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    PARAQUAT       JMPR 1976

    Explanation

         This compound was evaluated by the Joint FAO/WHO Meeting on
    Pesticide Residues in 1970 (FAO/WHO, 1971b) and in 1972 (FAO/WHO,
    1973b). Although an acceptable daily intake for man was estimated
    (0-0.002 mg/kg body weight), the 1972 Meeting considered it
    desirable that the following studies should be undertaken:

    1.   Detailed comparative toxicity and metabolism studies in order
         to elucidate the reason for the comparatively high sensitivity
         of man to this compound.

    2.   Comparative studies on the relationship between lung
         concentration and toxicity.

         Data on these subjects have now become available.

         Moreover, since in addition to its use as a contact herbicide,
    which does not usually result in residues in animal feedstuff,
    paraquat may also be applied as a harvest aid or desiccant for a
    number of animal fodder crops such as grass, maize and alfalfa, a
    large number of studies on paraquat in farm animals were reported.

         The available data on metabolism in cows, goats, sheep, pigs
    and poultry, and on residues in their various organs and milk and
    eggs, together with other relevant material, are summarized below.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, distribution, and excretion

         Studies have been carried out to a) compare the metabolism of
    paraquat in different species in an attempt to understand their
    different susceptibilities to paraquat, and b) to compare the
    distribution of paraquat in the organs of the rat to explain the
    affinity exhibited by paraquat for the lung.

         After oral administration of 14C-paraquat to rats, dogs and
    guinea pigs, most of the radioactivity was excreted in 4 days,
    mainly in the faeces as unchanged paraquat. The remaining label was
    present in urine which contained 12% (rats), 45% (dogs) and 9%
    (guinea pigs) of the dose administered.

         Thus dogs and guinea pigs absorb very different amounts of
    paraquat yet the oral LD50 is the same in the two species.

         Paraquat (I) was the main radioactive component of rat and dog
    urine (see Figure 1), with monoquat (II) and the dipyridone (IV) of
    paraquat accounting for 0.4%, 0.3% and 0.1% of the administered
    dose in rat urine and 0.4%, 0.5% and 0% of the dose in dog urine.
    Thus, there is very little metabolism of the parent compound
    following oral dosing.

         After subcutaneous administration of 14C-paraquat into rats
    over 90% of the administered radioactivity was excreted in the
    urine in 4 days. Whilst this was mainly paraquat, chromatography
    indicated that monoquat (II) (1.9%), paraquat monopyridone (III)
    (3.2%) and dipyridone (IV) (1.1%) were present.

         Although traces of monoquat and paraquat monopyridone were
    also found in rat faeces, there was no evidence for extensive
    metabolism of paraquat by gut microflora. Intestinal bacteria from
    rat caecal contents did not degrade paraquat in vitro to any
    measurable extent. It is concluded, therefore, that the previous
    observations of Daniel and Gage (1966), indicating a large amount
    of degradation by gut microflora were incorrect, and due to
    incomplete extraction of paraquat from faeces.

         There was no correlation between the toxicity of paraquat to
    the 3 species studied and the degree of absorption, rate of
    excretion or extent of metabolism. There were no species
    differences observed with respect to the metabolic products
    detected.

         Rat lung slices have been shown to possess an ability to
    accumulate paraquat in vitro to concentrations nearly ten times
    that of the medium over a period of two hours, brain slices to
    concentrations double that of the medium. The accumulation by both
    tissues has been shown to be energy, dependent. After oral dosing
    of paraquat to rats the lung concentration increased with time to
    six times that of plasma after 30 hours. Other organs, with the
    exception of the kidney, did not concentrate paraquat to the same
    extent.

         Lung slices from dog, monkey and rabbit have also been shown
    to possess the ability to accumulate paraquat in vitro but to a
    much lesser extent when compared with those from rat and man.

         Thus from the point of view of paraquat accumulation in the
    lung the rat is a good experimental model. Indeed the kinetics (V
    max and Km) of the process are very similar in the lung tissues of
    both species. (Rose et al., 1976).

         The cells in the lung that are damaged by paraquat are
    primarily the type I and II alveolar epithelial cells (Vijeyaratnam
    and Corrin, 1971). Accumulation of paraquat appears to be
    associated with these cells (Sykes et al., 1976) which only

    constitute a small fraction of the total cell population of the
    lung. After the initial damage of the type I cell, swelling of the
    type II cell mitochondria occurs and is followed by more extensive
    changes, including loss of microvilli, multivesicular bodies and
    electron density with an increase in the number of lipid droplets
    and damage.

         Thus, the selectivity of paraquat for lung is explained by
    accumulation and it is the type I and II cells in lung which
    accumulate high concentrations of paraquat via an energy-dependent
    process. This leads to the destruction of these cells with
    consequent impairment of the air/blood interface and death from
    respiratory failure.

    Biotransformation

         Studies of biotransformation in farm animals and poultry are
    described in this section. Further details of residues found in
    tissues, milk and eggs are given in the section "Fate of residues".

    Cows

         When cows were given a single oral dose of 14C-methyl paraquat
    at 8 mg/kg, 96% of the radioactivity was recovered in the faeces
    during the following 9 days; 0.7% was recovered in urine. Unchanged
    paraquat (I) accounted for most of the radioactivity in faeces
    (96%) and urine (62-90%), but traces of metabolites II and III were
    also detected in the urine.

         Only 0.003 - 0.004% of the radioactivity was recovered in
    milk; the maximum radioactive residue (0.005 mg/kg, paraquat ion
    equivalent) occurred on the day after dosing. About 15% of this
    radioactivity was present as unchanged paraquat (I). Compounds II
    and III (3-25%) were also found in milk. The radioactivity not
    identified as I, II or III was accounted for by incorporation into
    natural constituents of milk, resulting from the anabolism of the
    radioactive methyl group cleaved from paraquat (Hemingway et al.,
    1974).

         Cows were fed for three months with diets containing 25, 80
    and 170 ppm of paraquat ion (equivalent to 0.8, 2.6 and 5.5 mg/kg
    body weight). The paraquat was present as a residue in dried grass
    obtained from a pasture which had been sprayed with "Gramoxone" and
    subsequently weathered. The diet was accepted satisfactorily and no
    toxicological effects were observed during the trial. Pathological
    examination of tissues from animals slaughtered within 24 hours of
    the end of feeding trial showed no toxic effects attributable to
    paraquat. The tissue residues including muscle and liver determined
    in cows at the two higher dose rates varied between 0.01 and 0.09
    mg/kg except in the kidney where 0.21 - 0.31 mg/kg was found. These
    fell to low (0.04 mg/kg in kidney) or non-detectable levels in an
    animal fed the high paraquat rate diet for 30 days and then
    maintained on an untreated diet for 12 days before slaughter.

   FIGURE 1

         Only very low residues of paraquat were present in milk
    samples taken weekly during the trial (121 samples <0.0001 -
    0.0006 mg/kg: 1 sample = 0.001 mg/kg (Edwards et al., 1974).

    Goat

         14C ring labelled paraquat was administered to a goat in
    mid-lactation twice daily for seven days at a dose equivalent to
    100 ppm in the diet. Total radioactive residues in the milk were
    less than 0.01 mg/kg paraquat ion equivalent - 76% as unchanged
    paraquat. Total radioactive residues were 0.74, 0.56, 0.1 mg/kg in
    kidney, liver and muscles respectively. In all samples there was no
    significant metabolism of paraquat with the exception of the liver
    where 50% of the radioactivity was accounted for as paraquat and
    about 5% as each of the metabolites II and III (Hendley et al.,
    1976a).

    Sheep

         A dose of 14C-methyl labelled paraquat administered to a sheep
    via a rumen fistula was recovered quantitatively within 10 days.
    Approximately 4% of the dose was excreted in the urine and the
    remainder in the faeces. More than 95% of the radioactivity in
    urine and faeces was present as unchanged paraquat. Small amounts
    of compound II (1%) and compound III (2.3%) were also detected.
    (Hemingway et al., 1972)

         When injected subcutaneously, paraquat is also excreted
    rapidly in the urine (over 80% of the dose), 69% within the first
    day after treatment. Again unchanged paraquat accounts for most
    (90%) of the radioactivity, the monopyridone (III) derivative is
    present as 2-3% of the dose and monoquat (II) is a trace
    metabolite. This pattern of metabolism is virtually identical to
    that seen in the urine following dosing via the rumen. (Hemingway
    et al., 1972)

    Pigs and hens

         Oral dosing and feeding studies with pigs and hens are
    described in the section "Fate of residues", p.

    TOXICOLOGICAL STUDIES

    Acute toxicity

         The acute oral toxicity of paraquat was studied comparatively
    in rat, guinea pig and monkey. The LD50 was in the order rat monkey
    guinea pig. All animal species showed primary lesions in the lung.
    Rats and monkeys, but not guinea pigs, developed progressive
    interstitial fibrosis of the lung after 7-10 days. Focal necrosis
    in liver and kidneys was found in rats and guinea pigs but not in
    monkeys (Murray and Gibson, 1972).

    TABLE 1. Acute toxicity of paraquat

    oral

                        LD50 (mg/kg
    Species             body weight)                  References

    Mouse               104 (90-120)                  Fletcher, 1974
    Rat                 130 (110-160)                 "
    Guinea pig          30 (22-41)                    "
    Rabbit              126 (69-183)                  "
    Cat                 35                            "
    Hare                35                            "
    Monkey              75                            "
    Dog                 25-50                         "
    Sheep               65                            "
    Cow                 35-60                         "
    Man                 about 30                      "

    OBSERVATIONS IN MAN

         The potential of lungs from five different species (rat, dog,
    rabbit, monkey and man) to accumulate paraquat has been assessed by
    measuring the kinetic constants Km and Vmax of the process in lung
    slices (Rose et al., 1976). Human lung slices have the highest Vmax
    and one of the lowest Km's for this process which indicates that
    human lung possesses a very efficient accumulation system for
    paraquat. This will tend to make man one of the more sensitive
    species to paraquat as the lung will be able to accumulate toxic
    amounts of paraquat from very low concentrations present in the
    plasma.

         In studies of exposure of spray operators to paraquat which
    were probably closest to the extremes of exposure likely to occur
    in any agricultural operation, measurable levels of paraquat in the
    urine of certain workers were found but no noticeable clinical
    adverse effects (Staiff et al., 1975).

         The ingestion of 10-15 ml of the concentrate supplied to
    professional users (containing 20% paraquat cation) can be fatal if
    left untreated. The oral LD of paraquat cation to man has been
    estimated to be approximately 30 mg/kg body weight (Fletcher, 1974)
    which is similar to that measured for dogs and guinea pigs. Rats
    are less sensitive, having an oral LD50 of approximately 100 mg
    cation/kg body weight.

    COMMENTS

         In recent feeding studies with paraquat in farm animals, over
    90% was excreted within a few days. Thus, tissue accumulation
    giving rise to significant tissue residues is unlikely. Paraquat

    was only slightly absorbed and was metabolised mainly in the
    gastrointestinal tract of the animals. Milk and eggs were found to
    contain small residues of two identified metabolites.

         The Meeting found the recent data on comparative toxicity and
    the metabolic and toxicological studies in laboratory animals
    reassuring and reaffirmed the previously established acceptable
    daily intake.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

         Rat: 30 ppm in the diet, equivalent to 1.5 mg/kg bw

         Dog: 50 ppm in the diet, equivalent to 1.25 mg/kg bw

    ESTIMATION OF ACCEPTABLE DAILY INTAKE FOR MAN

         0 - 0.002 mg/kg bw as paraquat dichloride (equivalent to
    0 - 0.0014 mg/kg bw, expressed as paraquat ion).

    RESIDUES IN FOOD AND THEIR EVALUATION

         The use of paraquat as a contact herbicide does not usually
    result in residues of this compound animal feeding stuffs. However
    paraquat can also be used as a harvest aid or desiccant for a
    number of animal fodder crops. such as grass, maize and alfalfa. In
    this case paraquat residues of 5-1000 mg/kg may be found in the
    resulting feeding stuff; this has stimulated a large number of
    studies on the fate of paraquat in farm animals. This work is
    described in the section "Biotransformation," p.  Some additional
    details of residues arising in tissues, organs, milk and eggs are
    given in the following section, "Fate of residues".

    FATE OF RESIDUES

    In animals

    Cows

         When cows were given a single oral dose of 14C-methyl paraquat
    (I) at 8 mg/kg, 96% of the radioactivity was recovered in the
    faeces during the following 9 days. 0.7% was recovered in the
    urine. Unchanged paraquat accounted for most of the radioactivity
    in faeces (96%) and urine (62-90%) but traces of two metabolites
    (compounds II and III - Figure 1) were also detected in the urine.
    (Hemingway et al., 1974; Leahey et al., 1972; Stevens and Walley,
    1966). Only 0.003-0.004% of the radioactivity was recovered in
    milk. The maximum radioactive residue (0.005  g/g paraquat ion
    equivalents) occurred on the day after dosing. Only about 15% of
    this radioactivity was present as unchanged paraquat. Compounds II

    and III (Figure 1) were also found in the milk in the proportions
    shown in Table 2. The radioactivity not identified as I, II or III
    was accounted for by incorporation into natural constituents of
    milk (Hemingway et al., 1974; Leahey et al., 1972).

    TABLE 2. Radioactive compounds detected in the milk of a
             cow dosed with 14C-paraquat

                                                                          

                        Percentage of Radioactivity in milk present as
    Day Milk
    Collected           Paraquat       Compound II*      Compound III*
                                                                          

    1                   15             15                3

    2                   18             18                18

    3                   9              25                10
                                                                          

    * Identified in Figure 1


         Cows given 14C-methyl-labelled paraquat orally at 8 mg/kg/day
    for three successive days showed a maximum residue in the milk of
    0.01 mg/kg paraquat ion equivalents. No paraquat was detected by
    residue analysis (limit of detection 0.005 mg/kg) (Daniel et al.,
    1971).

         In other trials cows were allowed to graze treated grasses
    containing up to 1000 mg/kg at the start of the test. A maximum
    residue of 0.02 mg/kg paraquat was detected in milk on the first
    day after grazing freshly treated fodder; thereafter residues were
    less than the normal limit of detection for milk, i.e. below 0.005
    mg/kg (Calderbank et al., 1968).

         In a trial in which cows were fed for three months with diets
    containing 25, 80 and 170 mg/kg of paraquat, only very low residues
    of paraquat were found in weekly milk samples (121 samples in the
    range, <0.0001 - 0.0006 mg/kg; 1 sample 0.001 mg/kg (Edwards et
    al., 1974).

         Residues found in the meat, fat and offal of cows fed at
    various levels of paraquat in the diet for various periods are
    summarized in Table 3.

         Similar residue levels were found in the milk and tissues of
    two cows maintained for 30 days on a diet containing 150 ug/g of
    paraquat (Edwards et al., 1976).

    
    TABLE 3.  Residues of paraquat in tissues of cows fed on paraquat-
              containing fodder

                                                                                       

    Paraquat                 Interval between
    ion levels    Feeding    last feeding on      Paraquat residues
    in fodder     period     treated fodder       (mg/kg) in
    (mg/kg)       (days)     and sacrifice        Liver       Kidney    Meat      Fat
                                                                                       

    3.6           21         9 days               <0.05       <0.05     <0.05     <0.05

    25            86-95      <1 day               <0.01       <0.06-    <0.01     <0.01
                                                               0.13

    80            "          <1 day               <0.01       0.14-     <0.01     <0.01
                                                               0.31

    170           "          <1 day               <0.01-      0.20-     <0.01     <0.01
                                                   0.09        0.24      -0.02     0.02

    135-450       32         3 days               <0.01       0.05      <0.01     <0.01
                             13 days              <0.01       <0.01     <0.01     <0.01

    220-450       3          1 hour               0.04        0.15      <0.01     <0.01

                  7          1 hour               0.04        0.16      0.02      <0.01
                                                                                       

                              Calderbank et al., 1968
                              Edwards et al., 1974
                              Lazanas, 1969
                              Litchfield, 1969

    

    Goats

         Transfer of residues to the meat and milk of a goat fed on
    paraquat was very small, as in the cow. 14C-ring-labelled paraquat
    was administered to a goat in mid-lactation, twice daily for seven
    days at a dose equivalent to 100 ppm in the diet. Total radioactive
    residues in the milk were less than 0.01 mg/kg paraquat ion
    equivalents - 76% as unchanged paraquat (Hendley et al., 1976a). Total
    radioactive residues in goat tissues were as shown in Table 4.
    Unchanged paraquat accounted for at least 50%, and usually almost all,
    of these residues.

    TABLE 4. Total radiolabelled residues in tissues of a goat

                                                                       

    Paraquat    Feeding    Total radiolabelled residue
    ion level   Period     (mg/kg paraquat ion equivalent)
    in diet
    (mg/kg)     (days)     Liver     Kidney    Muscle    Heart     Fat
                                                                       

    100         7          0.56      0.74      0.08-     0.16      0.02-
                                               0.12                0.03
                                                                       

    (Animals sacrificed four hours after receiving last dose.)


    Sheep

         As with other ruminants, paraquat is rapidly excreted from sheep,
    principally in the faeces, and very little metabolism occurs. A dose
    of 14C-methyl-labelled paraquat, administered to a sheep via a rumen
    fistula, was recovered quantitatively within 10 days. Approximately 4%
    of the dose was excreted in the urine and the remainder in the faeces.
    More than 95% of the radioactivity in urine and faeces was present as
    unchanged paraquat. Small amounts of compound II (1%) and compound III
    (2.3%) were also detected (Hemingway et al., 1972).

    Pigs

         Pigs excrete an oral dose of paraquat, principally in the faeces
    as unchanged paraquat. Residues in meat are small. Two pigs were dosed
    with 14C-labelled paraquat for seven consecutive days at a rate
    equivalent to 50 ppm in the diet. One was dosed with 14C-methyl and
    the second with 14C-ring-labelled paraquat. The pigs were sacrificed
    two hours after receiving the final dose. At this point 69-73% of the
    administered residue had been recovered in the faeces and
    approximately 3% in the urine. More than 90% of the radioactivity in
    the faeces was present as unchanged paraquat.

         Total radioactive residues in the tissues were low (Table 5).
    More than 90% of these residues were due to unchanged paraquat except
    in liver where approximately 70% was due to unchanged paraquat and
    4-7% was due to compound II. (Leahey et al., 1976; Spinks et al.,
    1976)

         Pigs were also maintained on diets containing 8, 47 and 147 ppm
    of non-radioactive paraquat for 30 days. The residues of paraquat in
    the tissues of animals sacrificed within 24 hours of the cessation of
    feeding were similar to those detected in the experiment with the
    radioactive compound. Residues declined to 0.03 mg/kg or below after a
    further six days feeding on a control diet (Table 6) (Hemingway et
    al., 1975).

    TABLE 5. Total radio-labelled residue in tissues of pigs dosed
             at 50 ppm in the diet for 7 days, using 14C-labelled
             paraquat

                                                                  
                   Total radio-labelled residue (mg/kg paraquat
                   ion equivalent)
                                                                  

    Radio-label    Liver   Kidney   Muscle       Heart    Fat
                                                                  

    14C-methyl     0.20    0.46     0.03-0.06    0.12     0.02-0.06

    14C-ring       0.10    0.38     0.05         0.08     0.01

                                                                  

    
    TABLE 6. Residues of paraquat in tissues of pigs fed on paraquat-containing diet

                                                                                      

    Paraquat
    ion level                             Paraquat residues (mg/kg) in
    in diet                                                                           
    (mg/kg)    Feeding Regime             Liver    Kidney   Muscle   Heart    Fat
                                                                                      

    8          30 days on treated diet    <0.01    <0.01    <0.01    <0.01    <0.01
               30 days on treated diet

                         +

               6 days on control diet     <0.01    <0.01    <0.01    <0.01    <0.01

    47         30 days on treated diet    0.03     0.04     0.02     0.03     <0.01
               30 days on treated diet

                         +

               6 days on control diet     <0.01    <0.01    <0.01    <0.01    <0.01

    147        30 days on treated diet    <0.01    0.33     0.04     0.12     0.02
               30 days on treated diet
                         +

               6 days on control diet     <0.01    0.01-    0.01-    0.02-    <0.01
                                                   0.03     0.02     0.03
                                                                                      
    
    Hens

         As in other animals, there is little metabolism of paraquat in
    the hen. Residues in meat and eggs are small. When a single oral dose
    of 14C-methyl-labelled paraquat was administered to the hen, all of
    the dose was recovered quantitatively in the faeces within three days.
    At least 98% of the recovered radioactivity was as unchanged paraquat.
    Analysis of the tissues of hens after about 3 weeks dosing with
    14C-paraquat (6 ppm in the total diet) indicated that it did not
    accumulate in the hens (Hemingway and Oliver, 1974).

         Continuous dosing of hens with radio-labelled paraquat for up to
    22 days, at rates up to 30 ppm in the diet, resulted in total
    radioactive residues in the eggs up to approximately 0.05 mg/kg
    paraquat ion equivalent. At least 80% of the radioactivity was due to
    unchanged paraquat. The residue was present almost entirely in the
    yolk rather than in the albumen (Hemingway and Oliver, 1974; Hendley
    et al., 1976b).

         When hens were maintained for up to 30 days on diets containing
    up to 3.6 ppm of unlabelled paraquat, no residues were detected in the
    eggs (limit of detection 0.01 mg/kg). At 7.2 and 36 ppm dietary
    inclusion levels, paraquat residues were 0.05 mg/kg or below (Leary,
    1974).

         Paraquat was also administered to hens as a 40 mg/kg solution in
    their drinking water for 14 days. Residues in eggs were 0.1 mg/kg or
    below and declined rapidly once dosing ceased (Fletcher, 1967).

         During the above-mentioned continuous dietary feeding studies
    with radio-labelled and with unlabelled material, paraquat residues in
    tissues were small (Table 7). In the radio-labelled studies, paraquat
    was found to constitute 80% or more of the residue in the tissues.

    TABLE 7. Levels of paraquat in tissues of hens
                                                                        
    Paraquat
    ion level   Feeding   Paraquat residue (mg/kg) in
    in diet     Period
    (mg/kg)     (days)    liver    Kidney    Muscle    Heart     Fat
                                                                        

    1.8         30        <0.01    *         <0.01     <0.01     <0.01
    3.6         30        <0.01    *         <0.01     <0.01     <0.01
    7.2         30        <0.01    *         0.01      <0.01     <0.01
    36          30        0.01     *         0.01      <0.01     <0.01
    30          10        0.06     0.10      <0.01-    0.03      <0.01
                                             0.04
                                                                        

    (Animals sacrificed on cessation of dosing)
    * Tissue not analysed.            Hendley et al., 1976b

    NATIONAL TOLERANCES REPORTED TO THE MEETING

         The following tolerances have been reported to the Meeting.

                                            Tolerance
    Commodity                               mg/kg   

    USA

    Alfalfa                                 5
    Almond hulls                            0.5
    Apples                                  0.05(N)
    Apricots                                0.05(N)
    Avocados                                0.05(N)
    Bananas                                 0.05(N)
    Barley grain                            0.05(N)
    Beans (Dry) Exp. 8/28/76                0.5(T)
    Birdsfoot Trefoil                       5
    Cattle (Meat, Fat, Meat By-products)    0.01(N)
    Cherries                                0.05(N)
    Citrus fruit                            0.05(N)
    Clover                                  5
    Coffee Beans                            0.05(N)
    Corn fodder                             0.05(N)
    Corn forage                             0.05(N)
    Corn fresh (kernels plus cobs)          0.05(N)
    Corn grain                              0.05(N)
    Cottonseed                              0.5
    Eggs                                    0.01(N)
    Figs                                    0.05(N)
    Guar beans                              0.5
    Goats (meat, fat, meat by-products)     0.01(N)
    Guavas                                  0.05(N)
    Hogs (meat, fat, meat by-products)      0.01(N)
    Hops, dried                             0.2FA
    Hops, vine                              0.5
    Hops, fresh                             0.1
    Horses (meat, fat, meat by-products)    0.01(N)
    Lettuce                                 0.05(N)
    Melons                                  0.05(N)
    Milk                                    0.01(N)
    Nectarines                              0.05(N)
    Nuts                                    0.05(N)
    Oat grain                               0.05(N)
    Olives                                  0.05(N)
    Papayas                                 0.05(N)
    Passion fruit                           0.2
    Pasture grass                           5
    Peaches                                 0.05(N)
    Pears                                   0.05(N)
    Peppers                                 0.05(N)
    Pineapples                              0.05(N)

                                            Tolerance
    Commodity                               mg/kg  

    USA

    Plums (fresh prunes)                    0.05(N)
    Potatoes                                0.5
    Poultry (meat, fat, meat by-products)   0.01(N)
    Range grass                             5
    Rye grain                               0.05(N)
    Safflower seed                          0.05(N)
    Sheep (meat, fat, meat by-products)     0.01(N)
    Small fruit                             0.05(N)
    Sorghum forage                          0.05(N)
    Sorghum grain                           0.05(N)
    Sorghum grain (animal feed)             2(T)
    Soybeans                                0.05(N)
    Soybean forage                          0.05
    Sugar beets                             0.5
    Sugar beet tops                         0.5
    Sugarcane                               0.5
    Sunflower seed                          2
    Sunflower seed hulls                    6FA
    Tomatoes                                0.05(N)
    Wheat grain                             0.05(N)

    Netherlands
    Fruit and vegetables                    0.05
    Cereals                                 0.05
    Potatoes                                0.1

              

    FA = Food additive tolerance
    (N)= Negligible residue tolerance
    (T)= Temporary tolerance


    APPRAISAL

         Since paraquat was last evaluated by the Joint Meeting in 1972
    (FAO/WHO, 1973b) additional studies have been completed on the fate of
    paraquat in cows, goats, sheep, pigs and poultry.

         Although the use of paraquat as a contact herbicide does not
    usually result in residues of this compound on animal feed when it is
    used as a harvest aid or desiccant for fodder crops such as grass,
    maize or alfalfa residues; of 5-1000 mg/kg may be found in the
    resulting feed.

         Oral doses of paraquat given to cows are excreted mainly
    unchanged in faeces. Residues in milk and meat are extremely small.
    When cows were allowed to graze grasses containing up to 1000 mg/kg at
    the start of the test, a maximum residue of 0.02 mg/kg paraquat was
    detected in milk on the first day after grazing freshly treated
    fodder. Thereafter residues were less than the normal limit of
    detection for milk, i.e. below 0.005 mg/kg; it was estimated that the
    cows consumed one-half of the acute oral LD50 daily. The maximum
    residue limit of 0.01 mg/kg for milk, recommended by the Joint Meeting
    in 1972, is therefore confirmed. Levels in the meat are often below
    0.01 mg/kg and rarely above 0.05, but higher levels are possible
    especially in kidney.

         Levels in tissues of pigs fed on a paraquat-containing diet were
    again generally below 0.01 but sometimes up to 0.05 mg/kg, and in
    kidney levels approaching 0.5 mg/kg have been reached. As in other
    animals, there was little metabolism of paraquat in the hen: residues
    in meat and eggs were small and rarely exceeded 0.01 mg/kg.

         Paraquat is also used as a spray directed at the ground to
    control weeds, and as a pre-emergence and preplanting spray for cereal
    crops. Very small residues at or about the limit of determination can
    arise from these uses presumably from adventitious particles of soil
    and vegetation adhering to the crop.

    RECOMMENDATIONS

         The following additional maximum residue limits are recommended.
    They refer to paraquat ion.

    Commodity                                            Limit, mg/kg
    Sunflower seed                                         2
    Kidney of sheep, cattle and pigs                       0.5
    Dried hops, passion fruit                              0.2
    Food commodities of plant origin other than
    those for which specific recommendations have
    been made, meat and edible offals other than
    kidney of sheep, cattle and pigs                       0.05*
    Eggs                                                   0.01*

    REFERENCES

    Calderbank, A., McKenna, R.H., Stevens, M.A., and Walley, J.K.
    1968                Grazing trials on paraquat treated pastures.
                        J.Sci. Food Agr., 19: 246.

    Daniel, J.W., Edwards, M.J., Slade, P., and Walker, G.H.
    1971                Milk residues arising from the ingestion of
                        14C-paraquat by the cow. ICI Plant Protection
                        Ltd. Report No. AR2282A. (Unpublished)

                    
    *at or about the limit of determination

    Daniel, J.S., and Gage, J.C. Absorption and excretion of diquat
    1966                and paraquat in rats. Brit. J. Indus. Med., 23:
                        133-136.

    Edwards, M.J., Hemingway, R.J., Kinch, D.A., and Slape, P.
    1974                Paraquat: residue and toxicology trial with cows
                        fed a treated grass. ICI Plant Protection Ltd.
                        Report No. AR2465A(R), (Unpublished)

    Edwards, M.J., Hayward, G.J., and Ward, R.J. Paraquat: residues
    1976                in milk and tissues of cows fed on paraquat
                        treated grass. Unpublished report from ICI Plant
                        Protection Division.

    Fletcher, K. Production and viability of eggs from hens treated
    1967                with paraquat. Nature, 215: 1407 (Unpublished)

    Fletcher, K. In Forensic Toxicology, p. 86, ed. B. Ballantyne,
    1974                John Wright & Sons Ltd., Bristol.

    Hemingway, R.J., Edwards, M.J., Jagatheeswaran, T., Davis, J.A.,
    1975                and Hayward, G. Paraquat residue transfer and
                        toxicology trial in young growing pigs. ICI Plant
                        Protection Ltd. Report No. AR2572A (Unpublished).

    Hemingway, R.J., Leahey, J.P., Griggs, R.E., and Davis, J.A.
    1972                Paraquat: metabolism in sheep. ICI Plant
                        Protection Ltd. Report No. AR2359A (Unpublished).

    Hemingway, R.J., Leahey, J.P., Griggs, R.E., and Davis, J.A.
    1974                Paraquat-metabolism in ruminants. 3rd
                        International Congress of Pesticide Chemistry (I
                        PAC) Helsinki.

    Hemingway, R.J., and Oliver, C. Paraquat: A study of the metabolism
    1974                and residues in hens and their eggs. ICI Plant
                        Protection Ltd. Report No. AR2511A (Unpublished).

    Hendley, P., Leahey, P.J., Spinks, C.A., Neale, D., and Carpenter,
    1976a               P.K. Paraquat-metabolism and residues in goats.
                        ICI Plant Protection Division, Report No. AR2680A
                        (Unpublished).

    Hendley, P., Leahey, J.P., and Spinks, C.A. Paraquat: Metabolism
    1976b               and residues in hens. ICI Plant Protection
                        Division. Report No. AR2676A (Unpublished)

    Lazanas, J.C. A study of the effects of sub-acute administration
    1967                of paraquat to dairy cattle. Industrial Biotest
                        Report.

    Leahey, J.P., Hemingway, R.J., Davis, J.A., and Griggs, R.E.
    1972                Paraquat-metabolism in a cow. ICI Plant Protection
                        Ltd. Report No. AR2374A. (Unpublished)

    Leahey, J.P., Hendley, P., and Spinks, C.A. Paraquat: Metabolism
    1976                and residues in pigs using 14C-methyl labelled
                        paraquat. ICI Plant Protection Division Report No.
                        AR2694A. (Unpublished)

    Leary, J.B. Paraquat: Chicken feeding study. Chevron Chemical
    1974                Co., Ortho Division Report File No. 741. 11 PQ.
                        (Unpublished)

    Litchfield, M.H. Grazing trial on paraquat-treated pasture. Central
    1969                Toxicology Laboratory Report IHR/257.
                        (Unpublished)

    Murray, R.E., and Gibson, J.E. A comparative study of paraquat
    1972                intoxication in rats, guinea pigs and monkeys.
                        Exp. Mol. Pathol., 17: 317-325.

    Rose, M.S., Lock, E.A., Smith, L.L., and Wyatt, I. Biochem.
    1976                Pharmacol., 25: 419-423.

    Sarfaty, A.B. Diquat and paraquat. Observational trials on toxicity
    1963                to sheep and cattle.

    Staiff, D.C., Comer, S.W., Armstrong, J.F., and Wolfe, H.R.
    1975                Bull. Environ. Contam. & Toxicol., 14: 334-340.

    Stevens, M.A., and Walley, J.K. Tissues and milk residues
    1966                arising from the ingestion of single doses of
                        diquat and paraquat by cattle. J. Sci., Food Agr.,
                        17: 472.

    Spinks, C.A., Hendley, P., Leahey, J.P., and Carpenter, P.K.
    1976                Paraquat: Metabolism and residues in pigs using
                        14C-ring labelled paraquat. ICI Plant Protection
                        Division Report No. 2692A. (Unpublished) (This
                        contains newly produced data)

    Sykes, B.I., Purchase, I.F.H., and Smith, L.L. J. Path.
    1976                (In press)

    Vijevaratnam, G.S., and Corrin, B. J. Path., 103:123-129.
    1971
    


    See Also:
       Toxicological Abbreviations
       Paraquat (HSG 51, 1991)
       Paraquat (PIM 399)
       Paraquat (JMPR Evaluations 2003 Part II Toxicological)
       Paraquat (AGP:1970/M/12/1)
       Paraquat (WHO Pesticide Residues Series 2)
       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)