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    CARBENDAZIM     JMPR 1976

    Explanation

         This pesticide was evaluated by the 1973 Joint Meeting
    (FAO/WHO, 1974b). The data were not considered adequate for the
    estimation of an acceptable daily intake for man and the following
    studies were required.

         (1) Long term studies to investigate chronic toxicity and
    carcinogenicity.

         (2) Reproduction and teratogenicity studies.

         (3) Metabolism and distribution studies in several species.

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

         These studies have not been provided, and further evaluation
    for the estimation of an acceptable daily intake was not possible.

         Some further information on the occurrence and fate of
    residues and on methods of analysis which has become available
    since the 1973 Meeting is evaluated in this monograph addendum.

    RESIDUES IN FOOD AND THEIR EVALUATION

    RESIDUES RESULTING FROM SUPERVISED TRIALS

         New residue data derived from supervised trials with fruits,
    vegetables and individual industrial crops have been presented from
    various sources. Most of the residues fall within the ranges
    described in the earlier monograph (FAO/WHO, 1974b), and the data
    therefore give further support to the guideline levels already
    recorded.

    Lettuce

         Special mention should be made of the data on carbendazim
    applications to lettuce grown during the winter season in
    greenhouses (Netherlands, 1976). The residue data presented in
    Table 1 indicate that up to 2 months may be required before
    carbendazim residues fall below 5 mg/kg when application is at the
    rate of 4 kg/ha. This situation was dealt with in greater detail by
    the 1975 Meeting in the evaluation of benomyl (FAO/WHO, 1976b) and
    on the basis of the information then available the guideline level
    of 5 mg/kg for benomyl, calculated as carbendazim, was recorded.

         Unless carbendazim can be applied at lower dosage rates and
    the usual trimming prior to marketing is effective in removing the
    bulk of the residue, the level of 5 mg/kg would not be adequate to
    cover residues resulting from the direct application of


    carbendazim, even with a very long pre-harvest interval. The Meeting
    considered that it could not record a limit high enough to cover 
    residues of the order indicated in Table 1. It was agreed that the
    guideline level of 5 mg/kg recorded by the 1975 Meeting for benomyl
    in lettuce and applying to total residues of benomyl, carbendazim and
    2-aminobenzimidazole, expressed as carbendazim, should be retained.

    Animal feedstuffs

         New information on carbendazim residues in wheat (Netherlands,
    1976) and peanuts (Snelson, 1976) are summarized in Table 2. This
    supplements earlier data and confirms the previous guideline level
    of 0.1 mg/kg (at or about limit of determination) for raw cereals.
    Amendments, however should be made to include peanut hulls and hay
    and wheat straw for animal feeding purposes.

    FATE OF RESIDUES

    In plants and soil

         There is a continued interest in the behaviour of carbendazim
    and other benzimidazole fungicides in general plant metabolism.
    Rouchaud and co-workers (1974) confirmed the rapid uptake and
    translocation of carbendazim following the application of either
    carbendazim or benomyl) into the leaves of melon plants. Leroux &
    Gredt (1975) from work with maize plants, suggest that carbendazim
    is taken up in its non-ionic form, and they show that the maximum
    absorption is at the base rather than the apex of the roots.

         In the studies of Rouchaud et al. (1974) 7 metabolites were
    identified from non-radioactive benomyl, namely: carbendazim,
    2-aminobenzimidazole, benzimidazole, o-aminobenzonitrile, aniline
    and B-glycosidic conjugates of carbendazim and of
    2-aminobenzimidazole.

         The presence and rate of degradation of carbendazim in soils
    were investigated by van Wambeke & van Assche (1976) in a well
    designed 4-factor experiment to study the effects of soil
    composition, microbiological activity, moisture content and
    temperature. All of these greatly affect the degradation and their
    influence is illustrated by the findings that only 0.1% of the
    applied dosage of carbendazim was recovered after 126 days in a
    humid. organic soil kept at 23C, while about 60% was recovered
    from a dry sandy soil, which was steam sterilized and kept at 10C
    for the same period.

         Carbendazim is ionized by both acids and bases, and this
    affects its behaviour in soils. Aharonson & Kafkafi (1975a) have
    shown that acidity increases the absorption of carbendazim to soil
    particles and thereby hinders leaching. These authors also confirm
    the increased rate of degradation of carbendazim by increased
    humidity of the soil.

    
    TABLE 1. Carbendazim residues on greenhouse (winter) lettuce,
             Netherlands

                                                                                     
    Treatment      Dosage     Time after                 Residues, mg/kg,
                              last application,           mean (range)                
                              days                 Exp. 1              Exp. 2
                                                                                     

    Spraying       4 kg/ha    11                   -                   31 (25-36)
    (W.P. 47%)
                              20                   -                   19.5 (11-24)

                              27                   -                   10 (9-11.5)

                              32/34                17.9 (13-28)        6.5 (1.8-11.5)

                              41                   8.2 (5-12)          -

                              53                   6.5 (4-8.5)         -

                              62                   0.9 (0.5-1.2)       -
                                                                                     

    TABLE 2. Carbendazim residues in wheat and peanuts

                                                                                   
    Country         Application      Days after   Residues, mg/kg
    and                              last
    Crop            Rate,            treatment                  Straw/
                    kg/ha   No.                   Kernels       hay          Hulls
                                                                                   

    Netherlands     0.15    2        52           <0.1          <0.1

                            3        50-51        <0.1-<0.1     <0.1-<0.1

                    0.24    1        48-120       <0.1-<0.1     <0.1-<0.1

                            3        50-51        <0.1-<0.1     <0.1-<0.1

                    0.3     2        15-54        <0.1          0.15

                    0.5     1        54           -             <0.1

    Australia       0.3     5        28           <0.1          2.0          <0.2
    Peanuts
                                                                                   

    
    TABLE 3. Residues of carbendazim (including benomyl) in imported
              samples (Sweden)o)

                                                                  

    Crop                Number of samples containing .....mg/kg+)
                        0.1      0.1-0.5     0.6-2.0      2.1-5.0
                                                                  

    Apples              101      18          6            2

    Grapes              2


    Oranges             32       1                        1

    Peaches             5

    Pears               6

    Potatoes            18

    Strawberries        15       3           3
                                                                  

    Total               213 samples

    o) = February 1973 - July 1975

    +) = Calculated as benomyl

    Residues in food in commerce or at consumption

         Earlier reports from Belgium and the Netherlands on market sample
    surveys for benzimidazole fungicides have been described in a previous
    monograph on benomyl (FAO/WHO, 1976b) they are of equal interest in
    connection with carbendazim. A Further survey has now been reported
    from Sweden, covering a total of 213 samples of imported fruit (Table
    3). This survey gave broadly similar results, indicating that
    quantifiable residues of carbendazim may be found in about 25% of
    imported apples and strawberries at the time of marketing. Significant
    residues were also found in two of 34 samples of oranges.

    METHODS OF RESIDUE ANALYSIS

         As in the case of other benzimidazole fungicides (FAO/WHO,
    1976b), the greatest interest recently has been concerned with two
    problems, namely the efficiency of extraction from crops and soils and
    the selective determination of benzimidazole compounds, especially by
    means of high speed or high-performance liquid chromatography. In
    addition, a recent report on the gas-liquid chromatography of
    carbendazim after trifluoroacetyl derivatization has been published
    (Rouchaud and Decallonne, 1974).

         Valuable reviews have been published on these subjects by Austin
    et al. (1975), Baker & Hoodless (1974), Gorbach (1976), Watkins
    (1976) and others.

         For the final determination of carbendazim, UV-spectrophotometry
    still seems to be the preferred method of measurement. This method
    when combined with partition clean-up offers an adequate sensitivity
    for most routine purposes (Gorbach, 1976). In the recently published
    methods based on high speed liquid chromatography (Maeda & Tsuji,
    1976) and gas liquid chromatography (Rouchaud & Decallonne, 1974) the
    limit of detection is given as 0.02 mg/kg.

    NATIONAL TOLERANCES REPORTED TO THE MEETING

         Table 4 lists national tolerances reported to the Meeting. They
    are additional to those reported previously with the exception of the
    Netherlands tolerance "Grain (raw) 0.1 mg/kg" which replaces the
    earlier provisional tolerance "Raw cereals 0.5 ppm".

    TABLE 4. National tolerances reported to the Meeting

                                  Tolerance,
    Country        Crop           mg/kg

    Netherlands    Citrus         3.5
                   Grain (raw)    0.1
                   Potatoes       0.05

    New Zealand    Fruits         5
                   Vegetables     2
                   Cereals        1

    APPRAISAL

         This compound was evaluated by the 1973 Joint Meeting and
    guideline levels for a number of commodities were recommended. Since
    then new data have become available, partly in response to earlier
    requests and partly as supplementary information which supports the
    earlier recommendations.

         Data have been presented from supervised trials on carbendazim
    treatments of greenhouse lettuce grown during the winter season. The
    rate of decline of residues was so slow that even 50 days after
    treatment the mean residue was above the guideline level of 5 mg/kg
    previously recorded for benomyl but applying to total residues of
    benomyl, carbendazim and 2-aminobenzimidazole. The Meeting considered
    that it could not record a guideline level high enough to cover
    residues resulting from such a use of carbendazim. In view of the
    earlier evaluation of data on carbendazim and other benzimidazole
    fungicides, it confirmed the guideline level of 5 mg/kg for benomyl.

         On the basis of new information, recommendations can be made for
    guideline levels in certain peanut products and in straw of wheat.

         In the course of general studies on the fate of benzimidazole
    fungicides, a rapid uptake and translocation of carbendazim residues
    into plants has been confirmed. The behaviour and degradation of
    carbendazim residues in soils has been further described.

         In response to the request of the 1973 Meeting, information on
    market sample surveys made in Belgium, the Netherlands and Sweden has
    been presented to this and to the 1975 meeting. The data indicate that
    residues of benzimidazole fungicides, presumably including
    carbendazim, may be present in up to about 25% of a number of fruits.
    vegetables and berries. Residues in positive samples were generally
    low and only in occasional samples approached guideline levels.

         Spectrophotometric, gas chromatographic and high-performance
    liquid-chromatographic methods are now available for the determination
    of carbendazim in various commodities. A full validation of methods
    for regulatory purposes still seems to be lacking.

    EVALUATION

         The following guideline levels, additional to those of 1973, are
    recorded.

    Commodity              Guideline level,
                             mg/kg

    Peanut                   0.1

    Peanut hull              0.2

    Peanut hay, wheat straw  2

    FURTHER WORK OR INFORMATION

    Required (before an acceptable daily intake can be estimated and
    maximum residue limits can be recommended)

    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.

    Desirable

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

    2.   Validation of methods of residue analysis for regulatory
         purposes.

    REFERENCES

    Aagren, O. Residue data and other information on Benomyl and
    1976                carbendazim submitted by the Swedish Codex
                        Secretariat. Letter no. 308/76 of July, 30.

    Aharonson, N. & Kafkafi, U. Adsorption of Benzimidazole
    1975a               fungicides on montmorillonite and kaolinite clay
                        surfaces. J. agr. Fd Chem. 23, 434-437.

    Aharonson, N. & Kafkafi, U. Adsorption, mobility and persistence of
    1975b               thiabendazole and methyl-2-benzimidazole-carbamate
                        in soils. J. agr. Fd Chem. 23, 720-724.

    Austin, D.J., Briggs, G.G. & Lord, K.A. Problems in the assay
    1975                of residues of carbendazim and its precursors.
                        Proc. 8th Brit. Insec. Fung. Conf., Brighton,
                        November.

    Baker, P.B. and Hoodless, R.A. Analytical methods for the detection
    1974                and determination of residues of systemic
                        fungicides. Pestic. Sci., 5: 465-472.

    FAO/WHO. 1973 Evaluations of some pesticide residues in Food.
    1974                FAO/AGP/1973/M/9/1. WHO Pesticide Residues Series,
                        No. 3.

    Gorbach, S. Review on the residue analysis of the systemic
    1976                fungicides benomyl, carbendazim, thiophanate,
                        thiophanatemethyl and thiabendazole. Paper
                        presented to the International Union of Pure and
                        Applied Chemistry (IUPAC). 36 pages. Analytical
                        Laboratory, Hoechst, Germany.

    Leroux, P. & Gredt, M. Absorption of methylbenzimidazole-
    1975                2-yl-carbamate (carbendazim) by corn roots.
                        Pestic. Biochem. Physiol. 5, 507-514.

    Maeda, M. & Tsuji, A. Determination of benomyl and 2
    1976                (4-thiazolyl) benzimidazole in plant tissues by
                        high-performance liquid chromatography using
                        fluorometric detection. J. Chromat. 120, 449-455.

    Netherlands. Carbendazim residue data submitted by the Nation
    1976                al Codex Committee of the Netherlands.
                        Staatstoezicht op de Volksgezondheid, September
                        28.

    New Zealand. Information received from the National Codex
    1976                Committee of New Zealand.

    Rouchaud, J.P. & Decallonne, J.R. A gas chromatographic method
    1974                for the analysis of MBC in plants and soil. J.
                        agr. Fd Chem. 22, 259.

    Rouchaud, J.P., Decallonne, J.R. & Meyer, J.A. Metabolic Fate of
    1974                methyl-2-benzimidazole carbamate in melon plants.
                        Phytopathology, 64, 1513-1517.

    Snelson, J.T. Australian Residue data submitted through the
    1976                National Codex Committee of Australia.

    Van Wambeke, E. & van Assche, C. The importance of some factors
    1976                involved with the persistence of carbendazim (MBC)
                        in soil. Report presented at the 28th
                        International Symposium on Crop Protection in
                        Gent, May 4, 1976.

    Watkins, D.A.M. Benzimidazole Pesticides: Analysis and
    1976                Transformations. Pestic. Sci. 7, 184-192.
    


    See Also:
       Toxicological Abbreviations
       Carbendazim (EHC 149, 1993)
       Carbendazim (HSG 82, 1993)
       Carbendazim (ICSC)
       Carbendazim (WHO Pesticide Residues Series 3)
       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)