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    FAO/PL:1968/M/9/1

    WHO/FOOD ADD./69.35

    1968 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD

    THE MONOGRAPHS

    Issued jointly by FAO and WHO

    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Working Party of Experts and the WHO Expert
    Committee on Pesticide Residues, which met in Geneva, 9-16 December,
    1968.

    FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS

    WORLD HEALTH ORGANIZATION

    Geneva, 1969

    OXYDEMETON-METHYL

    IDENTITY

    Chemical name

    O,O-dimethyl S-2-(ethylsulfinyl)ethyl phosphorothioate
    S-[2-(ethylsulphinyl)ethyl] OO-dimethyl phosphorothioate
    (IUPAC)

    Synonyms

    demeton-S-methyl sulfoxide (English version)

    demeton-O-methyl sulfoxide (German version)

    Metasystox R(R)

    Formula

    CHEMICAL STRUCTURE 

    Other information on identity and properties

    Technical oxydemeton-ethyl contains 85 per cent to 90 per cent of
    the above phosphorothioate. Unless otherwise stated, all biological
    and residue investigations have been conducted on this technical
    material. The remaining 10-15 per cent were not identified.

    The various compounds in the so-called "demeton" group are shown in
    Figure 1. The meeting noted that a range of these compounds are, or
    have been, on the market. These have been available in various
    formulations, and under various names, as tabulated in Figure 1. In
    water, compound IV isomerizes to compound III. Compounds III and IV
    would be expected to yield compound V as a common intermediate or
    terminal residue. Thiometon (compound VII) would also be expected to
    yield compound III and then V. Studies of the fate of the compound
    appear to be limited to one involving the use of
    radioisotopically-labelled material. The fate of V is also implied by
    other studies with the O-ethyl analogue.

    FIGURE 

    RESIDUES IN FOOD AND THEIR EVALUATION

    Use pattern

    Pre-harvest treatments

    Oxydemeton-ethyl has been registered on a "no-residue basis" in the
    United States of America for a limited number of crops; however, these
    registrations are under review. It has been proposed for use in the
    United States as an emulsifiable spray on a variety of crops as
    indicated in Table I to control aphids, mites, thrips, and
    leafhoppers.

        TABLE I
                                                                            
                                 Rate of                        Pre-harvest
         Crop                  application         Number of     interval
                                 (kg/ha)          treatments      (days)
                                                                            

    Apples, pears, plums     0.03 kg/100 l            1-3          7-30
                             (applied as full
                             coverage spray)

    Blackberries,            0.03-0.04 kg/100 l        1            14
    raspberries              (not to exceed
                             2.29 kg/ha)

    Strawberries             0.48-0.95                 2             3

    Citrus                   0.03-0.04 kg/100 l        2             3
                             (applied as full
                             coverage spray)

    Muskmelon,               0.48-0.63                1-3           14
    cantaloupe, pumpkin,
    winter squash,
    head lettuce,
    cotton

    Watermelon               0.48-0.63                 2             7

    Summer squash            0.48-0.63                 1             1

    Cucumbers, peppers       0.48-0.63                 2             0

    Eggplant, cabbage        0.48-0.63                1-3            7
    potatoes, turnips,
    corn

    TABLE I (continued)
                                                                            
                                 Rate of                        Pre-harvest
         Crop                  application         Number of     interval
                                 (kg/ha)          treatments      (days)
                                                                            

    Leaf lettuce, turnip     0.48-0.63                 2           28-30
    tops, sugar beets

    Walnuts                  0.48                      1
                                                                            
    
    Oxydemeton-methyl is used in at least 14 European countries but
    specific conditions of use were not available to the meeting.
    Generally, a pre-harvest interval of 20-30 days is practised.
    Switzerland and Finland specify a 6-week pre-harvest interval;
    Yugoslavia, 8 weeks; and Portugal and Austria, 5 weeks. The United
    Kingdom recommends a 2-week pre-harvest interval for cereal grains.

    Post-harvest treatments

    No post-harvest treatment is known.

    Other uses

    Oxydemeton-methyl is used for the control of a number of insects on
    ornamentals and for a variety of field crops grown only for seed
    purposes.

    Residues resulting from supervised trials

    Data have been accumulated from field trials to show residues likely
    to occur from the recommended use of oxydemeton-methyl as summarized
    in Table I. These unpublished data, submitted by Chemagro Corporation
    to the United States Food and Drug Administration in the form of
    pesticide petitions, are summarized in Table II. The major portion of
    the data was obtained by a total organic phosphorous method of
    analysis with sensitivities of 0.1-0.3 ppm (see Methods of
    analysis). A gas chromatographic method was used for the data on
    lettuce, sugar beets and walnuts.

    Residues on apples appear to be the most persistent with an estimated
    half-life of greater than 30 days. Generally, where high initial
    residues were found either because of the type of crop or from an
    exaggerated dosage, the dissipation rate was rapid for the first
    several days and then became more gradual as the residue dropped below
    1.0 ppm. In the majority of crops the estimated half-life was 7 days
    or less.

    The use of oxydemeton-methyl on plants which would be used for animal
    feed prompted a milk and meat residue study. 32P-labelled
    oxydemeton-methyl was orally administered to two cows for 14 days at a
    dosage level equivalent to 5 ppm in fresh forage. By a method
    sensitive to about 0.005 ppm for both milk and tissue samples, no
    residues were detected in the milk samples collected daily nor in the
    liver, kidney, muscle, fat and various other organ samples examined at
    0 and 7 days after termination of the feeding.

    Feeding of the closely related Di-Syston to dairy cows at levels of 5
    and 12 ppm showed no residues in milk or meat by a method sensitive to
    0.005 ppm in milk and 0.02 ppm in meat.

    Soil dissipation studies were conducted in various types of soil in
    different geographical areas. When rota-tilled into the soil to give
    an initial concentration of 2 ppm in the soil, no residues were found
    during a period of 30-355 days after the application. Spraying of
    0.31-0.94 kg/ha in 1-3 applications resulted in residue values of 0.1
    ppm 27 days after the last application. (Not clear in petition whether
    soil or foliage application.) Foliar application to plants apparently
    does not result in accumulation of residues in the soil.

    TABLE II
                                                                       

                                         Pre-harvest         Residue
        Crop               Initial        interval         (at harvest)
                        residue (ppm)      (days)             (ppm)
                                                                       

    Raspberries           0.8-3.9            14           0.1-0.2

    Blackberries             -               14           0.1-0.6

    Strawberries          0.4-3.2             3           0.2-1.7

    Apples                0.8-1.5             7           0.5-1.4

    Pears                    -               30           0.1 or less

    Plums                    -               21           0.8

    Oranges                  -                7           0.2-1.1 (peel)
                                                         <0.1-0.4 (whole fruit)

    Lemons                   -                7           0.1-3.4 (peel)
                                                         <0.1-1.0 (whole fruit)
                                                         <0.1-0.2 (pulp)

    Grapefruit               -                7           0.1-0.3 (peel)

    Cantaloups and
    pumpkins                 -               14          <0.1

    Winter squash            -               14          <0.1-0.4

    Summer squash            -                1          <0.1-0.8

    Watermelons              -                7          <0.1

    Cucumbers             0.2-0.7             0           0.2-0.7

    Peppers               0.1-0.6             0           0.1-0.6

    Eggplant              0.1-0.2             7          <0.1-1.0

    Corn (maize)             -                7           0.1-0.5 (kernels)
                                                         <0.1-0.3 (husks or cobs)

    Corn fodder              -                7           0.4-2.2

    Cabbage            1.2 at 3 days          7           0.2-0.9

    Head lettuce           10.7              14          <0.05-1.9

    Leaf lettuce      0.8-24.3 at 3 days     28          <0.05-1.9

    Turnip tops            17.1              28           0.2-1.1

    Sugar beet tops          -               30          <0.05-0.2

    Turnips                 0.3               7          <0.1-0.2

    Sugar beets              -               30          <0.05

    Potatoes                 -                7          <0.1

    Walnuts                  -               30           0.1 or less

    Cottonseed         0.1 (3 days)          14          <0.1
                                                                       


    Fate of residues

    In plants

    Mühlmann and Tietz (1956) reported on studies of the residues
    resulting from the treatment of Vicia faba, sugar beets, cucumbers,
    potatoes, and cabbages with Methylsosystox and its sulfoxide
    (oxydemeton) and sulfone. It was shown that the major residue
    component which formed very rapidly was the sulfoxide. This converted
    very slowly to the sulfone which did not concentrate very greatly. The
    authors concluded that the speed of oxidation and decomposition of the
    active substances did not appear to go at a fixed rate but depended in
    part on weather conditions, especially temperature, and light
    conditions.

    The fate of Methylisosystox compounds appears to follow the same route
    as the ethyl analogues; however, there are no quantitative data on
    comparative rates.

    In storage and processing

    Storage of treated samples of alfalfa, apples, cabbage, green oat
    forage and raspberries at 0° to -10°F for 0-33 days did not result in
    appreciable loss of oxydemeton-methyl residues. (Method sensitivity
    about 0.1-0.3 ppm.)

    Prune trees treated with 0.48 kg/ha in one application had a gross
    residue of 0.13 ppm on the fresh fruit 40 days after treatment. The
    residue 10 days following sun drying was 0.19 ppm. No appreciable
    accumulation of residue is expected in dried fruit (method sensitivity
    about 0.1 ppm).

    Valencia orange trees were treated with two applications at 0.06
    kg/100 1.The fruit was harvested three days after the second
    application and processed immediately. No residue was detectable in
    the fresh fruit pulp. A residue of 0.8 ppm found on the orange peel
    was reduced to 0.6 ppm after washing. None of the processed products
    (e.g. juice, oil, water-phase emulsion, cattle feed and molasses)
    contained any detectable residues (method sensitivity about 0.1 ppm).

    Radiometric studies in sugar beet products using 32P-labelled
    oxydemeton-ethyl and the corresponding sulfone showed that 85
    per cent of the radioactivity was present in the form of degradation
    products in the juice. Liming and oxalation of the juice completed the
    decomposition of the remaining sulfoxide and sulfone to products which
    were not chloroform extractable. Radioactivity in the pulp, 8 per
    cent from the sulfoxide treatment and 5 per cent from the sulfone
    treatment, was in the form of decomposition products which remained in
    the aqueous phase after chloroform extraction.

    Evidence of residues in food in commerce or at consumption

    No data available.

    Methods of residue analysis

    At the present time no adequate method of analysis which could be used
    to enforce tolerances on samples of unknown spray history is available
    for oxydemeton-methyl.

    The major portion of the residue data presented in this monograph was
    obtained by a method which measures total organic phosphorus. This
    method provides satisfactory data on the level of residues from
    supervised trials and measures the parent compound as well as the
    sulfone analogue. However, it is nonspecific and not satisfactory for
    enforcement of tolerances on foods in commerce. The method consists of
    solvent extraction, cleanup with an activated carbon column, digestion
    by mineral acids and spectrophotometric determination based on the

    phospho-molybdenum blue reaction. Modified cleanup procedures are
    available for oily samples, milk and meat. The method has a
    sensitivity of 0.1-0.3 ppm. Recoveries ranged from 50-142 per cent
    but were generally in the range of 70-100 per cent at fortification
    levels of 0.1-2.3 ppm. Blanks gave values of <0.1-0.4 ppm. Similar
    results were obtained in fortification studies with the sulfone
    analogue.

    A gas chromatographic procedure has been developed which consists of
    solvent extractions, oxidation by potassium permanganate to convert
    the sulfoxide to the sulfone, and gas-liquid chromatography
    determination of the total sulfone using a phosphorus-sensitive
    thermionic emission detector. Among the 30 crops tested recoveries
    ranged from 75-117 per cent for the parent compound and 74-109 per
    cent for the sulfone at fortification levels of 0.1 and 0.4 ppm.
    Blank values of <0.01-<0.05 ppm were obtained. Adequate data are not
    available to evaluate the performance of this method with walnuts,
    milk and meat samples.

    Since some of the commonly used organo-phosphorus chemicals yield
    interfering peaks in gas-liquid chromatography, this method when used
    as proposed with only one column is inadequate for specific
    identification of residues of oxydemeton. If the above procedure can
    be supplemented by an identification technique such as that offered by
    a second column or an isolation step such as thin-layer
    chromatography, a suitable enforcement method might be realized which
    would lend assurance of positive residue identification and eliminate
    possible interference from other organo-phosphorus pesticides and
    degradation products.

    National tolerances

                                                                        

    Country             Crop                            Tolerance (ppm)
                                                                        

    Germany             Leafy and other sprouting       0.4
                        vegetables, fruit vegetables,
                        legumes, fruit, grapes and
                        hops
    Netherlands         No restrictions                 0.4
    Switzerland         Kernel fruit and grapes         0.5

    Tolerances proposed by manufacturer

    Australia                                           0.5
    Austria                                             0.4
    United States       Corn (fodder and forage)        2.5
    of America          strawberries and leaf lettuce   1.75
                        apples, blackberries,
                        raspberries,
                        plums, oranges, lemons,

    National tolerances (cont'd)

                                                                        

    Country             Crop                            Tolerance (ppm)
                                                                        

    United States       grapefruit, cabbage,
    of America          turnip tops                     1.5
                        summer squash, cucumbers, head
                        lettuce, eggplant               1.0
                        peppers                         0.75
                        corn (kernel and cob)           0.5
                        pears, melons, watermelons,
                        pumpkins, winter squash,
                        walnuts, sugar beet
                        tops, turnips                   0.3
                        potatoes, sugar beets,
                        cottonseed                      0.1

    RECOMMENDATIONS FOR TOLERANCES AND PRACTICAL RESIDUE LIMITS

    Appraisal

    This compound is a general systemic insecticide and acaricide and is
    used on plants in many countries. The meeting noted that a range of
    closely related compounds are, or have been, on the market.

    There appears to be no information on the fate of residue during
    storage and processing. This is important because existing data
    suggest that residues tend to be persistent.

    In the gas chromatographic method of analysis the sulfoxide is
    oxidized to the sulfone, so that the application of this method
    provides no information on the relative proportions of the sulfone and
    sulfoxide in the original residue. At the present time no suitable
    methods are available for regulatory or referee purposes.

    Recommendations

    Withdrawal (see above) of the earlier-established acceptable daily
    intake and lack of quantitative and qualitative information on the
    terminal residues preclude any recommendations for tolerances.

    Further work or information

    Required (before acceptable daily intake or tolerances can be
              established)

    1.   Further information on the nature and persistence of residues,
         especially as a result of comparative studies with the  O-ethyl
         analogues.

    2.   Specification of the compound (or compounds) in actual
         agricultural use.

    3.   Studies to compare the metabolite fate in plants, animals and
         man.

    4.   Adequate long-term studies in two species.

    Desirable

    1.   Further data on residue levels in raw agricultural products
         moving in commerce.

    2.   Investigation of cholinesterase inhibition in man.

    REFERENCE

    Mühlmann, R. and Tietz, H. (1956) The chemical behaviour of
    Methyli-sosystox in the living plant and the problem of residues.
    Höfchen Briefe 2/1956. Farbenfabriken Bayer, Leverkusen

    


    See Also:
       Toxicological Abbreviations
       Oxydemeton-methyl (JMPR Evaluations 2002 Part II Toxicological)
       Oxydemeton-methyl (FAO/PL:1967/M/11/1)