LEPTOPHOS          JMPR 1974


         Leptophos is a draft ISO common name.

    Chemical name

         O-(4-bromo-2,5-dichlorophenyl) O-methyl phenylphosphonothioate


         O-(4-bromo-2,5-dichlorophenyl) O-methyl phenylthiophosphonate


    Structural formula


    Empirical formula

         C13H10Br Cl2 O2 PS

    Other information on identity and properties

         a. Composition of technical leptophos

         The technical material as manufactured contains a minimum of 85%
         leptophos and about 15% related materials. Its composition is as
         shown in Table 1.

    TABLE 1.  Composition Of technical leptophos


    Compound                              Specification    Typical Sample

    leptophos                             85% min.         87%

    O,O-dimethyl phenylphos-phonothioate  8% max.          3.5%

    4-bromo-2,5-dichlorophenol            1% max.          <0.1%

    phenylphosphonothioate                8% max.          4%

    Volatile materials                    2% max.          0.5%

    Miscellaneous related
    compounds                                             approx. 5% total

    (A number of unidentified impurities at levels of less than 1% each,
    either present at these levels in the starting materials or resulting
    from reactions of these materials at a later stage. Halogenated
    dibenzo-p-dioxins are absent [limit of detection 0.1 ppm] [Velsicol,

    b. Physical and chemical properties of leptophos

         physical state:        white crystals

         molecular weight:      411.8

         melting point:         70.2 - 70.6C (99.4% purity)

         specific gravity:      D 25 = 1.53

         solubility (g/100 ml solvent at 25C):

         water                  practically insoluble in water
                                (0.03 mg/l)

         benzene                133

         xylene                 73

         acetone                62

         cyclohexane            14

         heptane                7

         isopropyl alcohol      2.4


      thermal                   stable at normal temperatures; at 180C
                                85% of the material is decomposed in 5
                                hours, at 208C in 2 hours.

                                The main product of thermal decomposition
                                is the S-methyl isomer
                                [O-(4-bromo-2,5-ichlorophenyl) S-methyl
                                phenylphospho-nothioate] [Schwemmer,

      acids and bases           leptophos is hydrolysed slowly under
                                alkaline conditions at normal
                                temperatures; the material is stable in
                                acid conditions.

      UV light                  In the laboratory, when irradiated with
                                high intensity UV light in the presence of
                                a strong UV sensitizer, leptophos is
                                rapidly converted first to 
                                O-methylphenyl-phosphonothioate, referred
                                to as the dichloro-photoproduct, and then
                                to a material with the empirical formula
                                C13H10 Cl O2 PS (tentatively identified
                                as 3-chloro-6-methoxydibenz [c, e]
                                [1,2]-oxaphosphorin-6-thione or 
                                O-methyl-O, P-(4-chloro 
                                biphenyl-2,6'ylene) phosphonothioate and
                                referred to as the monochloro-photoproduct
                                [Schwemmer, 1971b]

                                UV light increases the rate of hydrolysis,
                                under field conditions (see "Fate of
                                residues in water")

    c. Formulations

         Leptophos is used as EC, wettable powder, dust and ULV


         Insufficient information was available to the Meeting to evaluate
    the compound toxicologically. A preliminary discussion of some aspects

    of its toxicology appears in the Report of the Meeting (FAO/WHO, 1975)
    and a fuller evaluation at the next Meeting is proposed.



         Leptophos is an organophosphorus insecticide with no appreciable
    systemic action. The material is used especially against lepidopterous
    larvae, but is also effective against a relatively broad spectrum of
    insects including beetles and their larvae, aphids, jassids and
    thrips, on various field crops, vegetables and fruits. Particularly
    important uses are on cereal crops (including maize and rice), cotton,
    sugar-cane, sugar-beet, brassicas, lettuce, tomatoes, potatoes,
    tobacco etc. (see registered and recommended uses below). Leptophos is
    used in about 25 countries in North-, Central- and South-America,
    Asia, Australia and Europe. The compound is applied as a soil-, seed-,
    and foliar treatment. Leptophos is not recommended for post-harvest
    treatments, or for use on or near livestock.

    Pre-harvest treatments

         Leptophos is generally used at dosage rates of 0.35 - 1.5 kg

         The officially registered and/or recommended uses are summarized
    in Table 2, with some typical application rates, safety intervals and


    Residues in crops

         Residue data are available from trials, mainly in the USA, on
    various vegetables and field crops: brassicas (broccoli, Brussels
    sprouts, cabbage); lettuce, potatoes; tomatoes; cotton and cotton
    products; maize (field corn and sweet corn). Data on residues in
    products of animal origin, e.g. residues in milk and meat of dairy
    cattle, meat of chicken and eggs, resulting from the consumption of
    residues in feed are also available.

         The data from supervised trials on crops are summarized in Table
    3. Residues of leptophos and its three main metabolites, the oxygen
    analogue, the phenol and desbromo-leptophos were usually determined
    separately. In the Table, in order to avoid excessive length, the
    leptophos residue is given together with an indication of the nature
    and total content of the determined metabolites. Where a metabolite is
    not recorded as having been determined its residues were usually
    undetectable. In most cases the limit of detection was 0.01 mg/kg. The
    results are not generally corrected for apparent residues in untreated

    TABLE 2.  Registered or recommended uses of leptophos


                                                                       Type of        Dosage rate       interval
    Country             Crop                                         application*     kg a.i./ha         (days)        Limitations

    Canada              Cabbage                                      young plants                       50

                        Carrots, celery, onions, rutabagas,
                        barley, oats, wheat                          young plants                       60             not on green
                                                                                                                       bunching onions

                        Cucumbers, peppers                           soil                               50

                        Tomatoes                                     soil                               70

                        Potatoes                                     soil                               88

                        Potatoes                                     foliar                             21

                        Head lettuce                                 young plants                       28

                        Sugar beet, sunflower                        young plants                       100

                        Rape                                         young plants                       16

    Dominican Rep.      Tomato                                       foliar           0.5-1.5           5
    and other
    Caribbean           Broccoli, cabbage, lettuce, potatoes         foliar           0.5-1.5           7
                        Cotton                                       foliar           1.2               10-14

                        Sweet corn (fresh market)                    foliar           0.9-1.35          3              when tassels first
                                                                                                                       emerge, do not feed
                                                                                                                       treated fodder to

    TABLE 2.  (Cont'd.)


                                                                       Type of        Dosage rate       interval
    Country             Crop                                         application*     kg a.i./ha         (days)        Limitations

                        Citrus                                       foliar           0.5                              not on fruit-bearing

                        Sugar-cane                                   foliar           0.5-1.5

                        Tobacco                                      foliar           0.5-1.1           10-14

    Japan and           Azuki bean, cabbage and chinese
    Korea               cabbage, rice                                foliar           0.23-0.34

                        Sugar-cane                                   foliar           0.17-0.34

                        Tobacco                                      foliar           0.34

    Mexico              Beans, soybeans, other vegetables,
                        alfalfa, cotton, rice, sugar-cane,
                        citrus fruit, grapes                         foliar           0.5-1.5

    Philippines         Rice                                         foliar           1-1.5

                        Maize, oil palm, tobacco                     foliar           0.34-0.7

                        Vegetables                                   foliar           0.34-0.6

    USA                 Broccoli, cabbage, russels sprouts,
                        tomatoes, maize                              foliar           0.9-1.35          7              do not apply to corn
                                                                                                                       or sweet corn which
                        Lettuce                                      foliar           0.9               7              is to be used for
                                                                                                                       silage or will be
                        Cotton                                       foliar           0.9-1.35          28             fed to livestock

                        Sweet corn (canning and fresh market)        foliar           0.9-1.35          3

    TABLE 2.  (Cont'd.)


                                                                       Type of        Dosage rate       interval
    Country             Crop                                         application*     kg a.i./ha         (days)        Limitations

                        Citrus fruit                                 foliar           1.25 g/100 1                     only on trees that
                                                                                                                       will not bear fruit
                                                                                                                       within a month

                        Potatoes                                     foliar           0.9-1.35          21

    Venezuela           Black beans, soybean, cabbage,
                        cauliflower, lettuce, onions,
                        potatoes                                     foliar           0.9-1.25          10

    *  Type of application: young plants = spraying or dusting the crops at an early stage
       foliar = spraying or dusting aerial parts at a later stage of development


    FIGURE 1

         The numbers used to identify the oxon (II), phenol (V) and
    desbromo-leptophos (VI) correspond to those in the metabolic scheme
    shown in the section "Fate of residues (Figure 1).

    General comments on Table 3.

         The main residue component in vegetables and grain crops is the
    parent compound leptophos which comprises 82.8 to 95.4% of the total
    residue detectable in any samples analysed. The other components of
    the residue, the oxygen analogue, the phenol and desbromo-leptophos,
    occur in varying proportions. The ratio of metabolites to parent
    compound increases with time and the main metabolite is usually the
    phenol or apparently the oxon. In a relatively large number of trials,
    however, the major part (and sometimes all) of the apparent "oxon
    residue" is likely to be an artifact derived from the analytical
    equipment. This interfering material was shown to be
    bis - (2-ethylhexyl) phthalate.

         In root crops such as potatoes, in which the insecticide does not
    come in direct contact with the edible parts, the primary residue
    component is the phenol hydrolysis product. In corn grain only
    leptophos is detected. There is some doubt as to whether this residue
    is genuine or caused by contamination from the husks during their


         The half-life of the residues on broccoli is about 3-6 days.
    After observing a pre-harvest interval of 7 days the residues were
    about 4-5 mg/kg when treatment was at the usual rate (0.9-1.35 kg/ha).
    After 14 days the residues were well below 0.5 mg/kg in the single
    trial reported.


         After application of leptophos at normal rates the maximum
    residue after a 7 days pre-harvest interval was about 3.5 mg/kg, after
    14 days well below 1 mg/kg.


         Removal of the wrapper leaves significantly reduces residues on
    lettuce. The lettuce samples which were analysed with the wrapper
    leaves on only one sample, taken 7 days after the last application,
    had residues which exceeded 5 mg/kg.


         When leptophos was applied at the recommended rate of 0.9-1.35 kg
    a.i./ha and after observing the recommended pre-harvest period of
    three weeks the total residues at harvest were about 0.1 mg/kg or


         When application was made at the recommended rate of 0.9-1.35 kg
    a.i./ha, and after a pre-harvest interval of 5-8 days, residues ranged
    from about 0.3 to 3 mg/kg. Only one sample exceeded 2 mg/kg, and in
    eight of the twelve the residues were below 1 mg/kg.


         The residues of leptophos and its metabolites in cottonseed after
    the application of leptophos to cotton at normal rates (0.9-1.35 kg
    a.i./ha) and a pre-harvest interval of 28 days were below 0.2 mg/kg in
    four of the five trials reported. The residues in crude and processed
    cottonseed oil are discussed in the section "Fate of residues in
    storage and processing."


         After observing a pre-harvest interval of 7 days for field corn
    and 3 days for sweet corn, the residues in the ears or kernels varied
    between < 0.01 (limit of detection) and 0.05 mg/kg.

         Application to field corn which is to be used for silage or when
    forage or fodder will be fed to livestock is not permitted, nor is the
    feeding of treated sweet corn forage or fodder. Residues in canning
    wastes (cobs and husks) varied between 4 and 12 mg/kg; residues in
    stalk and leaf of field and sweet corn between 9 and 82 mg/kg. Such
    commodities are often used as animal feed. The cob and grain of sweet
    corn for table uses contained residues of <0.01-0.16 mg/kg, usually
    at or below 0.05 mg/kg. It is to be noted that in several trials
    leptophos was applied at normal dosage rates but many times and at
    intervals of only two or three days. Lower residues in stalks and
    leaves may be expected after less frequent applications and/or longer

    Residues in products of animal origin

         Leptophos is not used on or near animals. Any residues in milk,
    meat or eggs occurring as a result of recommended uses of leptophos
    could only arise from residues in raw agricultural commodities used as
    feed. The data summarized below provide a basis for estimating the
    magnitude of residues, if any, likely to result in milk, meat, poultry
    and eggs from such sources.

    Beef cattle

         Beef cattle were fed with diets spiked with leptophos at levels
    of 15, 45, and 150 ppm for 28 days, after which all but one animal at
    each feeding level was sacrificed (Bio/toxicological Research
    Laboratories Inc., 1971). The remaining animal from each level was
    placed on a leptophos-free withdrawal diet for 14 days and then
    slaughtered. The results of the analysis of omental fat, muscles and
    organs are summarized as follows in Table 4.

        TABLE 3.  Residues of leptophos and its main metabolites (oxon (II)1, phenol (V) and desbromolepthos (VI) resulting from supervised trials


                              Application (EC                                 Leptophos, mg/kg, at interval (days) after
                              unless otherwise                                application.3
                              stated)               Metabolites
    Crop             Year     No.     Kg a.i./ha    determined2     0-1       3-4       6-8       9-10      14-15     18-22     29-30

    Broccoli head    1971     5       1.35          II,VI                                                   0.25e

                     1968     5       0.9           V               7.9a                3.8a      1.7a

                     1969     7       0.45          V               5.0a      2.6a      1.7a

                                      0.9           V               16a       14a       5.2a

    Brussels         1970     5-8     0.9           II,V,VI         2.8a                1.6e                                    0.14c
                              5-8     1.35          II,V,VI         3.6c                                    3.1b                0.58f

                     1970     5       0.9           II,V                                                              0.33e

    Cabbage          1969     5       0.9 (WP)      -               0.28                0.03               <0.01      <0.01

                              5       0.9           -               0.23                0.01               <0.01

                     1971     3       0.9           II,V,VI         5.6c      3.9d      3.1d               0.58d      0.05f

                     1970     6       0.9           II,V,VI         0.40f                                  0.49e                0.02g
                                                                                                                                (II 0.07)

                     1970     5       0.9           II,V,VI                                                           0.18d

                     1970     5       1.35          II,V,VI                                       0.46d

                     1971     8       0.9           II                                            1.2a

                     1971     4       0.9           II,V,VI                             0.08g

    TABLE 3.  (Cont'd.)


                              Application (EC                                 Leptophos, mg/kg, at interval (days) after
                              unless otherwise                                application.3
                              stated)               Metabolites
    Crop             Year     No.     Kg a.i./ha    determined2     0-1       3-4       6-8       9-10      14-15     18-22     29-30

                     1969     3-4     0.9           -                                   0.96      0.17
                                                                                        3 app     4 app

                     1969     6       0.9 WP        -                                                                 0.17

                                                    -                                                                 0.19

    Lettuce          1971     3       1.35(dust)    II,V,VI         3.0b      1.5b      0.18d               0.02f
                     1971     3       0.9           II,V,VI         35b       20b       16b                 0.21d

                              3       1.80          II,V,VI         50b       30b       22b                 0.07g
                                                                                                            (II 0.12)

                     1970     6       0.9           II,V            5.6b      7.0b      3.7c                1.1d      3.4d      0.76e

                     1971     3       1.80          II,V,VI         28b                 4.7b,               3.4c
                                                                                        6.4c                4.1b

    Potatoes         1971     4       0.9           II,V,VI                                                           0.02g
                                                                                                                      (V 0.04)

                     1971     7       1.35 (WP)     II,V,VI                                                           0.01g
                                                                                                                      (II 0.02)

                                                    II,V                                                              0.01g

                                                                                                                      (II,V 0.02)

    TABLE 3.  (Cont'd.)


                              Application (EC                                 Leptophos, mg/kg, at interval (days) after
                              unless otherwise                                application.3
                              stated)               Metabolites
    Crop             Year     No.     Kg a.i./ha    determined2     0-1       3-4       6-8       9-10      14-15     18-22     29-30

                     1970     4       0.9           II,V                                                               0.01g
                                                                                                                      (II 0.06)

                     1970     4       1.35          II,V                                          <0.01g
                                                                                                  (II 0.06)

                                      0.9           II,V                                                              <0.01g
                                                                                                                      (V 0.08)

                                      0.9 (WP)      II,V                                                              <0.01
                                                                                                                      (II 0.06)

    Tomato           1969     6       0.9           V               1.6b                0.87c               0.83c     0.48c     0.84c
    (fruit)                   6       0.9 (WP)      V               2.0a                0.88b               0.52c               0.31b
                     1968     5       0.9           V               0.52c               0.56d     0.60d

                     1968     7       0.9           V                                                       0.25d

                     1970     4       1.35          V                         0.35d

                     1971     2       1.35                                              0.16

                                      1.35          II,VI                               0.76c

    TABLE 3.  (Cont'd.)


                              Application (EC                                 Leptophos, mg/kg, at interval (days) after
                              unless otherwise                                application.3
                              stated)               Metabolites
    Crop             Year     No.     Kg a.i./ha    determined2     0-1       3-4       6-8       9-10      14-15     18-22     29-30

                     1971     6       1.02          V,VI                                0.88e

                              6       1.02          V,VI                                1.6c

                     1971     6       1.02          -                                             0.02

                     1971     3       1.35          -                                   0.27

                     1971     10      0.9 (WP)      II,V,VI         0.70d               0.09g     0.36d     0.06g
                                                                                        (VI 0.12)           (II 0.12)

                     1971     10      1.35          II,V            0.05f               0.21e     0.22e     0.08g (V 0.30)

                     1970     4       0.9           II,V,VI         1.5d                0.57e               0.32f               0.48e

                     1970     2       0.9           II,V,VI         2.7d      1.6f
                                                                              (2 days)

                     1971     2       1.35          II,V,VI                             2.5c
                                                                                        (5 days)

    Cotton seed      1968     10      0.9           -                                                                           0.05-
                                                                                                                                (26 days)

    whole plant      1970     4       1.35          II,V,VI                                                 0.21f

    TABLE 3.  (Cont'd.)


                              Application (EC                                 Leptophos, mg/kg, at interval (days) after
                              unless otherwise                                application.3
                              stated)               Metabolites
    Crop             Year     No.     Kg a.i./ha    determined2     0-1       3-4       6-8       9-10      14-15     18-22     29-30

     seed            1970     4       1.35          II,V,VI                                                 0.04f

                     1971     6       1.35          II,V,VI                                                                     0.02g
                                                                                                                                (34 days)

                     1971     2       1.35          II,V,VI                                                                     0.11f
                                                                                                                                (35 days)

                     1971     2       0.9           II,VI                                                             0.14f

                                      0.9           II,VI                                                                       0.16e

    Maize            1969     1       0.9           V               19a       11a       4.3c                0.80d     0.96e     0.80d
     (field corn)
     whole plant

     ear             1968     1       0.9           II              <0.01g              <0.01g                        <0.01g
                                                                     0.04f               (II                           (II
                                                                     (II                 0.03)                         0.2,)
                                                                     0.04)                                            <0.01)

     ear                      1       1.8           II              <0.01g              <0.01g                        <0.01f
                                                                     (II                 (II
                                                                     0.03)               0.03)

     stalk                    1       0.9           II,V,VI         18b                  8.3c                          3.5f
                                                                    19b                  8.8c                          3.1f

     stalk                    1       1.8           II,V,VI         23a                 13b                           11d
                                                                    8.2b                12b                           1.8d

    TABLE 3.  (Cont'd.)

                              Application (EC                                 Leptophos, mg/kg, at interval (days) after
                              unless otherwise                                application.3
                              stated)               Metabolites
    Crop             Year     No.     Kg a.i./ha    determined2     0-1       3-4       6-8       9-10      14-15     18-22     29-30

     whole plant     1968     1       0.9           II,V            13b                 11c                 5.4e       3.1e

                              1       1.8           II,V            21a                 18c                 11c        0.76g
                                                                                                                      (V 2.8)

     ear                      1       0.9           -                0.01     <0.01     <0.01

     ear                      1       1.8                            0.01     <0.01     <0.01

     whole plant     1968     1       0.9           II,V             28c                 8.0e                5.2f      4.1g
                                                                                                                      (V 5.0)

     ear             1968     1       0.9           II,V            <0.01               <0.01               <0.01     <0.01

                              1       1.8           II,V             52c                 22e                 18e       12f

    Sweet corn       1971     5       0.9 4         II                                   0.03f

     grain + cob     1971     6       1.35          II                                   0.11e

     forage                                         II,V,VI                              30c

     grain + cob     1971     2       1.35 4        II                        0.02e

     stalks                                         II,V,VI                   26b

     grain + cob     1971     7       1.35          II                        0.05f
     forage                                         II,V,VI                   53b

     grain + cob     1971     4       1.35          II                        0.01f

     stalks                                         II,V,VI                   20b

    TABLE 3.  (Cont'd.)

                              Application (EC                                 Leptophos, mg/kg, at interval (days) after
                              unless otherwise                                application.3
                              stated)               Metabolites
    Crop             Year     No.     Kg a.i./ha    determined2     0-1       3-4       6-8       9-10      14-15     18-22     29-30

    Sweet corn for
    canning ear     1969     23      0.9           -                                   <0.01,

     stalks                                         II,V                               36c,

     kernel          1971     22      0.94          II                        <0.01g
                                                                              (II 0.05)
     cob+husk                                       II,V,VI                   9.5b

     stalk+leaf      1971     22      0.94          II,V,VI                   80b

     kernel          1970     4       1.354         II                                  0.01f

     husk+cob                                       II,V,VI                             7.6b

     stalk                                          II,V,VI                             35d
    a) Sum of residues of determined metabolites <2% of leptophos residue.
    b) Sum of residues of determined metabolites 2-5% of leptophos residue.
    c) Sum of residues of determined metabolites 5-10% of leptophos residue.
    d) Sum of residues of determined metabolites 10-20% of leptophos residue.
    e) Sum of residues of determined metabolites 20-50% of leptophos residue.
    f) Sum of residues of determined metabolites 50-100% of leptophos residue.
    g) Sum of residues of determined metabolites >100% of leptophos residue.
    1 Most of the apparent oxon residue is often a contaminant (see text)
    2 II = oxon; V = phenol; VI = desbromo-leptophos
    3 Where metabolites exceed leptophos (g) main residue (mg/kg) is also shown in Table
    4 Normal application rate, but frequent applications (2-3 day intervals)

    TABLE 4.  Residues of leptophos and its metabolites in tissues of beef cattle fed fortified diets


                        Total residue*, mg/kg (Mean of duplicates)                                                Estimated
    Leptophos           At end of 28-day feeding period                 After 14-day            Reduction         half-life
    in                                                                  withdrawal period       in fat            of total
    diet,                                                 Omental       Omental                 after 14          residue in
    ppm                 Liver      Kidney     Muscle      fat           fat                     days, %           fat, days

    15                  0.05       0.02       <0.01       0.26          0.13                    50                14

    45                  0.10       0.05        0.02       1.65          0.46                    72                 7.6

    150                 0.35       0.35       <0.01       8.48          2.60                    69                 8.2

    *  Leptophos + oxon, corrected for artifact, + phenol. Desbromo-leptophos was sought but not detected.
       (Detection limit 0.01 mg/kg).


         The residues in fat and muscle consisted mainly of the parent
    material (92-100%) whereas in the liver and kidney the "phenol"
    (metabolite V, Figure 1) predominated at the feeding levels of 15 and
    45 ppm.

         The highest concentration storage ratio, CSR (level in the tissue
    divided by level in the feed), is observed in omental fat. For the
    leptophos feeding levels of 15, 45 and 150 ppm, the respective CSRs
    are 0.017, 0.037 and 0.057. Dissipation of residues from fat is fairly
    rapid (half-life 7-14 days).

    Dairy cattle

         Johnson et al. (1971) studied the effect of feeding weathered
    residues of leptophos including metabolites to dairy cattle. Maize
    (field corn) was treated in the field at rates of 0, 0.56, 1.12 and
    2.24 kg a.i./ha, harvested, ensiled 1 day later and subsequently fed
    to lactating cows for a period of about 8 weeks. All samples were
    analysed for leptophos, its oxon and its phenol. The oxon had
    disappeared from the silage before feeding began, however, and none
    was found in any of the milk samples. All the milk samples contained
    leptophos and its phenol in a ratio varying from about 3 to 15. The
    results of this study are summarized as follows in Table 5.

    TABLE 5.  Residues of leptophos and its phenol in silage and in the
              milk of cows eating it


                                                                       Total detectable
                    Total residue    Total residue                     residue in whole
    Leptophos       in silage,       in silage,       Total residue    milk, mg/kg
    application     mg/kg (mean      mg/kg (mean,     ingested, mean   (maximum values
    rate, kg/ha     wet basis)       dry basis)       mg/kg body       during 8 weeks
                                                       weight/day       feeding)

    0.56             6.77            21.8             0.41             0.037

    1.12            16.30            49.5             0.84             0.104

    2.24            29.50            91.6             1.71             0.230

         One week after the feeding of treated silage was terminated, the
    milk of cows fed at the two lower levels was free from residues. Milk
    from cows fed at the highest residue level contained an average of
    0.012 mg/kg. Bowman (1970) studied the partition of leptophos and its
    metabolites between the fat and aqueous phases of milk. He found fat/
    water partition coefficients of 3.55 and 1.38 for leptophos and the
    phenol respectively. From these figures it can be calculated that, for
    milk containing 4% butterfat, the residue levels of leptophos and
    phenol in the fat will be respectively 20 and 15 times their levels in
    whole milk. In the experiments of Johnson et al., if the residue is
    assumed to consist of 90% leptophos + 10% phenol, the total residue
    content of the butterfat would be 19 times the whole milk content. The
    maximum total residues in the fat would then be 0.7, 2.0 and 4.4 mg/kg
    at the three treatment levels, and the corresponding CSRs 0.10, 0.12
    and 0.15.

         In preliminary residue studies by Bowman and Beroza (1969), pairs
    of lactating cows were fed oat silage spiked with 25, 50 and 100 mg/kg
    (dry silage basis) of technical leptophos. The average total residue
    levels in the wet silage as analysed were 8.6, 17.3 and 30.0 mg/kg
    respectively, of which the components averaged 85% leptophos and 15%
    phenol. The average total residues in whole milk produced by the three
    groups of cows were 0.057, 0.14 and 0.50 mg/kg respectively of which
    96% was leptophos and 4% phenol. In comments on this study the authors
    stress the possible complication from non-uniform distribution of
    leptophos in the experimental feeds. This factor may have contributed
    to the disproportionately high residues in milk from the highest
    feeding level.

         In another study dairy cattle were fed diets spiked at levels of
    3, 10 and 38 mg/kg for a period of 28 days. All animals except one at
    each feeding level were then slaughtered and the survivor was put on a
    12-day withdrawal period.

         For the lower two levels of leptophos intake the residues in milk
    were below the limit of detection (0.01 mg/kg). The highest feeding
    level gave residues in milk on the 27th day of 0.01 and 0.04 mg/kg in
    two samples; the phenol residue was too low to be measured. Residues
    could not be detected after the 12-day withdrawal period. The residues
    in the tissues and organs of cows slaughtered on the last day of
    feeding are shown in Table 6; they are corrected for the "oxon"

    TABLE 6.  Residues of leptophos and metabolites in
              tissues of cattle fed fortified silage


    Leptophos in              Total residues, mg/kg
    feed, mg/kg         Muscle      Fat         Kidney      Liver

    9.96                 -          0.07         0.01        0.01

                         -          0.04         0.03        0.03

                         0.01       0.01        <0.01       <0.01

    37.35               <0.01       0.20         0.08        0.12

                        <0.01       0.21        <0.01       <0.01

                        trace       0.53         0.05        0.07

    Chickens and eggs

         In a study carried out at Bio/toxicological Research Laboratories
    (1971c), white leghorn chickens received a diet spiked with leptophos
    at levels of 0, 0.04, 0.09 and 0.2 mg/kg for a period of 4 weeks
    followed by a withdrawal period of 14 days. No residues of leptophos
    or its metabolites were detected in eggs one week after withdrawal of
    the leptophos at the highest level. The levels of leptophos +
    metabolites found in chickens and eggs at the end of the 28 day
    feeding period are shown in the following table.

    TABLE 7.  Residues of leptophos and its metabolites in tissues
              and eggs of chickens fed leptophos in the diet

                             Total residues, mg/kg, at end
    Leptophos level          of 28-day feeding period
    in feed, mg/kg           Fat               Muscle            Eggs

    0.04                     0.01-0.03*      <0.01-0.10*       <0.01-0.06*

    0.09                     <0.01-0.04      <0.01-0.04*       <0.01-0.05*

    0.2                      0.01            <0.01             <0.01-0.02*

    * These values probably include some interference by the "oxon"
      artifact although partial corrections were made.


    In animals

         The fate of leptophos in the mouse was found to be qualitatively
    similar to its fate in cotton (Holmstead et al., 1973, see next
    section). The fate in livestock is partly indicated in the previous

    In plants

         Holmstead et al. (1973) studied the metabolism of 14C-leptophos,
    labelled in the trihalophenoxy and unsubstituted phenyl rings, in
    cotton plants under glasshouse conditions. Similar studies were
    carried out by Diaz (1973) on tomato plants and by Schwemmer (1973) on
    small head lettuce (bibb type).

         They found that leptophos did not readily penetrate into the leaf
    but was gradually lost from the surface mainly by volatilization. For
    example in the experiment on cotton 73-75% of the applied
    radioactivity, of which 91-96% was unchanged leptophos, was recovered
    1 week after application and 11%, of which about 30% was leptophos,
    after 9 weeks. Relatively small amounts of radioactivity were found
    inside the leaf. Some of this was extractable with benzene or
    methonol, but a significant amount of phenyl-14C was not extractable
    and was considered by the authors to be "bound." Its identity was not

         It was shown that the primary metabolite detected is the phenol
    hydrolysis product (metabolite V, see scheme of metabolism, Figure 1).
    Traces of leptophos oxon (II) (corresponding to less than 0.1% of the
    applied 14C) were detected occasionally. Of equally low significance
    from a residue standpoint is the photo product IV.

         The results of the metabolism study on cotton are summarised in
    Table 8.

         The metabolism studies on tomatoes and lettuce showed similar
    results, leptophos itself being the principal residue. The results of
    the study on lettuce are summarized in Table 9. Some of the lettuce
    metabolites were also found as conjugates, which could be released by
    refluxing with 1 N KOH. This treatment yielded 4.9-9.4% of the
    recovered radioactivity as metabolite V, 0.3-0.8% as VIII and 0.6-0.8%
    as X.

    TABLE 8.  Metabolism of leptophos by cotton plants


                                                                % of recovered radioactivity
    Location of 14C label         Compound                      after indicated period (weeks)
                                                                1            3            5            9

    trihalophenoxy ring           Leptophos                     91.4         61.4         57.9         42.9

                                  Leptophos-oxon (II)           none         trace*       trace*       none

                                  Metabolite V (including
                                  its salt)                      8.6         33.1         28.1         29.0

                                  Unknown (bound to pulp)       none          5.5         14           28.1

    phenyl ring                   Leptophos                     96.4         78.3         68.8

                                  Leptophos-oxon (II)           none         none         none

                                  Metabolite IV                  2.3          2.1          7.0

                                  Metabolite VIII                1.3          0.6          2.1

                                  Metabolite X                  trace*       16.2         10.3

                                  Unknown (bound to pulp)       trace*        2.8         11.8

    *  Less than 0.1% of recovered radioactivity

    TABLE 9.  Radioactive residues resulting from application of 14C leptophos to lettuce

                                                                % of recovered radioactivity
    Location of 14C label         Compound                      after indicated period (days)
                                                                1            15           24

    trihalophenoxy ring           Leptophos                     98.5         91.7         81.5

                                  Leptophos-oxon (II)            1.1          0.2          0.3

                                  Metabolite V                   0.4          3.2          8.8

                                  Metabolite V conjugates         -           4.9          9.4

    phenyl ring                   Leptophos                     99.8         95.3         90.0

                                  Leptophos-oxon (II)            0.2          0.2          0.3

                                  Metabolite VIII                 -           1.8          3.1

                                  Metabolite VIII conjugates      -           0.8          0.3

                                  Metabolite X                    -           1.1          5.6

                                  Metabolite X conjugates         -           0.8          0.6


    Conjugated and bound residues in plants

         Schwemmer (1973) compared the efficiency of hydrolysis of
    conjugated metabolites by acids, bases and enzymes. He found basic
    hydrolysis (3 hours reflux with 1 N KOH) to be the most effective. On
    the 14th day after treatment of tomatoes and lettuce, conjugated
    residues were respectively 0.7% and 6.5% of the total residue. Much
    less effective hydrolysis was obtained with 1 N HCL (3 hours reflux),
    beta-glucosidase (4 hours) and beta-glucuronidase (4 hours).

    In water

         When exposed to sunlight leptophos residues in water decline
    fairly rapidly (70-76% loss after 120 hours of exposure) either by
    volatilization or breakdown to undetectable moieties. The influence of
    pH on the degradation of aqueous solutions of leptophos was studied
    (Velsicol, 1971e). There was little degradation below pH 8.3 in the
    dark. (At pH 3.1 in the dark at 50C very little dissipation of
    leptophos residues occurred over a period of more than 420 hours.)
    Leptophos in water at pH 10.8 and 50C is rapidly cleaved yielding
    O-methyl phosphonothioic acid (compound IV, in Figure 1) and
    4-bromo-2,5-dichlorophenol (Compound V).

    In soil

         Studies on the fate of leptophos residues in soil were carried
    out at 4 locations in the USA, where leptophos was applied to the soil
    surface at various dosage rates (1-6 kg a.i./ha) (Velsicol, 1971d). In
    about 16-30 days 50% of the applied dosage was dissipated. The
    remaining residue consisted mainly of the parent compound (80-97%)
    together with the oxon, 4-bromo-2,5-dichlorophenol and
    desbromo-leptophos. Details are given in Table 10.

    TABLE 10.  Fate of leptophos residues in soil


                             Time (days) for                     Residue, mg/kg in top 5 cm of soil,
                             decline of applied                  28-30 days after application of
                             leptophos by                        leptophos (3kg a.i./ha)

    Location of study        50%           90%          Leptophos        Oxon            Phenol         Desbromo-leptophos

    Glendora, Miss.          approx 30     < 120        1.61             0.04            0.20           0.03

    Arlington, Wis.          approx 16     <  90        0.76             0.04            0.08           0.02*

    Clayton, N.C.            approx <30    <  30*       1.02             0.04            0.62           0.04

    Cornelius, Ore.          approx 28     90-120       1.05               -             0.52           0.02

    * Area hit by hurricane during test; 53 cm rainfall in 24 hours.

         The above mentioned study and others in which 14C leptophos was
    applied to soil columns (WARF Institute Inc., 1971a), show that
    leptophos is adsorbed readily by the upper layers and hardly moves
    downwards. Table 11 shows results from the WARF experiments.

        TABLE 11.  Movement of 14C-leptophos applied to soil columns*


                              Radioactivity calculated as leptophos, mg/kg
    Soil level          Sandy loam     Silty loam     Muck soil      Lakeland Fine

    top - 7.5 cm         2.0            2.0            3.2            6.0

    7.5 - 15 cm          0.2            0.2            0.02           0.03

    below 15 cm         <0.04          <0.04          <0.04          <0.04

    * Height of column 45 cm; 14C labelled leptophos applied at a rate equivalent
      to 1.5 kg a.i./ha; simulated rainfall equivalent to 25 cm during the 30-day
      test period.
         Only trace amounts (<0.1%) of 14C leached through the soil
    columns. The residues remaining in the soil were identified as
    leptophos. Extraction generally recovered more than 70% of the applied
    radioactivity in silty loam, muck soils and lakeland Fine, but only
    55-58% in sandy loam.

         In a run-off test carried out on a grassy hill (mowed prior to
    the application) which sloped 10-15% it was shown that no residues of
    leptophos or its main metabolites were found in the water collected 45
    and 90 m down the slope; at 9 m down the slope residues of the order
    of 0.0001 mg/kg were detected at the 4th and 35th day after
    application (WARF Institute Inc., 1971b).

         The role of micro-organisms in the degradation of leptophos
    residues in soil was studied in sterile and nonsterile soils (WARF
    Inst. Inc., 1971a). It was shown that soil bacteria slowly degrade the
    residues of leptophos and its metabolites. The rate of residue
    dissipation in the laboratory experiments was somewhat slower than the
    rate observed in field studies, showing that such factors as
    volatilization play a role in the residue loss under field conditions.
    Degradation is most rapid after 14 days and is more pronounced at
    higher soil moisture levels and higher temperatures.

    In storage and processing

         Commercial processing of cottonseed reduces leptophos residues.
    In pilot studies, hydrogenation and deodorization of cottonseed oil
    resulted in a decrease of 92-98% of the initial residue, leading to
    residues of 0.04-0.09 ppm in the refined oil.

         Removing the wrapper leaves of head lettuce results in a
    substantial loss of residues; in normal commercial practice in the USA
    and other countries the outer leaves are removed prior to shipment or


         No data on residues in food in commerce or at consumption were
    available to the Meeting.


         Bowman and Beroza (1969) developed a GLC method which determines
    concurrently leptophos and its main metabolites in milk and maize,
    using a flame-photometric detector for the parent compound and the
    Oxon and a 63Ni electron-capture detector for the phenol. The
    compounds are separated by chromatography of the extract on two
    columns; buffer-deactivated silica gel and alumina. Recoveries of the
    parent compound and its oxygen analogue added at levels between 0.05
    and 5 mg/kg were 91-99% and 72-92% respectively; the recoveries of the
    phenol were 55-69% from maize and 93-95% from milk. The limit of
    detection for the three compounds is 0.01 mg/kg.

         GLC methods for concurrent determination of the parent compound
    and the main metabolites including the desbromo-compound in non-fatty
    crop samples have been developed by Velsicol. The phenol is
    partitioned from the residue extracts with sodium carbonate, dried and
    silylated or methylated. The product is then determined by GLC.
    Leptophos, its oxon and desbromo-leptophos are determined concurrently
    by flame-photometric detection on another GLC column following an
    appropriate clean-up procedure. Limits of detection on non-oily crops
    are 0.02 mg/kg for the oxon and 0.01 mg/kg for the parent compound,
    the desbromo-analogue and the phenol. The method can be adapted for
    regulatory purposes. When using the above methods attention has to be
    given to possible interference in the determination of the oxon. In a
    survey of over 200 untreated check samples about two thirds of the
    samples apparently contained the oxon. The frequencies of apparent
    oxon residues were highest in food products with a high lipid content.
    It became evident that the interfering compound was bis-(2-ethylhexyl
    phthalate) a plasticizer component of general plastic laboratory
    equipment. Interference by this compound can be largely overcome by
    rinsing thoroughly glassware etc. with chromic acid or special


         The following tolerances were reported.

    TABLE 12.  National tolerances reported to the meeting


      crop                                                         mg/kg

         pome fruit (apples and pears)                             2

         cabbage                                                   2
         lettuce                                                   2

         (outer leaves stripped, cabbage and lettuce washed)

         Azuki bean                                                0.4
         cabbage, Chinese cabbage                                  0.4
         potatoes                                                  0.4
         rice                                                      0.4

         lettuce                                                   10
         tomatoes                                                  2

    * Leptophos, including metabolites (oxon, phenol and
      desbromo-leptophos), calculated as leptophos.


         Leptophos is a virtually non-systemic organophosphorus
    insecticide with stomach-poison as well as contact action. It is used
    on a considerable scale in various countries in Asia, North, Central
    and South America, Australia and Europe. The main uses are soil
    application against soil-borne insects and foliar application, either
    on young plants (seedlings or transplanted plants) or at a later stage
    until 3-7 days before harvest. The insecticide is used against a wide
    range of insects, especially lepidopterous larvae. Until now no
    post-harvest treatment on vegetable commodities has been recommended;
    the pesticide is not recommended for use on or near livestock against
    ectoparasites etc.

         Technical leptophos contains not less than 85% of the pure
    compound. The impurities in the technical product are known.

         Leptophos is marketed in the form of wettable powder, dust,
    emulsifiable liquid and ULV formulations. Concentrations and rates of
    application vary, depending on pest, crop and method of application.
    Normal application rates are 0.9-1.35 kg a.i./ha. The recommended
    pre-harvest intervals in various countries vary considerably for one
    and the same crop.

         The residue data available were obtained mainly from the United
    States. They are from several regions with different environmental and
    pest conditions. The data presented for leptophos and its main
    metabolites are, with few exceptions, representative of those likely
    to result from good agricultural practice.

         Extensive information is available on the fate of residues in
    plants and their levels in livestock animals. In plants they are more
    stable than those arising from many other organophosphorus compounds.
    They are eliminated fairly quickly from livestock.

         The residues which may occur at harvest in food of plant origin,
    following recommended directions for use and Pre-harvest intervals,
    usually consist largely of the parent compound and to a smaller extent
    of the oxygen-analogue, the phenol (4-bromo-2,5-dichlorophenol) and
    desbromo-leptophos [O-(2,5-dichlorophenyl) O-methyl
    phenylphospho-nothioate]. On root crops such as potatoes, which show
    low levels of total residue, the main compound in the residue is the

         Only limited information is available on the decrease of residues
    of leptophos and its main metabolites during storage and processing,
    including household cooking. Hydrogenation and deodorization of crude
    vegetable oils resulted in considerable loss of residue.

         No information was presented on the carry-over of residues in
    tobacco smoke following application on tobacco.

         Data on residues and their rates of disappearance were available
    from supervised trials on broccoli, Brussels sprouts, cabbage,
    lettuce, potatoes, tomatoes, cotton and maize (field corn and sweet
    corn). Residue data from other fields of application for which
    leptophos is registered and/or recommended were not presented; these
    include rice, other small grains, fruit (apples and pears), sugar-cane
    and sugar beet.

         No information was available on leptophos residues in food moving
    in commerce.

         Gas-chromatographic procedures are available for specific and
    concurrent determination of leptophos and the main metabolites
    leptophos oxon, desbromo-leptophos and the phenol. These methods are
    suitable or may be adapted for regulatory purposes.


         The following guideline levels are recommended as limits which
    need not be exceeded when leptophos is used according to good
    agricultural practice. They refer to the sum of leptophos, its oxygen
    analogue and desbromo-leptophos, expressed as leptophos.



                                                Pre-harvest intervals on
                                      Limit     which recommendations
    Commodity                         mg/kg     are based

    Broccoli, Brussels sprouts
    cabbage                           2         28-50

    Lettuce                           2         28 (outdoor)

    Tomatoes                          2         7

    Crude cotton-seed oil             1         28

    Cotton-seed                       0.2       28

    Cotton-seed meal                  0.2       28

    Potatoes                          0.1       21

    Maize: field corn (kernels)       0.05      7

    Sweet corn (kernels and cobs,
    husks and silk removed)           0.05      3-7


    REQUIRED (by July 1975)

    1.   Residue data on other major crops for which recommendations are
         made including rice, other small grains, fruit, sugar-cane, sugar

    2.   Additional residue data from countries other than the USA.

    3.   Residues in those parts of agricultural crops which are used
         either as such or as agricultural waste for feeding purposes
         following normal agricultural practices.


    Bio/Toxicological Research Laboratories, Inc. (1971a) Chicken feeding
    study with Phosvel.TM

    Bio/Toxicological Research Laboratories, Inc. (1971b) Beef cattle
    feeding study. Velsicol Report 107. (Unpublished)

    Bio/Toxicological Research Laboratories, Inc. (1971c) Eff fertility,
    progeny, viability and residues in eggs and tissues following intake
    of Phosvel by chickens. Velsicol Report 106.

    Bowman, M.C. (1970) USDA-ARS Report PCT-70-3. Analysis of oat silage,
    milk, urine, faeces and blood of cows.

    Bowman, M.C. and Beroza, M. (1969) Determination of insecticide,
    [O-(4-bromo-2,5-dichlorophenyl)0-methyl phenylphosphonothioate]
    (Velsicol VCS-506) its oxygen analogue, and its phenolic hydrolysis
    product in corn and milk by gas chromatography. J. agr. Food Chem.,

    Diaz, L.I., et al. (1973) Radiotracer study of leptophos on tomatoes.
    Velsicol. Chem. Corp. Laboratory Report No. 166.

    FAO/WHO. (1975) Pesticide Residues in Food. Report of the 1974 Joint
    Meeting of the FAO Working Party of Experts on Pesticide Residues and
    the WHO Expert Committee on Pesticide Residues. FAO Agricultural
    Studies No.       ; WHO Technical Report Series No.

    Holmstead, R.L., Fukuto T.R. and March, R.D. (1973) The metabolism of
    0-(4-bromo-2,5-dichlorophenyl) 0-methyl phenylphosphonothioate
    (leptophos) in white mice and on cotton plants. Arch. Environ. Contam.
    Toxicol., 1(2):1973.

    Johnson, J.C., Jr., Bowman, M.C., Leuck, D.B. and Knox, F.E. (1971)
    Persistence of Phosvel in corn silage and effects of feeding dairy
    cows the treated silage. J. Dairy Sci., 54(12):1840-1847.

    Schwemmer, B.A. (1971a) Heat conversion of VCS-506 to
    0-(4-bromo-2,5-dichlorophenyl)-S-methylphenylphosphonate. Velsicol
    Chem. Corp. Laboratory Report 83. (Unpublished)

    Schwemmer, B.A. (1971b) UV photolysis of leptophos in solution.
    Velsicol Chem. Corp. Laboratory Report 86. (Unpublished)

    Schwemmer, B.A., et al. (1973) Radiotracer studies of leptophos on
    bibb lettuce. Velsicol Chem. Corp. Laboratory Report 167.

    TRW/Hazleton Lab. (1971) Continuous feeding and residue study on cows
    with technical phosvel (VCS 506). Velsicol Report 108.

    Velsicol Chemical Corp. (1967/1971) Residue studies on corn (Field
    corn, sweet corn, including sweet corn for canning).

    Velsicol Chemical Corp. (1967/1971) Residue studies on potatoes.

    Velsicol Chemical Corp. (1968/1971) Residue studies on cole crops
    (broccoli, Brussels sprouts, cabbage).

    Velsicol Chemical Corp. (1968/1971) Residue studies on cotton and
    cotton products.

    Velsicol Chemical Corp. (1968/1971) Residue studies on tomatoes.

    Velsicol Chemical Corp. (1970/1971) Residue studies on lettuce.

    Velsicol Chemical Corp. (1971a) Analysis of technical leptophos for
    halogenated dibenzo-p-dioxins. Velsicol Method T 0117.

    Velsicol Chemical Corp. (1971b) Analytical method T 0110 B:
    Determination of leptophos, its oxon and its phenolic hydrolysis
    product in non-fatty crop samples (GLC method).

    Velsicol Chemical Corp. (1971c) Analytical method T 0111 B:
    Determination of residues of photolytic conversion products of

    Velsicol Chemical Corp. (1971d) Analytical method T 0122 B:
    Determination of leptophos and its conversion products in soil and

    Velsicol Chemical Corp. (1971e) Report 112: Fate of leptophos in
    aqueous environments.

    Velsicol Chemical Corp. (1973) Analytical method T 0122 A: The
    determination of leptophos, its oxon, the desbromo photoproduct and
    its phenolic hydrolysis product in crop and animal samples (GLC

    Velsicol Chemical Corp. (1974a) Analytical method T 0162:
    Determination of 4-bromo-2,5-dichlorophenol residue in crop, animal
    and milk samples (methylation method).

    Velsicol Chemical Corp. (1974b) Analytical method T 0163: Leptophos,
    its oxon, desbromo-leptophos and bromophenol residues in eggs.

    WARF Inst. Inc. (1971a) Report: Effects of microorganisms on residues
    of leptophos in soil.

    WARF Inst. Inc. (1971b) Report: A study of Phosvel; effects on run-off

    See Also:
       Toxicological Abbreviations
       Leptophos (WHO Pesticide Residues Series 5)
       Leptophos (Pesticide residues in food: 1978 evaluations)