above; no cataract at 7.2 mg/kg

Rat      15, 25, and 75 mg       2 years       no deaths; "no effect" level for          FAO/WHO (1978)
         diquat ion/kg diet                    cataractogenesis 15 mg diquat ion/kg 
                                               diet

Rat      oral - 6.5, 13, and 40  30 days       dose-related biochemical and              Bainova (1969,
         mg/kg body weight per                 histological changes in kidney, liver,    1975)
         day 2.1 and 4.3 mg/kg   4 1/2 months  gastrointestinal system, and lung; no 
         body weight per day                   haematological changes; increased 
                                               G-6-P-isomerase serum activity;
                                               histological changes at 4.3 mg/kg 
                                               body weight per day

Rat      oral - 0.2, 2.1, and    1 year        the higher doses were toxic for the       Makovskii (1972)
         5.3 mg/kg body weight                 2 species; no-observed-effect levels      
         per day

Guinea-  day 0.1, 1.0, and 2.5                 0.2 and 0.1 mg/kg body weight per day 
pig      mg/kg body weight per                 for rat and guinea-pig
         day

Dog      10, 20, 50, 140, and    up to 4       no cataracts at dietary levels up to and  FAO/WHO (1971)
         420 mg diquat ion/kg    years         including 50 mg/kg; cataract at 2 higher
         of diet                               dietary levels; no mortality; no effects
                                               on growth

Rat      oral - 2 and 4 mg/kg    1 and 2       no increase in mortality rates;           Bainova &
         per day                 years         histological changes in lungs after       Vulcheva (1978)
                                               treatment with 4 mg/kg per day in 
                                               drinking-water; minimal effective dose
                                               2 mg/kg per day
---------------------------------------------------------------------------------------------------------

Table 7.  (contd.)
---------------------------------------------------------------------------------------------------------
Species  Dosage                  Duration      Results obtained                          Reference
---------------------------------------------------------------------------------------------------------
rat      dermal - 5, 10, 20      20 days       slight skin irrritation, death and toxic  Bainova (1969a)
         60, and 120 mg/kg                     effects at 10 - 120 mg/kg per day;
         per day                               dilation of the gastrointestinal system  
                                               at toxic levels; histological changes in
                                               kidney, gastrointestinal system, liver, 
                                               and lung at toxic levels, LD50 35 mg/kg 
                                               per day without occlusion; no-observed- 
                                               effect dose 5 mg/kg per day             

Rabbit   dermal - 20 and 40      20 days       mild skin irritation; toxic effects at    Clark & Hurst
                                               at 40 mg/kg per day; no clinical signs    (1970)
                                               of toxicity at 20 mg/kg per day; LD50 
                                               between 20 and 40 mg/kg per day

Rat      inhalationa - 0.50,     15 days       clinical signs of irritation and          Gage (1968)
         1.60, and 2.0 mg/m3                   histological changes in lungs at 2mg/m3;                                
         6 h daily                             no clinical haematological, and       
                                               histological deviations at 0.50 mg/m3;
                                               minimum effective concentration 1.0   
                                               mg/m3 diquat aerosol                  

Rat      inhalationa - 0.32      4 1/2 months  biochemical and histological changes in   Bainova (1972)
         and 1.90 mg/m3,                       lungs at 1.90 mg/m3; minimal effective
         6 h daily                             concentration 0.32 mg/m3 diquat aerosol

Rat      inhalationa - 0.4,      4 months      clinical signs of irritation and toxic    Makovskii
         0.7, and 1.9 mg/m3,                   effects at 1.9 mg/m3; 0.7 mg/m3 produced  (1972)
         4 h daily                             changes in some rats; minimal effective 
                                               concentration 0.4 mg/m3 diquat aerosol
---------------------------------------------------------------------------------------------------------
a  Respirable diquat aerosol.

7.  EFFECTS ON MAN

7.1.  Case Reports

    Several cases of acute diquat poisoning among the general 
population have been reported in the literature.  Fitzgerald et al. 
(1978) found 5 cases from 1967 to 1977 in Ireland.  Vanholder et 
al., (1981) summarized the clinical outcome and the treatment of 11 
patients with diquat poisoning (6 fatal and 5 non-fatal). 

(a) Suicidal diquat poisoning

    Schönborn et al. (1971) reported the fatal case of a man who 
drank 2 - 3 mouthfuls of Reglone(R) (estimated 15 - 22 g diquat) 
with the intention of committing suicide.  Severe vomiting occurred 
after 2 h and, 2 h later, watery diarrhoea, the stools having a 
peculiar yellow-greenish colour.  During the next 6 h, the patient 
lost about 3.5 litres of liquid through faeces and 4 litres of 
liquid through vomiting.  The urine was very concentrated, the 
haematocrit was 55%.  Serum enzyme activity showed toxic liver 
damage, and proteinuria and metabolic acidosis were registered.  On 
the 2nd day, there were ulcers and severe oropharyngeal 
inflammation, on the 3rd day, increasing restlessness, optical 
hallucinations, and delirium and stridulous breathing developed.  
During the 4th-6th days, anuria, raised body temperature, 
generalized convulsions, and coma were registered, and the patient 
died on the 7th day of cardiac insufficiency and thrombocytopenia. 

    The autopsy revealed extensive necrosis of the pharynx and 
oesophagus, and petechial bleeding and erosions in the 
gastrointestinal tract; pulmonary oedema with haemorrhages, hyaline 
membrane production, and bronchopneumonic foci were noted in the 
lungs; fatty degeneration was found in the liver and heart, and 
severe degeneration of the tubulus epithelium with necrosis in the 
kidneys, while the signs of circulatory failure with oedema and 
haemorrhagic diapedesis of the brain explained the central nervous 
system effects.  The diquat concentrations measured on the 1st day 
after ingestion were 1.85 mg/litre in the urine and 0.47 mg/litre 
in the blood.  Higher diquat levels were determined post mortem in 
the kidneys, spleen, and lungs (1.19, 1.04, and 0.56 mg/kg, 
respectively). 

    In a second case of suicide, the subject had taken unknown 
quantities of Reglone(R) during a period of 3 days (Okonek & 
Hofmann, 1975).  One day after the second ingestion, she was 
admitted to hospital - shocked, sleepy, anuric, with haemorrhagic 
mucosal necrosis in the mouth, throat, and eosophagus.  Four h 
after admission to hospital, the diquat serum level was 1.038 
mg/litre.  This decreased to 0.30 mg/litre following dialysis.  
Death from cardiovascular collapse ensued 46 h after admission. 

    Vanholder et al. (1981) concluded, from their review of 11 
cases, that the lethal dose of Reglone(R) is 30 - 60 ml or 
approximately 6 - 12 g diquat dibromide. 

    An unusual case of diquat poisoning was described by Narita et 
al. (1978).  A clerk, after drinking heavily, swallowed about 200 
ml 30% diquat dibromide formulation.  Vomiting was accompanied by 
great thirst, severe irritation of the mouth, diarrhoea, and a 
temperature of 39 °C.  After 24 h, the patient became anuric and 
developed acute renal failure; he was comatose and inarticulate, 
and had meiosis and unclear light reflexes.  He died from dyspnoea 
38 1/2 h after ingestion of diquat.  Autopsy revealed renal failure 
with tubular necrosis, lung haemorrhages, haemorrhagic ulcers, and 
erosions in the stomach, and severe congestion of the lungs, 
kidneys, liver, gastrointestinal system, and adrenal glands.  High 
diquat residues were determined in the kidneys, liver, lungs, and 
intestines.  Vanholder et al. (1981) reported 2 cases of Reglone(R) 
ingestion (50 ml and 20 ml) in suicide attempts.  Because of 
vomiting and diarrhoea, they were admitted to local hospitals, but 
no specific treatment was given and the patients were released in 
satisfactory clinical condition.  However, because of the 
development of progressive oliguria several h later, the patients 
returned to the hospital.  The diquat serum levels were found to be 
4.5 and 0.4 mg/litre, respectively.  The patients died 1 and 5 days 
after the ingestion of diquat. 

(b)  Accidental diquat poisoning

    Oreopoulos & McEvoy (1969) described a patient who accidentally 
took a mouthful of Reglone(R) from a soft drink bottle.  He spat 
out part of it.  After 8-10 h, he had diarrhoea and 2 ulcers in the 
mouth, but there was no clinical evidence of respiratory, renal, or 
central nervous system effects on examination in hospital, and all 
laboratory and biochemical examinations were within the normal 
physiological limits.  The patient continued to excrete diquat in 
the urine for 11 days after ingestion.  He underwent forced 
diuresis and left the hospital in good condition. 

    Another case of acute poisoning following the accidental 
ingestion of less than a mouthful of diquat was reported by Fel et 
al. (1976).  Nausea, vomiting, and diarrhoea were the first 
effects.  The patient then developed uraemia, oliguria, and anuria 
despite forced diuresis for 2 - 3 days after the accident.  
Haemodialysis proved more successful.  Bilateral pneumonia was 
noted during the 2nd week, but was cured with antibiotics, and the 
patient was discharged on the 26th day in good health. 

7.2.  Effects on Agricultural Operators

    A few studies have been performed on workers spraying diquat.  
Air concentrations of diquat aerosol were measured by Makovski 
(1972) (Table 3).  The dermal exposure of the spraymen ranged from 
0.05 mg to 0.08 mg on the face and hands after 2 - 3 h of daily 
work.  The spraymen did not have any complaints, and the clinical 
and laboratory examinations did not reveal any significant 

differences in comparison with control groups.  Wojeck et al. 
(1983) studied the exposure of workers applying 1.76% diquat by 
hand-operated spray against water hyacinths or using direct 
injection of 4.41% spray mixture into the water for hydrilla 
control.  The spray crews applied diquat 2 - 5 h daily for 4 days 
weekly.  The inhalatory exposure was found to be < 0.01 mg/h.  The 
dermal exposure of the spraymen and the airboat drivers were 
estimated to be 1.82 and 0.20 mg diquat/h, during the treatment of 
water hyacinths.  The dermal exposures of the spraymen and the 
mixer of diquat for the treatment of water hydrilla were 0.17 and 
0.47 mg/h, respectively.  The results of urine analysis of all 
workers involved in the study were negative (< 0.047 mg/litre).  
The dermal exposure to diquat was closely related to the 
concentrations used in the working solutions. 

    Inflammation and bleeding of the nasal mucosa were observed in 
people handling crystalline diquat powder in the laboratory or 
under field conditions (Clark & Hurst, 1970).  Epistaxis during 
agricultural diquat application is related to the inhalation of 
droplets or splashes from the careless mixing of liquid 
concentrates.  A worker who spent some considerable time in an 
aerosol spray drift developed irritation of the upper respiratory 
tract. 

    According to Clark & Hurst (1970), if a 20% diquat solution 
comes into contact with the nail base, nail growth disturbances may 
result, and discoloured spots, white bands, and shedding of the 
nail were seen after prolonged contact with concentrated diquat.  
The nail re-grew normally once exposure was discontinued.  No 
adverse effects on the nails were observed following the use of 
diluted diquat spray solutions in agriculture.  Concentrated diquat 
formulations have also been reported to delay the healing of 
superficial cuts on the hands of spray workers. 

    Cataracts have never been observed in man following exposure to 
diquat (FAO/WHO, 1978; Hayes, 1982). 

7.3.  First Aid and Medical Treatment

    These are essentially the same as those given for paraquat 
(section 8.4).  See also WHO/FAO (1979). 

8.  EVALUATION OF RISKS FOR HUMAN HEALTH AND EFFECTS ON THE ENVIRONMENT

8.1.  Exposure

8.1.1.  Relative contributions of soil, water, air, and food sources 
to total diquat uptake

     Introduction

    Diquat is a contact herbicide and dessicant that is used to 
destroy weeds in various agricultural situations.  It is used in 
the form of an aqueous spray, which means that the potential 
exposure of man may occur as a result of its presence in air, on 
plants, in soil, or in water. 

     Degradation of Diquat

    Photochemical degradation takes place, when diquat treated 
plants are exposed to normal daylight, and continues after plants 
are dead.  The products formed are of lower toxicity than diquat.  
The rapidity of photochemical degradation on plant and soil 
surfaces minimizes the hazard of diquat for the environment. 

     Soil

    Diquat is rapidly and tightly bound to clay particles in the 
soil, and is thereafter inert.  In normal agricultural use, no 
toxic breakdown products are to be expected in the soil (section 
4.2) where diquat is less persistent than paraquat.  Total diquat 
residues in the soil after repeated spraying ranged from 0.2 to 3.9 
mg/kg.  On the 15th day after a single application of diquat, 
residues were less than 0.1 mg/kg in field studies.  Even at high 
rates of application, no specific adverse effects are found on soil 
microorganisms, fungi, or invertebrates, and no phytotoxic effects 
have been reported on crops. 

     Water

    Following its use as an aquatic herbicide at normal application 
rates, diquat residues in water have been found to decrease rapidly 
to essentially undetectable levels within 7-14 days (section 4.3).  
Toxic effects on fish and other living organisms in the water are 
unlikely, because diquat is rapidly photodegraded, absorbed by 
aquatic weeds, or adsorbed to soil particles at the bottom.  
However, caution should be taken in the application of diquat to 
water containing heavy weed growth, since oxygen consumed by 
subsequent weed decay may decrease the oxygen content of the water 
to such an extent that it is dangerous for fish or other aquatic 
organisms.  No phytotoxic damage should occur on crops irrigated 
with diquat-treated water, if at least 10 days is allowed to elapse 
between treatment and irrigation. 

     Air

    Diquat is not volatile.  Inhalation exposure can occur via 
spray aerosols or contaminated dust but, if correctly applied, 
diquat should not give rise to significant inhalation exposure of 
the sprayers (section 4.5).  Total airborne aerosol concentrations 
of diquat in the air in working areas ranged from 0.06 to 0.56 
mg/m3, depending on the method of application and the period of 
time after the spraying. 

     Food

    Extensive studies on forage desiccated with diquat have 
demonstrated that the residues are very low within some days of the 
application of the desiccant.  Diquat residues in the treated 
herbage following pre-harvest desiccation ranged from 0.02 to 25 
mg/kg at different intervals after spraying.  Trials in which such 
forage was fed to cattle and sheep have demonstrated insignificant 
residue levels in the milk, meat, and internal organs (section 
4.4).  Residues found in vegetables, fruits, and cereals have been 
low.  There is no bioaccumulation. 

8.1.2. General population exposure

    Inhalation exposure of the general population to diquat may 
occur from spray drift off the treated fields, but this is thought 
to be insignificant.  There are no published data on total diquat 
intake among the general population but this again is expected to 
be insignificant on the basis of known residue levels.  Studies on 
its environmental distribution point to a low environmental hazard.  
Due to diquat's rapid and complete binding to clay minerals in 
soil, contamination of water supplies either from field runoff or 
percolation through soil to the water table is not expected 
(section 4.2). 

    Few cases of diquat poisoning have been reported (section 7.1).  
Most cases are due to the intentional ingestion of concentrated 
formulations, but accidental ingestion has occurred.  The decanting 
of liquid concentrate formulations into beer, wine, or soft drink 
bottles, and subsequent inappropriate storage, is very dangerous. 

    The acute lethal dose of diquat dibromide is considered to be 
6 - 12 g for man.  Recovery from diquat poisoning depends on the 
cause of ingestion, the dose absorbed, the renal damage, and prompt 
initiation of therapy.  No long-term adverse effects have been 
reported in those who have survived acute diquat poisoning. 

8.1.3.  Occupational exposure

    There may be inhalation, dermal, and to some extent oral 
occupational exposure.  Spray aerosols and dust particles settle in 
the upper respiratory tract.  Diquat aerosol concentrations range 
from 0.06 to 0.56 mg/m3, according to the spraying method.  At a 
distance of 200 - 400 m from the treated field, they decrease to 
0.09 mg/m3 and less than 0.01 mg/m3.  Inhalation exposure was found 

to be very low in comparison with dermal (0.17 - 1.82 mg/h) 
exposure to diquat during application for aquatic weed control.  
Skin irritation, epistaxis, nail damage, and delayed wound healing 
have been reported.  However, no data on severe or fatal cases of 
occupational intoxication, acute ocular damage, or occupational 
contact dermatitis caused by diquat were found in the literature. 

8.2.  Effects

8.2.1.  Diquat toxicity in animals

    Diquat is less toxic than paraquat and does not cause the 
specific lung disease so typical of paraquat exposure. 

    The primary toxic effect of diquat in animals is 
gastrointestinal damage resulting in diarrhoea with consequent 
dehydration.  After high doses of diquat, minor toxic effects have 
been noted in the liver, kidney, and the nervous and endocrine 
systems.  High concentrations of diquat are irritating to the skin, 
although less so than paraquat.  Development of eye cataracts has 
been reported in rats and dogs following long-term treatment with 
diquat (section 6.1.3).  This observation has not been reported in 
man.  Diquat is embryotoxic but it has not been found to be 
teratogenic in rats and mice or carcinogenic in long-term feeding 
studies on rats given diquat at levels up to 720 mg/kg diet 
(sections 6.1.7 and 6.1.8).   In vitro mutagenicity studies have 
been inconclusive, although generally suggesting weak activity, 
while the results of  in vivo studies have been negative (section 
6.1.8).  Thus, the results of animal studies suggest that low-level 
exposure to diquat is unlikely to induce toxic effects in man.  The 
no-observed-effect level in rats has been estimated to be 0.75 mg 
diquat ion/kg body weight per day (FAO/WHO, 1978). 

8.3.  Earlier Evaluations of Diquat by International Bodies

    The Joint Meeting on Pesticide Residues (JMPR) reviewed and 
published residue and toxicity data on diquat in 1970, 1972, 1976, 
1977, 1978 (FAO/WHO 1971, 1973, 1977a,b, 1978, 1979).  In 1977, it 
estimated the acceptable daily intake (ADI) for man as 0 - 0.008 
mg/kg body weight expressed as diquat ion (FAO/WHO 1978). 

    The same JMPRs have recommended maximum residue levels 
(tolerances) for diquat in food commodities of plant and animal 
origin. 

    Regulatory standards established by national bodies in 12 
different countries (Argentina, Brazil, Czechoslovakia, Federal 
Republic of Germany, India, Japan, Kenya, Mexico, Sweden, the 
United Kingdom, the USA, and the USSR) and the EEC are available 
from the IRPTC (International Register for Potentially Toxic 
Chemicals) legal file (IRPTC 1983). 

    A data sheet on diquat has been prepared by WHO/FAO (1979) in a 
series of "Data sheets on chemical pesticides".  Based on a brief 
review of use, exposure, and toxicity, practical advice is given on 

labelling, safe-handling, transport, storage, disposal, 
decontamination, selection, training and medical supervision of 
workers, first aid, and medical treatment. 

8.4.  Conclusions

    On the basis of the above findings, it can be concluded that: 

    General population

    Residue levels of diquat in food and drinking-water, resulting 
from its normal use, are unlikely to result in a health hazard for 
the general population. 

    Diquat has caused some fatalities following suicidal ingestion.  
Occasional accidental fatalities have followed ingestion of 
decanted diquat.  Ill-effects similar to those caused by paraquat 
occur, but the characteristic fibrosis of the lungs is not a 
feature. 

    Occupational exposure

    With reasonable work practices including safety precautions, 
hygiene measures, and proper supervision, occupational exposure 
during the manufacture, formulation, and application of diquat will 
not cause a hazard.  However, the undiluted concentrate must be 
handled with great care, because contamination of eyes and skin 
(with possible consequent dermal absorption) can result from 
improper work practices. 

    Environment

    Diquat in soil binds rapidly and tightly to clay particles and 
residual phytotoxicity from freely available diquat is unlikely.  
Under normal conditions of use, the toxicity of diquat for aquatic 
organisms is low, though resulting depletion of water oxygen due to 
weed decay may pose a problem.  Diquat does not seem to represent 
an environmental hazard. 

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    See Also:
       Toxicological Abbreviations