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    BENOMYL      JMPR 1973

    IDENTITY

    Chemical names

         Methyl 1-(butylcarbamoyl)benzimidazol-2-ylcarbamate
         Methyl 1-(butylcarbamoyl)-2-benzimidazole carbamate
         1-(butylcarbamoyl)-2-benzimidazole carbamic acid methyl ester

    Synonyms

    Benlate (R), Du Pont Fungicide 1991

    Structural formula

    CHEMICAL STRUCTURE 1


    Other information on identity and properties

    Molecular weight:             290.3
    State:                        White crystalline solid
    Melting point:                Decomposition before melting
    Solubility:                   Water:  practically insoluble
                                  Oil:    practically insoluble
                                  Chloroform:         9.4  g/100 ml
                                  Dimethylformamide:  5.3  g/100 ml
                                  Acetone:            1.8  g/100 ml
                                  Xylene:             1.0  g/100 ml
                                  Ethanol:            0.4  g/100 ml
                                  Heptane:            0.04 g/100 ml
    Purity:                       Technical benomyl better than
                                  98% (w/w)

    Chemical stability:           Benomyl is easily hydrolyzed to
    (see Fig. 1)                  methyl 2-benzimidazole carbamate
                                  (MBC) in very dilute aqueous, and
                                  in acidified methanolic solutions.
                                  MBC in turn hydrolyzes under basic
                                  conditions to give 2-aminobenzimidazole
                                  (2-AB)

                                  By direct alkaline treatment of benomyl
                                  a triazine ring-closure takes place,
                                  forming 3-butyl-S-triazino [1.2 a]
                                  benzimidazole-2.4(1H, 3H)dione (STB)
                                  which is not stable in hot alkali. It is
                                  further converted to the stable
                                  2-(3-butylureido)-benzimidazole (BUB)
                                  (Ogawa et al., 1971; White et al.,
                                  1973). By exclusion of moisture
                                  formulated benomyl products are stable.

    Use pattern

         Benomyl is, since 1970, registered as a systemic fungicide in a
    great number of countries, including the United States of America. It
    is marketed mostly as a 50% wettable powder. Similar to other
    benzimidazole fungicides it is active against a broad spectrum of
    fungi, among which are Ascomycetes, Basidiomycetes and some
    Deuteromycetes, while it is found completely inactive against the
    Phycomycetes fungi (Edgington et al., 1971; Bollen, 1972). Among the
    well-controlled fungal diseases are powdery mildew, apple scab
    (Venturia inaequalis) and the grey mould fungus Botrytis cinerea
    (Evans, 1971).

         The major uses of benomyl for the control of fungal diseases on
    fruits, vegetables and ornamenthals are preharvest applications which
    usually involve one or more sprayings with from about 20 g to about 20
    g a.i. per 100 litres (Table 1). Post-harvest treatments, by either
    dipping or dusting, within the same concentration range are approved
    for the protection of fruits, seeds and vegetables in storage. The
    United States Environmental Protection Agency has registered
    post-harvest uses of benomyl for apricots, cherries, citrus,
    nectarines, peaches, plums and prunes.

    Residues resulting from supervised trials

         The levels of benomyl residues found in various crops in the
    United States of America and other countries are summarized in Table 1
    (Anonymous, 1972, 1973). The data are based on information supplied to
    the United States Environmental Protection Agency to support the
    establishment of United States tolerances, indicating the residues
    resulting from approved use patterns, Residue levels are given as the
    range of values observed in those crops showing benomyl residues
    (incl. MBC).

    FIGURE 1

    TABLE 1. RESIDUES OF BENOMYL IN VARIOUS CROPS
    (Supervised trials)
                                                                          

                        Application                           Benomyl
    Crop                Rate               No. per            residue
                        (approx.)          season             founda
                                                              range (ppm)
                                                                          
    Apricots            0.3-0.6 g/l        2-3                2.6-6.5
                                           Dip
                                           post-harvest       0.9-5.1

    Almonds

    nutmeats            1-2 kg/ha          1-3                <0.1
    hulls               1-2 kg/ha          1-3                0.2-0.74

    Apples              0.4-1.2 g/l        6-12               0.5-4.8
                                           Dip
                                           post - harvest     0.12-0.88

    Avocados            1-2 kg/ha          3-6                0.11-0.18

    Bananas             0.2-0.3 kg/ha      6-9                Pulp <0.1
                        0.3-0.6 g/l        Dip                0.15-0.43
                                           post-harvest

    Barley              0.5 kg/ha          2                  Straw 0.54
                                                              1.53 (53
                                                              days)
                                                              Grain 0.1

    Beans dry           1.5-2 kg/ha        2-3                0.1-0.73
          lim           1.5-2 kg/ha        2-3                0.5-1.8
          snap          1.5-2 kg/ha        1-2                0.11-0.94

    Bean vines          1.5-2 g/ha         2-3                0.2-4.6

    Blackcurrant        0.45 kg/ha         1                  4.0-5.1
                                                              (0 day)
                                                              1.7-2.4
                                                              (7 day)
                                                              1.3-2.4
                                                              (14 day)

    Caneberries         0.5-2 kg/ha        2-5                0.75-6.0

    Celery              0.2-0.5 kg/ha      4-11               0.1-2.6

    TABLE 1. (Cont'd.)
                                                                          
                        Application                           Benomyl
    Crop                Rate               No. per            residue
                        (approx.)          season             founda
                                                              range (ppm)
                                                                          
    Cherries            0.3-0.6 g/l        2-3                0.2-12.6
                        0.3 g/l            Dip                0.5-2.3
                                           post-harvest

    Citrus (whole       0.6-1.1 g/l        1-5                0.2-1.3
    fruit)              500 ppm            Dip                0.54-1.26
                                           post-harvest

                        1000 ppm           Dip                0.39-2.35
                                           post-harvest
                        1250 ppm           Dip                1.3-1.8
                                           post-harvest

                        2500 ppm           Dip                2.7-3.9
                                           post-harvest

                        5000 ppm           Dip                4.5-5.4
                                           post-harvest

    Cucumbers           0.2-0.5 kg/ha      2-6                0.13-0.55

    Grapes              1-1.5 kg/ha        3-5                0.14-10.3

    Macadamia nuts      2-2.5 kg/ha        4-10               <0.1

    Mangoes             1-2 kg/ha          5-17               0.15-3.0

    Melons              0.2-0.4 kg/ha      2-7                0.27-0.32

    Mushroom            0.25 g/m2          1                  0.31-0.57
                        0.5 g/m2 (peat
                        treatment)         1                  0.23-0.51
                        1.0 g/m2 (peat
                        treatment)         1                  0.88-1.5

    Nectarines          0.5 kg/ha          1-3                1.6-2.2

    Peaches             0.2-0.6 g/l        1-15               0.2-8.2
                        0.3 g/l            Dip                3.9-4.7
                                           post-harvest

    Peanuts             0.2-0.5 kg/ha      2-13               <0.1

    Peanuts hay         0.4-1 kg/ha        3-13               1.4-1.6


    TABLE 1. (Cont'd.)
                                                                                                  Application                           Benomyl
    Crop                Rate               No. per            residue
                        (approx.)          season             founda
                                                              range (ppm)
                                                                          
    Pears               0.6-1.2 g/l        3-5                1.7-3.2
                                           Dip 
                                           post-harvest       0.1-0.55



    Pecans              1-1.25 kg/ha       3-6                <0.1

    Prunes, plums       0.3-0.6 g/l        2-4                0.4-1.4
                        0.3 g/l            Dip                0.5-1.9
                                           post-harvest

    Potato              50 g/100 kg        Tuber              <0.1
                                           dressing

    Squash              0.4-0.8 kg/ha      2-5                0.10-0.50

    Strawberries        0.3-0.6 g/l        3-7                0.43-2.6
                        0.3-0.6 g/l        6-7                2.7-15.2
                                           (Under glass)      (0.day)
                        0.3-0.6 g/l        (Under glass)      1.5-2.6
                                                              (17.day)

    Sugarbeet
    roots               0.2-0.5 kg/ha      3-6                <0.1
    tops                0.4-1 kg/ha        1-6                0.15-4.7

    Tomato              0.3 g/plant        1                  1.1-2.2
                        0.3-0.7 kg/ha      3                  0.15-2.1
                                           (Under glass)

                                                                                                  Application                           Benomyl

    a Total residue comprising benomyl, methyl benzimidazolecarbamate
        and 2-aminobenzimidazole, expressed as benomyl.

    (Nominal blank values either 0.1 or 0.2 ppm, apart from citrus,
    strawberries, peanut hay, barley straw and lettuce (0.3-0.4 ppm).)

    Fate of residues

    General remarks on mode of action

         As suggested by Clemons and Sisler (1969) (Kilgore and White,
    1970; Helweg, 1973) and others, it is generally accepted that methyl
    2-benzimidazole carbamate (MBC), which is the major metabolite of

    benomyl, is primarily responsible for the fungitoxicity of the latter.
    Comparisons between the effects of benomyl and MBC (Hammerschlag and
    Sisler, 1973) indicated that both compounds caused an inhibition in
    the synthesis of DNA, but that this was secondary to a mitotic arrest
    of fungal cell division, followed by an inhibition of cytokinesis.

         Benomyl partially inhibits respiration of subcellular particles
    from fungal cells, while MBC had essentially no such effect. This
    differential effect of benomyl and MBC on metabolism is attributed to
    the formation, from benomyl, of volatile butyl isocyanate (BIC),
    simultaneously to MBC production. Fungitoxicity of benomyl
    preparations may thus be attributed to the combined effects of its two
    first breakdown products, MBC and BIC.

         Although the fungitoxic effects of benomyl are thus assumed to be
    caused by its metabolites, MBC and BIC, much of its systemic functions
    may be connected to benomyl per se. Controlled experiments of foliar
    treatments on apples, cucumber, banana, orange and grape plants
    indicate that from 48% to 77% of the 14C-benomyl remaining 21-23 days
    after application under outdoor conditions was still in the form of
    intact benomyl (Baude et al., 1973). Several workers have recently
    found that plant penetration and movement through the cuticle after
    foliar application is greater for benomyl than for MBC (Upham and
    Delp, 1973; Hammerschlag and Sisler, 1972, 1973; Solel and Edgington,
    1973). Systemic translocation within the plant, on the other hand, is
    mostly in the form of MBC plus smaller amounts of 2-AB (Siegel and
    Zabbia, 1972).

         The two theoretical metabolites, STB and BUB (see Fig. 1), which
    are formed chemically under alkaline conditions could not be detected
    by Baude et al. (1973) as actual conversion products from benomyl
    under greenhouse conditions or in field tests, even when subjected to
    the influence of two alkaline pesticides, basic copper sulfate and
    lime sulfur.

    Plants

         Under practical conditions a considerable part of the applied
    benomyl is claimed to remain on the foliar surfaces, as relatively
    stable residues, only gradually degrading to form MBC (Baude et al.,
    1973).

         Studies of the systemic uptake of benomyl after foliar treatments
    indicate that while the total amount which penetrates the surface is
    relatively small, residues can still be traced in untreated portions
    of the plant (Lowen, 1973). The translocated residues consist mainly
    of MBC together with smaller amounts of 2-AB. To the plants these
    compounds move only passively, i.e. they are carried by the
    intercellular transpiration stream towards the edges and tips of
    leaves (Foldo, 1973), where they then accumulate.

         Benomyl is readily absorbed through the root-system of plants.
    The uptake in vegetable crops, such as lettuce and cucumber is clearly
    demonstrated through greenhouse trials (see Table 2) in which normal
    and excessive rates were applied through watering or through admixing
    benomyl with the soil (Green-Lauridsen and Voldum-Clausen, 1973).

    Citrus

         The total 14C-benomyl residue (benomyl + MBC) was found to
    decrease slowly in oranges during two months storage after
    post-harvest dipping. While the major part of the residue remained in
    the peel, a smaller, but significant amount gradually penetrated into
    the edible portion (see Table 3). Two weeks after the dipping 61% of
    the surface residue was present as unchanged benomyl, the remaining
    39% being MBC (Lowen, 1973).

    Grapes and wine

         Lemperle et al. (1973) found that benomyl residues, as well as
    other benzimidazole fungicides, are transferred almost quantitatively
    into unclarified musts during wine production.  During clarification
    and fermentation a small amount may disappear but a considerable part
    of the benomyl residue present in grapes may be found in wine.

    Animals and animal products

         Benomyl is readily hydrolyzed into MBC through cleavage of the
    1-butyl carbamoyl side chain when ingested by mice, rabbits and sheep
    (Douch, 1973). Further hydrolysis of the carbamate ester bond was
    shown by these studies to yield 2-AB suggesting that benomyl may not
    remain in the unchanged form more than momentarily when residues are
    ingested into the alimentary tract of animals. Hydroxylated
    derivatives of MBC and 2-AB were identified by these studies in urine
    and faeces of all three species.

         After feeding rats with benomyl Gardiner et al, (1968) identified
    methyl 5-hydroxy-2-benzimidazole carbamate as the major metabolite
    which was liberated in urine by enzyme hydrolysis of glucuronide
    and/or sulfate conjugates. MBC is assumed to be the possible
    intermediate metabolite for this conversion as well as for the
    formation of a minor isomeric metabolite, methyl
    4-hydroxy-2-benzimidazole carbamate, which was found in milk and meat
    in later studies (Gardiner et al., 1972) when feeding cows with
    rations containing 2, 10 and 50 ppm benomyl for 32 days (see Table 4).
    Neither intact benomyl nor MBC was detected in these studies.

    
    TABLE 2. BENOMYL RESIDUES ABSORBED THROUGH THE ROOTS UNDER GREENHOUSE CONDITIONS

                                                                                                                   

                                            Sampling after            Sampling after
    Treatment           Application         0-14 days                 15-23 days                 Remarks
                        rate
                                            Range        Average      Range        Average
                                                                                                                   

    Summer lettuce

    Watering            1.5-3.8 g/10 m2     5.21-17.8    11.3         n.d.-3.09    1.38          Practical use rate

    Watering            7.5-15 g/10 m2      4.33-39.7    15.8         0.49-5.01    2.63          Excessive rates

    Watering            22.5 g/10 m2        17.7-29.3    23.0

    Winter lettuce

    Watering            1.5-3.8 g/10 m2     11.7-18.6    15.3         7.08-14.7    10.5          Practical use rate

    Watering            7.5-15 g/10 m2      20.4-60.6    36.8         6.74-27.1    15.9          Excessive rates

    Watering            22.5 g/10 m2        56.5-97.1    74.5         28.2-32.1    30.2

    Cucumber

    Watering            1 g/plant           n.d.-0.64    0.27         0.15-0.53    0.37

    Soil treatmenta     1 g/plant                                     0.53-2.02    1.10b
                                                                                                                   

    a Composite Soil: 1/3 soil, 1/3 fertilizer, 1/3 peat mulch.

    b Sampling after 34-55 days.

    

    TABLE 3. 14C-BENOMYL RESIDUES ON ORANGES FOLLOWING POST-HARVEST
             DIPPING (From Lowen, 1973)

                                                                        

    ppm benomyl    Days                                       Whole
    in dip         post-treatment   Peel         Pulp         fruit
                                                              (calculated)
                                                                        

    Untreated      -                <0.05        <0.05        <0.05

    100            0                0.80         <0.05        0.30

                   31               0.46         <0.05        0.16

                   62               0.54         <0.05        0.19

    500            0                1.5          0.08         0.46

                   31               1.4          0.12         0.38

                   62               1.6          0.17         0.50

    1 000          0                5.6          <0.05        1.3

                   31               4.4          0.11         0.95

                   62               3.0          0.40         0.93

                                                                        


         After withdrawing the treated diet for one or two days the
    residues of 5-hydroxy-MBC and 4-hydroxy-MBC in milk dropped to below
    0.01 ppm.

    Water

         Benomyl rapidly breaks down on contact with water to give MBC,
    conversion being complete within four days (Kilgore and White, 1970;
    Peterson and Edgington, 1969).

    Soil

         Helweg (1973) isolated from soils four strains of bacteria and
    two fungi which promoted the breakdown of benomyl to nonfungistatic
    compounds. High humus content increased the rate of breakdown of
    benomyl. Generally, however, it was concluded that benomyl is
    relatively stable as a soil residue under temperate climatic
    conditions.

    TABLE 4. RESIDUES (PPM) OF METHYL 5-HYDROXY-2-BENZIMIDAZOLECARBAMATE
    (5-HYDROXY MBC) AND METHYL 4-HYDROXY-2-BENZIMIDAZOLECARBAMATE
    (4-HYDROXY MBC) FOUND IN MEAT AND MILK AFTER FEEDING COWS RATIONS
    CONTAINING 2, 10, AND 50 PPM BENOMYL FOR 32 DAYS
    (From Gardiner et al., 1972)

                                 Feeding level
                                                                        
              2 ppm              10 ppm              50 ppm
    Sample
                                                                        
              5-       4-        5-        4-        5-       4-
              hydroxy  hydroxy   hydroxy   hydroxy   hydroxy  hydroxy
              MBC      MBC       MBC       MBC       MBC      MBC

    Milk      <0.01    <0.01     0.01      <0.01     0.05     0.03

    Meata     <0.05    <0.05     <0.05     <0.05     <0.05  
    <0.05
                                                                        
    a "Meat" represents liver, kidney, fat and muscle.


         Studies over two years in experimental fields in Delaware, North
    Carolina and Florida (Baude, 1972) showed that the amount of
    non-volatile decomposition products of 14C-benomyl remaining in the
    soil after one year were 57%, 49% and 57%, respectively, of the
    quantity originally applied. After two years in soil in Florida, 27%
    of the amount originally present remained. After one month only minor
    amounts of unchanged benomyl were present, the principal metabolite
    being MBC, with smaller amounts of 2-AB.

         Uptake by crops grown in treated soils was studied in the same
    experiments by Rhodes (1972) using 14C-benomyl. Trace amounts,
    ranging from 0.02 to 0.08 ppm, could be found in tissues of carrots,
    tomatoes, corn and beans, while edible snap beans, corn and tomatoes
    contained less than the detection limit (i.e. <0.01 ppm). In this
    study the benomyl content of the soil at the time of harvest was
    0.9 ppm.

    Methods of residue analysis

         Pease and Gardiner (1969) describe colorimetric and fluorometric
    procedures for determining benomyl in a variety of plant and animal
    tissues and in soil. The residue is extracted, purified by partition,
    converted to 2-aminobenzimidazole, and determined by direct
    fluorometric measurement or by colorimetric analysis following
    bromination. The procedure thus determines benomyl, its principal
    degradation product methyl 2-benzimidazole carbamate, and the minor
    residual component 2-aminobenzimidazole as a composite value. With a
    sensitivity of 0.1 ppm for 50 g samples, recoveries were about 87% for

    both methods. Pease and Holt (1971) improved this method to make it
    less time-consuming and to include the analysis of citrus fruits. By
    using fluorometric measurement from both acidic and basic media it was
    possible to distinguish between benomyl residues and other
    benzimidazole fungicides.

         Peterson and Edgington (1969) report a method to determine
    benomyl and the hydrolysis product, MBC, using a bioautograph
    technique. A thin-layer plate is sprayed with a mixture of agar and
    Penicillium spores, and the diameter of the zone of inhibited growth
    above the fungitoxic spot is related to the amount of active material
    in the spot. The sensitivity of the method is 0.1 ppm for a 50 g
    sample. Somewhat similar agar plate methods have also been described
    by Erwin et al. (1968), Baron (1971) and Holman and Fuchs (1970). A
    two-dimensional TLC-technique for separation of benomyl, MBC, 2-AB and
    thiophanate as well as thiophanate-methyl is described by von Stryk
    (1972).

         A UV-spectrophotometric method for determining residues in
    grapes, must and wine has been described by Lemperle and Kerner
    (1971). After addition of acetone the samples are extracted with
    chloroform, the chloroform evaporated to dryness and the residues
    measured in methanol at 301.5 nm. The limit of detection reported is
    0.3 ppm for 100 g samples and recoveries of 89% for grapes, 75% for
    must and 56% for wines. Mestres et al. (1971) used a
    spectrophotometric method for fruits and vegetables, measuring the
    hydrolysis product, MBC, at 282 nm. The limit of detection was 0.1 ppm
    for 25 g samples.

         Residues in meat and milk have been determined by the liquid
    chromatographic procedure of Kirkland (1973). The method detects
    4-hydroxymethyl-2-benzimidazole carbamate and
    5-hydroxymethyl-2-benzimidazole carbamate, which are found in animal
    systems, as well as benomyl and methyl-2-benzimidazole carbamate.
    Kirkland et al. (1973) further adapted this method for the
    determination of benomyl and/or MBC and 2-AB in soil and plant
    material. Recoveries of the three compounds were 92, 88 and 72%,
    respectively. The lower limit of sensitivity of the method is 0.05 ppm
    for each of the components.

         The methods based on spectrophotofluometry of 2-AB, on
    UV-spectophotometry of MBC and the liquid chromatographic procedure
    may all be adapted for regulatory purposes.

    National tolerances (as notified to the meeting)

                                                                      

    Country      Commodity                            Tolerance, ppm
                                                                      

    Australia    Pome fruits, stone fruits            5
                 Vegetables, citrus                   3
                 Grapes, mangoes, avocados
                   strawberries                       2

                 Bananas                              1
                 Peanuts                              0.2

    Belgium      Apples, pears, cucumbers,
                   strawberries, celery,
                   small grain                        1

    Canada       Peaches                              15
                 Blackberries, boysenberries,
                   raspberries                        6
                 Apples, apricots, cherries,
                   crabapples, grapes,
                   nectarines, pears, plums,
                   prunes, strawberries               5

    Federal      Citrus fruits                        10
    Republic     Grapes                               3.0
    of           Berries                              2.0
    Germany      Vegetables (exc. cucumber),               Total
                   stone fruit, bananas, citrus            residue
                   fruits (without peel)              1.0  calculated
                 Cereals, cucumbers                   0.5  as benomyl
                 Banana (without peel)                0.2
                 Other vegetable products             0.1

    United       Apricots, cherries, nectarines,
    States of      peaches and plums (including
    America        fresh prunes) (from post-
                   harvest and/or pre-harvest
                   applications), peanut hay,
                   peanut forage, sugar beet tops     15

                 Mushrooms                            10
                 Apples, pears, blackberries,
                   boysenberries, dewberries,
                   loganberries, raspberries          7
                 Strawberries                         5
                 Celery, mango                        3
                 Snapbeans, peanut hulls              2


    National Tolerances (cont'd)
                                                                      

    Country      Commodity                            Tolerance, ppm
                                                                      

 
                 Bananas (whole), cucumbers,
                   melons, summer squash, winter
                   squash, avocado, almond hulls      1
                 Banana (pulp), peanuts, sugar
                   beets (roots), nuts (almonds,
                   Brazil nuts, bush nuts,
                   butternuts, cashews, chestnuts,
                   filberts, hazelnuts, hickory nuts,
                   macadamia nuts, pecans, walnuts)   0.2
                 Milk and the meat, fat and meat
                   by-products of cattle, goats,
                   hogs, horses and sheep             0.1

    Netherlands  Fruit and vegetables                 2   ) Determined
                 Raw cereals                          0.5 ) and
                 Citrus fruits                        3.5 ) expressed
                                                          ) as
                                                          ) MBC

    South        Fruits and vegetables                3
    Africa
                                                                      


    Appraisal

         Benomyl is a relatively new systemic broad-spectrum fungicide
    already established in most countries.  It is marketed as wettable
    powders and used in foliar applications, seed treatments and
    post-harvest dipping procedures on a great number of food and forage
    crops.

         Benomyl is chemically easily hydrolysed into the relatively
    stable methyl-2-benzimidazole carbamate (MBC) which is considered to
    be the major fungitoxic principle of the compound. Formulated benomyl
    may hydrolyze if not kept dry in storage.

         A fungicidal effect additional to the MBC activity is claimed to
    be connected with the simultaneous release of volatile butyl
    isocyanate. Recent data has been presented suggesting that the
    hydrolytic breakdown is of significance for the systemic properties of
    benomyl facilitating the cuticular penetration. Evidence is given that
    in the case of benomyl residues on foliar surfaces the formation of
    MBC proceeds gradually. In a typical example a 50% cleavage of
    residues remaining on apple leaves occurs three weeks after
    application.

         A further metabolic product found in plants is
    2-aminobenzimidazole formed from MBC. The amount of this metabolite
    found in plant material is, however, usually relatively small; so far
    not being found in excess of 1% of total residues. For practical
    purposes therefore, residues in plant material following application
    of benomyl could be considered as the composite of benomyl, MBC and
    2-AB or as the sum of benomyl and MBC alone.

         Residue data justifying the establishment of several national
    tolerances were available to the meeting, together with limited
    information on residues on citrus fruits sampled from trade channels.
    Included also is evidence of uptake into crops from treated soils.
    Half-life of benomyl (metabolized to MBC) in soils varies from about
    four months to one year indicating relatively long persistence with a
    possibility of unintentional uptake by following crops.

         Cow feeding trials show that hydroxylated methyl benzimidazole
    carbamates are formed from benomyl with MBC as the probable
    intermediate metabolite.

         The most recent published report has confirmed this information
    indicating that MBC (and possible 2-AB) are likely to be the primary
    chemical entities to be absorbed from the alimentary tract following
    the ingestion of benomyl residues.

         The presence of hydroxylated MBC was demonstrated in milk and
    meat residues of intact benomyl or MBC were detected.

         Suitable methods of analysis for benomyl, MBC and 2-AB or for
    benomyl and MBC as composite values have been published, both methods
    being effective at the 0.1 ppm level. For one of these methods which
    is based on spectrophotofluorometric measurement, modifications have
    been introduced which allow the determination of benomyl and
    metabolites and to differentiate these from other benzimidazole
    fungicides such as thiabendazole. Although useful for regulatory
    purposes neither of the two methods, however, permits the separate
    determination of benomyl and metabolites when these are present
    together.

    RECOMMENDATIONS

         As no acceptable daily intake was established it was not possible
    to recommend tolerances. Following officially acceptable use in
    various countries residues of benomyl and its metabolites can occur in
    the following commodities up to levels indicated. Residues of benomyl
    should be measured as the composite of benomyl and its main
    metabolite, methyl benzimidazolecarbamate with or without minor
    amounts of 2-aminobenzimidazole (usually less than 1% of total
    residues), calculated as methyl benzimidazolecarbamate. The levels
    indicated are not likely to be exceeded when benomyl is applied in
    accordance with good agricultural practice, including either or both

    pre-harvest and post-harvest treatments (when applicable). These
    levels have been recommended as guideline levels.

         For the underlined commodities adjustments have been made to
    recommendations in order to accommodate good agricultural practices
    for such alternative systemic fungicides of which MBC is also
    recognized and identified as the major metabolite and/or chemical
    entity (i.e. carbendazim and thiophanatemethyl).

    Guideline levels

                                                                ppm

    Citrus fruit (whole), cherries, grapes, peaches             10

    Apples, pears, apricots, tomatoes, blackberries,
    boysenberries, dewberries, loganberries, raspberries,
    strawberries, blackcurrants                                 5

    Celery, prunes, plums, beans (lima), mangoes,
    beans (dry), beans (snap), nectarines                   2

    Mushroom, banana (whole)                                  1

    cucumbers, melons, squash, brussels sprouts, avocados       0.5

    Sugar beet, raw cereals, peanuts, almonds, macadamia        0.5

    Nuts, pecans, potatoes                                      0.1a

    Animal feedstuffs

    Bean vines                                                  30

    Sugar beet leaves                                           5

    Peanut hay, barley straw                                    2

    Almond hulls                                                1

    Meat of cattle and sheep                                    0.1a

    Milk (whole)

              

    a At or about limit of determination.

         Residues to be measured as a composite of benomyl, MCB, 2-AB and
    expressed as MBC.

    FURTHER WORK OR INFORMATION

    Required (before an acceptable daily intake can be estimated)

    1.   Full toxicological data.

    Desirable

    1.   Further development of analytical methods to adapt them
         for regulatory purposes, especially to permit separate
         determination of benomyl and metabolites when present together.

    2.   Information on residues in food in commerce.

    3.   Information on the nature and level of residues in poultry and
    eggs following the feeding of benomyl residues in rations.

    REFERENCES

    Anon. Residues of benomyl in certain foods. E.I. du Pont de
    1972, 1973          Nemours & Co., Delaware. Unpublished reports filed
                        with FAO

    Baron, M. Determination, migration and distribution of a
    1971                systemic fungicide (benomyl) in the leaves of the
                        banana plant. Fruits, 26: 643

    Baude, F. J. Disappearance of benomyl-2-14C from field soil
    1972                in Delaware, North Carolina, and Florida. Paper
                        submitted by E.I. de Pont de Nemours & Co.,
                        Delaware (Unpublished)

    Baude, F. J., Gardiner, J. A. and Han, J. C.-Y. Characterization
    1973                of residues on plants following spray applications
                        of benomyl. Prepublication of paper submitted to
                        the J. Agr. Food Chem.

    Bollen, G, J. A comparison of the in vitro antifungal spectra
    1972                of thiophanates and benomyl. Neth J. Plant. Path.
                        78: 55

    CIVO-TNO Unpublished reports on benomyl residues from Central
    1972, 1973          Institute of Food Research (CIVO-TNO) of 11
                        January 1972 and 9 August 1973

    Clemons, G.P. and Sisler, H. D. Formation of a fungitoxic
    1969                derivative from Benlate. Phytopathology, 59: 705

    Douch, P. G. C. The metabolism of benomyl fungicide in animals.
    1973                Xenobiotica, 3: 367

    Edgington, L. V., Khew, K.L. and Barron, G.L. Fungitoxic spectrum
    1971                of benzimidazole compounds. Phytopathology, 61:
                        42

    Erwin, D. C., Mee, H. and Sims, J. J. The systemic effect of
    1968                1-(butylcarbamoyl)-2-benzimidazole carbamic acid,
                        methyl ester, on verticillium wilt of cotton.
                        Phytopathology, 58: 528

    Evans, E. Systemic fungicides in practice, Pesticide Science,
    1971                2: 192

    Foldo, N. E. Systemic fungicides. Effect, advantages and
    1973                disadvantages (in Danish), Ugeskr. f. agronomer og
                        hortonomer, 40: 730

    Gardiner, J. A., Brantley, R. K. and Sherman, H. Isolation
    1968                and identification of a metabolite of methyl
                        1-(butylcarbamoyl)-2-benzimidazolecarbamate in rat
                        urine. J. Agr. Food Chem. 16: 1050

    Gardiner, J. A., Kirkland, J. J., Pease, H. L., Wall, E. N.
    1973                and Morales, R. Unpublished studies. Cited from
                        Kirkland (1973)

    Green-Lauridsen, M. and Voldum-Clausen, K. Reports on
    1973                experiments on pesticide residues Nos 285-287,
                        290-293, 298-300, 302, 306, 308-310 from the
                        Danish National Food Institute and Government
                        Plant Pathology Institute, Copenhagen
                        (Unpublished)

    Hammerschlag, R. S. and Sisler, H. D. Differential action
    1972                of benomyl and methyl-2-benzimidazolecarbmate
                        (MBC) in Saccharomyces pastorianus. Pesticide
                        Biochem. Physiol. 2: 123

    Hammerschlag, R. S. and Sisler, H. D. Benomyl and methyl-2
    1973                benzimidazole (MBC): biochemical, cytological and
                        chemical aspects of toxicity to Ustilago
                        mavdis and Saccharomyces cerevesiae; Pesticide
                        Biochemistry and Physiology, 3: 42

    Helweg, A. Persistence of benomyl in different soil types
    1973a               and microbial breakdown of the fungicide in soil
                        and agar culture. Tidskr. for Planteavl
                        (Copenhagen), 77: 232

    Helweg, A. Influence of the fungicide benomyl on micro-organisms
    1973b               in soil. Tidsskrift for Planteavl (Copenhagen),
                        77: 375

    Holman, A. L. and Fuchs, A. Direct bioautography on TLC as
    1970                a method for detecting fungitoxic substances. J.
                        Chromatography, 51: 327

    Kilgore, W.  W. and White, E.R. Decomposition of the systemic
    1970                fungicide 1991 (Benlate). Bull. Environm. Contam.
                        & Toxicol. 5: 67

    Kirkland, J. Method for high-speed liquid chromatographic
    1973                analysis of benomyl and/or metabolite residues in
                        cow milk, urine, feces and tissues. J. Agric. Food
                        Chem. 21: 171

    Kirkland, J., Holt, R.F. and Pease, H.L.  Determination of
    1973                benomyl residues in soils and plant tissues by
                        high-speed cation exchange liquid chromatography.
                        J. Agr. Food Chem. 21: 368

    Lemperle, E. and Kerner, E. UV-spektrophotometrische
    1971                Bestimmung von Rücksttänden in Weintrauben,
                        Traubenmost und Wein nach Anwendung von Du Pont
                        Benomyl. Z. Anal. Chem. 254: 117

    Lemperle, E., Kerner, E., Strecker, H. and Waibel, A.
    1973                Wirkstoffrückstände und Gärbeeinflussungen nach
                        Anwendung von Fungiziden im Weinbau. Deutsche
                        Leb.-Rdschau, 69: 313

    Mestres, R., Tourte, T. and Campo, M. Dosage des residus de
    1972                benomyl dans les fruits et les legumes. Ann. Fals.
                        Exp. Chim. 65: 239

    Ogawa, J. A., Bose, E., Manji, B. T., White, E. R. and
    1971                Kilgore, W. W. Phytopathology, 70: 905 (Cited
                        from Baude et al., 1973)

    Pease, H. L. and Gardiner, J. A. Fluorometric and colorimetric
    1969                procedures for determining residues of benomyl. J.
                        Agr. Fd. Chem. 17: 267

    Pease, H. L. and Holt, R. F. Improved method for determining
    1971                benomyl residues. J. Assoc. Off. Anal. Chem. 54:
                        1399

    Peterson, C. A. and Edgington, L. V. Quantitative estimation
    1969                of the fungicide benomyl using a bioautograph
                        technique. J. Agr. Food Chem. 77: 898

    Rhodes, R. C. Uptake of 2-14 C-benomyl soil residues by
    1972                crops. Paper submitted by du Pont de Nemours &
                        Co., Delaware (Unpublished)

    Siegel, M. R. and Zabbia, A. J., jr Distribution and metabolic
    1972                fate of the fungicide benomyl in dwarf pea.
                        Phytopathology, 62: 630

    Solel, Z. and Edgington, L. V.  Transcuticular movement of
    1973                fungicides. Phytopathology, 63: 505

    Upham, P. M. and Delp, C. J. Phytopathology (In press).
    1973                (Cited from Baude et al., 1973)

    von Stryk, F. G. Separation and determination of some
    1972                systemic fungicides and their metabolites by thin-
                        layer chromatography. J. Chromatogr. 72: 410

    White, E. R., Bose, E. A., Ogawa, J. M., Manji, B. T. and
    1973                Kilgore, W. W. J. Agr. Food Chem. (in press)
                        (Cited from Baude et al., 1973)
    


    See Also:
       Toxicological Abbreviations
       Benomyl (EHC 148, 1993)
       Benomyl (HSG 81, 1993)
       Benomyl (ICSC)
       Benomyl (WHO Pesticide Residues Series 5)
       Benomyl (Pesticide residues in food: 1983 evaluations)
       Benomyl (JMPR Evaluation 1995 Part II Toxicological and environmental)