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    CARBENDAZIM       JMPR 1973

    IDENTITY

    Chemical names

         Methyl-2-benzimidazole carbamate
         Methyl benzimidazole-2-ylcarbamate
         2-(methoxy-carbamoyl)-benzimidazole
         2-(methoxycarbonylamino)benzimidazole
         Carbomethoxyaminobenzimidazole

    Synonyms

         Bavisitin(R), MBC, MCAB, BCM, Hoe 17411, Drosal

    Structural formula

    CHEMICAL STRUCTURE 1


    Other information on identity and properties

    Molecular weight:             191.2
    State:                        light grey powder
    Melting point:                307-312°C (decomposition)
    Vapour pressure:              0.1 × 10-6 mmHg (20°C)
    Solubility:                   Soluble in acetic acid and 
                                  dimethyl-formamide
                                  Water, pH 4:        28 ppm
                                  Water, pH 7:        8 ppm
                                  Water, pH 8:        7 ppm
                                  Hexane:             0.5 ppm
                                  Benzene:            36 ppm
                                  Methylenechloride: 68 ppm
                                  Ethanol:            300 ppm
                                  Acetone:            300 ppm
                                  Chloroform:         100 ppm

    Stability:                    Stable in acidic and alkaline solutions
                                  at room temperature and when exposed to
                                  light. Stable in storage at 35-50°C
    Purity of
    technical product:            Better than 98%

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    Biochemical aspects

         Methyl-2-benzimidazole carbamate has been proposed as an
    intermediate in the degradation of thiophanate and benomyl in plants.
    The quantitative aspects of this conversion have not been fully
    reported although it appears that, while carbendazim is a major
    metabolite, there may only be limited conversion of the two parent
    molecules (Douch, 1973). Sims et al. (1969) found only carbendazim but
    not benomyl four weeks after treatment of cotton. In aqueous solution
    benomyl and thiophanate methyl were reported to convert rapidly to
    carbendazim (Clemons and Sisler, 1969; Buchenauer and Edgington,
    1973). In pea plant treated with benomyl, only carbendazim was
    recovered as a plant residue (Siegel and Zabbia, 1972). In aqueous
    solution on glass following irradiation by ultra-violet or sunlight,
    conversion of both thiophanate and thiophanate methyl to
    ethyl-2-benzimidazole carbamate and carbendazim was effected. There
    are no data available on the metabolism of carbendazim in either
    mammals or plants.

         Metabolism of benomyl in mammals also results in the occurrence
    of 5-hydroxy carbendazim and other products (Douch, 1973; Gardiner et
    al., 1968). This might arise directly from benomyl by oxidation and
    hydrolysis or by hydrolysis of benomyl to carbendazim followed by
    oxidation. Carbendazim is the major metabolite of benomyl in plants. A
    minor metabolite from benomyl is believed to be 2-amino benzimidazole.

         The probable metabolic pathway of carbendazim based upon data
    derived from thiophanate and benomyl conversion is suggested as
    follows:

    CHEMICAL STRUCTURE 2

         Clemons and Sisler (1971) have suggested that carbendazim appears
    to interfere with DNA synthesis or some closely related process such
    as nuclear or cell division in fungi. RNA and protein synthesis were
    not affected. Hammerschlag (1973) indicated an effect of carbendazim
    on mitosis, DNA synthesis and cytokinesis in two fungi species.
    Certain differences in effects of benomyl and carbendazim were
    attributed to the occurrence of butylisocyanate, a potential
    metabolite of benomyl.

    TOXICOLOGICAL STUDIES

    Special studies on mutagenicity

    Mouse. Groups of mice (20 male mice per group) were used in a
    dominant lethal study where one group was administered a dose of 1280
    mg/kg carbendazim by i.p. injection and three other groups served as
    controls (Hofmann and Peh, 1973). One group was a solvent control, one
    an unhandled control and one a positive control. Each male mouse was
    mated with three females for seven days over a period of eight weeks.
    The females were sacrificed at day 18 following introduction to the
    males and various reproduction parameters examined, including
    implantation, total number of live and dead fetuses, and resorption
    sites. There were no apparent effects as a result of MBC
    administration to males except a slight growth depression during week
    1. During the same week, the mutagenic index was higher in the treated
    group than in the untreated controls, although not different from that
    in the solvent controls. The effect was considered to be within the
    normal variation. A positive control (Trenimon, 2,3,5-triethyleneimino
    benzoquinone-1,4) showed definitive effects especially during the
    first three weeks of the experiment. Methyl-benzimidazole carbamate
    does not appear to be mutagenic to mice as evidenced by this dominant
    lethal study (Hofmann and Pen, 1973).

    Acute toxicity

         Dermal injection of 0.01% (2 µg) to rabbits caused slight
    reddening around the injection site (Scholz and Weigand, 1972). There
    were no effects noted following five daily dermal applications of 500
    mg to unbroken skin of rabbits. Application of 10 mg to the
    conjunctival sac of rabbits caused a transient reddening.  No such
    effects were noted with 5 mg.

                                                                            

    Species     Sex       Route    LD50            Reference
                                   (mg/kg)
                                                                            

    Rat         M & F     oral     > 15 000        Hofmann, 1971, 1972c;
                                                   Scholz and Weigand, 1973a
                M         oral     > 15 000        Scholz and Weigand, 1972b

                                                                            

    Species     Sex       Route    LD50              Reference
                                   (mg/kg)
                                                                            

                F         oral     14 000            Scholz and Weigand, 1972b

                M         i.p.     7 230             Scholz and Weigand, 1972a

                F         i.p.     715 000           Scholz and Weigand, 1972a

    Mouse       M & F     i.p.     > 5 000           Scholz and Weigand, 1972a;
                                                     Hofmann and Peh, 1973

    Dog         M & F     oral     > 8 000           Zeller and Kirsch, 1971a;
                                                     Scholz and Weigand, 1972a

    Rabbit      M & F     oral     > 8 000           Zeller and Kirsch, 1971b

    Japanese    M         oral     10 996            Scholz and Weigand, 1973b
    quail                          (sesamol)
                                   15 595            Scholz and Weigand, 1973b
                                   (starke-schleim)

                F                  5 826             Scholz and Weigand, 1973b
                                   (sesamol)
                                   9 813             Scholz and Weigand, 1973b
                                   (starke-schleim)
                                                                            


    Short-term studies

    Rat. Groups of rats (10 males per group) were administered
    carbendazim orally for two weeks (by gavage) at dosage levels of 0,
    10, 20, 30 and 40 mg/kg per day. The object of the study was to assess
    toxicity with special reference to the effect on bone marrow and the
    male reproduction system. One hour before sacrifice, each animal was
    injected with tritiated thymidine. At the conclusion of the study, the
    following tissues were removed, organ weights were recorded and organ
    to body weight ratios were calculated: adrenal glands, brain, heart,
    kidney, liver, pituitary gland, spleen, testes and thyroid gland.
    Microscopic examination was perfumed on the bone marrow and testes of
    all rats from the control and high-dose group. Microscopic
    radio-autography was used to determine bone marrow mitosis. Bone
    marrow was dissected, fixed and processed in paraffin wax. Sections
    were mounted on microscope slides and exposed to Kodak stripping film.
    After 20 days, the slides were developed, fixed and counted as well as
    examined following staining with haematoxylin.

         There were no effects noted in behaviour, mortality, food
    consumption and body weight gain. On gross examination of tissues, it
    was observed that the absolute and relative liver weight of rats at
    the 40 mg/kg dosage was higher than the controls. A decrease in
    relative testes weight, although significant, did not appear to be
    dose related and did not appear to be significant in this study,
    especially as there were no histological abnormalities observed in
    testes. Bone marrow examinations in both control and treated animals
    were within normal limits and showed no significant abnormalities
    either histologically or on radio-autography of the bone marrow cells.
    This study indicates that a dosage level of 30 mg/kg per day
    administered orally for two weeks would be a no-effect level with an
    effect noted at 40 mg/kg per day with regard to liver to body weight
    ratio (Hunter et al., 1973a).

         Groups of Sprague-Dawley strain rats (10 male and 10 female per
    group) were fed carbendazim in the diet at dosage levels of 0, 2000,
    4000 and 8000 ppm for 28 days. Haematological examination, clinical
    chemistry and urinalyses were performed at three weeks of testing.
    Gross and microscopic examination of tissues and organs was Performed
    at the end of the feeding study. Food consumption and growth were
    depressed at 4000 and 8000 ppm. Urinalysis and blood chemistry were
    not affected by the treatment, while a tendency was noted at 8000 ppm
    of an increase in haemoglobin concentration and white and red blood
    cell counts. Gross Pathology appeared normal and at histopathological
    examination degeneration of testicular tissue was found at 4000 and
    8000 ppm. Also spermatogenesis and oogenesis were affected at these
    feeding levels. Some changes were found in the weights of different
    organs relative to body or heart weight. of most significance was the
    increase in absolute and relative liver weight, which was also found
    in the lowest dosage group, 2000 ppm in the diet. No changes relative
    to the controls were found at histological examination of livers from
    the dosed groups (Hofmann and Kitsch, 1972).

         Groups of Sprague-Dawley albino rats (30 male and 30 female rats
    per group) were fed carbendazim at dose levels of 0, 50, 150, 450 and
    1350 ppm in the diet for 13 weeks. At the conclusion of this study, 10
    males and 10 females from each group were maintained on a control diet
    for a recovery period of six weeks. Food consumption and behavioural
    changes were examined daily and body weights weekly. Urine analysis,
    haematological and blood chemistry investigations were carried out
    periodically. Gross and microscopic examinations of tissues and organs
    were performed at the end of the study. Food intake in females
    receiving 1350 ppm was slightly depressed during recovery phase. Body
    weight gains in all groups at any dose level remained closely
    comparable to controls. Growth, urine analysis, blood chemistry and
    haematological findings were within the normal range except females
    receiving 1350 ppm who exhibited depression of total serum proteins.

         Relative liver weight in males and females was significantly
    increased at 1350 ppm. Absolute liver weight was elevated
    significantly at 1300 ppm in females. In rats allowed a recovery
    period of six weeks, no treatment-related differences in relative or
    absolute liver weight was observed. Gross and microscopic examinations
    of tissues and organs did not show any consistent finding at any dose
    level (Hunter et al., 1973b).

         Groups of rats (20 male and 20 female rats per group) were fed
    carbendazim at dose levels of 0, 80, 400, 2000 and 10 000 ppm in the
    diet for 93 days. Food consumption and behaviour were examined daily
    and body weight gain was measured weekly. Haematological examinations,
    blood chemistry and urinalyses were perfumed at 0, 45 and 92 days. At
    the conclusion of the study, half of the animals were sacrificed and
    the remaining animals were maintained on normal feed for two weeks
    after which they were sacrificed. Gross and microscopic examinations
    were made on tissues and organs. A minor reduction in growth occurred
    at 10 000 ppm and mortality was noted at this level. There was no
    effect on food consumption at any dose level. There were no effects on
    behaviour, and haematological and urinalyses values were normal. Blood
    chemistry was normal except that, at the conclusion of the study,
    there appeared to be a slight increase of uric acid in the blood at 10
    000 ppm in both males and females. Gross examination of the tissues
    and organs of females sacrificed immediately at the conclusion of the
    feeding study indicated an increase in the absolute liver weight. The
    absolute liver weight of males was increased at the two highest dose
    levels only. There was a slight increase in liver to body weight ratio
    in females sacrificed 12 days after the feedings study ended. This was
    not reflected in males.

         The increase in absolute liver weight observed in females at 80
    ppm which did not begin to occur until 2000 ppm in males appears to be
    the most sensitive parameter noted in the study. As this effect was
    not observed to influence the liver to body weight ratio, except at
    dietary concentrations of 400 ppm and above, the no-effect level in
    rats was 80 ppm. Gross pathology was not consistently different from
    the controls at any dose level. At histological examination no lesions
    were demonstrated to be a result of feeding carbendazim at levels
    including 10 000 ppm. No histological changes of the liver tissue were
    found (Scholz et al., 1973).

    Dog. Groups of dogs (three male and three female beagle dogs per
    group) were fed carbendazim in the diet at dose levels of 0, 500, 1500
    and 4500 ppm for three months. Haematological examinations, blood
    chemistry and urinalyses were performed at 0, 6 and 12 weeks. There
    were no signs of poisoning observed in the study and animals showed no
    differences in behavioural response. A reduction in body weight was
    observed at 4500 ppm. Clinical chemistry and haematological values
    were normal. An increase in absolute and relative liver weight in
    males was noted at 4500 ppm and in females at 1500 ppm. The relative
    weight of adrenals was slightly increased in males at 1500 ppm. The
    heart weight was significantly reduced in females at 4500 ppm.

    Histological examination of the liver in the 4500 ppm dose group
    revealed perivenous infiltrates and zones of asymmetric proliferation
    in the periportal areas or in the liver parenchyma with liver cell
    regeneration and local hyperaemia. These changes together with signs
    of broncho pneumonia were considered to be of infectious origin and
    not related to the carbendazim treatment. No other tissues showed any
    adverse histological effects. A slight and not significant effect on
    the liver weight of female dogs of the level 500 ppm of carbendazim in
    the diet is considered marginal, but cannot be completely dismissed on
    the basis of examination of three animals (Kirsch et al., 1973).

    Long-term studies

         None available.

    Comments

         Carbendazim, methyl 2-benzimidazole carbamate, is a fungicide of
    low acute toxicity. Its fate in animals is not known and needs to be
    clarified.

         Limited studies on mice and rats have indicated no mutagenic
    potential or adverse effect on the male sex organs although high
    levels resulted in testicular damage. Data is not available on the
    effect of carbendazim on reproduction or on its teratogenic potential.
    In short-term studies in the rat and the dog an increase in the liver
    weight was the most significant Pinding. This effect was marginal at
    80 ppm in the rat and at 500 ppm in the dog and was substantial at 400
    ppm and at 1500 ppm in the rat and dog respectively. No histological
    changes were seen in the liver. Because of the observed effect on the
    liver and as no long-term or reproduction studies were available, an
    acceptable daily intake for man was not established.

    RESIDUES IN FOOD AND THEIR EVALUATION

    Use pattern

         Carbendazim, or MBC, was introduced as a commercial fungicide in
    1972 and has through 1972-1973 obtained registration and approval for
    specified pre-harvest treatments in a number of countries in
    temperate, subtropical and tropical regions (see Table 1). It is
    available as wettable powder formulations or as dispersions containing
    60 and 20% active ingredient, respectively.

         Carbendazim is generally recognized as the chemical entity, which
    is mainly responsible for the fungitoxic activity of some other
    systemic benzimidazole fungicides, including benomyl and
    thiophanate-methyl. From these, MBC is formed as the major metabolite
    in and on plant material. Accordingly, the antifungal effects of
    carbendazim are described as practically similar to the two mentioned
    chemicals, i.e. it is a broad-spectrum, systemic fungicide which is
    active against moulds, rots and blight. It is claimed effective

    against apple scab, powdery mildew, botrytis and Penicillim induced
    decay of citrus fruits.

    TABLE 1. INFORMATION ON REGISTERED AND APPROVED USES OF
             CARBENDAZIM (SEPTEMBER 1973)

                                                                     

    Countries in which       Registered for following crops
    registered
                                                                     

    Australia                stone fruit, strawberries, apples,
                             pears, peanuts, cucumbers

    Austria                  apples, cucumbers, grapes, lettuce

    Colombia                 bananas, coffee, rice

    Costa Rica               tropical crops, grapes, vegetables,
                             ornamentals, hops

    El Salvador              coffee, vegetables, cotton

    England                  apples, blackcurrants, beans,
                             gooseberries, tomatoes, cucumbers,
                             ornamentals, bulbs, grapes

    Ecuador                  bananas, rice

    France                   grapes, cereals, fruit

    Guatemala                coffee, vegetables, cotton

    Holland                  bulbs

    Morocco                  bananas, pineapples

    New Zealand              apples, citrus, roses, stone fruit

    Spain                    stone fruit, ornamentals, vegetables,
                             pome fruit

    South Africa             cotton, tobacco, vegetables

    Switzerland              strawberries

    Uruguay                  vegetables, grapes, sugar beet, fruit
                                                                     

    Residues resulting from supervised trials

         Carbendazim residue data from pre-and post-harvest uses in
    different countries covering a range of single or repeated
    applications on fruits and vegetables has been presented by the
    manufacturers (Hoechst, 1973). A summarized list of residue ranges
    extracted from these data are presented in Table 2.

         Generally, most sprayings and dipping procedures tend to leave
    residues, the level of which is primarily governed by the applied
    dosages (concentration of active ingredient and number of treatments).
    The decrease in carbendazim residue levels with time seems consistent
    with a normal growth dilution effect following application, while
    chemical and/or physical losses seem to be of lesser importance,
    justifying the classification of carbendazim as a relatively
    persistent fungicide.

         Relatively stable deposits of carbendazim remain after the
    dipping of apples, citrus and bananas. In these fruits the residues
    are mostly concentrated on the peels. Citrus fruits, however,
    regularly show MBC residues penetrating into the edible inner parts of
    fruit in concentration ranges up to about one tenth of the
    corresponding peel concentrations.

    Fate of residues

    Plant material

         Gorbach et al. (1973) showed that MBC after foliar application to
    cucumber plants under greenhouse conditions mostly remained on the
    leaf surfaces. Only about 10% penetrated into the plant tissue. A
    translocation to other parts of the plant thereafter was hardly
    detectable (about 0.1% of the applied amount), but the dominant route
    of transportation was with the transpiration stream, i.e. towards the
    leaf edges.

         Solel and Edgington (1973) and others showed that plant
    penetration after foliar applications and movement through the cuticle
    is less for MBC than for bonomyl. They found, however, a definite
    translocation (1.11-1.68% of the applied amount) of MBC to roots,
    stems and shoots, when the application rates were 5-10 times higher
    than those used in normal practice (Solel et al., 1973). They suggest
    that a downstream movement in treated plants is insignificant at lower
    concentrations.

         MBC is more readily absorbed into plants through the roots
    (Gorbach et al., 1973). Seven days after adding 14C-carbendazim to a
    hydroponic-culture of cucumber plants up to 16 ppm was found in the
    plant material. Of these, 95% were present as MBC. The remaining 5% of
    radio-active material behaved like a single substance on TLC,
    concluded to be 2-aminobenzimidazole (2-AB).



        TABLE 2. RESIDUES OF CARBENDAZIM IN VARIOUS CROPS FROM PRE- AND POST-HARVEST TREATMENTS
                                                                                                        
                             Application                MBC-residues (ppm)
    Crop                                                                                      Country
                    Rate                  Frequency     Range                      (number)
                                                                                                        

    Apples          50-60 g/100 l         Dipping       1.1-2.4                       (27)    Germany
                    100-500 g/ha          4-11 ×        0.3-1.9                       (53)    Germany
                    600-900 g/ha          7-11 ×        0.2-2.1                       (27)    Germany
                    1200-2400 g/ha        9-15 ×        1.6-8.4                       (36)    Germany
                    490 g/ha              3             2.2-3.6                       (12)    Netherlands
                    825 /h.               3             2.1-4.9                       (12)    Netherlands

    Bananas         5-20 g/100 l          Dipping       Int.: n.d.-0.2                 (8)    Ivory Coast
                                                        Peel: 0.5-2.0                  (8)    Ivory Coast
                    15-50 g/100 1         Storage       Int.: n.d.-0.2                (35)    Costa Rica
                                          Spray         Peel: 0.1-0.9                 (35)    Costa Rica

    Barley          300-500 g/100 kg      Seed          n.d.-n.d.                     (10)    Germany
                                          treatment

    Celery          450-1200 g/ha         7 ×           n.d-2.0                       (12)    England

    Cherries        3-4 g/tree            2 ×           n.d.-0.14                      (6)    Germany

    Coffee          660-1380 g/h.         1-7           n.d.-n.d.                      (5)    Kenya
    (raw beans)

    Cucumber        250-500 g/ha.         2 ×           n.d.-0.35                     (28)    Gernany

    Gherkins        1000 g/ha             1 ×           0.3-1.5                        (8)    Netherlands
    (under glass)

    Dwarf beans     450-1200 g/ha.        1             n.d-0.1                        (6)    England

    Gooseberries    720-900 g/ha.         4             1.6-2.2                        (5)    England

    Grapes          100-1120 g/ha.        4-10          0.3-9.3                       (57)    Germany

    Lemon           250 g/1100 l          Dipping       Int: 0.1-0.2                  (13)    Israel

    TABLE 2. (Cont'd.)
                                                                                                        
                    Application                         MBC-residues (ppm)
    Crop                                                                                      Country
                    Rate                  Frequency     Range                      (number)
                                                                                                        

                                                        Peel: 4.3-12.7                (13)    Israel

    Mandarins       25-75 g/100 l         Dipping       Int: 0.2-1.2                  (16)    Spain
                                                        Peel: 2.1-10.5                (16)    Spain

    Oranges         23-75 g/100 l         Dipping       Int: n.d-1.4                  (27)    Spain
                                                        Peel. 0.2-3.7                 (27)    Spain
                    250 g/100 l           Dipping       Int.: 0.1-0.7                 (24)    Israel
                                                        Peel: 4.0-16.0                (24)    Israel
                    600 g/ha              1 ×           Int: n.d.                      (2)    South Africa
                                                        Peel: n.d.                     (2)    South Africa

    Peaches         400 g/h.              4             0.2-1.1                       (12)    Germany

    Strawberries    375 g/ha.             4-7 ×         n.d.-18a                      (32)    Netherlands
                    600-2160 g/h.         2-3 ×         n.d.-1.2b                     (30)    Germany

    Sugar beets     90-180 g/ha           2-3           Leaves: 0.1-4.8               (12)    Germany
                                                        Beets: n.d.                   (12)    Germany

    Tomatoes        0.026-0.053 g/plant   4-8 ×         0.5-1.4c                      (22)    Netherlands
                    600-660 g/ha

    Winter wheat    125-480 g/ha          1 ×           Straw (0-14 days): 3.4        (16)    Germany
                                                        Straw (21-136 days): <0.1     (16)    Germany
                                                        Grains: n.d.                   (4)    Germary

    Melons          0.01 g/plant          3 ×           Int.: n.d.                            Netherlands
                                                        Peel: 0.6-0.8                  (3)    Netherlands
    Mushroom        6 kg/ha               1 ×           0.5                            (1)    Netherlands
                                                                                                        
    a Sampled at 0-14 days after last application.
    b Sampled at 9-39 days after last application.
    c Surface residues only. Interior: not detectable.
    n.d. - not detected = < 40.05 ppm.

    
         Carbendazim treatment of sugar beets by spraying gives
    significant deposits of MBC on the leaves, but uptake of active
    material by the beet roots is not detectable (Anon., 1973).

    Animal tissues

         Studies of the metabolic degradation of MBC after direct feeding
    to animals has not been Presented, but by analogy to the available
    evidence on metabolism of benomyl it is anticipated that hydroxylation
    may take place to produce 5-hydroxymethyl-2-benzimidazolecarbamate,
    followed by urinary excretion as glucuronide or sulfate conjugates
    (Gorbach, 1973).

    Soil

         Carbendazim is a relatively stable compound and it is known to
    show some persistence in soil (Gorbach, 1973). Only data on low dosage
    treatments (90-180 g/ha) of sugar beets in the soil are presently
    available and these indicate no detectable residues (i.e. <0.01 ppm).

    Methods of residue analysis

         So far the most reliable analytical methods for the determination
    of benomyl are based on the conversion to MBC and eventual
    saponification to 2-aminobenzimidazole (Pease and Gardiner, 1969;
    Pease and Holt, 1971). These methods can easily be adapted for the
    determination of MBC.

         Details of U.V.-spectrophotometric methods used by the
    manufacturers of MBC have been presented (BASF, 1972; Gorbach, 1972).
    MBC is extracted from the slightly alkaline sample material with ethyl
    acetate. The ethyl acetate solution is extracted into 1 N sulfuric or
    hydrochloric acid and again transferred into ethyl acetate after pH
    adjustment. This procedure is repeated and MBC is finally partitioned
    into 1 N acid solution for spectrophotometric measurement at 281 nm.
    The detection limit of the method is given as 0.05 ppm and recoveries
    are 70-80% for various crops containing 0.1-0.5 ppm MBC.

    National tolerances

         According to the information available to the meeting, the
    following tolerances for carbendazim have been established:

    Australia           Apples and pears                      2 ppm
                        Cucumbers                             0.5 ppm
                        Peanut kernels                        0.1 ppm

    Federal Republic    Citrus fruit                          10 ppm
    of Germany          Grapes                                3.0 ppm
    (MBC residues       Berries                               2.0 ppm
    calculated as       Vegetables (except cucumbers),
    benomyl)            bananas, citrus fruits

                        (without peel), stone fruit         1.0 ppm
                        Cucumbers, cereals                  0.5 ppm
                        Bananas (without peel)              0.2 ppm
                        Other plant produce                 0.1 ppm

    Netherlands         Fruit and vegetables                  2 ppm
                        Raw cereals (provisional)           0.5 ppm


    Appraisal

         Carbendazim is recognized as one of the major fungitoxic
    principles of the systemic benzimidazole fungicides, benmyi and
    thiophanate-methyl. Marketed as a fungicide on its own merits, it has
    obtained official registration in various countries and it is claimed
    to be effective in combating several fungal diseases, including apple
    scab, mildew and botrytis, and is applied both pre-harvest and
    post-harvest.

         A fair amount of data on residue in crops following approved
    foliar applications and dipping procedures has been made available to
    the Joint Meeting. Data were derived from supervised trials. Some
    studies involved excessive rates resulting in residue levels higher
    than would be likely following good agricultural practice.

         The residue levels reported generally reflect the dosages applied
    and the decline of residue levels mostly follows the pattern which
    characterizes growth dilution.

         Carbendazim is a chemically stable and relatively persistent
    fungicide which only metabolizes to a limited extent in plants and in
    soil. The only detected metabolite is 2-aminobenzimidazole, which
    constitutes less than 5% of the total residues in leaves.

         Although direct experimental data is lacking, carbendazim is
    expected to show relatively high persistence in soils. It is readily
    absorbed through the root systems of plants and, accordingly, there
    may be a possibility of unintentional uptake into subsequent crops. 
    Data, on the other hand, that indicates that carbendazim may not reach
    through the soils into groundwater has been made available to the
    meeting.

         By analogy to other benzimidazole compounds, carbendazim may be
    anticipated to metabolize in the animal into hydroxylated analogues
    which may appear in meat and milk products.

         Analytical methods which may be adapted for regulatory purposes
    are available.

    RECOMMENDATIONS

         As no ADI could be established, no tolerances are recommended.
    Following officially acceptable use in various countries, residues of
    carbendazim can occur in the following commodities up to the levels
    indicated. The guideline levels indicated below are not likely to be
    exceeded when following good agricultural practice, including
    pre-harvest and postharvest treatments where applicable.

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

    Guideline levels                                          ppm

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

    Apples, pears, strawberries, tomatoes, lettuce,
    gooseberries                                              5

    Gherkins, beans (dwarf), celery, plums                    2

    Mushrooms, bananas (whole)                                1

    Cucumbers, melons, bananas (pulp)                         0.5

    Raw cereals, sugar beet, coffee beans (raw)               0.11

    Sugar beet tops                                           5

    FURTHER WORK OR INFORMATION

    Required (before an acceptable daily intake can be estimated)

    1.   Long-term studies to investigate chronic toxicity and
         carcinogenicity.

    2.   Reproduction and teratogenicity studies.

    3.   Metabolism and distribution studies in several animal species.

    4.   Elucidation of the effect on the liver in female rats and dogs.

    5.   Information on the nature and level of residues in meat, milk,
         and eggs, after feeding animals on crops or feedstuffs treated
         with carbendazim.
              

    1 At or about the limit of determination

    Desirable

    1.   Further studies to define the apparent "high-level" effects on
         male reproductive organs.

    2.   Information on the possible uptake from soils into subsequent
         crops.

    3.   Information on residues in food in commerce.

    REFERENCES

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    Hoechst AG and BASF Aktiengesellschaft (Unpublished)

    BASF Aktiengesellschaft (1972) Landwirtschaftliche Versuchsstation
    1972 Limbürgerhof. Spektralphotometrische Bestimmung von BCM. Dated
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    Buchenauerp H, Edgington, L.V. and Grossmann, F. (1973) Photochemical
    transformation of thiophanate-methyl and thiophanate to alkyl
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    Clemons, G.P. and Sisler, H.D. (1969) Formation of a fungitoxic
    derivative from Benlate. Phytopath. 59: 705

    Clemons, G.P. and Sisler, H.D. (1971) Localization of the site of
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    Douch, P.G.C. (1973) The metabolism of benomyl fungicide in mammals.
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    Gardiner, J.A, Brantley, R.K. and Sherman, H. (1968) Isolation and
    identification of a metabolite of methyl
    1-(butylcarboyl)-2-benzimidazole carbamate in rat urine. J. Agr. Food
    Chem. 16: 1050-1052

    Gorbach, S. (1972) Analysenmethode zur Beatimmung von 2-Carbomethoxy
    aminobenzimidazole in Pflanzlichen Material. Paper presented by
    Farbewerke Hoechst AG (Unpublished)

    Gorbach, S. (1973) Ubersicht das Abbauverhaltens von Carbendazim (BCM)
    in Tier und Pflanze (Stand August 1973). Summary report presented by
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    Gorbach, S, Thier, W. and SchuIze, E,F. (1973) Untersuchungen zum
    Rüchstandsverhalten und Metabolismus von Hoe 17411 OF-2-14C an
    Gurkenpflanzen unter Gewächshaus bedingungen. Forschungsbericht No.
    221/73 submitted by Farbewerke Hoechst AG (Unpublished)

    Hammerschlag, R.S. (1973) Benomyl and methyl-2-benzimidazole carbamate
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    Hofmann, H. Th. (1971) Acute oral toxicity of methyl-2-benzimidazole
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    Hofmann, H. (1972) Bericht uber die Prufung der akuten oralen oxizitdt
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    Hofmann, H. Th. and Kirsch, P. (1972) Bericht uber die Prufung von
    2-(methoxy-carbamoyl)-benzimidazole im 28-tage-futterungsversuch an
    der Ratte. Unpublished report submitted by BASF AG

    Hofmann, H. Th. and Peh, J. (1973) Bericht uber die Prufung von MCB
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    Hunter, B., Batham, F. and Newman, A.J. (1973a) BCM oral toxicity to
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    Hunter, B. Benson, H.G., Street, A.E., Heywood, R. and Newman, A.J.
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    Kirsch, P., Koob, K.  Freisberg, K.O. and Birnsteil, H. (1973) Bericht
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    Pease, H.L. and Holt, R.F. (1971) Improved method for determining 
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    See Also:
       Toxicological Abbreviations
       Carbendazim (EHC 149, 1993)
       Carbendazim (HSG 82, 1993)
       Carbendazim (ICSC)
       Carbendazim (Pesticide residues in food: 1976 evaluations)
       Carbendazim (Pesticide residues in food: 1977 evaluations)
       Carbendazim (Pesticide residues in food: 1978 evaluations)
       Carbendazim (Pesticide residues in food: 1983 evaluations)
       Carbendazim (Pesticide residues in food: 1985 evaluations Part II Toxicology)
       Carbendazim (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
       Carbendazim (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
       Carbendazim (JMPR Evaluations 2005 Part II Toxicological)