Parathion-methyl was evaluated by the Joint Meeting in 1968
    (FAO/WHO, 1969) and in 1972 (FAO/WHO, 1973).

         Arising out of the list of requirements published in the report
    of the 1972 Joint Meeting (FAO/WHO, 1973) some information became
    available on residue levels from supervised trials in various areas,
    on residues in food in commerce and on national tolerances and
    pre-harvest intervals.

         At the 1972 Joint Meeting, the data on which the temporary ADI
    were based were re-evaluated and the temporary ADI was extended for a
    further three years. The following additional studies have been
    received and are discussed in this monograph addendum.




         The metabolism of methyl parathion and parathion was studied in
    sunfish and mice. Fish and mouse liver homogenates catalyzed
    glutathione (GSH)-dependant metabolism of methyl parathion and methyl
    paraoxon but not of parathion or paraoxon. Hydrolysis of methyl
    paraoxon by fish liver homogenates exceeded that for parathion by
    five-fold, while methyl paraoxon hydrolysis in mice was half of that
    of paraoxon (Benke et al., 1974).

         In vitro metabolism of methyl parathion and parathion has been
    studied in male and female rats of several ages to determine the
    mechanism responsible for the variations in toxicity. Oxidative
    formation of the oxygen analogues, oxidative aryl cleavage,
    glutathione-dependent dealkylation and dearylation were assayed in
    liver homogenates. Rates of enzymatic detoxification of the
    corresponding oxygen analogues by A-esterase, glutathion-S-aryl, and
    S-alkyl-transferase and inactivation by binding were also studied.
    Changes in LD50 values with age for methyl parathion and parathion
    correlated better with changes in rates of reactions which represented
    detoxification pathways for methyl paraoxon and paraoxon than for
    reactions which represented direct metabolism of the parent
    insecticides. Both male and female rats became much less sensitive to
    the acute lethal effects of methyl paraoxon and paraoxon with
    increasing age (Benke & Murphy, 1975).


    Special studies on comparative toxicity

         The comparative toxicity, anticholinesterase action and
    metabolism of methyl parathion and parathion were studied in sunfish
    and mice to determine the basis for the low toxicity of methyl
    parathion in sunfish (LD50>2500 mg/kg) and the LD50 value in mice
    (13.5 mg/kg). Times of death were much shorter for both compounds in
    mice than in fish. Low sensitivity of fish cholinesterases to paraoxon
    as compared to mice accounted for the 10-fold lower toxicity of
    parathion in fish LD50, 110 mg/kg). By contrast, sunfish had similar
    cholinesterase sensitivities to methyl paraoxon and paraoxon (Benke et
    al., 1974).

    Special studies on potentiation

         Intraperitoneal pre-treatment with triorthotolyl phosphate (TOTP)
    has been shown to have a potentiation action on the toxicity of
    paraoxon in the rat (Lauwerys & Murphy, 1969) and in the mouse (Lynch
    & Coon, 1972). A 2.5-fold potentiation of methyl paraoxon toxicity was
    shown in a study in the rat in which TOTP (125 mg/kg) had no
    significant effects on rates of liver and plasma hydrolysis of
    paraoxon and methyl paraoxon by A-esterases, or on GSH-dependent liver
    enzymes (Benke & Murphy, 1974). It was indicated that TOTP could be
    used as a specific inhibitor of the binding pathway of detoxification
    of paraoxon and methyl paraoxon and perhaps other oxygen analogues of
    organophosphorus insecticides (Cohen & Murphy, 1972).

    Acute toxicity


    Animal            Route                mg/kg bw      References

    Mouse (M)         Intraperitoneal        11.0        Benke et al., 1974

    Mouse (M)         Intraperitoneal         6.4        Kamienski & Murphy,

    Rat               Intraperitoneal         7.0        DuBois & Kinoshita,

    Rat (M)           Oral                   14.0        Gaines, 1969

    Rat (F)           Oral                   24.0        Gaines, 1969

    Observations in man

         In further studies (Rider et al., 1968, 1969a, 1969b)
    parathion-methyl was administered orally to groups of five test
    subjects at dosage levels ranging from 14 to 20 mg/day increasing in
    increments of 1 mg/day for a period of approximately 30 days. No
    significant changes were observed in plasma and red blood cell
    cholinesterase levels. When administered at levels of 28 and 30 mg/kg
    a significant depression of 37% in red blood cell cholinesterase was
    noted (Rider et al., 1971).


         The teratogenicity and reproduction studies requested by the 1968
    and 1972 Joint Meetings have not been provided. Data pertaining to
    long-term studies are not available. Information on further studies in
    man, however, has become available. These short-term studies indicate
    that man can tolerate the ingestion of up to 20 mg of parathion-methyl
    daily for short periods without effect.

         As studies required by previous Joint Meetings have not been
    submitted no definitive acceptable daily intake can be estimated.
    However, studies to provide the required information are presently
    under way. Thus the temporary acceptable daily intake based on the
    data in man was extended.


    Level causing no toxicological effect

         Man: 0.3 mg/kg bw.


         0-0.001 mg/kg bw.



         Residue data from, supervised trials carried out in various areas
    were required. New data were obtained from supervised trials on
    fruits: apples, peaches and pears; on vegetables: cucumber
    (glasshouse), kale, onions, tomatoes (glasshouse); on field crops:
    sugar beet and on tea. The data are summarized in Table 1.

         The references given in Table 1 are all to unpublished reports of
    Bayer, 1975. The analytical methods used in the trials were as

    TABLE 1.  Residue of parathion-methyl resulting from supervised trials


                                                    Application                  Residues in mg/kg, at intervals (days) after application

        Crop                Country    Year   No.   kg a.i./ha    Formulation     0        1      3/4      7      14/16    20/21           Ref.



        Abate Fetel         Italy      1964    7    1.4-1.8 k/ha    E.C. 40%                                      0.11                     1
        Boskoop             Belgium    1965    2    0.32 g/tree     E.C. 50%     0.32     0.31    0.25    0.09    0.06     0.04            2
        Court Pendu         Belgium    1965    2    0.32 g/tree     E.C. 50%     0.78     0.22    0.23    0.12    0.07     0.04            3
        Golden Delicious    Belgium    1965    2    0.32 g/tree     E.C. 50%     0.33     0.12    0.14    0.10    0.05     0.02            4
        Golden Delicious    Belgium    1965    3    0.32 g/tree     E.C. 50%     0.4      0.4     0.24            0.17     0.14            5
        King David          Italy      1964    7    0.4-1.2 k/ha    E.C. 50%                                               <0.05           6

                                                                                 10       18      20      25      29
        Amsden              Italy      1965    3    7-10 g/tree     wp 80%       <0.05                                                     7
        Redhaven            Italy      1964    3    10-12 g/tree    E.C. 50%              0.11                                             8
        Veechi 74           Italy      1964    3    10-12 g/tree    E.C. 50%              0.05                                             9

        Santa Maria         Italy      1964    5    0.5 kg/ha       E.C. 40%                              0.05                             10
        Santa Maria         Italy      1964    5    0.5 kg/ha       E.C. 40%                              0.12                             11
        Santa Maria         Italy      1964    5    0.5 kg/ha       E.C. 40%                                      <0.05                    12
        Williams            Italy      1964    3    1.25-1.5 kg/ha  E.C. 40%                      0.08                             13

    TABLE 1.  (Cont'd.)


                                                    Application                  Residues in mg/kg, at intervals (days) after application

        Crop                Country    Year   No.   kg a.i./ha    Formulation    0/1      3/4     7/8     9/10    14/15     41/44


    Cucumbers               Belgium    1966    1    0.45 kg/ha      dust 2%                                                                14
        Total fruit                                                              0.14     0.05    0.05    <0.01
        peel                                                                     0.64     0.26    0.12
        pulp                                                                     0.04     0.02    0.04
    Kale                    Belgium    1965    1    0.2 g/plant     gran 10%                                                <0.01         15

    Red cabbage             Belgium    1965    1    0.2 g/plant     gran 10%                                                <0.01         16

    Hop                     Belgium    1965    1    0.5 g/plant     E.C. 50%                                                               17
        leaf                                                                     0.12             n.d.            n.d.

        cones                                                                    0.17             n.d.            n.d.

    Onions                  Belgium    1965    1    0.25 g/m        gran 10%                                                n.d.           18

                                                    0.125 g/m       gran 10%                                                n.d.

    Tomatoes                Belgium    1966    1    0.6 kg/ha       dust 2%      0.10     0.075   0.035   0.01                             24

    TABLE 1.  (Cont'd.)


                                                    Application                  Residues in mg/kg, at intervals (days) after application

        Crop                Country    Year   No.   kg a.i./ha    Formulation     0        1      3/4      7      14/16    20/21           Ref.


    Sugar beet

        Total plant         Finland    1969    1    0.3 kg/ha       dust 15%     0.5      0.15    0.04    0.04                             19

                                                                                  5        6       7      13/14   20/21

        fermented*          East       1964    1    1.2 kg/ha       E.C. 50%                      <0.2                                    20
                            Pakistan           2    1.2 kg/ha       E.C. 50%              <0.2
                                               3    1.2 kg/ha       E.C. 50%              <0.2
                                               4    1.2 kg/ha       E.C. 50%                      <0.2

                            East       1964    1    0.6 kg/ha       E.C. 50%              <0.2                                            21
                            Pakistan           2    0.6 kg/ha       E.C. 50%     <0.2
                                               3    0.6 kg/ha       E.C. 50%              <0.2
                                               4    0.6 kg/ha       E.C. 50%              <0.2

                            East       1964    1    0.3 kg/ha       E.C. 50%              <0.2                                            22
                            Pakistan           2    0.3 kg/ha       E.C. 50%     <0.2
                                               3    0.3 kg/ha       E.C. 50%              <0.2
                                               4    0.3 kg/ha       E.C. 50%              0.2

                            East       1964    1    0.3 kg/ha       E.C. 50%                              <0.2   <0.2                    23
                            Pakistan           1    0.6 kg/ha       E.C. 50%                              <0.2   0.25
                                               1    1.2 kg/ha       E.C. 50%                              <0.2   <0.2

    * Leaves are dried 18-20 hours, two hours fermentation, and afterwards 45 minutes dried at 82C.


    1-13: calorimetric method, Gunther and Blinn, Adv. Chem. Ser., 1,
    72, (1949). Limit of detection 0.05 mg/kg

    14-18 and 24: calorimetric method Averell and Norris, Anal. Chem.,
    20, 750 (1958). Limit of detection 0.01 mg/kg

    20-23: GLC method (Bayer). Limit of detection 0.2 mg/kg


    Data obtained from a food inspection survey in Hungary are summarized
    in Table 2. (Commodities of which fewer than 10 samples were taken
    have been omitted.)

    TABLE 2.  Residues in food inspection samples in Hungary


                                    No. of samples with residues
                     No. of               in range (mg/kg)
    Commodity        analysed       <l.d.1      l.d.-0.25     >0.25-0.5

    Apples             129             123          5               1

    Apricots            16               8          6               2

    Cabbage             40              24         16               -

    Parsley             14              14          -               -

    Peaches             37              30          5               2

    Potatoes            61              52          9               -

    Strawberries        20              18          2               -

    1  l.d. = limit of detection, varying from 0.01-0.05 mg/kg.
    Note: national tolerance = 0.5 mg/kg.


         Officially recommended pre-harvest intervals and national
    tolerances reported to the Meeting are shown in Tables 3 and 4

    TABLE 3.  Officially recommended pre-harvest intervals


      Country                   Crops                                  Days

    Australia                 Fruit, vegetables, field crops            21

    Belgium                   Fruit, vegetables, field crops            21
                              Leafy vegetables glasshouse
                               (period 1/3 - 1/11)                      28

    Brazil                    All crops                                 15

    Denmark                   All crops                                 14

    Federal Republic          field crops such as alfalfa,
      of Germany               clover, lupine, grain,
                               potatoes, rape, sugar beet               35
                              Grapes                                    35
                              Fruits: pome- and stone-fruit,
                               small fruits except
                               strawberries                             28
                              Vegetables: cabbage, leafy
                               vegetables (glasshouse)                  21
                              Leafy vegetables (outdoors),
                               carrots, celery, beans,
                               peas, leek, onions, radish,
                               horse-radish                             14
                              Cucumbers, tomatoes (both
                               outdoors and under glass)                14

    Democratic                Field crops                               14
      Republic of             Fruit, vegetables                         10
      Germany                 Crops used for production of
                               baby food, diet foods etc.              21-302

    Finland                   All crops                                 21
                              Soil drenches                             35

    France                    All crops                                 15

    Italy                     All crops                                 20

    Yugoslavia                Fruit, vegetables, field crops,
                               grapes                                   21

    Morocco                   All crops                                 15

    TABLE 3.  (Cont'd.)


      Country                   Crops                                  Days

    New Zealand               Oil containing concentrates               21
                              All other formulations                    14

    Netherlands1              Pome- and stone-fruit, berries
                               (all outdoors)                           21
                              Fruit (glasshouse)                        28
                              Spray and dust smokes                     10
                              Vegetables, except leaf celery,
                               parsley, bread beans, 
                               pole-beans                               21
                              Peas for canning                          10
                              Bell peppers, cucumbers, melons,
                               tomatoes (all under glass)               3
                              Leafy vegetables (glasshouse)
                               except leaf celery and
                               smokes only, period 1/3-1/11             10
                                   period 1/1-1/3                       21

    Austria                   All crops                                 21

    Poland                    Fruits, field crops, vegetables           21

    Sweden                    All crops                                 28

    Switzerland               Fruit, vegetables, field crops            21

    Spain                     All crops except cotton                   21

    Hungary                   All crops                                 14

    United States of          Fruits, field crops                      15-212
      America                 Vegetables                                7-212

    1  Including mixtures with parathion.
    2  Depending on dosage rates and/or formulations used.

    TABLE 4. National tolerances reported to the meeting


     Country                   Crops                                  mg/kg

    Australia               Fruit, vegetables, grain                  1

    Belgium1                Fruit, vegetables, except                 0.5

    Brazil                  Fruits or vegetables, cabbage             0.2
                            Vegetables such as lettuce,
                              endive, spinach, chard,                 1
                              cresses, chicory, parsley, etc.
                            Cottonseed-oil                            0.05
                            Fresh fodder                              1

    Federal Republic        Fruit and vegetables                      0.15
     of Germany

    Democratic Republic     Fruit and vegetables                      0.5
     of Germany             Meat, fish, eggs, fat (of
                              animal and plant origin),
                              milk                                    0.0042
                            Potatoes, onions                          0.0042
                            Baby food                                 0.0042

    France                  Fruit and vegetables                      0.15

    India                   Raw cereals                               0.2
                            Milled cereal products                    0.005
                            Fruit                                     0.2
                            Vegetables                                1

    Israel                  Fruits, cabbage, cucumbers,
                              egg-plant, melons, squash,
                              water-melons                            0.2
                            Other vegetables                          1
                            Cottonseed-oil                            0.05

    Italy                   Fruit and vegetables
                              (except potatoes)                       1

    New Zealand             Fruit and vegetables                      0.5

    Netherlands             Fruit and vegetables                      0.5
     and -ethyl

    TABLE 4. (Cont'd.)


     Country                   Crops                                  mg/kg

    Poland                  Fruit                                     0.5

    Switzerland             Fruit and vegetables                      0.5
     and -ethyl

    Hungary                 All crops                                 0.5

    United States of        Alfalfa hay                               5
     America                Alfalfa (fresh)                           1.25
     parathion-methyl         apples, apricots, artichokes,
     and -ethyl               avocados, barley, beans,
     together                 beets (with or without tops)
                              or beet greens alone, 
                              blackberries, blueberries
                              (huckleberries), boysenberries,
                              broccoli, Brussels sprouts,
                              cabbage, carrots, cauliflower,
                              celery, cherries, citrus fruits,
                              clover, collards, corn, corn
                              forage, cranberries, cucumbers,
                              currants, dates, dewberries,
                              eggplants, endive (escarole),
                              figs, garlic, gooseberries,
                              grapes, grass for forage,
                              guavas, hops, kale, kohlrabi,
                              lettuce, loganberries, mangoes,
                              melons, mustard greens,
                              nectarines, oats, okra, olives,
                              onions, parsnips (with or
                              without tops) or parsnip greens
                              alone, peaches, pea forage,
                              peanuts, pears, peas, peppers,
                              pineapples, plums (fresh
                              prunes), pumpkins, quinces,
                              radishes (with or without
                              tops) or radish tops,
                              raspberries, rice, rutabagas
                              (with or without tops) or
                              rutabaga tops, soybean hay,
                              spinach, squash, strawberries,
                              summer squash, Swiss chard,

    TABLE 4. (Cont'd.)


     Country                   Crops                                  mg/kg

                              tomatoes, turnips (with or
                              without tops) or turnip
                              greens, vetch, wheat,
                              young-berries                           1
                            Cottonseed                                0.75
                            Sunflowerseed                             0.2
                            Soybeans                                  0.1

    1  Total residues of parathion-methyl and parathion.
    2  At or about the limit of detection.


         Residue data from supervised trials in areas other than those
    included in the 1968 Evaluations (FAO/PL: 1968/M/9/1) have become
    available. Such data were required by the 1972 JMPR (FAO/WHO, 1973).

         Data were available from supervised trials on apples, peaches,
    pears, cucumbers (glasshouse), red cabbage, curly kale, onions,
    tomatoes (glasshouse), sugar beets and tea (fermented).

         Although most of the data were not obtained recently, they still
    provide useful additional information. The methods of analysis used
    are reliable and sufficiently sensitive.

         Taking into account the very broad field of application of
    parathion-methyl in many areas of the world the amount of information
    available is still unsatisfactory.

         Because of the lack of such data, the Meeting was not able to
    propose any changes in the tolerance figures already established at
    the 1968 Meeting and only a few additional maximum residue limits can
    be proposed.

         Extensive information was obtained on pre-harvest intervals
    officially recommended in various areas, on national tolerances and on
    rates of application on several crops.

         Only limited data were obtained on residues in food moving in
    commerce. It has however to be recognized that in many countries in
    routine surveys on residue levels no differentiation is made between
    parathion(-ethyl) and parathion-methyl residues.

         The new data available at the 1975 Meeting confirm some of the
    temporary tolerances established at the 1968 Meeting. Additional data
    from supervised trials on tomatoes, together with the data available
    at the 1968 Meeting make it possible to recommend a temporary maximum
    residue limit for parathion-methyl on tomatoes. Temporary maximum
    residue limits for parathion-methyl or hops (dry cones), sugar beets
    and tea (fermented) are also recommended in the light of the new data
    on these commodities.


         The temporary tolerances established by the 1968 Meeting for
    fruit, cucumbers and cole crops (brassicas) could be confirmed as
    temporary maximum residue limits in the light of the additional data
    from supervised trials on apples, peaches, pears, cucumbers
    (glasshouse), red cabbage and curly kale. The following additional
    temporary maximum residue limits are also recommended. They refer to
    parathion-methyl and its oxygen analogue, expressed as



                                                      Pre-harvest interval
                                  Limit,              on which
    Commodity                     mg/kg               recommendation is
                                                      based, days

    Tea (fermented
    and dried)                    0.2                 14-21

    Tomatoes                      0.2                 3 (glasshouse)

    Sugar beet                    0.05                21

    Hops (dry cones)              0.05*

    *At or about limit of determination.


    REQUIRED (by 30 June 1978)

    1.   Oral studies on teratogenesis and on reproduction in species
    appropriate to such tests.


         1.   Adequate long-term studies in at least one mammalian

         2.   Information on current use patterns in various countries on
    crops for which no recommendations are made and on residue levels
    resulting from such uses.


    Bayer. (1975) Unpublished reports of Bayer Leverkusen (Federal
    Republic of Germany). 1:162/68; 2:183/65; 3:18/65; 4:182/65; 5:181/65;
    6:161/68; 7:172/68; 8:170/68; 9:169/64; 10:168/68; 11:167/68;
    12:165/68; 13:164/68; 14:203/66; 15:180/65; 16:179/68; 17:178/68;
    18:175/65, 176/65; 19:265/69; 20-22:19a, 19b, 19c/66; 23:19d/66;

    Benke, G. M., Cheever, J. L., Mirer, F. E. & Murphy, S. D. (1974)
    Comparative toxicity, anticholinesterase action, and metabolism of
    methyl parathion and parathion in sunfish and mice. Toxicol. Appl.
    Pharmacol., 28:97-109.

    Benke, G. M. & Murphy, S. D. (1974) Effect of TOTP pre-treatment on
    paraoxon and methyl paraoxon detoxification in rats. Res. Com. Chem.
    Path. Pharmacol., 8:665-672.

    Benke, G. M. & Murphy, S. D. (1975) The influence of age on the
    toxicity and metabolism of methyl parathion and parathion in male and
    female rats. Toxicol. Appl. Pharmacol., 31:254-269.

    Cohen, S. D. & Murphy, S. D. (1972) Inactivation of malaoxon by mouse
    liver. Proc. Soc. Exp. Biol. Med., 139:1385-1389.

    DuBois, K. P. & Kinoshita, F. K. (1968) Influence of hepatic
    microsomal enzymes by phenobarbital on toxicity of organic phosphate
    insecticides. Proc. Soc. Exp. Biol. Med., 129:699-702.

    Gaines, T. (1969) Acute toxicity of pesticides. Toxicol. Appl.
    Pharmacol., 14:515-534.

    Kamienski, F. & Murphy, S. D. (1971) Biphasic effects of
    methylene-dioxyphenyl synergists on the action of hexobarital and
    organophosphate insecticides in mice. Toxicol. Appl. Pharmacol.,

    Lauwerys, R. R. & Murphy, S. D. (1969) Interaction between paraoxon
    and tri-o-tolyl phosphate in rats. Toxicol. Appl. Pharmacol., 14:

    Lynch, W. T. & Coon, J. M. (1972) Effect of tri-o-tolyl phosphate
    pre-treatment on the toxicity and metabolism of parathion and paraoxon
    in mice. Toxicol. Appl. Pharmacol., 21:153-165.

    Rider, J. A., Moeller, H. C., Puletti, E. J. & Swader, J. I. (1968)
    Studies on the anticholinesterase effects of methyl parathion,
    guthion, dichlorvos, and gardona in human subjects. Federation
    Proceedings, 27 (2):597.

    Rider, J. A., Moeller, H. C., Puletti, E. J. & Swader, J. I. (1969a)
    Toxicity of parathion, systox, octamethyl pyrophosphoramide, and
    methyl parathion in man. Tox. Appl. Pharm., 14:603-611.

    Rider, J. A. & Puletti, E. J. (1969b) Studies on the
    anticholinesterase effects of gardona, methyl parathion, and guthion
    in human subjects. Federation Proceedings, 28 (2):479.

    Rider, J. A., Swader, J. I. & Puletti, E. J. (1971) Anticholinesterase
    toxicity studies with methyl parathion, guthion and phosdrin in human
    subjects. Federation Proceedings, 30 (2):443.

    See Also:
       Toxicological Abbreviations
       Parathion-methyl (FAO/PL:1968/M/9/1)
       Parathion-methyl (WHO Pesticide Residues Series 2)
       Parathion-methyl (Pesticide residues in food: 1978 evaluations)
       Parathion-methyl (Pesticide residues in food: 1979 evaluations)
       Parathion-methyl (Pesticide residues in food: 1980 evaluations)
       Parathion-methyl (Pesticide residues in food: 1984 evaluations)
       Parathion-methyl (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)