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    DICHLOFLUANID        JMPR 1977

    Explanation

    The Joint Meeting evaluated dichlofluanid in 1969 and 1974 (FAO/WHO,
    1970, 1975). A temporary ADI was established in 1974, when further
    information was required on the absorption, distribution and excretion
    of dichlofluanid and on the pharmacokinetics of the
    dichlorofluoromethylthio moiety. Further information was recorded as
    desirable on the fate of the fluorine-containing moiety of the
    molecule in and on plants, on residues resulting from supervised
    trials on various specified crops, on residues in raw agricultural
    products moving in commerce and on the suitability of Becker's
    analytical method for regulatory purposes.

    Some of the required information has been provided, and is reviewed
    below.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    Absorption, distribution, biotransformation and excretion

    Groups of rats received a single oral dose of 14C-dichlofluanid (0.1,
    5 or 20 mg/kg b.w.) in order to establish the excretion rate and
    distribution over various organs. The 14C-label was incorporated in
    the dichlofluoromethylthio moiety and thus, activities reflect the sum
    of the unchanged compound and some of its metabolites. 40-60% of the
    dose was eliminated in urine and 20-30% in faeces, while 22% was
    exhaled within the first 48 hr. In 24 hr the elimination through bile
    following an intraduodenal injection (0.5 mg/kg b.w.) was 7% of the
    initial activity. From these data it was calculated that 70-80% of
    orally administered dichlofluanid was absorbed.

    The distribution over various organs was measured during the 10 days
    following oral administration of 5 mg dichlofluanid/kg b.w.

    In a period from 2 hr to 2 days after injection, about a ten-fold
    decrease in the amount of labelled substances in the whole body was
    observed. After 10 days a residue of 1% was measured. Similar
    decreases were found in pancreas, spleen, lungs, brain, testes,
    muscle, skin, perirenal fat, erythrocytes and plasma, while liver,
    kidneys and adrenals showed somewhat higher residues. A dissimilar
    pattern was found in the thyroid. The maximal concentration was
    reached after 1 day (compare e.g., plasma, 1.5 hr) and at each time of
    measurement a relative concentration about 50 times that in the whole
    body was observed (Weber et al., 1977).

    COMMENTS

    Adequate information on absorption, distribution, excretion and
    pharmacokinetics of the dichlorofluoromethylthic moiety has been
    provided. Within 2 days about a ten-fold decrease in the amount of
    labelled dichlofluanid was observed in most of the organs. After 10

    days a residue of 1% of the dose was present. The consequence of
    relatively high residues of this organic fluorine compound in the
    thyroid was of some concern and should be further investigated.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

        Rat: 1500 mg/kg in the diet, equivalent to 75 mg/kg bw

        Dog: 1000 mg/kg in the diet, equivalent to 25 mg/kg bw

    ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR HUMANS

    0-0.3 mg/kg bw

    RESIDUES IN FOOD AND THEIR EVALUATION

    RESIDUES RESULTING FROM SUPERVISED TRIALS

    Some of the trials data requested in 1974, together with data on some
    other crops, were supplied (Table 1). Residues were below the
    following levels (mg/kg): 15 in blackberries, 7 in gooseberries and
    onion leaves, 2 in paprika, 1 in dried hops, 0.5 in wheat straw and
    0.1 in wheat grain and onions (bulbs). In addition, residues resulting
    from supervised trials on eggplants and gherkins were at or below 1
    mg/kg and on potatoes below 0.1 mg/kg. New residue data for currants,
    beans with pod, strawberries (under glass), cucumber, lettuce (under
    glass) and tomatoes were below the limits recommended by the 1974
    Joint Meeting.

    No information was provided on residue levels in loganberries,
    mulberries, raspberries, leaf brassicas, melons, kohlrabi or barley.

    FATE OF RESIDUES

    In soil

    Different types of soil were field-treated with 15 kg
    dichlofluanid/ha; 2-3 months after application, residues of
    dichlofluanid + dimethylphenylsulphamide (DMSA) in the upper layers
    (0-10 cm depth) were below 0.1 mg/kg. Columns containing 30 cm layers
    of sand or sandy loam were treated with dichlofluanid at a rate
    corresponding to 2.5 kg/ha and leached to simulate a rainfall of 200
    mm. Less than 1% of the applied dose (as dichlofluanid + DMSA) was
    found in the leachate (Bayer, 1975/77).

    In Japan, volcanic ash, diluvial and alluvial soils treated 1-3 times
    each with 2 mg dichlofluanid/kg soil, contained < 0.03-0.4 mg/kg 7-11
    days after the last application; 27 days after the last of 4-5
    applications, residues were < 0.03-1.4 mg/kg (Takase and Terada,
    1976).

    In processing

    Field-treated strawberries with original levels of 8.6 and 5.1 mg
    dichlofluanid + DMSA/kg contained 1.9 and 1.5 mg/kg respectively after
    washing. After canning, residues declined to 1.3 and 1.0 mg/kg. 08
    mg/kg was found in jam made from the strawberries (Wrieden, 1976).

    RESIDUES IN FOOD MOVING IN COMMERCE

    In 1976 a total of 449 samples of 19 fruits and vegetables (especially
    strawberries, currants and blackberries) moving in commerce were
    analysed for dichlofluanid (including DMSA calculated as the parent
    compound) in the Netherlands (Food Inspection Services, 1976). Only 15
    of the samples, all of strawberries, currants or raspberries, had
    residues above 2mg/kg of which three samples of strawberries contained
    residues higher than 5 mg/kg (5.4, 14.5 and 20 mg/kg). In 189 samples,
    the residues were at or below 0.1 mg/kg. Residue levels (except in two
    samples of strawberries) were well below the limits recommended by the
    Joint Meeting.

    METHODS OF RESIDUE ANALYSIS

    A gas-chromatographic method has been developed which determines
    dichlofluanid + DMSA (Vogeler, 1975/77). After extraction with
    water/acetone and dichloromethane, dichlofluanid is saponified and the
    total DMSA determined by a flame photometric detector in the sulphur
    mode. The lower limit of determination is at or about 0.1 mg/kg
    expressed as dichlofluanid. The method is less suitable for regulatory
    purposes than the multi-residue method of Becker.

    The Becker method was studied collaboratively by 4 laboratories
    (Thier, 1977). 16 species of fruit and vegetables were spiked within a
    range of 0.01-15 mg dichlofluanid/kg and analysed. Recoveries were
    between 71 and 106% with an average of about 90%. The method of Becker
    is suitable for regulatory purposes.

    APPRAISAL

    Residue data requested by the 1974 Joint Meeting confirmed that the
    temporary maximum residue limits recommended then for beans,
    cucumbers, currants, lettuce, strawberries and tomatoes were
    appropriate. They also provided a basis for the new temporary limits
    recommended below.

    Dichlofluanid was shown not to be readily leached from soil. Residues
    in soil after field application were below 0.5 mg/kg after one month
    and below 0.1 mg/kg after 2-3 months.

    Residues in strawberries were reduced to about 20-30% of the original
    level by washing, 15-20% by canning and 10-15% by jam making.


        TABLE Residues of dichlofluanid + dimethylphenylsulphamide (DMSA) expressed as dichlofluanid on different crops from
    supervised trials
                                                                                                                                 

    Crop            Country1/         Dose kg      No. of           Days after      Residue (mg/kg)     References
                                      a.i./ha   applications        last appl.
                                                                                                                                 

    blackberries        D             2.0           5                  0           11.6 - 47.0        Bayer, 1975/77
                                                                       4           8.4 - 22.5
                                                                       7            7.0 - 7.2
                                                                      14            3.1 - 5.2
                                                                     21/22          1.0 - 3.2

    beans, green,       D             1.3           5                  0            1.6 -2.6          Bayer, 1975/77
    with pods                                                         4-7           0.4 -0.8
                                                                     14-28          0.1 -0.3

    cucumber            D              1            8                0-10           <0.1 -0.1         Bayer, 1975/77
                        J            1.5-2         10                 1-7            <0.1 2/          Nitokuno, 1971/74

    cucumber,           D            0.6-2         10                 0-1           0.5 - 3.2
    under glass                                                      3-10           0.3 - 1.8

    currants            D             2.0           3                  0           11.1 - 18.7        Bayer, 1975/77
    (black)                                                            4            7.0 - 8.9
                                                                       7            3.6 - 3.9
                                                                      14            2.7 - 2.8
                                                                      21            0.6 - 0.9

    eggplant            J              4           1-2                0-1          <0.1 - 1.0 2/      Nitokuno, 1971/74
                                                                      3-7           0.1 - 0.5  2/

    gooseberries        D             2.0           4                  0            5.2 - 7.9         Bayers 1975/77
                                                                       4            4.1 - 6.7
                                                                       7            2.7 - 6.1
                                                                     14-21          0.7 - 2.2

    TABLE (Continued)

                                                                                                                                 

    Crop            Country1/         Dose kg      No. of           Days after      Residue (mg/kg)     References
                                      a.i./ha   applications        last appl.
                                                                                                                                 
    gherkins,           D             1.2          10                 0-1           0.5 - 0.8         Bayer, 1975/77
    under glass                                                      3-10           0.3 - 0.6


    hops                J            5.0-5.8        3                 21              0.42            Nitokuno, 1971/74
                                                                      26              0.041

    lettuce             J              2           4-9               2-10          <0.1-0.1 2/        Nitokuno, 1971/74

    lettuce,            D             0.6           6                  0               31
    under glass                                                      14-28           0.1-2.4          Bayer, 1975/77

    onions,             D             1.0           6                  0           12.3 - 19.0        Bayer, 1975/77
    leaves                                                             4            3.7 - 7.9
                                                                       7            3.0 - 6.9
                                                                      14            1.8 - 3.4
                                                                     21-28          0.3 - 2.1

    bulbs               D                                            0-28             <0.1

    bulbs               J           0.8-1.3       7-14               7-20             <0.1            Nitokuno, 1971/74

    peppers,            D              1            6                 0-1           1.3 - 3.5         Bayer, 1975/77
    sweet                                                            3-14           <0.1 - 0.8

    potatoes            D             0.6           6                  7              <0.1            Bayer, 1975/77

    strawberries,       J            2.5-3         2-4               1-10           0.3 - 4.6 2/      Nitokuno, 1971/74
    under glass

    tomatoes            D             1.2           6                 0-7           0.3 - 1.0         Bayers 1975/77
                        J            1.5-4        1-10                0-7           <0.1 - 0.3 2/     Nitokuno, 1971/74

    TABLE (Continued)

                                                                                                                                 

    Crop            Country1/         Dose kg      No. of           Days after      Residue (mg/kg)     References
                                      a.i./ha   applications        last appl.
                                                                                                                                 
    tomatoes,           D             1.2           6                 0-7           0.1 - 0.5         Bayer, 1975/77
    under glass

    wheat grain         D              1            1                 42           <0.1 - 0.1         Bayer, 1975/77

    wheat                                                              0           14.1 - 23.4
    ears/straw                                                        14            1.5 - 2.9
                                                                     28-35          0.1 - 0.3
                                                                                                                                 

    1/ D =  Federal Republic of Germany
       J = Japan

    2/ analysed for dichlofluanid only

    

    The gas-chromatographic multi-residue analytical method of Becker has
    been validated for regulatory purposes by collaborative study. A
    method for determining both dichlofluanid and dimethylphenylsulphamide
    (DMSA) by gas chromatography has been developed, but is less suitable
    for regulatory analysis.

    RECOMMENDATIONS

    The following temporary maximum residue limits are recommended in
    addition to those proposed in 1974. They refer to dichlofluanid only.

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

    Blackberries        15                  3-7
    Gooseberries        7                   0-7
    Sweet peppers       2                   1-3
    Eggplants,
    hops (dried)        1                   0-1
    Wheat straw         0.5                 28
    Onions, bulb        0.1                 0-28
    Potatoes            0.1                 0-21
    Raw grain
    (barley, oats,
    rye, wheat)         0.1                 42

    FURTHER WORK OR INFORMATION

    REQUIRED (by July 1979)

    1. Studies to elucidate the accumulation seen in the thyroid.

    2. Results from current studies on the pathways of degradation,
    especially the fate of the fluorine-containing moiety of the molecule
    in or on plants.

    DESIRABLE

    1. Further residue data on dichlofluanid residues (parent compound)
    resulting from supervised trials especially on melons and leaf
    brassicas.

    REFERENCES

    Bayer, A.G. 1975/77 Pflanzenschutzmittel-Rückstände, Dichlofluanid
    (Euparen); Leverkusen, Federal Republic of Germany (unpublished).

    Food Inspection Services; 1976 Information from the Netherlands on
    pesticides included in the priority lists. Dichlofluanid. Ref: CL
    1977/15; Oct. 20, 1977.

    Nitokuno Institute; 1971/74 Analytical Test Results on Residues,
    Dichlofluanid (Euparen), Nihon Tokushu Noyaku Seizo K.K., Japan

    Takase, I. and Terada, H. 1976 Residues of Euparen and Morestan in
    Upland Soils after Multiple Treatment. Nihon Tokushu Noyaku Seizo
    K.K., Agric. Chemicals Inst., Japan; Report No. 1043; 30 March 1976.

    Thier, H.-P. 1977 Arbeitsgruppe zur Rückstandsanalytik der Pestizide
    in Lebensmitteln. Unpublished

    Vogeler, K. 1975-7 in Bayer A.G., 1975-77, reference above

    Weber, H., Patschke, K., Wegner, L.A. Dichlofluanid - 14C
    (EuparenR-Wirkstoff); Biokinetische Untersuchungen an Ratten. Bayer
    AG Bericht Nr. 7081. Submitted to the WHO (1977) (unpublished report)

    Wrieden, J. 1976 Untersuchungen von Fungizidrückständen (EUPAREN) in
    Erdbeeren nach deren Verarbeitung zu Marmelade und Obstkonserven.
    Diplomarbeit, Inst. f. spezielle Lebensmitteltechnologie, Univ.
    Hohenheim; Fed. Rep. Germany.

    FAO/WHO, 1970 1969 evaluations of some pesticide residues in food.
    FAO/PL:1969/M/17/1; WHO/Food Add./70.38.

    FAO/WHO 1975 1974 evaluations of some pesticide residues in food. AGP:
    1974/M/11; WHO Pesticide Residues Series, No. 4.
    


    See Also:
       Toxicological Abbreviations
       Dichlofluanid (FAO/PL:1969/M/17/1)
       Dichlofluanid (WHO Pesticide Residues Series 4)
       Dichlofluanid (Pesticide residues in food: 1979 evaluations)
       Dichlofluanid (Pesticide residues in food: 1981 evaluations)
       Dichlofluanid (Pesticide residues in food: 1982 evaluations)
       Dichlofluanid (Pesticide residues in food: 1983 evaluations)