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    THIABENDAZOLE         JMPR 1977

    Explaination

    Thiabendazole was evaluated by the Joint Meeting in 1970, 1971, 1972
    and 1975 (FAO/WHO 1971, 1972, 1973, 1976). An ADI was allocated in
    1970 and maximum residue limits have been proposed for apples, pears,
    bananas, citrus fruits and potatoes. In view of the evidence that the
    administration of thiabendazole to livestock or the feeding of
    livestock on treated commodities or food wastes containing
    thiabendazole residues produces no significant residues in milk, meat
    and edible offals a maximum residue limit at or about the limit of
    determination was recommended.

    Some additional data were obtained on residues from both pre-harvest
    and post-harvest treatments and on the fate of these residues in
    processing: further data were obtained on the fate of thiabendazole
    residues in livestock. Results of a study with human volunteers were
    also received. This monograph addendum is an evaluation of the new
    data.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Tissue residue studies in animals

    These are described in the section "Fate of residues", "In animals".

    OBSERVATIONS IN HUMANS

    A double blind study was carried out with about 100 male volunteers,
    half of them receiving 250 mg/day thiabendazole during 6 months and
    half of then a placebo. Each subject was interviewed weekly and any
    potential side effect was recorded. General physical examination and
    laboratory examinations (haematology, cholesterol, glucose, urea,
    alkaline phosphatase, thymol turbidity, bilirabin in serum and
    urinalysis) were carreid out before the test and after 4, 12 and 24
    weeks. PBI in serum and BOG were carried out only at the beginning and
    after 24 weeks. 36 subjects on thiabendazole and 41 on placebo
    completed the study (none was removed from the study in relation with
    the drug). As thiabendazole has a possible influence on the thyroid
    the values for PBI were evaluated carefully. No indication, however,
    was found of a decrease or increase in PBI values under influence of
    thiabendazole. Under the conditions of the study thiabenclazole was
    well tolerated at a dosage of 250 mg/clay during 24 weeks. go effect
    on any of the parameters studied could be clearly ascribed to the drug
    (Colmore, 1965).

    COMMENTS

    A study in human volunteers with a dose of 250 mg/day corresponding to
    3-4 mg/kg bw was reviewed. No effects could be ascribed to the
    thiabendazole administration, although many parameters were measured
    including a thyroid function test.

    In 1970 an ADI for humans established of 0.05 mg/kg bw based on a
    no-effect level in the rat of 10 mg/kg bw. Observations on humans
    allowed the meeting to increase the ADI for humans.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

    Rat.      10 (mg/kg bw)/day
    Dog:      20 (mg/kg bw)/day
    Humans:   3  (mg/kg bw)/day

    ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR HUMANS

    0-0.3 mg/kg bw

    RESIDUES IN FOOD AND THEIR EVALUATION

    USE PATTERN

    The world-wide use of thiabendazole as an agricultural fungicide has
    grown greatly since it was first introduced as a post-harvest
    treatment for citrus, bananas and pome fruit in the late 1960s.
    Thiabenclazole products are now registered for 40 or more uses as
    pre-plant and pre-harvest treatments as well as for post-harvest use.
    Table 1 gives a comprehensive review of current use patterns. Not all
    uses are registered in all countries. Many applications are limited to
    the control of only a few diseases on each crop.

    A wide variety of formulations are available including dusts, wettable
    powders, flowable pastes and thermal dusting tablets (smoke
    generators). Thiabendazole is often formulated along with other
    fungicides to increase the range of diseases controlled.

    RESIDUES RESULTING FROM SUPERVISED TRIALS

    Bananas

    In addition to the data evaluated in 1970 (FAO/WHO 1971) extensive
    data are available from the study of pre-harvest applications of
    thiabendazole to bananas in Brazil, Costa Rica, Dominican Republic,
    Equador, Guadeloupe and Honduras. These are summarized in Table 2.

    For the control of important fungal diseases of bananas, thiabendazole
    is applied as a suspension in mineral oil emulsified in water. These

    sprays are applied every four weeks throughout the year. Bananas take
    many months to develop to maturity and they may be harvested
    throughout the year. Extensive studies from many trials in all of the
    above countries indicate that the residue from the pre-harvest
    application of thiabendazole seldom exceeds 0.1 mg/kg. Only
    insignificant amounts are found in the pulp, indicating relatively
    little systemic transfer.

    Bananas analysed after both pre-and post-harvest application of
    thiabendazole were found to contain increased quantities of residue
    with the maximum in the range of 1 mg/kg. In this case the
    concentration in the peel was usually about 20 times higher than in
    the pulp, the concentration in the pulp seldom exceeding 0.1 mg/kg.
    There appears to be a trend for unripe fruit to take up slightly more
    thiabendazole than ripe fruit. In the case of ripe fruit there appears
    to be no tendency for migration of the deposit from the peel into the
    pulp whereas in unripe fruit a small but measurable migration occurs.

    Cabbage

    Thiabendazole has proved effective for use as a fungicide in red and
    white cabbage, applied post-harvest as a mist spray to protect the
    cabbage in store prior to the production of sauerkraut. Two sprays are
    recommended, to be used soon after harvest and 60 days later. In
    practice, the use rate amounts to 0.34 mg/kg on the cabbage. An
    extensive experiment carried out in Germany revealed residues ranging
    from 0.06 to 2.6 mg/kg.

    Cereals

    Thiabendazole has proved effective for use as a fungicide in cereals,
    applied as a foliar spray to control footrots and ear diseases. It is
    generally applied in combination with contact fungicides to broaden
    the spectrum of activity. Although a number of applications may be
    made the last application is generally not later than 6 weeks before
    harvest.

    Extensive residue trials carried out in the Netherlands, Germany and
    the United Kingdom indicate that for the most part the residues in
    grain following such treatments are less than the limit of
    determination though several studies revealed residues ranging up to
    0.25 mg/kg. The data indicate that the residue in straw is not
    significantly greater than in the grain.

    Thiabendazole has found application for the control of seed-borne
    diseases of meat, oats, barley and rice.


        TABLE 1. Thiabendazole - use pattern

                                                                                                                                        

    Crop                           Pre-plant applications         Pre-harvest applications            Post-harvest applications

                             No.         Rate                   No.              Rate              No.                Rate
                                                                                                                                        

    Apples and pears                     -                      2-10             450-1350 g/ha     1                  500-2000 mg/l
    Asparagus                            -                      3                280 g/ha                             -
    Avocado                              -                      1                -                 1                  1000-3250 mg/l
    Bananas                              -                      10               30-150 g/ha       1                  150-300 mg/l
    Berries                              -                      3                270-1200 g/ha                        -
    Cabbage                              -                                       -                 1                  0.34 g/tonne
    Celery                               -                      3                270-1200 g/ha                        -
    Cereals                  1           60-200 g/100kg seed    2                500-100 g/ha                         -
    Cherries                             -                      1                270-360 mg/l                         -
    Citrus                               -                      1                300-900 mg/l      1                  500-5000 mg/l
    Cotton                   1           265 g/100 kg seed                       -                                    -
    Cucurbits                            -                      1                600-1350 mg/l     1                  650-1000 mg/l
    Grapes                               -                      3                900-1350 mg/l                        -
    Mango                                -                                       -                 1                  1000-2500 mg/l
    Mushrooms                            -                      3                12-24 g/100m3                        -
    Onions and garlic        1           900-1800 mg/l          1                1260-1800 g/ha                       -
    Pastures                             -                      1                140-280 g/ha                         -
    Potatoes                 1           40-150 g/tonne                          -                 1                  42 g/tonne
    Rice                     1           60-150 g/100 kg seed   2                112-315 g/ha                         -
    Soybeans                 1           30-240 g/100 kg seed   2                225-315 g/ha                         -
    Sugar beet                           -                      2                200-400 g/ha                         -
    Sweet potato             1           400 mg/l                                -                                    -
    Tobacco                              -                      1                1350 mg/l         1                  600 mg/l
    Tomato                               -                      3                225-450 g/ha                         -
    Turf                                                        2                20-36 g/100m2                        -
                                                                                                                                        

    TABLE 2. Thiabendazole - residues resulting from pre-harvest uses
                                                                                                                                          

                                            Application                  Residues (mg/kg) at intervals (days) after application
    Crop           Country       Year  no.  rate        formulation    1         2       5         10        20        40        60
                                            g.a.i/ha
                                                                                                                                          

    Bananas        Costa Rica    1973  12   146         flowable                 0.01
    (WHOLE)        Dominica Rep. 1974  14   145         flowable                                                       0.05
                                 1975  10   145         flowable                         0.05

                   Honduras      1972  1    158         flowable                 0.06

                   Brazil        1976  6    135         flowable                                                       0.06
                                 1977  8    135         flowable       0.14

                   Ecuador       1976  10   125         flowable                         0.03

    Bananas        Various                  Various                    0.0       0.0     0.0                           0.0
    (PULP)

    Onions         Netherlands   1974  2    300         WP                                                             <0.1      <0.1

    Soybean        USA           1974  3    200         flowable                                                       0.01
                                       4    350         flowable                                                       0.02
                                       4    1100        flowable                                                       0.04

    Strawberries   Netherlands   1974  4    3200        fumigant                 0.24
                                 1975  6    2400        fumigant                         <0.05
                                 1976  7    2400        fumigant                         <0.05

    Sugar beet     USA           1967  2    200         flowable                                             0.07
                                 1967  4    200         flowable                                             0.18
                                 1967  6    200         flowable                                             0.01

    Tomatoes       Netherlands   1973  1    1200        fumigant       <0.1      <0.1    <0.1
                                       2    1800        fumigant       <0.1      <0.1
                                       4    1200        fumigant       <0.1      <0.1
                                 1973  1    300         WP                                                             <0.1

    TABLE 2. Thiabendazole - residues resulting from pre-harvest uses

                                                                                                                                          

                                            Application                  Residues (mg/kg) at intervals (days) after application
    Crop           Country       Year  no.  rate        formulation    1         2       5         10        20        40        60
                                            g.a.i/ha
                                                                                                                                          

    Wheat          Netherlands   1974  1    300         WP                                                             <0.2
    (GRAIN)        Germany       1975  1    675         flowable                                                                 0.23
                   UK            1976  1    300         WP                                                                       0.03

    Wheat          Netherlands   1974  1    300         WP                                                             <0.2
    (STRAW)        Germany       1975  1    675         flowable                                                                 0.15
                   UK            1976  1    300         WP                                                                       0.25
                                                                                                                                          

    

    Extensive trials carried out over several years in a number of
    different regions of the USA have indicated that when a variety of
    thiabendazole formulations are applied to seed wheat the highest
    residue of thiabendazole recovered from grain harvested from various
    cultivar seed was 0.03 mg/kg. This residue resulted only when the
    application rate was increased to 2.5 times the recommended rate.
    There is some reason to believe that even this residue is possibly an
    artifact due to interference with the fluorophotometric method used
    for the determination of thiabendazole residues.

    Onions

    Several studies carried in the Netherlands on onions grown from seed
    treated with thiabendazole seed dressing and thereafter by two foliar
    sprayings, indicated that the residues were below the limit of
    determination (0.1mg/kg) 40 and 60 days after the application of the
    foliar spray.

    Potatoes

    In addition to the extensive data evaluated in 1975 (FAO/WHO 1976),
    further studies carried out in Canada, the United Kingdom, USA, the
    Netherlands and Germany on potatoes treated with various formulations
    of thiabendazole at rates ranging from 10 to 45 g/tonne indicates that
    the residue on the unwashed whole potato may range from 1 to 16 mg/kg.
    The thiabendazole residues found on potatoes treated by a mist spray
    application at the recommended rate of 42 g/tonne ranged from 4.3 to
    13 mg/kg with an average of 9.2 mg/kg.

    This level is much higher than the residues found following spray
    application conditions used in the US, which apply 6 to 12 g/tonne and
    leave a residue of 1.8 to 2.3 mg/kg on the potatoes (see Table 3). In
    Germany and the Netherlands the treatment of potatoes by fog
    application is popular. Residue levels on potatoes treated with this
    fogging technique tend to be quite low ranging from 2.2 to 4.4 mg/kg
    following the application of 25 and 75 g thiabendazole per metric ton
    respectively.

    Obviously the residue detected on potatoes treated with a given rate
    of thiabendazole will vary widely with the application technique. In
    addition, the amount of residue found on the potato will depend on
    whether the tuber is washed or not before analysis. Reduction in
    residues of 20-50% have been shown in various trials after washing the
    treated potatoes (see "Fate of residues" "In storage and processing".

    Soybean

    Thiabendazole is effective against a range of diseases which affect
    soybeans and during 1974, 27 field trials were conducted in 14 states
    which involved from 1 to 4 applications and a range of application
    rates. Harvested seed was found to contain from 0.0 to 0.04 mg/kg of
    thiabendazole. The highest residue was found in harvested soybean seed
    from crops treated with 6 times the recommended rate.


        TABLE 4. Thiabendazole residues in potatoes

                                                                                                                             
                         Application                       Storage          Unwashed                         Washed
    Country      Year   No.   g ai/tonne   Formulation    (days)         Whole    Peel    Edible        Whole       Peel
                                                                                         portion
                                                                                                                             
    Canada       1974   1     -            WP             -              4.2
    (Estey)             1     -            WP             -              6.2

    UK
    (Tisdale
    and Lord)    1972   1     -            WP             -              16.2

    UK
    (Tisdale
    and Lord)    1972   1     45           Dust           -              2.3
                              22           Dust           -              4.8

    UK
    (Logan)      1974   1     42           WP             -              11.0
                              42           WP             -              8.4

    USA          1975   1     12           Flowable       -              2.38

    Netherlands  1976   1     10           WP             8 days         4.6                            1.1
                              20           WP             8 days         14.0                           1.8
                              40           WP             8 days         16.0                           4.3
                              30           WP             5 months       5.8                            1.5

    UK           1976   1     40           WP             0 days         18.0

    USA          1973   1     9.7          WP             -              1.8                            0.64

    Germany      1975   1     27           Flowable       1 day          7.6      14.8    0.6           1.3
                                                          14 days        6.3      16.2    0.7           1.9
                                                          28 days        6.2      13.0    0.7           2.2
                                                          56 days        9.7      17.8    0.4           3.6
                                                                                                                             
    

    Strawberries

    Thiabendazole has proved effective for use as a fungicide on
    strawberries in greenhouses, applied by fumigation. In trials made in
    the Netherlands treatments were made weekly applying 24 g of
    thiabendazole per 100 m2. Strawberries harvested 3 and 4 days after
    the last Treatment were mostly found to contain less than 0.05 mg/kg
    of residue though in one trial a residue of 0.24 mg/kg was found.

    Sugar beet

    The manufacturers have demonstrated the usefulness of thiabendazole as
    a post-harvest application on sugar-beet roots as they enter pile
    storage for protection against beetrotting fungi and official approval
    has been given for this use in the USA. Use on sugarbeets pre-harvest
    has been approved in several countries. In an extensive trial in the
    USA 5,000 tons of sugar beets were treated with a thiabendazole
    suspension containing 1,500mg/l at the rate of 4 litres per ton. The
    treated sugar beets going into storage were systematically sampled and
    analysed as were sugar beets from the stock pile during removal for
    processing 120 days later. Although the theoretical application rate
    was 6 mg/kg, analysis revealed only 1.75 mg/kg immediately following
    application though the concentration an individual samples ranged from
    0.6 to 4.7 mg/kg. Apparently much of the spray w" absorbed on dirt
    clinging to the sugar beet roots. After the sugar beets had been in
    storage for 120 days the concentration of thiabendazole had declined
    to approximately one-third (0.65 mg/kg), Individual samples indicating
    residues in the range 0.2 to 2.1 mg/kg (See Tables 4 and 5).

    Tomatoes

    Thiabendazole has proved effective for use as a fungicide on tomatoes
    in greenhouses, applied by fumigation. The rate of application is
    12-18 g/100 m2

    Trials carried out at a number of locations in the Netherlands
    indicated that the residues on the tomato fruit were less then
    0.1 mg/kg at all stages following repeated treatments.

    FATE OF RESIDUES

    In animals

    Thiabendazole is rapidly metabolized and excreted in all species and
    concentrations of the drug and its metabolites in tissues and excreta
    diminish quickly to control levels. The major metabolite is the
    5-hydroxy analogue generally found as its glucuronide or sulphate
    ester.

 

    The levels of thiabendazole or its metabolites are readily determined
    in the various tissues and excreta of animals by a photofluorometric
    procedure which, as used, is quite specific for these substances. A
    description of the procedure used in the preparation of tissues and
    the results of extensive investigations are given by
    Tocco et al., (1965).

    Additional data were supplied by the manufacturers (Merck Sharp and
    Dohme, 1975); this information is summarized as follows.

    Pigs

    8 Pigs were given a single oral dose of 100 mg thiabendazole per kg
    b.w. Four pigs were killed after 7 days, and 4 after 28 days. The
    residue was determined in liver, kidneys and skeletal muscle by the
    fluorimetric method of Tocco et al. (1965). No tissue residues of
    thiabendazole or 5-hydroxythiabendazole (limit of detection
    0.05 mg/kg) were found.

    Three pigs received 1000 ppm thiabendazole in the feed during 2 weeks
    and were killed at 0, 2 and 7 days after withdrawal. In 16 organs and
    tissues thiabendazole and metabolites were determined. At day 0 tissue
    residues ranged from 1.6-8 mg/kg, the highest levels being in kidney
    and liver. At day 2 in muscle, livery kidney and brain, values of
    0, 0.12, 0.19 and 0.31 mg/kg were found respectively, while at day
    7 thiabendazole and metabolites were absent (< 0.05 mg/kg).

    Cattle

    The kidney, liver and muscle tissues of cattle become rapidly free of
    thiabendazole and metabolite residues. Three day after an oral dose of
    50 or 110 mg/kg thiabendazole no residues were detected in these
    tissues (limit of detection 0.1 mg/kg). Thiabendazole was given to
    3 lactating cows in dosages of 66, 110 or 220 mg/kg body weight.
    Residues of thiabendazole and metabolites were determined in milk.
    After 0-24 hr the highest residues were found, mainly as metabolites,
    varying between 0.2-0.67 mg/kg. Approximately 0.1% of the total dose
    was excreted in the milk. No residues were detectable 60 hr after
    administration of the thiabendazole (Tocco et al., 1965).

    5 Calves were fed continuously for 14 weeks a grain diet containing 0,
    0.031, 0.10, 0.32 and 1.0% thiabendazole. When the animals were
    sacrificed after 14 weeks, relatively high tissue levels of
    thiabendazole plus metabolites could be determined: at a dose of
    1% 16.7, 11.6 and 12.1 mg/kg in muscle, liver and kidney respectively.
    At the lower dose levels the highest concentration was found in the
    kidneys.


        TABLE 4. Thiabendazole residues resulting from post-harvest uses

                                                                                                                                              

                                                Application                     Residues (mg/kg) at intervals (days) after application
    Crop           Country          Year  no.  rate         formulation          1            5         10      20      120          150
                                               g.a.i./ha
                                                                                                                                              

    Pears          Israel           1974  1    500                                                                                   1.04
                                               1000                                                                                  2.0
                                               2000                                                                                  3.5

    Bananas        Costa Rica       1973  1    200          flowable             0.36
    (WHOLE)        Doninica Rep.    1974  1    400          flowable             0.75
                                    1975  1    400          flowable             0.21
                   Honduras         1972  1    200          flowable             0.03
                   Brazil           1974  1    400          flowable             1.22

    Bananas        Various                1    200-400      flowable             0.02-0.05

    (PULP)

    Sugar beet     USA              1976  1    1500         flowable             0.6-4.7                                0.2-2.1
                                               (6 g/tonne)                       (1.75)                                 (0.65)
                                                                                                                                              

    

    Sheep

    Thiabendazole was orally administered to sheep in dosages of 60, 82
    and 100 mg/kg body weight. After 4 hr the sheep receiving 60 mg/kg was
    killed, the other 2 sheep after 7 days. At 7 days no residues were
    detectable (thiabendazole only)q except for a residue of 0.09 mg/kg in
    the liver of the sheep that received 100 mg/kg body weight.

    In storage and processing

    Studies carried out in Germany in 1975 (Table 3) indicate that there
    is no significant change in the level of thiabendazole deposits on
    potatoes treated post-harvest and kept in store for up to 56 days. The
    level of residues in the whole potato, in the peel and in the edible
    portion remain much as they were on the day following application.
    However there seems to be a slight but significant trend for the
    deposit to become transferred from the surface into the potato since
    the residue in the whole washed potato increased from 1.3 mg/kg to
    3.6 mg/kg over the 56 day period.

    In separate experiments carried out in the United Kingdom in 1976,
    when potatoes were treated at 40 and 80 g/tonne, a similar trend could
    be observed. Although the concentration of thiabendazole in the
    unwashed potatoes did not change significantly over a 21 day storage
    period the concentration in the washed potatoes increased from 1.7 to
    6.3 mg/kg and 2.2 to 7.5 mg/kg between days 4 and 21 of this period
    (Table 5).

    The effect of washing potatoes treated post-harvest with thiabendazole
    is clearly demonstrated in Tables 3 and 5. In the UK experiments,
    washing in running water removed approximately 90% of the residue when
    carried out 4 days after treatment and approximately 75% when carried
    out 21 days after treatment. It is assumed that after 21 days more
    thiabendazole had been absorbed into the skin surface. Washing,
    peeling and boiling removed approximately 99% of the thiabendazole
    residues on the unwashed tubers. This was not influenced by the time
    which elapsed after treatment. There was a slight but probably
    insignificant increase in the residue in the chips prepared from
    potatoes held 21 days following treatment.

    The results from the experiments with boiled and chip potatoes suggest
    that thiabendazole is only absorbed into the outer skin layer of the
    tubers. This is confirmed by further experiments where the washed
    tubers were baked without removing the skins. The residue in the whole
    baked potato was considerably higher than in the corresponding potato
    which were peeled before cooking. The baking of washed potatoes does
    not significantly reduce the residue level present prior to cooking.

        TABLE 5. Effect of processing on thiabendazole residues in potatoes; UK, 1976
                                                                                              
                                                    Rate of application
                                       40 g/tonne                    80 g/tonne
    Held in store                 4 days         21 days        4 days         21 days
                                                                                              
    Unwashed                      22.6 mg/kg     24.9 mg/kg     25.2 mg/kg     28.5 mg/kg

    Washed                        1.7  "  "      6.3  "  "      2.2  "  "      7.5   "  "

    Washed, peeled,
    chipped                       0.1  "  "      0.2  "  "      0.2  "  "      0.5   "  "

    Washed, peeled,
    chipped                       0.2  "  "      0.2  "  "      0.4  "  "      0.3   "  "

    Washed, baked                 1.7  "  "      3.8  "  "      2.3  "  "      11.9  "  "
                                                                                              

    
        TABLE 6. Effect of processing sugar beets on thiabendazole residues
                                                                                

    Rate of application                     6 g/tonne

    Residue level at application            0.6-4.7 (mean 1.75 0.68) mg/kg

    Residue level after 120 days storage    0.2-2.1 (mean 0.65 0.39) mg/kg

    Residues in flume water                 0.2 mg/kg

    wet pulp                                0.08 mg/kg

    diffusion juice                         0.1 mg/kg

    pressed pulp                            0.2 mg/kg

    dried pulp                              2.5 mg/kg

    thick juice                             0.44 mg/kg

    sugar                                   0.00 mg/kg

    molasses                                0.70 mg/kg

    pellets                                 1.26 mg/kg
                                                                                
    
    Studies on the fate of thiabendazole applied to sugar beet going into
    storage indicate that approximately two-thirds of the residues
    disappear during 120 days storage. This appears to be due to the
    sorption of the thiabendazole on the fine soil particles adhering to
    the beet roots. This sorted material is not recovered by analysis and
    in commercial practice is removed from the roots before processing.
    The extensive study carried out under commercial conditions in the USA
    (Merok Sharp and Dohme, 1977b; Table 6) indicates that thiabendazole
    can be traced in most fractions of the sugar beet process through to
    but not including the finished sugar. Since the thiabendazole content
    of the sugar beet molasses was 0.7 mg/kg, it is clear that not all of
    the residue is removed during the activated carbon and lime treatment
    stages.

    The sugar beet pellets, which are formed by adding about 4.2 tons of
    molasses to 10.8 tons of dried pressed pulp and further drying the
    composite back to 10.8 tons of extruded pellets, contain thiabendazole
    residues from both pulp and molasses.

    RESIDUES IN FOOD IN COMMERCE OR AT CONSUMPTION

    Monitoring of fruit in the Netherlands in 1976 revealed that none of
    137 samples of various varieties of citrus fruits, plums and
    pineapples examined contained thiabendazole residues at levels above
    national (and Joint Meeting) maximum residue levels. Only 16 of the
    137 samples contained no thiabendazole (Netherlands Food Inspection
    Services, 1976).

    Data from the US Food and Drug Administration indicate that of eight
    samples of citrus fruits examined four contained thiabendazole
    residues at levels ranging from 0.02 to 1.0 mg/kg.

    NATIONAL MAXIMUM RESIDUES LIMITS REPORTED TO THE MEETING

    National maximum residue limits reported to the Meeting as established
    or amended since the 1972 Joint Meeting are listed below.

                                                                                              

    Country                            Commodity                          MRL (mg/kg)
                                                                                          

    Australia                          apples, pears  citrus              10
                                       bananas whole)                     3
                                       bananas (pulp)                     0.4
                                       meat                               0.2
                                       milk                               0.05

                                                                                          

    Country                            Commodity                          MRL (mg/kg)
                                                                                          

    Canada                             bananas (pulp)                     0.4
                                       potatoes                           4
                                       apples, citrus, pears              10

    Israel                             citrus, pears                      10
                                       celery                             5
                                       bananas, strawberries              3

    Netherlands                        tomato                             0.1
                                       grain                              0.2
                                       banana                             3
                                       citrus fruit                       10
                                       apples                             6

    New Zealand                        bananas, citrus                    3

    South Africa                       all food products                  3

    Sweden                             fruit and Vegetables except
                                       potatoes                           6

    Switzerland                        banana (whole)                     3
                                       banana (pulp)                      0.4
                                       citrus fruit                       6

    USA                                dried citrus pulp                  35
                                       dried apple pomace                 33
                                       potato processing waste            30
                                       citrus molasses                    20
                                       apples, citrus fruit, pears,
                                       sugar beet tops                    10
                                       dried sugar beet pulp              3.5
                                       bananas, potatoes                  3
                                       hubbard squash                     1
                                       sugar beets                        6
                                       wheat straw                        0.2
                                       milk, fat, meat, meat
                                       by-products
                                       of cattle, goats,
                                       hogs, horses, sheep                0.1
                                       soybeans, wheat grain              0.1
                                       sweet potatoes                     0.02
                                                                                          
    
    APPRAISAL

    The world-wide use of thiabendazole as an agricultural fungicide has
    grown greatly since it was first introduced as a post-harvest
    treatment for bananas, citrus and pome fruit in the late 1960s. It is
    now applied to many classes of crop and commodity in preplant and
    pre-harvest as well as post-harvest treatments. Information was
    available on many of these new applications together with data from
    residue studies related to many of these uses.

    The residue data indicate that the residues resulting from the
    pre-plant and pre-harvest application of thiabendazole are generally
    low to very low, some of the more important applications resulting in
    no detectable residues.

    Among the more important uses is the application of thiabendazole
    alone or with other fungicides as seed dressings for a wide variety of
    cereals and cotton. These uses do not give rise to residues in the
    harvested crop. The use of thiabendazole, either alone or in
    conjunction with other fungicides, pre-harvest on bananas, rice,
    soybeans and teat has been studied and data on the residues arising
    from such applications were evaluated. The use of thiabendazole as a
    fumigant in glasshouses and similar situations has become increasingly
    important. The residues resulting from such uses on tomatoes and
    strawberries are remarkably low.

    Thiabendazole has become increasingly important for the treatment of
    stored potatoes to protect them against a variety of fungal rots. The
    method of application has an important bearing on the level of the
    resulting residue which is largely confined to the outer part of the
    skin. Much of this residue is removed by washing. The amount removable
    by washing decreases as the potatoes remain longer in storage. Farther
    evidence has become available to demonstrate the fate of thiabendazole
    residues in processed potatoes. This shows that up to 99% of the
    residue present in the unwashed potato is removed prior to
    consumption.

    Extensive studies have been carried out with a view to proposing the
    use of thiabendazole on sugar beets as they enter pile storage for
    protection against beet rotting fungi whilst stored outdoors. These
    studies revealed that a large proportion of the applied thiabendazole
    becomes bound in the soil coating the beet roots. There is a further
    loss during storage. The fate of the thiabendazole during the various
    stages of beet sugar production has been studied. Whilst a significant
    residue remains in the sugar beet pulp and in the molasses, no
    residues remain in the beet sugar. These studies provide an adequate
    basis for recommending maximum residue limits in sugar beet, sugar
    beet pulp and sugar beet molasses.

    Since a number of the commodities treated with thiabendazole, or food
    wastes from such treated commodities, form the basis of a variety of

    animal feedstuffs, the meeting considered further information on the
    fate of thiabendazole in a variety of livestock. These studies showed
    that when thiabendazole is administered to livestock, even at levels
    vastly in excess of those likely to occur in practice, significant
    residues occur in animal tissues but these disappear completely within
    a few days of withdrawing the thiabendazole. These new studies serve
    to confirm the recommendations made for a maximum residue limit in
    milky meat and edible offal of cattle, goats, horses, pigs and sheep
    at or about the limit of determination (0.1 mg/kg).

    The meeting took note that a number of countries have extended or
    amended their maximum residue limits for thiabendazole in a variety of
    commodities.

    Whereas in 1974 it was stated that residues resulting from the use of
    thiabendazole consisted of thiabendazole and 5-hydroxythiabendazole,
    it is recognized that this applies only to residues in foods of animal
    origin such as meat, edible offal, milk and eggs. An analytical method
    for measuring both parent compound and metabolite in such commodities
    is available. Residues in foods of plant origin consist entirely of
    thiabendazole. The recommendations are amended accordingly.

    RECOMMENDATIONS

    In the light of the new and previously available data, the following
    additional or amended maximum residue limits are recommended. They
    refer to thiabendazole only. The limits for potatoes (unwashed) and
    potatoes (washed) have been replaced by a recommendation which directs
    that potatoes be washed before analysis.

    Commodity                          Limit, mg/kg
    Sugar beet tops                    10
    Potatoes (washed before analysis)  5
    Sugar beets                        5
    Sugar beet pulp                    5
    Sugar beet molasses                1
    Raw grain                          0.2
    Onions                             0.1
    Strawberries                       0.1
    Tomatoes                           0.1

    FURTHER WORK OR INFORMATION

    DESIRABLE

    1. Information on the use pattern m cereals and an indication as to
    whether the residue pattern on rice, barley and oats is similar to
    that on wheat.

    REFERENCES

    Colmore, J.P. (1965) Chronic toxicity study of thiabendazole in
    volunteers. Merok, Sharp and Dohme, unpublished report.

    Estey. (1977) Results of Canadian potato trials 1974/75. Analysis
    performed by Merok, Sharp and Dohme, Rahway, N.J., U.S.A.

    Logan, C. Potato tuber disinfestation by thiabendazole mist
    application. Agriculture in Northern Ireland, 48:, 438-440.

    Logan, C. Tuber disinfestation by mist application. Potato Research,
    17: 347.

    Merok, Sharp and Dohme. (1975) Thiabendazole tissue residue studies in
    animals. (Unpublished report).

    Tisdale, M.J. and Lord, K.A. (1973) Uptake and distribution of
    thiabendazole by seed potatoes. Pestic. Sci., 4: 121-130.

    Tocco, D.J., Egerton, J.R., Bowers, W., Christensen, V.W. and
    Rosenblum, C. (1965) Absorption, metabolism and elimination of
    thiabendazole in farm animals and a method for its estimation in
    biological materials. J. Pharmacol and Exp. Therapeutics 149 (2)
    263-271.

    FAO/WHO (1971) 1970 evaluations of some pesticide residues in food.
    FAO/AGP/1970/M/12/1; WHO/Food Add/71.42.

    FAO/WHO (1972) 1971 evaluations of some pesticide residues in food.
    FAO/AOP/1971/M/9/1, WHO Pesticide Residue Series No. 1.

    FAO/WHO (1973) 1972 evaluations of some pesticide residues in food.
    FAO/AGP/1972/M/9/1; WHO Pesticide Residues Series No. 2.

    FAO/WHO (1976) 1975 evaluations of some pesticide residues in food.
    FAO/AGP/1975M/9/1; WHO Pesticide Residues Series No. 6.
    


    See Also:
       Toxicological Abbreviations
       Thiabendazole (WHO Food Additives Series 39)
       Thiabendazole (AGP:1970/M/12/1)
       Thiabendazole (WHO Pesticide Residues Series 1)
       Thiabendazole (WHO Pesticide Residues Series 2)
       Thiabendazole (WHO Pesticide Residues Series 5)
       Thiabendazole (Pesticide residues in food: 1979 evaluations)
       Thiabendazole (Pesticide residues in food: 1981 evaluations)