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Paraquat

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Main brand names/ Main trade names
   1.6 Main manufacturers, main importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substances
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/form
      3.3.3 Description
   3.4 Hazardous Characteristics
4. USES
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstances of poisoning
   4.3 Occupationally exposed populations
5. ROUTES OF ENTRY
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination and excretion
7. TOXICOLOGY
   7.1 Mode of Action
   7.2 Toxicology
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI)
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall interpretation of all toxicological analyses and toxicological investigations
   8.6 References
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects:
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurologic
         9.4.3.1 CNS
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.3 Gastrointestinal
      9.4.4 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Others
      9.4.7 Endrocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ear, nose, throat: local effects
      9.4.10 Hematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic treatment
   10.3 Decontamination
   10.4 Enhanced elimination
   10.5 Antidote treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from the literature
12. ADDITIONAL INFORMATION
   12.1 Specific preventive measures
   12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S) DATA (INCLUDING EACH UP-DATE), COMPLETE ADDRESSES
    Paraquat

    International Programme on Chemical Safety
    Poisons Information Monograph 399
    Chemical

    1.  NAME

        1.1  Substance

             Paraquat

        1.2  Group

             Bipyridilium herbicides

        1.3  Synonyms

             Paraquat dichloride;
             Methyl viologen;

        1.4  Identification numbers

             1.4.1  CAS number

                    4685-147 (Cation)
                    1910-42-5 (Dichloride)
                    2074-50-2 (Dimethyl Sulphate)

             1.4.2  Other numbers

                    UN 2781
                       2782
                       3016
                       3015

                    N.B. No Hazchem Code.

        1.5  Main brand names/ Main trade names

                                                                    
             Paraquat only      Paraquat +        Paraquat + 
                                Diquat            Urea Herbicides
                                                                    
    
             Barclay Total(R)   Actor(R)          Anuron(R)
             Crisquat(R)        Dukatalon(R)      Dexuron(R)
             Cyclone(R)         Opal(R)           Gramocil(R)
             Dextrone X(R)      Pathclear(R)1,2   Gramonol(R)
             Dragocson(R)       PDQ(R)            Gramuron(R)
             Esgram(R)          Preeglox L(R)     Tota-Col(R)

             Efoxon(R)          Preglone(R)
             Goldquat(R) 276    Seccatuto(R)
             Gramoxone(R)       Spray Seed(R)
             Herbaxon(R)        Weedol(R) 1
             Herbikill(R)
             Katalon(R)
             Osaquat(R)
             Parakill(R)
             Pilarxone(R)
             Plusquat(R)
             Priquat(R)
             R-Bix(R)
             Scythe(R)
             Speeder(R)
             Speedway(R)
             Starfire(R)
             Sweep(R)
             Total(R)
             Weedless(R)
                                                                    
    
             1  granular formulation
             2  also includes simazine and amitrole

        1.6  Main manufacturers, main importers 

             Comlets, Crystal, Kuo Ching, Pilarquim, Productos OSA,
             Sanex, United Phosphorus, Sinon, Zeneca 

    2.  SUMMARY

        2.1  Main risks and target organs

             The main risks are from deliberate ingestion and are
             related to the dose ingested. Serious accidental/occupational 
             poisoning is comparatively rare, and when it does occur there
             usually has been inappropriate handling of the product and/or
             inadequate treatment especially of skin exposure.
    
             The risk is largely dependent on route of exposure as well as
             dose.  The target organs are: lungs, kidneys, liver and
             myocardium
    
             a)     Ingestion of large amounts result in multiple organ
                    failure and death.
    
             b)     Ingestion of modrate amounts result inrenal failure
                    and or massive pulmonary infiltration and fibrosis. 
                    Fatalities are not uncommon.
    

             c)     The concentrated product is severely irritant and
                    local exposure can result in mucous membrane, skin and
                    eye damage.
    
             d)     Minor exposures
    
                    There are many incidents of minor exposure which cause
                    great alarm.  These often concern properly diluted
                    household or professional preparations.  For example a
                    child licking a stick used to mix the granules or
                    eating food that has been touched by contaminated
                    hands is unlikely to come to great harm.  Skin and eye
                    exposure to these dilute solutions is also unlikely to
                    cause any sequelae.

        2.2  Summary of clinical effects

             Clinical effects are dose and route dependent. Ingestion
             can cause a burning sensation in the mouth, nausea, vomiting,
             abdominal pain and diarrhoea, occasionally bloody). Nearly
             all products contain an emetic and if this has been ingested
             vomiting may be severe and repeated. After some hours,
             inflammation and ulceration of the mouth, throat and
             gastrointestinal tract may occur.
    
             Other effects 
    
             a)     Ingestion
    
                    Low dose (<20 mg paraquat ion per Kg body wieght =
                    10mls of a 20 to 24% concentrate)
    
                    Patients are often asymptomatic or may develop
                    vomiting or diarrhoea.  Complete recovery occurs but
                    there may be a transient impairment of lung function
                    tests.
    
                    Moderate dose (20 to 40 mg paraquat ion per Kg body
                    weight = 10 to 20 mLs of 20 to 24% concentrate)
    
                    Initially renal and hepatic dysfunction are common. 
                    Mucosal damage may become apparent with sloughing of
                    the mucous membranes in the mouth.  Dyspnoea may
                    develop after a few days in the more severe cases.  By
                    about 10 days crepitations and radiological signs of
                    lung damage  usually develop.  Renal function often
                    returns to normal at this stage.  Massive pulmonary
                    fibrosis manifested by progressive dyspnoea may cause
                    death between 2-4 weeks after ingestion.
    

                    High dose (> 40 mg paraquat ion per kg body weight =
                    20 mL of 20 to 24% concentrate)
    
                    Toxicity is much more severe and death occurs early
                    (24-48 hrs) from multiple organ failure.  The initial
                    gastrointestinal symptoms are similar but very severe
                    with considerable fluid loss.  Renal failure, cardiac
                    arrythmias, coma, convulsions, oesophageal perforation
                    and death soon follow.
    
             b)     Inhalation
    
                    Paraquat is not volatile but most liquid paraquat
                    formulations contain an unpleasant 'stenching agent'
                    which may occasionally cause feelings of nausea or
                    headaches. In typical spray applications the droplets
                    are too large to be inhaled into the lungs. Inhalation
                    of paraquat can result in a sore nose and throat as
                    well as possible nose bleeds but there are no reports
                    of serious systemic toxicity from inhalation. Contact
                    of the nasal mucosa with fingers contaminated with the
                    concentrate may also cause nose bleeds.
    
             c)     Eye
    
                    Concentrated paraquat splashes may cause severe eye
                    irritation which may result in extensive loss of
                    superficial areas of the corneal and conjunctival
                    epithelium, ulcerated areas are at risk from secondary
                    infection. Corneal oedema may persist for up to 3 to 
                    4 weeks with temporary blurring of vision.
    
             d)     Skin
    
                    Paraquat, especially in concentrated forms, is
                    irritating to the skin and if contact is prolonged
                    skin damage may occur.  In cases with extensive skin
                    damage systemic poisoning can occur due to absorption
                    of paraquat through damaged skin and may result in
                    severe toxicity or even death.  Nail contact may
                    result in white spotting or in severe cases transverse
                    cracking dermatitis and nail atrophy.  There are
                    however no other chronic affects described.

        2.3  Diagnosis

             The diagnosis is based on the history of exposure and
             symptoms and signs such as vomiting, abdominal pain,
             diarrhoea, anuria, dyspnea, liver dysfunction. 
    

             Blood and urine samples should be taken for paraquat analysis
             (10 and 20 mLs respectively). A rapid urine spot test can
             confirm the presence of paraquat. Then quantitative
             measurement in the blood should be performed.The samples must
             not be put into glass containers of any type as paraquat ion
             is absorbed by glass.  A plastic heparinized tube is suitable
             for blood and a plastic sterile universal container is
             suitable for urine. 
    
             Urea, creatinine and electrolytes
             Full blood count
             Liver function tests
             Blood gases
             Qualitative test for paraquat
             Quantitative test analysis for paraquat
    
             Chest X-ray, ECG

        2.4  First-aid measures and management principles

             First aid:
    
             The immediate priority is to prevent any further absorption
             of paraquat.  In the first aid situation if the patient is
             not already vomiting induce vomiting. Give ipecacuanha syrup
             if it is available.  Contaminated skin should be thoroughly
             washed with water and soap.  If the skin is damaged the
             possibility of absorption be considered.  Any contaminated
             clothing should be removed immediately and should be washed
             before reuse or burnt.  The patient should immediately be
             transferred to the nearest hospital.
    
             Hospital management:
    
             Aspirate gastric contents and perform gastric lavage and give
             adsorbents.
             An asorbent such as activated charcoal or Fuller's Earth
             together with a purgative such as mannitol or sorbitol should
             be administered.  The dose of absorbent and purgative should
             be repeated until the adsorbent can be seen in the stools or
             the urine spot test becomes negative.
    
             Paraquat adsorbents
    
             In order of preference
    
                         Type                   Dose
    
             1.  Activated charcoal         100 gm
                                            (child 2gm/Kg)
    

             2.  Fullers Earth              1 liter 15% aqueous
                                            suspension & purgative
    
             3.  Bentonite                  1 liter 7% aqueous
                                            suspension & purgative
    
             Gastrointestinal fluid losses should be replaced with normal
             saline.  Having instituted measures to prevent further
             absorption and start fluid replacement, the diagnosis should
             be confirmed by the "spot" test for paraquat and the
             prognosis assessed by the measurement of plasma paraquat. In
             view of the risk of renal failure the central venous pressure
             should be monitored and used as guide to fluid replacement. 
             If paraquat level is very high and the prognosis hopeless
             adequate pain relief and terminal care is appropriate. 
             Although oxygen is in general contraindicated it may be
             administered to the dying patient with severe dyspnoea.
    
             Profound acidosis should be corrected with intravenous sodium
             bicarbonate.  Dialysis may be required and the indications
             are as in any another form of acute renal failure. 
             Purgatives may produce further fluid losses which should be
             replaced with intravenous normal  saline.  Mouth ulceration
             may produce severe pain which may be helped by symptomatic
             treatments.  If there is any possibility of oesophageal
             perforation the patient should not be allowed to take
             anything by mouth until perforation is excluded by endoscopy
             or radiological studies.  Secondary infection of mouth ulcers
             should be treated with antibiotics.  
    
             Elimination techniques such as dialysis, forced diuresis, and
             charcoal haemoperfusion are largely ineffective in removing
             paraquat but prolonged haemoperfusion may be considered in
             early cases where the blood concentration indicates
             moderately poor outcome (see 10.5).  The prevention of
             pulmonary complications using cyclophosphamide and
             dexamethasone has been advocated, but the effectiveness of
             this regime has not as yet been proven.  Broken skin should
             be treated as for superficial burns after thorough cleansing. 
             Antibiotics may be required for secondary skin infection. 
             Contaminated eyes should be copiously irrigated with running
             water for at least 15 minutes.  An ophthalmic examination
             should be carried out 24 hours after exposure, secondary
             infection should be prevented with a topical antibiotic
             Steroid creams will aid resolution of granulation tissue.
    
             Lung transplantation has been tried but not alltogether
             successful.
    

             Management of fire and disposal
    
             Paraquat is non flammable.  If exposed to fire, keep
             containers cool by spraying with water.  Extinguish with dry
             powder, chemical foam (preferably alcohol resistant) or water
             sprays.  Avoid if possible the use of water jets.  Absorb
             liquid spills with sand or earth, move the earth to safe
             place then flush the area with water. 
    
             Disposal of contaminated adsorbents, containers, leftover
             pesticide: these should be buried in an approved dump, or in
             an area where there is no risk of injury to plants or of
             contamination of surface or ground water.
    
             Decontaminate empty containers with 10% sodium carbonate
             (washing soda) solution, added at the rate of at last 1 liter
             per 20 litre drum capacity.  Swirl round to rinse the walls,
             empty and add rinsings to sawdust, sand or earth.  Puncture
             the container to prevent reuse.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of the substances

             Paraquat is a synthetic product.  It was first described
             in 1882 by  Weidel and Russo. In 1933, Michaelis and Hill
             discovered its redox properties and called the compound
             methyl viologen. The herbicidal properties of paraquat were
             first described in 1958 and it became commercially available
             in 1962.

        3.2  Chemical structure 

             Chemical name:
    
             1,1'-DIMETHYL-4',4'-BIPYRIDILIUM DICHLORIDE
    
             Formula (C12 H14 N2 CL2)
    
             Molecular weight 257.16
    
    STRUCTURAL FORMULA
    
             The term Paraquat applies also to
    
             1,1'-DIMETHYL-4',4'-BIPYRIDILIUM DIMETHYLSULPHATE
    
             Formula (C12 H14 N2 CH3 SO4)2)

        3.3  Physical properties

             3.3.1  Colour 

                    yellowish-white

             3.3.2  State/form

                    Solid, but usually available as concentrated
                    (20-24%) solution

             3.3.3  Description

                    Melting point = decomposes at about 300°C
    
                    Vapour pressure = < 0.1 kPa
    
                    Flammability  = Non flammable and not explosive
    
                    Solubility  = Very soluble in water (700 g/l at 20°C).
                    Practically insoluble in most other organic solvents.
    
                    Stability  =  Stable in acid or neutral solutions but
                    decomposes in the presence of UV light, unstable in
                    alkaline solutions, inactivated by inert clays and
                    ionic surfactants.
    
                    pH  =   6.5 - 7.5 (liquid formulation)

        3.4  Hazardous Characteristics

             Pure paraquat salts are white and the technical products
             yellow.  They are crystalline, odorless, hydroscopic,
             nonvolatile powders.  They are corrosive to metals and
             incompatible with alkyl aryl sulphonate wetting agents.
    
             Normal potential at 30°C  =  -0.44 volts.

    4.  USES
    
             4.1.1  Uses

                    Herbicide

             4.1.2  Description

                    Paraquat is a non-selective foliage applied
                    contact herbicide which is inactivated on contact with
                    soil, so that replanting can be performed almost
                    immediately after spraying.  Usage is worldwide.
                    Household formulations are also available for clearing
                    paths and flower or vegetable beds.

        4.2  High risk circumstances of poisoning

             Risk is greatest to those who have access to paraquat
             where inadequate precautions are taken during transport,
             storage and use.

        4.3  Occupationally exposed populations

             Farmers, especially in tropical countries, where the
             climate is not conducive to wearing full protective
             clothing.

    5.  ROUTES OF ENTRY

        5.1  Oral 

             Ingestion with suicidal intent is by far the commonest
             route of entry.  Oral ingestion may also occur accidentally
             or from swallowing spray droplets deposited in the pharynx,
             usually without systemic poisoning.

        5.2  Inhalation

             There have been no substantiated cases of systemic
             poisoning by inhalation of microscopic paraquat droplets,
             although animal experiments suggest high toxicity of aerosols
             with a particle size of <5 µm. 
    
             Inhalation of sprayed mist does occur, but the systems used
             deliver only large droplets, which are deposited in the upper
             respiratory tract where they cause irritation .

        5.3  Dermal

             Intact, normal skin provides a good barrier against
             absorption and systemic toxicity.  However, if there is
             prolonged contact and extensive skin damage , systemic
             poisoning can occur and may result in severe toxicity or even
             death.  Prolonged skin contact and trauma exacerbate skin
             damage.  This is, however rare.

        5.4  Eye

             Concentrated paraquat splashes may cause severe eye
             irritation, which if not properly treated, may result in
             extensive loss of superficial areas of the corneal and
             conjunctival epithelium.  The inflammation develops over 24
             hrs and ulcerated areas are at risk from secondary infection. 
             If adequate medical attention is given, healing although
             slow, is usually complete.

        5.5  Parenteral

             Systemic toxicity has followed rare cases of deliberate
             subcutaneous, intraperitoneal, and intravenous injection of
             paraquat.

        5.6  Others

             No data available.

    6.  KINETICS

        6.1  Absorption by route of exposure

             Rat and dog studies  (Smith et al., 1974; Bennet et al.,
             1976) revealed that rapid but incomplete absorption of
             paraquat occurred from the gastrointestinal tract somewhere
             beyond the stomach. Probably less than 5% is absorbed.
             Information on paraquat absorption in man is sparse but is
             assumed to be the same, however there is limited evidence to
             support this (Smith, 1987).
    
             Information on absorption from other routes is even more
             scanty.  However it is known that absorption does occur from
             damaged skin, but is very limited from intact skin (0.3% of
             an applied dose, Wester et al., 1984).

        6.2  Distribution by route of exposure

             The 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 distribution of paraquat is best described by a
             three-compartment open model with input to and elimination
             from the central compartment (Hawksworth et al., 1981).  The
             lung then selectively accumulates paraquat from the plasma,
             by an energy dependent process.

        6.3  Biological half-life by route of exposure

             Houze et al. (1990) found that the concentration-time
             curve in 15 adult patients (not haemodialysed) was best
             described by a bi-exponential curve, with the elimination
             half lives of the early and late phase being 5 and 84 hours,
             respectively.

        6.4  Metabolism 

             Paraquat is not metabolized but is reduced to an
             unstable free radical which is then re-oxidized to reform the
             cation and produce a superoxide anion.

        6.5  Elimination and excretion 

             Animal studies have shown paraquat to be excreted
             rapidly by the kidneys.  80 to 90% is excreted within 6 hours
             and almost 100% within 24 hours, in the absence of paraquat
             induced renal disease.  However paraquat may cause renal
             tubular necrosis which can prolong excretion up to 10 to 20
             days.  Excretion in humans is though to be similar and to
             involve active renal secretion as well as glomerular
             filtration (Hawksworth et al., 1981).

    7.  TOXICOLOGY

        7.1  Mode of Action

             It is now well established that "Redox Cycling"  is the
             primary reaction responsible for the toxicity of paraquat. 
             In anaerobic conditions the paraquat cation can be reduced by
             NADPH-dependant microsomal flavoprotein reductase to form the
             reduced radical.  This then reacts with molecular oxygen to
             reform the paraquat cation and the superoxide ion.  Paraquat
             will then continue to cycle from its oxidized to reduced form
             with the electrons and oxygen.  Paraquat is thought to cause
             cell death by lipid peroxidation or NADPH depletion, as in
             the lung where there is selective accumulation (Smith,
             1987).

        7.2  Toxicology

             7.2.1  Human data 

                    7.2.1.1  Adults

                             The minimum single oral toxic dose
                             for man is  estimated to be 20mg per
                             Kg.

                    7.2.1.2  Children

                             Based on human poisoning cases
                             children are considered to show a similar
                             susceptibility and clinical picture of
                             paraquat poisoning compared to
                             adults.

             7.2.2  Relevant animal data

                    The oral LD50 of paraquat dichloride in rats
                    is about 150 mg/kg. Mice are less sensitive to orally
                    administered paraquat than rats, while guinea pigs,
                    cats, monkeys and rabbits are more susceptible.
    

                    Dermal toxicity in the rabbit was found dependent on
                    application technique, whether the site was occluded
                    and whether the animals were prevented from grooming.
                    Under conditions where this was prevented the LD50
                    was found to be >480 mg/kg paraquat ion (McElligott,
                    1972)

             7.2.3  Relevant in vitro data 

                    No data available

             7.2.4  Workplace standards

                    UK HSE: 0.08mg/mg3 (8hr TWA) respirable dust
                    ACGIH:  0.5 mg/m3 (TLV-TWA) total dust (as cation)
                            0.1 mg/m3 (TLV-TWA) respirable fraction

             7.2.5  Acceptable daily intake (ADI)

                    JMPR 1986:  0.004 mg/kg/day as paraquat ion

        7.3  Carcinogenicity

             The potential carcinogenicity of paraquat has been
             investigated in long term studies in the rat and in the
             mouse.  In both species, it was concluded that paraquat was
             not a carcinogen (FAO/WHO, 1986). 
    
             The US EPA classifies paraquat  as a "Group E" chemical which
             evidences that it is not a human carcinogen (US Environmental
             Protection Agency, 1997.

        7.4  Teratogenicity

             Paraquat has no effect on fertility, is not teratogenic
             and only produces fetotoxicity at doses that are maternally
             toxic. The main finding in multigeneration studies was lung
             damage (IPCS, 1984).

        7.5  Mutagenicity

             Paraquat has minimal to no genotoxic activity when
             evaluated in a variety of in vitro and in vivo systems (IPCS,
             1984).

        7.6  Interactions

             Oxygen is contraindicated in the treatment of paraquat
             poisoning as it may worsen lung damage, except to relieve
             pain and distress in terminal care.

    8.  TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

                    8.1.1.1  Toxicological analyses

                    8.1.1.2  Biomedical analyses

                    8.1.1.3  Arterial blood gas analysis

                    8.1.1.4  Haematological analyses

                    8.1.1.5  Other (unspecified) analyses

             8.1.2  Storage of laboratory samples and specimens

                    8.1.2.1  Toxicological analyses

                    8.1.2.2  Biomedical analyses

                    8.1.2.3  Arterial blood gas analysis

                    8.1.2.4  Haematological analyses

                    8.1.2.5  Other (unspecified) analyses

             8.1.3  Transport of laboratory samples and specimens

                    8.1.3.1  Toxicological analyses

                    8.1.3.2  Biomedical analyses

                    8.1.3.3  Arterial blood gas analysis

                    8.1.3.4  Haematological analyses

                    8.1.3.5  Other (unspecified) analyses

        8.2  Toxicological Analyses and Their Interpretation

             8.2.1  Tests on toxic ingredient(s) of material

                    8.2.1.1  Simple Qualitative Test(s)

                    8.2.1.2  Advanced Qualitative Confirmation Test(s)

                    8.2.1.3  Simple Quantitative Method(s)

                    8.2.1.4  Advanced Quantitative Method(s)

             8.2.2  Tests for biological specimens

                    8.2.2.1  Simple Qualitative Test(s)

                             There is a simple "spot" test for
                             paraquat in the urine and gastric aspirate
                             which should be available on an emergency
                             basis for a quick confirmation of paraquat
                             poisoning.  It is based on the reduction of
                             paraquat cation to a stable blue radical ion
                             in the presence of alkali and sodium
                             dithionate.  This test is only reliable up to
                             12 hours after ingestion and can detect
                             concentrations of paraquat in urine down to 1
                             mg/L.  Depending on the result of this test
                             and/or clinical observation, a quantitative
                             test should be initiated.

                    8.2.2.2  Advanced Qualitative Confirmation Test(s)

                    8.2.2.3  Simple Quantitative Method(s)

                    8.2.2.4  Advanced Quantitative Method(s)

                             There are a variety of
                             spectrophotometric, liquid chromatographic
                             and radioimmunoassay techniques available for
                             measurement of paraquat in biological fluids. 
                             A few of the more reliable and rapid
                             techniques are outlined here.  A more
                             detailed review has been published by
                             Braithewaite (1986).
    
                             Radioimmunoassay
    
                             A specific radioimmunoassay procedure for the
                             determination of paraquat at low
                             concentrations in plasma and urine has been
                             developed by Levitt (1977 & 1979).  The
                             procedure is based on antibodies, raised
                             against a paraquat derivative of monoquat, in
                             rabbits and used 3H-labelled paraquat as the
                             tracer and a dextran/charcoal separation
                             technique.  Liquid scintillation counting is
                             used to determine the radioactivity of
                             separated unbound paraquat. The sensitivity
                             of the assay is  6 ng paraquat ion per ml of
                             plasma.
    

                             High Performance Liquid Chromatography
                             (HPLC):  Gill et al. (1983) have described an
                             HPLC method based on the initial extraction
                             of paraquat and diquat using a sep-pak C18
                             cartridge, with ethyl viologen
                             (1,1 dimethyl-4.4'-bipyridium salt as an
                             internal standard.  Chromatography is carried
                             out using an ods - silica column and ion pair
                             separation with methanol and sodium heptane -
                             paraquat in urine is 1 mg/L.
    
                             Spectrophotometry following solid-phase
                             extraction and reduction with sodium
                             dithionite has been described by Smith et al.
                             (1993) for quantification of paraquat in
                             biological fluids.

                    8.2.2.5  Other Dedicated Method(s)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

                    8.3.1.1  Blood, plasma or serum

                    8.3.1.2  Urine

                    8.3.1.3  Other fluids

             8.3.2  Arterial blood gas analyses

             8.3.3  Haematological analyses

             8.3.4  Interpretation of biomedical investigations

        8.4  Other biomedical (diagnostic) investigations and their 
             interpretation

        8.5  Overall interpretation of all toxicological analyses and 
             toxicological investigations

             Accurate and rapid qualitative and quantitative analysis
             of paraquat in blood and urine is important for the diagnosis
             and prognosis of a patient poisoned with paraquat.
    
             Toxic lethal concentrations
    
             Time is a considerable factor in determining what is a lethal
             concentration.  For example a concentration of 100 g/l at
             4 hrs indicates a 70% chance of survival but at 20 hrs
             indicates less than a 10% chance of survival.

        8.6  References

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    Ingestion, particularly of the concentrates,
                    causes a burning sensation in the mouth, nausea,
                    vomiting, abdominal pain and diarrhoea occasionally
                    bloody.  After some hours, inflammation and ulceration
                    of the mouth, throat and gastrointestinal tract may
                    occur.  The initial gastrointestinal symptoms settle
                    after two to three days if the patient survives. 
                    Other effects are dose dependant. 
    
                    Low dose (<20 mg paraquat ion per Kg body weight =
                    <10 mL 20 to 24% concentrate):
    
                    Patients are often asymptomatic or may develop
                    vomiting or diarrhoea.  Complete recovery occurs but
                    there may be a transient impairment of lung function
                    tests.
    
                    Moderate dose (20 to 40 mg paraquat ion per Kg body
                    weight =  10 to 20 mL of 20 to 24% concentrate):
    
                    After 2 to 3 days urea and creatinine may rise and the
                    liver function tests may become abnormal.  For the
                    next 3 to 4 days renal function tends to continue to
                    deteriorate and the patient may become acidotic and
                    anuric. Mucosal damage may become apparent with
                    sloughing of the mucous membranes in the mouth.
                    Dyspnoea may develop at this stage in the more severe
                    cases.  By 10 days crepitations and radiological signs
                    of lung damage have usually developed although this
                    may rarely be delayed to 14 days.  Renal function may
                    return to normal at this stage. 
    
                    Massive pulmonary fibrosis manifested by progressive
                    severe dyspnoea may cause death from 2 to 4 weeks from
                    ingestion.  Death may also occur earlier from renal
                    failure.  If the patient survive the lungs usually
                    recover completely, although some abnormalities of
                    lung function have been observed months after an
                    episode of acute poisoning.
    
                    High dose (>40 mg paraquat ion per kg body weight =
                    > 20 mL of 20 to 24% concentrate):
    
                    Toxicity is much more severe and death occurs early
                    (24-48 hrs) from multiple organ failure. The initial
                    gastrointestinal symptoms are similar but very severe
                    with considerable fluid loss.  Renal failure, cardiac

                    arrythmias, acute cardiac failure, coma, convulsions,
                    oesophageal perforation and death soon
                    follows.

             9.1.2  Inhalation

                    There have been no substantiated cases of
                    systemic poisoning by inhalation of microscopic
                    paraquat droplets although animal experiments suggest
                    pulmonary uptake is significant.  Inhalation of
                    sprayed mist does occur but the systems used deliver
                    only large droplets which are deposited in the upper
                    respiratory tract where they cause irritation only. 
                    The patient may present with a sore nose and throat as
                    well as possible nose bleeds (Bismuth, 1995).

             9.1.3  Skin exposure

                    Paraquat, especially in concentrated forms, is
                    irritating to skin and if left in contact for several
                    hours skin damage may occur.  Necrosis with skin loss
                    and weeping areas are seen.  Intact, normal skin
                    provides a good barrier against absorption and
                    systemic toxicity.  However, if extensive skin damage
                    occurs in the presence of sufficient paraquat,
                    systemic poisoning can occur and may result in severe
                    toxicity or even death.  Prolonged skin contact and
                    trauma exacerbate skin damage and hence absorption and
                    systemic toxicity is then more likely.  Nail contact
                    may result in white spotting or in severe cases
                    transverse cracking with loss of nail.  Damage may be
                    delayed from the time of exposure, since the effect is
                    on the nail bed and it takes some weeks for damage to
                    grow with the nail.  Regrowth of the nail is
                    uncomplicated.  Chronic occupational exposure may
                    produce a cracking dermatitis and nail atrophy
                    (Bismuth, 1995).

             9.1.4  Eye contact

                    Concentrated paraquat may cause severe eye
                    irritation, which if untreated, may result in
                    extensive loss of superficial areas of the corneal and
                    conjunctival epithelium. Corneal oedema may persist
                    for up to 3 to 4 weeks with temporary blurring of
                    vision. The inflammation develops over 14hrs and
                    ulcerated areas are at risk from secondary infection.
                    If adequate medical attention is given, healing
                    although slow is usually complete (Bismuth,
                    1995).

             9.1.5  Parenteral exposure

                    Systemic toxicity has followed subcutaneous,
                    intraperitoneal, and intravenous injection of paraquat
                    (Chandrasiri, 1999).

             9.1.6  Other

                    No data available

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    No data available

             9.2.2  Inhalation

                    There are very few problems from chronic
                    exposure. However contact of the nasal mucosa with
                    fingers contaminated with the concentrate may also
                    cause nosebleeds as well as direct skin and nail
                    toxicity.
    
                    Comprehensive medical surveys in paraquat-exposed
                    spray operators in Malaysia (Howard et al., 1981) and
                    Sri Lanka (Senanayake et al., 1993), including
                    detailed clinical examinations, lung function
                    measurements (CO diffusion capacity), haematological
                    and biochemical investigations, concluded that the
                    long term spraying of paraquat was not associated with
                    any measurable adverse health effects.

             9.2.3  Skin exposure

                    Chronic occupational exposure may produce a
                    cracking dermatitis and nail atrophy.

             9.2.4  Eye contact

                    No data available

             9.2.5  Parenteral exposure

                    No data available

             9.2.6  Other

                    There are very few problems reported on chronic
                    exposure, however contact of the nasal mucosa with
                    fingers contaminated with the concentrate may also
                    cause nosebleeds as well as direct skin and nail
                    toxicity described above

        9.3  Course, prognosis, cause of death

             Symptoms are largely dependent on the route of exposure,
             concentration of paraquat in the product and the amount
             involved.  Some products contain an emetic causing
             vomiting.
    
             After massive ingestion the symptoms and signs are: vomiting,
             abdominal pain, diarhoea, renal failure as well as hepatic
             and cardiac failure develop within the first 24 hours,
             sometimes ending with death due to acute cardiac failure.
    
             Ingestion of moderate amounts of paraquat causes the sequence
             of 3 stages of morbid course:
    
             Stage I:  lasting 1 to 5 days. Local corrosive action
             Haemoptysis, ulcerations of mucous membranes, nausea,
             diarrhea, oliguria
    
             Stage II: lasting 2 to 8 days. Signs of liver, kidney,
             cardiac damage
             Jaundice, fever, tachycardia, myocarditis, respiratory
             distress, cyanosis, elevated BUN, creatinine, serum alkaline
             phosphatase, serum bilirubin, serum transaminases, low
             prothrombin.
    
             Stage III: lasting 3 14 days. Pulmonary fibrosis
             Coughe, dyspnea, tachypnea, edema, pleural effusions,
             atelectasis, low arterial oxygen tension, inceasrd alveolar
             oxygen tension gradient, respiratory failure
    
             Ingestion of small amounts may cause minor symptoms followed
             by full recovery.
    
             Overall mortality rate of accidental poisoning is estimated
             to be 33 - 50% (ref. Haddad, L.M. and Winchester J.F.:
             Poisoning and Drug Overdose, eds. Second edition, 1990,
             Saunders)

        9.4  Systematic description of clinical effects:

             9.4.1  Cardiovascular

                    Patients develop tachycardia and sometimes
                    arrhythmia. Circulatory failure may cause death within
                    24 hours

             9.4.2  Respiratory 

                    Victims of paraquat poisoning, who survive the
                    first two weeks usually make a full recovery within a
                    few weeks.  Even patients who survive severe pulmonary
                    complications, when followed up, have little residual

                    evidence of lung damage.  Smokers are an exception and
                    have been shown to have mild to moderate disturbances
                    of lung function, but it is not known whether these
                    would have been present prior to paraquat
                    ingestion.
    
                    Unless the patient is considered to be terminal,
                    oxygen therapy is contraindicated as it may potentiate
                    pulmonary damage.  Occasionally pneumothorax, pleural
                    effusion, or iatrogenic pulmonary oedema, may
                    precipitate dyspnoea and should be treated as
                    usual.
    
                    In severely poisoned patients, cough, respiratory
                    failure with progressive dyspnoea and cyanosis develop
                    within 5 to 14 days. This is usually due to pulmonary
                    edema, atelectases and sometimes pleural effusions.
                    Arterial blood gases indicate hypoxaemia. If the
                    patient survives pulmonary fibrosis ensues with signs
                    of severe respiratory failure, which is usually fatal.
                    Some patients have survived, eventually returning to
                    near normal lung function.

             9.4.3  Neurologic

                    9.4.3.1  CNS

                             Coma and convulsions may be due to
                             multiorgan damage.

                    9.4.3.2  Peripheral nervous system

                             No data available

                    9.4.3.3  Autonomic nervous system

                             No data available

                    9.4.3.4  Skeletal and smooth muscle 

                             Paraquat induced myopathy, where
                             remarkable degeneration of type 1 muscle
                             fibers, was observed in prolonged paraquat
                             poisoning (Tabata et al., 1999).

             9.4.3  Gastrointestinal

                    Burning sensation in the mouth and throat,
                    nausea,  vomiting, diarrhoea with haematemesis and
                    abdominal pain are the early gastrointestinal features
                    The abdomen is tender and rigid. Withina few days
                    painful sloughing mouth ulcers develop. The tongue is

                    swollen and there is dysphagia. Ulcerations and 
                    perforation of the oropharynx and oesophagus causes
                    subcutaneous emphysema.

             9.4.4  Hepatic

                    Within 2 to 3 days of ingestion, hepatotoxicity
                    is manifested by jaundice, and a tender enlarged
                    liver. The liver function tests are abnormal. If the
                    patient survives up to the second week, liver function
                    may improve.

             9.4.6  Urinary

                    9.4.6.1  Renal

                             Within 2 to 3 days of ingestion,
                             renal toxicity is manifested by oliguria,
                             proteinuria, and rising creatinine and urea
                             levels. Acute renal failure usually improve 
                             in the second week.

                    9.4.6.2  Others

             9.4.7  Endrocrine and reproductive systems

                    No other information available.

             9.4.8  Dermatological

                    Paraquat, especially in concentrated forms, is
                    irritating to skin and if left in contact for several
                    hours skin damage may occur.  Necrosis with skin loss
                    and weeping areas are seen.  Intact, normal skin
                    provides a good barrier against absorption and
                    systemic toxicity.  However, if extensive skin damage
                    occurs due to extensive exposure to  paraquat,
                    systemic poisoning can  follow and may result in
                    severe toxicity or even death.  Prolonged skin contact
                    and trauma exacerbate skin damage and hence absorption
                    and systemic toxicity is then more likely.  Nail
                    contact may result in white spotting or in severe
                    cases transverse cracking with loss of nail.  Damage
                    maybe delayed from the time of exposure, since the
                    effect is on the nail bed and it takes some weeks for
                    damage to grow with the nail.  Regrowth of the nail is
                    uncomplicated.  Chronic occupational exposure may
                    produce a cracking dermatitis and nail atrophy

             9.4.9  Eye, ear, nose, throat: local effects

                    Eye

                    Concentrated paraquat may cause severe eye irritation,
                    which if untreated, may result in extensive loss of
                    superficial areas of the corneal and conjunctival
                    epithelium. Corneal oedema may persist for up to 3-4
                    weeks with temporary blurring of vision. The
                    inflammation develops over 14hrs and ulcerated areas
                    are at risk from secondary infection. If adequate
                    medical attention is given, healing although slow is
                    usually complete (Bismuth, 1995).

             9.4.10 Hematological

                    No data available

             9.4.11 Immunological

                    No data available

             9.4.12 Metabolic

                    9.4.12.1 Acid base disturbances

                             Metabolic acidosis mainly due to
                             renal failure.

                    9.4.12.2 Fluid and electrolyte disturbances

                             Vomiting and diarhoea may cause
                             hypovolaemia. Hyperkalaemia may develop due
                             to renal failure. Hypokalaemia of uncertain
                             origin was also observed (Sato, S: Human
                             Paraquat Toxicology, in Bismuth, Ch, Hall,
                             Paraquat Poisoning, Marcel Dekker, Inc. New
                             York,1995). 

                    9.4.12.3 Others

                             No data available

             9.4.13 Allergic reactions

                    There has been one case report of immune
                    complex glomerulonephritis following exposure to
                    paraquat (Stratta, 1988). Exposure to paraquat was
                    followed 1 week later by mild respiratory distress in
                    a previously healthy farmer who developed a mixed
                    nephrotic/nephritic syndrome 3 moths later.

             9.4.14 Other clinical effects

                    No data available

             9.4.15 Special risks

                    There are very few problems from chronic
                    exposure, however contact of the nasal mucosa with
                    fingers contaminated with the concentrate may also
                    cause nosebleeds as well as direct skin and nail
                    toxicity described above.

        9.5  Others

             There is no evidence of carcinogenicity.
    
             Animal studies have shown no evidence of teratogenicity, or
             effects on reproduction.  There is also no evidence of such
             effects in man.

        9.6  Summary

    10. MANAGEMENT

        10.1 General principles 

             Ingestion
    
             The immediate priority is to prevent any further absorption
             of paraquat.  In the first aid situation if the patient is
             not vomiting give activated charcoal (100 g for adults or
             2 g/kg body weight for children or Fuller's Earth (15%
             slurry, 1 litre for adults or 15 mL/kg body weight for
             children).  Do not give oxygen as this may potentiate
             harmfull superoxide formation.  Superoxides are thought to be
             involved in the pathogenesis of pulmonary damage.  The
             patient should immediately be transferred to the nearest
             hospital.
    
             On arrival in hospital vomiting should be controlled with
             phenothiazine or ondansetron.  An adsorbent should be given
             orally or via a nasogastric tube. Previous guidelines have
             considered Fullers Earth to be the absorbent of choice but
             activated charcoal appears to be equally effective and is
             usually more readily available.  A purgative such as mannitol
             or sorbitol (200 mL of a 20% aqueous solution or magnesium
             sulphate should also be given.  The dose of absorbent and
             purgative should be repeated until the absorbent can be seen
             in the stools.  In patients with acute renal failure large
             amounts of Magnesium salts may be hazardous and Mannitol
             would therefore be preferable.  Different preparations of
             activated charcoal are known to produce diarrhoea (U.K.
             Medicoal) or constipation (U.K. Carbomix).  This should also

             be taken into consideration when deciding on type and amount
             or purgative.  Some other charcoal preparations are poor
             binders for paraquat and local poisons unit should be
             consulted.
    
             Gastric lavage must be considered within the first hour after
             ingestion.
    
             Patients may have considerable fluid loss from diarrhoea and
             vomiting and an intravenous fluid infusion should be
             commenced on admission.  Having instituted measures to
             prevent further absorption and fluid replacement the
             diagnosis should be confirmed by the "spot" test for paraquat
             and the prognosis assessed by the measurement of plasma
             paraquat.  The paraquat level should be interpreted together
             with the time of ingestion on the graph attached.  If the
             levels are very high and the prognosis hopeless good pain
             relief and terminal care are more important than heroic
             attempts to save the patient.  Oxygen supplements are in
             general contraindicated but are appropriate in the dying
             patient with severe dyspnoea.  Diarrhoea from purgatives
             given to clear the gut may produce further fluid loss and
             supplement should be given to replace such losses.  Mouth
             ulceration may produce severe pain which may be helped by
             mouth washes, ice-cold fluids (e.g. milk, ice-cream, lemon
             mucilage), and local anaesthetic preparations.  If there is
             any possibility of oesophageal perforation the patient should
             not be allowed to take anything by mouth until perforation
             has been excluded.  Secondary infection of mouth ulcers
             should treated with antibiotics.  Profound acidosis may occur
             in the early stages due to poor tissue perfusion and should
             be corrected with intravenous sodium bicarbonate.
    
             Renal Damage
    
             Acute renal failure may require treatment with haemodialysis
             or peritoneal dialysis and if the patient survives complete
             recovery of renal function occurs.  The indications for
             commencing dialysis are as in any another form of acute renal
             failure.  Although these methods are to some extent 
             effective at removing paraquat from the body they do not
             influence the pulmonary complications.
    
             Skin exposure
    
             Any contaminated clothing should be removed and the skin
             washed with soap and copious amount of water, taking care to
             avoid abrasions.
    

             Eye exposure
    
             The eyes should be irrigated with running water for at least
             15 minutes.  An ophthalmic examination should be carried out
             24 hours after exposure when the irritation is beginning to
             subside and secondary infection should be prevented with a
             topical antibiotic.  Steroid creams will aid resolution of
             granulation tissue.  Blurring of vision may persist up to
             three weeks due to corneal oedema.

        10.2 Life supportive procedures and symptomatic treatment

             Make a proper assessment of airway, breathing,
             circulation and neurological status of the patient.
             Maintain a clear airway.
             Open and maintain at least one iv route
             Administer iv fluids
             Monitor vital signs
             Correct hypotension as required
             Monitor fluid and electrolyte balance
             Monitor acid/base balance
             Relieve pain as required.
    
             An ophthalmic examination should be carried out 24 hours
             after exposure when the irritation is beginning to subside
             and secondary infection should be prevented with a topical
             antibiotic.  Steroid creams will aid resolution of
             granulation tissue.  Blurring of vision may persist up to
             three weeks due to corneal oedema.

        10.3 Decontamination 

             The immediate priority is to prevent any further
             absorption of paraquat. Any contaminated clothing should be
             removed immediately and once removed, should be washed before
             re-use or burnt.  The skin should be thoroughly washed in
             running water and soap on two occasions. The eyes should be
             irrigated with running water for at least 15 minutes.
    
             In the first aid situation if the patient is not vomiting
             give activated charcoal (100 g for adults or 2 g/kg body
             weight for children or Fuller's Earth (15% slurry, 1 litre
             for adults or 15 mL/kg body weight for children).  Do not
             give oxygen as this may potentiate harmfull superoxide
             formation.  Superoxides are thought to be involved in the
             pathogenesis of pulmonary damage.  The patient should
             immediately be transferred to the nearest hospital.

        10.4 Enhanced elimination

             Unfortunately dialysis, forced diuresis, and charcoal
             haemoperfusion are largely ineffective in that they make no
             difference to outcome.  The only possible exception is

             prolonged haemoperfusion in a small group of patients who are
             moderately poisoned with paraquat, and who develop early
             renal failure.  The procedure also needs to be started within
             6 to 18 hrs after ingestion.  As there is no conclusive
             evidence of benefit we would consider haemoperfusion to be a
             research tool and all cases should be carefully documented
             with the cooperation of a poisons information centre.

        10.5 Antidote treatment

             10.5.1 Adults

                    There is no antidote as such available

             10.5.2 Children

                    There is no antidote as such available

        10.6 Management discussion

             The management outlined above is not controversial,
             however many approaches at treatment have been tried without
             much success.  These include superoxide dismutase,
             propranolol, Vitamin E, ascorbic acid, selenium, clofibrate,
             acetylcysteine, nitric oxide, magnesium sulphate and
             pulmonary irradiation. Lung transplantation has also been
             tried but has been successful only in one patient (Licker et
             al., 1998). At  present, the use of cyclophosphamide and
             dexamethasone seems the most promising, in moderately
             poisoned patients who are at risk of developing pulmonary
             fibrosis.The effectiveness of this regime has not as yet been
             proven and it should only be used in a specialist centre
    
             Jones et al. (1999) has worked out an equation to predict the
             probability of survival for any specified time (up to at
             least 200 hours) and concentration.
    
             Paraquat adsorbents
    
             In order of preference
    
                    Type                    Dose
    
    
             1.  Activated charcoal         100 gm
                                            (child 2 g/Kg)
    
             2.  Fullers Earth              1 liter 15% aqueous
                                            suspension & purgative
    
             3.  Bentonite                  1 liter 7% aqueous
                                            suspension & purgative

    11. ILLUSTRATIVE CASES

        11.1 Case reports from the literature

             Death following subcutaneous injection
    
             NPIS 88/010456 A 24 year old woman injected paraquat liquid
             concentrated subcutaneously into her left arm.  Next morning
             she injected herself again then went to hospital.  On
             admission she had a tachycardia of 130 beats/min and blood
             pressure 120/80.  There was a green papule at the injection
             site. Chest X ray showed the lungs were clear and white blood
             cell count was raised at 14.7 × 106 per litre.  The
             paracetamol and salicylate screens were negative, and the
             serum paraquat  concentration was 1300 milligrams per litre
             (concentrations greater than 1000 milligrams per litre are
             usually fatal).  The papule at the injection site was
             excised. Within 12 hours of admission kidney function began
             to deteriorate, over the next 23 days there was progressive
             deterioration in liver, kidney and respiratory function.  She
             developed widespread muscle pain, oedema, jaundice, hypoxia
             and myocarditis with widespread T wave inversion.  Treatment
             was supportive with buprenorphine then diamorphine to control
             pain.  She became comatose 6 days after admission and died 2
             days later.
    
             Death following subcutaneous injection:
    
             A case of homicidal paraquat poisoning by intramuscular
             injection has been reported (Chandrasisi, 1999)
    
             Skin exposure
    
             NPIS 89/011455. While decanting paraquat liquid concentrate
             from a large to a small container, a 46 year old man spilt it
             onto his trousers soaking the scrotal region.  He did not
             wash the skin until 48 hours afterwards.  He became
             progressively dyspnoeic over the next week  and went to
             hospital 9 days afterwards.  On admission he was cyanosed,
             tachypnoeic, and auscultation showed diffuse fine bilateral
             crepitations in the mid and lower lung zones.  Pulse rate was
             130 per minute and blood pressure 160/90 mmhg. The perineal
             skin was raw, macerated and oozing pus.  Arterial blood gas
             analysis on air showed a pH of 7.352, PaO2 2.8 kPa, PaCO2
             2.7 kPs and base excess of 3.2.  On 100% oxygen arterial
             blood gas analysis showed a pH of 7.443, PaO2 6.9 kPa, Pa CO2
             5.0 kPa and base excess + 1.5.  Serum potassium was 2.8 
             mmol/l, urea 25 mmol/l and creatinine 311 micromol/l.  Serum
             haemoglobin was 14.5 g/dl, and the white cell count was 25 ×
             10/l with neutrophilia.  ECG was normal and chest X ray
             showed diffuse bliateral alveolar infiltrates in mid and
             lower zones.  Urine screen showed paraquat was present.  He
             was given intermittent positive pressure ventilation,

             intravenous fluids and antibiotics.  Renal failure on
             developed on day 10 and was treated with dopamine and
             haemodialysis for 24 hours until renal function. Lung
             function deteriorated and he died 15 days after the accident. 
             Post mortem examination showed acute pleurisy with bilateral
             panlobular pneumonitis.
    
             Ingestion
    
             NPIS 86/06961.  A 45 year old man drank 2 sachets of solid
             paraquat (3.00g paraquat ion) mixed with soda water and
             alcohol.  He was admitted to hospital 2 hours later. He
             vomited within 2 hours before treatment was given, thus it
             was suspected that he had taken a formulation of paraquat
             containing an emetic.  Some irritation of the fauces was
             noticed 24 hours after ingestion.  He was given a gastric
             lavage and fuller's earth with a purgative 2hr 15 minutes
             after ingestion and vomited a second time.  Blood ethanol
             concentration after 2 hours was 3162 mg/l/, and plasma
             paraquat concentration at 5hrs 30mins was 1.1 mg/l. 
             Haemoperfusion was started 8hr 30 minutes after ingestion. 
             Magnesium sulphate enemas were given after 30 hours to induce
             diarrhoea.  Cyclophosphamide 5mg/kg/day and dexamethasone 8
             mg three times daily were given for 2 weeks, with high fluid
             intake and diuretics.  There was transient hepatic damage
             shown by raised AST, alkaline  phosphatase and bilirubin, but
             no evidence of renal damage.  Formal lung function tests
             showed a marked fall in lung volumes and gas transferance 6
             weeks after the overdose.  After 4 months the patient was
             asymptomatic and the formal tests showed improvements in lung
             function. 

    12. ADDITIONAL INFORMATION

        12.1 Specific preventive measures

        12.2 Other

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    14. AUTHOR(S), REVIEWER(S) DATA (INCLUDING EACH UP-DATE), COMPLETE 
        ADDRESSES

        Author:     Dr C. Ashton and Mr N. Leahy
                    Poisons Unit
                    New Cross Hospital
                    Avonley Road
                    London SE14 5ER
                    United Kingdom
    
        Date:       April 1989
    
        Reviewer:   Dr N. Besbelli
                    Ankara
                    Turkey
    
        Peer review:         London, United Kingdom, September 1992
                             (group members: Dr N. Besbelli, Dr C.
                             Dell'Acqua, Dr B. Fahim, Dr T. Matainaho, Dr
                             B. Sener, Dr W. Temple, Dr A.N.P. van
                             Heijst)
    
        Review:     Prof. Ravindra Fernando
                    National poisons information Centre
                    National Hospital of Sri Lanka
                    Colombo 8
                    Sri Lanka
    
                    October 2000
    
        Peer review:         INTOX 12 Meeting, 7 - 11 November 2000
                             Drs J. Szajewski, C.Alonzo, R. Fernando.
    



    See Also:
       Toxicological Abbreviations
       Paraquat (HSG 51, 1991)
       Paraquat (JMPR Evaluations 2003 Part II Toxicological)
       Paraquat (AGP:1970/M/12/1)
       Paraquat (WHO Pesticide Residues Series 2)
       Paraquat (Pesticide residues in food: 1976 evaluations)
       Paraquat (Pesticide residues in food: 1978 evaluations)
       Paraquat (Pesticide residues in food: 1981 evaluations)
       Paraquat (Pesticide residues in food: 1982 evaluations)
       Paraquat (Pesticide residues in food: 1986 evaluations Part II Toxicology)