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    PESTICIDE RESIDUES IN FOOD - 1979


    Sponsored jointly by FAO and WHO






    EVALUATIONS 1979





    Joint meeting of the
    FAO Panel of Experts on Pesticide Residues
    in Food and the Environment
    and the
    WHO Expert Group on Pesticide Residues
    Geneva, 3-12 December 1979



    CARBOFURAN

    Explanation

    This pesticide was evaluated in 1976 when a temporary ADI and some
    limits were established.

    Short term dietary studies in rodents were listed as a requirement for
    reviewing the temporary nature of the ADI.  Findings from comparative
    biochemical studies with a view to defining the apparent sensitivity
    of juveniles and further information on residues resulting from
    approved uses on major crops were also recorded as desirable.

    At its 11th Session, the CCPR requested clarification of the
    commodities to be covered by the previously recommended limit for
    "other animal feeds".

    New information on these points is reviewed in this monograph
    addendum.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    TOXICOLOGICAL STUDIES

    Special Studies on Cholinesterase Inhibition

    Groups of rats were fed carbofuran in the diet at dosage levels of 0,
    10, 20, and 100 ppm for two years.  At periodic intervals, animals
    were sacrificed and plasma, red blood cell, and brain cholinesterase
    activity was measured in 10 rats of each dietary level at 6, 12, and
    18 months of the study.  At 24 months, cholinesterase activity was
    determined in 20 animals per sex per treatment level.  Technical
    carbofuran was found to cause no physiologically significant
    depression (<25 percent vs. control) in erythrocyte cholinesterase
    activity at any dietary level (10, 20 or 100 ppm) in both male and
    female rats at 6, 12, 18, and 24 months.  No depression (< 15 percent
    vs. control) was observed in brain cholinesterase activity at 10 and
    20 ppm in male and female rats at 6, 12, 18 and 24 months.  A
    depression of brain cholinesterase activity was observed at 100 ppm in
    males at 18 and 24 months, and in females at all time intervals.  The
    cholinesterase inhibition in brain at 24 months was shown to be 21
    percent in males and 43 percent in females (Case and Wilson 1979).

    Special Study on Mutagenicity

    Carbofuran was tested for mutagenicity by the in vitro Salmonella
    assay ("Ames test") for screening chemicals for point-mutations.
    Mammalian metabolism was simulated by the 9000 g fraction of mammalian
    livers (S-9 mix).  All groups were tested with the S-9 mix, and
    additionally, the highest dose group was tested without an S-9 mix.
    The following doses were tested: 0, 1.2, 3.7, 11.1, 33.3, and 100
    µg/plate.  The solvents used were DMSO for carbofuran and distilled
    water for endoxane (positive control, tested at 500 ug/plate).

    Doses of up to and including 100 µg/plate did not cause bacterial
    toxicity.  The test provided no indication of mutagenic effect induced
    by carbofuran.  The numbers of mutants neither showed a dose-related
    increase nor were they doubled.  On the other hand, the positive
    control increased the number of mutants to more than double that found
    in the negative control (Herbold, 1978).

    COMMENTS

    Carbofuran was evaluated for an acceptable daily intake by the Meeting
    in 1976 and a temporary ADI was established.  Preliminary results of a
    study to define the level causing no cholinesterase depression were
    reviewed.  In addition, data were reviewed which showed no evidence of
    mutagenic potential as suggested by microbial bioassays.  The Meeting
    was informed that several toxicological studies are in progress and
    decided to extend the temporary ADI.

    TOXICOLOGICAL EVALUATION

    Levels Causing No Toxicological Effect

    Rat:  10 ppm in the diet, equivalent to 0.5 mg/kg body weight
    Dog:  50 ppm in the diet, equivalent to 1.25 mg/kg body weight

    Estimate of Temporary Acceptable Daily Intake for Man

    0-0.003 mg/kg body weight

    RESIDUES IN FOOD AND THEIR EVALUATION

    RESIDUES RESULTING FROM SUPERVISED TRIALS

    Brassica leafy vegetables, Maize Leek and Onion

    Field trials were carried out with granules (Currater 5%) at various
    locations of Germany, the Netherlands in 1976-1978 and Denmark
    (Furadan 10) in 1975.  The treatments were in accordance with
    recommended uses.  The details are summarized in Table 1.



        Table 1.  Residues Resulting from Supervised Trials with Carbofuran (Years 1975-1978)

                                                                                                                            

               Single
               applications   Residues1 in mg/kg, at intervals (days) after application
    Crop       granules
               at a.i.        50-51      59-62     70        79-80      92      104-109    115-125    136-151     161-176
                                                                                                                            

    Cabbage    0.1 g/m        13.4       6.4        8.2       7.6
    /savoy/    0.1 g/m         0.3       0.1        0.1       0.1
               0.1 g/m         2.02      1.12       2.43      0.26

    Kohlrabi   0.1 g/m         0.2       0.2       <O.1      <0.1
               0.1 g/m         0.15      0.12      <0.1      <0.1
               0.1 g/m        23.72      0.192     23.22      0.54

    Cabbage    0.5 kg/ha                                                         0.07                  0.04
               1 kg/ha                                                           0.1                   0.05
               2kg/ha                                                            0.3                   0.23

    Kohlrabi   0.5 kg/ha                                                        <0.05                 <0.05
               1.0 kg/ha                                                         0.05                 <0.05
               2.0 kg/ha                                                         0.07                  0.1

    Leek       0.06 g/m                                                         <0.1                  <0.1
               0.06 g/m                                                                    <0.05      <0.05
               1.25 kg/ha     0.5                            0.26                0.13

    Onions     0.5 kg/ha                                                                               0.07
                                                                                                       0.04
                                                                                                       0.06
               0.05 g/m                                                         <0.1                  <0.1
               0.05                                                                        <0.1                   <0.1
               1.5 kg/ha                                                                                          <0.1
               1.5 kg/ha                                                                                          <0.1
                                                                                                                            

    Table 1.  Continued...

                                                                                                                            

               Single
               applications   Residues1 in mg/kg, at intervals (days) after application
    Crop       granules
               at a.i.        50-51      59-62     70        79-80      92      104-109    115-125    136-151     161-176
                                                                                                                            

    Maize      0.075 g/m                                                0.3                 0.7                    0.4
                                                                                                                  <0.13
               0.075 g/m                                                0.4                 0.6                    0.3
                                                                                                                  <0.13
               0.075 g/m                                                0.3                 0.8                    0.9
                                                                                                                  <0.13
                                                                                                                            

    1  Sum of carbofuran and 3-hydroxy carbofuran
    2  leaf samples
    3  in kernel
    


    Alfalfa

    Carbofuran (as Furadan 4F) was applied to mixed stands of alfalfa at a
    rate of 0.3, 0.6, 1.12 kg a.i/ha 7, 14, 28 days before harvest
    respectively in 10 states of US with two replicates at each location.
    Carbamate and phenolic residues were determined.  The limit of
    determination was 0.25 mg/kg for each carbamate derivatives and 0.5
    mg/kg for the phenols.  The composition of stands varied between:
    alfalfa 50-80%, orchard grass 20-50%, bromegrass 15-50% fescue 0-10%,
    other grass weeds 0-15%.  The average moisture content of samples was
    76% (66-86%).

    The residue found was mainly 3-OH-carbofuran.  Intact carbofuran was
    detected /0.26 mg/kg only in one of the 60 treated samples.  12
    samples were analysed for phenols but residues were at or below the
    limit of determination /0.5 mg/kg/ (FMC 1976a).  The total carbamate
    residues /mg/kg/ ranged at does rates:

    0.3 kg ai./ha            0.25-4.54      / 7 days after treatment/
    0.6 kg ai./ha            0.29-4.4       /14 days after treatment/
    1.12 kg ai./ha           0.25-3.18      /28 days after treatment/

    Alfalfa and bromegrass samples were taken from 11 locations of Canada.
    The treatments were made (with Furadan 4.8 F) at dose rates of 0.3 kg
    a.i/ha and 2 × 0.15 kg a.i/ha.  Samples were analysed for the residues
    of carbofuran (CF), 3-hydroxycarbofuran (3OHCF), their phenols and
    3-ketocarbofuran phenol.  The carbamate residues are summarised in
    Table 2.  Measurable phenol residues (2.09, 1.46 mg/kg) were only
    found 1 day after treatment in alfalfa and none was in bromegrass (FMC
    1976b).

    The results of these experiments agree with those discussed above. 
    The low or not detectable residues soon after the treatments may be
    due to rainfall which appears to remove the carbofuran carbamate
    residues from the plant surfaces of alfalfa and bromegrasses.  The
    quantity of rain after the treatments was as follows:

    No. of exp.       Rain /mm/      after       treatment    /days/
                                                                       

    2                 3.2 mm /2/     39.5 mm /3/   6.6 mm /4/  58.1 /5/
    4                 2.7 mm /3/     1 mm    /4/  19.6 mm /5/
    6                 6.6 mm /0/     1.7 mm  /1/   2.5 mm /2/
    7                 16.2 mm /3/
                                                                       



        Table 2.  Residues of Carbofuran and 3-hydroxycarbofuran resulting from Supervised Trials in Canada in 1976

                                                                                                                                            
                        Spray
                        application          Residues in mg/kg, at intervals/days/after application
    Crop         No.    rate
                        kg a.i./ha                0               1                3                7               14           dry /14/
                        (4.8F formulation)   CF     3OHCF    CF     3OHCF     CF     3OHCF      CF   3OHCF       CF  3OHCF      CF   3OHCF
                                                                                                                                            

    Alfalfa      2            0.15            4.66   nd       3.50   nd        1.3    nd        0.93   nd        nd   nd       <0.5  <0.5
                                              3.8    nd       4.37   nd        0.9    nd        0.50   nd        nd   nd       <0.5  <0.5
    Alfalfa      2            0.15            5.09   nd       2.33   nd        nd    <0.5       nd    <0.5       nd   <0.5       nd   <0.5
                                              6.4    nd       3.9   <0.5       nd    <0.5       nd    <0.5       nd  <0.5       nd   <0.5
    Bromegrass   2            0.15            9.79   nd       7.5    nd        5.38   1.0       nd     0.97      nd  <0.5       nd    1.3
                                             14.2    nd      10.3    nd        3.42   1.0       nd    <0.5       nd  <0.5       nd    0.98
                                             17.9    nd                                         nd     0.52
    Bromegrass   2            0.15            5.03   nd       2.67   nd       <0.5   <0.5       nd     nd        nd   nd        nd   <0.5
                                              4.28   nd       1.94   nd        0.77  <0.5       nd     nd        nd  <0.5       nd   <0.5
    Alfalfa      2            0.15            3.86  <0.5      3.16   0.58     <0.5    0.88      nd    <0.5       nd  <0.5       nd   <0.5
                                              4.76   0.58     3.2    1.85     <0.5    1.02      nd    <0.5       nd   nd        nd    nd
    Bromegrass   2            0.15           15.7    nd       nd    <0.5       nd      nd       nd     nd        nd   nd        nd    nd
                                             14.6    nd       nd     nd        nd      nd       nd     nd        nd  <0.5       nd    nd
    Alfalfa      2            0.15           14.4    nd       8.35   nd        nd    <0.5       nd     0.5       nd   0.56      nd    0.8
                                              7.07   nd       5.58   nd        nd     0.74      nd     0.63      nd   0.5       nd    1.0
    Alfalfa      1            0.3                            15.1    5.29      nd     2.08      nd     2.4       nd   0.98      nd    4.3
                                                             14.3    5.38      nd     2.14      nd     2.16      nd   1.72      nd    4.24
    Alfalfa      1            0.3                             9.46   4.07      nd     1.62      nd     1.40      nd   1.45     <0.5   4.88
                                                              9.58   4.07      nd     2.35      nd     1.53      nd   1.60     <0.5   3.66
    Alfalfa      1            0.3            10.4    0.7                       3.53   2.14      0.76   3.5       nd   1.79
                                             12      nd                        2.5    2.62      0.5    2.9       nd   1.18
                                                                                                                                            

    nd = non detectable
    


    Egg Plants

    Egg plants from three locations in Mexico were analysed for carbofuran
    and 3-hydroxy-carbofuran.  Treatment was one soil application (as
    Furadan 3 G at 2 kg ai/ha following by three individual foliar
    applications of 75 WP at 1 kg ai/ha per application.  Sampling was 7
    and 14 days after treatment.  No residues were detected at <0.05
    mg/kg limit (FMC 1977a).

    Garlic

    Garlic cloves were treated with 30% seed treater at a rate of 0.5%
    ai/100 kg of seed immediately before planting in Argentina.  Samples
    were taken at harvest 176 days after planting and 0.18 mg/kg
    carbofuran but none of 3-hydroxy-carbofuran were detected.

    Potatoes

    Potatoes from test plots located in ten different states of US were
    analysed for carbamate and phenolic residues of carbofuran.  The
    treatments were 3.4 kg ai/ha (Furadan 10G) at planting plus 3 times of
    11 kg ai/ha foliar spray (Furadan 4 F)/experiment A/ applied with a
    dose of 6 times 1.1 kg ai/ha/experiment B/.  The total residue values
    in each sample have been calculated by adding in nondetectable
    residues as being equal to the limit of determinations and placing a
    "less than" prefix with the sum.  The limit of determination for the
    various compounds analysed was not reported.  The average residue in
    10 samples taken at the same time, was calculated by adding in ND as
    zero and less than values in as the listed number disregarding the
    less than symbol (FMC 1978a).  The average, minimum and maximum
    residue values found after application are listed in Table 3.

    In Canada, Furadan 1OG and 4.8 F were applied on potato field to give
    a total toxicant per hectare ranging from 2.2-3.1 kg.  At harvest the
    residues (carbofuran and 3-hydroxycarbofuran) in 8 samples fell in the
    range of 0.01-0.17 mg/kg.  The harvested tubers were stored at 5°C and
    analysed for carbofuran and 3-hydroxycarbofuran at 0, 30, 60, 90 days.
    The total residues were in the range of 0.06-0.11 mg/kg after 90 days.
    There was no evidence for conversion of parent compound to its
    metabolite during storage (Canada).

    Carbofuran applied at a dosage rate of 5-10 kg ai/ha at seeding in
    four supervised trials resulted in nondetectable residues in potatoes
    134 days after treatment in Finland.



        Table 3.  Residues in Potatoes mg/kg

                                                                                                        
      Days                     Experiment A                                    Experiment B
      after           carbamates            Phenols                  carbamates               phenols
    Treatment      average    min.      average    min.          average     min.       average    min.
                              max.                 max.                      max.                  max.
                                                                                                        


                              ND                   0.1                       ND                    0.2
    0-2            0.1        0.64      0.4        1.03          0.05        0.2        0.34       0.7


                              ND                   0.1                       ND                    0.1
    12-15          0.08       0.23      0.3        0.48          0.06        0.1        0.3        0.5


                              ND                   ND                        ND                    0.2
    27-43          0.05       0.3       0.02       0.45          0.05        0.16       0.34       0.06
                                                                                                        
    


    Soybean

    Two separate plots were treated with a foliar spray (Furadan 4F) at a
    rate of 0.28 kg ai/ha.  One plot received a single application and was
    sampled 63 days after treatment.  The second plot was treated twice
    and the samples were taken 36 days after last application.  The
    observed carbamate residue was solely carbofuran in the range of
    0.05-0.1 mg/kg (FMC 1979b).

    Sweet Corn

    Sweet corn at various locations of U.S. was treated (with Furadan 10G)
    at rates of:

    - 4.5 kg ai/ha in furrow at planting;
    - 2.24 kg ai/ha at planting as a band of 29-37 cm width;
    - 4.5 kg ai/ha in furrow at planting and twice (with Furadan 3G) at a
    rate of 0.56 kg ai/ha as foliar spray;
    - 1.12 kg ai/ha in furrow at planting and four times (with Furadan 4F)
    at a rate of 0.56 kg ai/ha at intervals of 4-6 days during ear
    formation.

    The carbofuran and hydroxycarbofuran residues in the cobs, kernels,
    husks and stalks were determined using nitrogen selective Coulson
    detector.  The limit of determination was 0.05 mg/kg for carbofuran
    and 0.1 mg/kg for 3-hydroxycarbofuran.

    The kernels contained no detectable residues regardless of type of
    treatment.  The residues in cobs were at or about the limit of
    determination.  The highest residue (4.09 mg/kg) was observed in stalk
    87 days after treatment (FMC 1976c, 1976 d).  The ranges of residues
    measured are summarized in Table 4.

    Sugarcane

    Supervised trials were carried out in South Africa at dose rates of 3
    kg ai/ha (registered dosage) and 4.5 kg ai/ha.  The residue in sugar
    cane was lower than limit of determination (0.2 mg/kg) in both
    experiments.



        Table 4.  Residues of Carbofuran and 3-hydroxyfuran in Sweet Corn

                                                                                                                           
          Sample            Dose Rate          Days             Minimum - maximum residues mg/kg
    Type           No.      Kg a.i./ha        Lapsed         CF               3OHCF              Total           Reference
                                                                                                                           

    Cobs           16       4.5               66-111      nd     0.1        nd     nd          nd     0.1        MC-1371
    Kernels        16                                     nd     nd         nd     nd          nd     nd
    Husks          16                                     nd     0.35       nd     0.95        nd     1.3
                                                          nd     0.99       nd     3.1         nd     4.09
    Cobs            2       4.5+2 × 0.56       28         0.09   0.1        0.13   0.14        0.22   0.26
    Kernels         2                                     nd     nd         nd     nd          nd     nd
    Husks           2                                     0.1    0.2        0.5    0.7         0.9    1.2
    Stalks          2                                     0.33   0.7        0.9    1.24        1.2    1.94
    Cobs           16       2.24              76.81       nd     nd         nd     nd          nd     nd
    Kernels        16                                     nd     nd         nd     nd          nd     nd
    Husks          16                                     nd     0.1        nd     0.1         nd     0.2
    Stalks         16                                     nd     0.1        nd     0.14        nd     0.24
    Cobs           10       4.5+3 × 0.56        7         nd     0.08       nd     nd          nd     0.08
    Kernels        10                           7         nd     0.05       nd     nd          nd     0.05
    Husks          10                           7         0.06   0.44       nd     0.45        0.08   0.89
    Stalks          6                         21-27       0.2    0.38       0.37   1.82        0.59   2.19
                                                                                                                           
    


    Tobacco

    Burley tobacco fields at five locations of U.S. were treated (with
    Furadan 10 G or 4 F) before planting at a dose rate of 4.5 kg ai/ha;
    another 12 plots received 6.73 kg ai/ha.

    Upon harvesting each tobacco plant was separated into upper, middle
    and lower leaves for separate analysis.  All samples were taken at
    normal harvest and then commercially air cured before analysis.
    Following the 4.5 kg/ha dose, the total carbamate residues found (CF +
    3OHCF) ranged from non-detectable to a maximum of 13.6 mg/kg in lower
    leaves, 8.27 mg/kg in middle leaves and 4.72 mg/kg in upper leaves.
    The quantitable residue found averaged 24.3% carbofuran and 75.7%
    3-hydroxycarbofuran (FMC 1977b).  While the total residue ranged from
    non-detectable to 19 mg/kg at 6.73 kg ai/ha.  The average residue was
    2.84 mg/kg for the 72 samples analysed (FMC 1979c).  The limit of
    determination was 0.5 mg/kg for carbofuran and 1.0 mg/kg for 3-hydroxy
    carbofuran in both experiments.

    Tomatoes

    Two foliar sprays (of Furadan 4.8 F) were applied to ripe tomatoes in
    Canada.  Samples were taken 1, 3, 6, 10 an 27 days after treatment.
    The carbamate residues on fruit declined from 0.25 mg/kg one day after
    last application to non-detectability at ten days, with limit of
    determination 0.05 mg/kg (FMC 1975).

    Experiments on 9 plots treated at planting (with Furadan 10 G) at a
    dose rate of 3.36 kg ai/ha in a 29 cm band resulted in non-detectable
    residues in the fruits (FMC 1977c).

    FATE OF RESIDUES

    In Animals

    The bio-availability of bound (i.e. unextractables) and conjugated
    (i.e. water solubles) carbofuran residues from bean plants was
    investigated by administering the radioactive residues orally to
    female rats.  Whereas the water-soluble metabolites were eliminated
    primarily in the urine, most of the bound residues were excreted in
    the faeces.  In both cases, biliary excretion was minor (Marshall and
    Dorough, 1977).

    Carbofuran was degraded rapidly also in laying hens (Hicks et al.,
    1970); 54% of the dose was hydrolyzed after only 6 hours, and 72% had
    been hydrolyzed by the end of 24 hours.  Laying hens eliminated most
    of the radioactivity in the excreta, in which the 3-hydroxycarbofuran
    was identified as the major metabolite.  Additionally, free and
    conjugated forms of 3-ketocarbofuran, carbofuran phenol,
    3-hydroxycarbofuran phenol, 3-ketocarbofuran phenol,
    N-hydroxymethylcarbofuran and 3-hydroxy-N-hydroxymethyl carbofuran
    were detected in excreta, liver and gizzard.  The eggs of laying hens
    (Hicks et al., 1970) given an oral dose of radio-labelled carbofuran

    [0.3 mg 14C carbofuran/kg body weight; 2.7 mg ring 14C carbofuran/kg
    body weight] contained only small amounts of carbofuran equivalents
    not exceeding 0.02 mg/kg.  All tissues taken from the laying hens for
    analysis at 6 and 24 hours contained residues [maximum levels in liver
    and kidney amounted to 2.6 mg/kg carbofuran equivalents].  None was
    detected thereafter in tissues of hens treated with ring 14C
    carbofuran, although certain tissues from the 14C carbofuran-treated
    hens contained residues at 3 days.  The authors considered that some
    of the 14CO carbofuran equivalents may have been naturally occurring
    chemicals, which was in agreement with the findings obtained in the
    feeding studies on cows (JMPR 1976).

    In Plants

    Carbofuran was rapidly taken up by plants through the roots from soil,
    water or nutrient solution and translocated mainly into the leaves
    (Ashworth and Sheets 1972, Penner and Early 1973).  The rapidity of
    carbofuran degradation differed in the various plant species and the
    main metabolite was identified as 3-hydroxycarbofuran.

    Soybean seeds and kernels of maize contained only 0.0l% of the applied
    radioactivity (Talker et al., 1977) or non-detectable residues -  0.01
    mg/kg - (Turner and Caro 1973) respectively at harvest following soil
    treatment.

    Residues in following crops:

    No residues of carbofuran plus 3-hydroxycarbofuran were found in
    carrots grown after maize in treated soil.  The limit of determination
    was 0.1 mg/kg.

    In lettuce planted after savoy cabbage, residues of carbofuran plus
    3-hydroxycarbofuran amounted to 0.3-0.4 mg/kg 129 days after the final
    application, and to n.d.-0.1 mg/kg after 140 and 147 days.

    In Soil

    The influence of different parameters on carbofuran degradation in
    soil was studied.  Degradation was seen to accelerate with increasing
    pH in laboratory experiments (Stanovick, 1968; Getzin, 1973) and in
    field trials (Caro et al., 1973).  Degradation was accelerated also by
    higher temperature and water contents of the soils (Caro et al.,
    1973; Talakar et al., 1977b).

    Talekar et al. (1977b) noted that in subtropical soils, carbofuran was
    more persistent during the dry and relatively cooler autumn and winter
    months than in summer.  After ten months, only 0.6% of the residues
    present initially could be recovered as parent compound.  In
    laboratory studies, flooding of soils was likewise found to accelerate
    degradation (Venkateswarlu et al., 1977).  Only 20 to 35% of
    carbofuran remained intact after 40 days of flooding, except in a
    relatively acid soil /PH 4.2/ from which 77% unchanged parent compound

    was recovered.  On the other hand, in a laboratory study, the rate of
    carbofuran dissipation was observed to increase, in the order: sandy
    loam, silt loam, muck soil (Stanovick, 1968).

    Getzin (1973) found that the effect of soil sterilization upon the
    degradation rate of carbofuran varied in different soils.  Whereas
    only slight or no differences were noted in silt loam and organic
    soils, the rate of degradation was slower in irradiated, sterilized
    clay loam.  Williams et al. (1976b) found that the rate of degradation
    of carbofuran was forty times greater in non-sterile soil during the
    second week after application.

    Carbofuran seemingly is metabolized to a lesser extent in soil than in
    animals and plants. Several authors (Stanovick, 1968; Caro et al.,
    1973; Getzin, 1973) found that unchanged parent compound accounted for
    most of the radioactive residue.  Getzin (1973) established that most
    of the radioactivity - up to 79% - from the degraded carbonyl-labelled
    carbofuran was expired as CO2.  With ring 14C carbofuran, an
    increase in soil-bound radioactivity was observed as time progressed.
    Metabolites detected were carbofuran phenol (Stanovick, 1968; Getzin,
    1973, Gupta and Dewan, 1975) which accounted for a maximum of 0.8% of
    the total activity added as carbofuran 3-keto-carbofuran which
    accounted for 5-10% of the carbofuran present and 3-keto-carbofuran
    phenol (Caro et al., 1973); Gupta and Dewan, 1975 and Talekar et
    al., 1977b).

    Carbofuran phenol was immediately bound to the soil constituents and
    slowly metabolized by micro-organisms (Stanovick, 1968; Getzin, 1973).
    3-ketocarbofuran disappeared from the soil at about the same rate as
    carbofuran (Caro et al., 1973).  In soil 3-hydroxycarbofuran, the
    principal carbofuran metabolite in some plants and animals, either was
    not found at all (Gupta and Dean, 1975) or was recovered only in
    traces (Caro et al., 1973; Talekar et al., 1977b).  On the other
    hand, Thinrumurthi et al. (1975) found in experiments with
    unlabelled carbofuran at 1 kg ai/ha that 3-hydroxycarbofuran was the
    principal metabolite in soil, reaching a maximum of 12.70 mg/kg on Day
    20.

    In Water

    The rate of hydrolysis is strongly pH-dependent.  In buffer solution
    at pH 5/28°C the carbofuran was stable for 28 days, 48.4% of
    carbofuran remained unchanged at pH 7/28°C after 21 days, while 50% of
    the compound hydrolysed at pH 9/26°C in 0.46 days. (Cook and Robinson
    1972).

    The results are in good agreement with the findings of other authors
    (McDonald, 1972, Metcalf, 1968).

    In field experiments, the behaviour was studied in rice paddy water
    (Deuel, 1975).  Applied in granular form (as Curaterr) to flood water,
    carbofuran was dissipated within 96 hours.  No significant levels of
    3-keto or 3-hydroxycarbofuran were found in the water.

    Metcalf et al. (1974) treated water with 0.1 mg/kg carbofuran.  At
    13-20°C the residues declined from 0.08 mg/kg immediately after
    treatment to 0.01 mg/kg on Day 21 post-treatment.  At temperatures of
    23-32°C, no more residues were detectable after only 7 days.

    In Processing

    Tomato fields were treated at planting (with Furadan 10 G) at a dose
    rate of 3.36 kg ai/ha in a 29 cm band.  The crops were processed.
    Samples were taken from tomatoes, juice, puree, juice pomace and puree
    pomace and were analysed for the carbamate and phenolic residues of
    carbofuran.  All samples contained residue of less than the 0.05 mg/kg
    limit of determination.  Since all processed products of tomatoes are
    acidic, any carbamate or phenol residues in tomato samples should
    likely be present in the processed products.  Thus the negative
    results indicate that the residues in tomatoes are much lower than the
    0.05 mg/kg limit of determination (FMC 1977c).

    EVIDENCE OF RESIDUES IN FOOD IN COMMERCE OR AT
    CONSUMPTION

    26 samples of barley, sugarbeet, maize, onion, rape, carrot, known to
    have been treated with carbofuran at sowing were taken and analysed
    for carbofuran, but none contained detectable residues (Hungary,
    1979).

    NATIONAL MRLs REPORTED TO THE MEETING

                                                                        
    Country        Crops                         MRLs in  Preharvest
                                                 mg/kg    Intervals/days
                                                                        

    Argentina      Apples, pear                           60
                   peaches                                45
                   tobacco, tomatoes                      no waiting-times
                   corn, potatoes                         fixed

    Austria        general                                35

    Belgium        sugar-beet, corn grains       0
                   corn fodder                   0.5
                   general                                150

    Brazil         milk                          0.02
                   rice                          0.2      30
                   cabbages                      1        90
                   peanut and cotton seed        0.1      14

    Canada         carrots, rutabages, turnips   0.5
                   corn, grain                   0.1
                   strawberries                  0.4
                                                                        

                                                                        
    Country        Crops                         MRLs in  Preharvest
                                                 mg/kg    Intervals/days
                                                                        

    Cyprus         potatoes, bananas
                   vegetables, beans, brassicas
                   tomatoes, eggplants,
                   cucumbers, onions, etc,
                   groundnuts, fodder beets,
                   tobacco                                21-28

    Fed. Republic  corn, hops, beets               fixed by registered
    of Germany                                         application
                   cabbage                                70
                   wine grapes                            56

    German         potatoes                               21
    Democratic     drift-treated cultures
    Republic       /provisions/                           21
                   drift-treated cultures
                   /fodder/                               14

    Hungary        general                       0.1      30

    Italy          sugar-beet                    0.1

    Kenya          maize grain                   0.1
                   sugar cane                    0.1
                   rice                          0.2
                   turnips                       0.5

    Mexico         alfalfa                                7-14
                   cotton                                 10
                   sugar cane                             17
                   potatoes                               14

    Netherlands    onions                        0.1
                   others                        0

    New Zealand    grapes, pipfruit                       42
                   pastures                               42

    Switzerland    Field applications                     21
                   mushrooms                     0.8
                   corn                          0.1

    Spain          beet, corn, sorghum                    60

    South Africa   corn, fodder                           56
                   mealies/green                 0.2
                   sugar cane
                                                                        

                                                                        
    Country        Crops                         MRLs in  Preharvest
                                                 mg/kg    Intervals/days
                                                                        

    Taiwan         vegetables                             15
                   fruits                                 10
                   rice                                   21
                                                                        

    APPRAISAL

    Carbofuran is applied at planting or sowing or as foliar treatment at
    various times during the growing season.  Trials indicate that the
    residues in treated crops such as egg plant, potatoes, soybean sweet
    corn, tomatoes are generally very low or not detectable even if a
    foliar treatment was applied shortly before harvest.

    Only plants having a large leaf surface such as alfalfa, cabbage,
    forage, grasses, maize and tobacco, contain high residues, which
    consist mainly of the intact carbofuran and the conjugated
    3-hydroxycarbofuran.  The residue found in mixed stands of alfalfa and
    forage grasses is covered by the limit given for alfalfa.  There are
    no data available for the residue in fodder beet or animal feeds other
    than those discussed in 1976 or in this addendum, and no new data were
    provided for Brussels Sprouts.

    Most of the bound residues in bean plants administered orally to
    female rats were excreted in the faeces, whereas the conjugated
    metabolites were excreted in the urine.  Carbofuran was degraded
    rapidly in laying hens and eliminated in the faeces, in which
    3-hydroxycarbofuran was the major metabolite.  The eggs contained less
    than 0.02 mg/kg residues calculated as carbofuran.

    No residues of carbofuran or 3-hydroxycarbofuran were found in carrots
    grown after maize, but in lettuce planted after cabbage, the residue
    amounted to 0.3-0.4 mg/kg 129 days after the final application.

    The degradation of carbofuran in soil is influenced by several factors
    such as pH, humidity, temperature, soil type and microbial activity.
    Carbofuran phenol was immediately bound to the soil and slowly
    metabolized by micro-organisms.

    The new information on methods of analysis supports the conclusions of
    the 1976 Meeting.

    RECOMMENDATIONS

    In the light of the data available, the limits recommended previously
    for "fodder beets" and "other animal feeds not otherwise listed" are
    withdrawn.  The limit for sugar beet leaves in amended.  The remaining
    recommendations of the previous Meeting are supported by more recent
    studies.  In addition, new limits are recommended for kohlrabi and egg
    plants, as follows:

    New or Amended Recommendations

    Commodity        Temporary MRL,    Pre-harvest intervals on which
                     mg/kg             recommendations are based/days

    Egg plants           0.1                         14
    Kohlrabi             0.1                         80
    Sugar beet
    leaves               0.2

    FURTHER WORK OR INFORMATION

    Required by July 1980:

    1.  Submission of the long-term feeding studies in appropriate
    species.

    2.  Teratogenicity and reproduction studies.

    Desirable:

    1.  Comparative animal studies to evaluate the apparent sensitivity of
    juveniles with respect to adults.

    2.  Observations in occupationally exposed people.

    3.  Further information on the level of residues in brassica cole
    leafy vegetables, especially Savoy cabbage and Brussels sprouts, and
    in bulb vegetables resulting from approved uses of carbofuran.

    4.  More information on use patterns on sugar cane and on the residue
    in the cane, raw sugar and refined sugar.

    5.  Selective surveys of residues in crops known to have been treated
    under practical circumstances.

    REFERENCES

    Ashwrot, R.J., Sheets, T.J.  Metabolism of Carbofuran in Tobacco.  J.
    Agric. Food Chem. 20, 407-412.

    Bayer, A.G.  Unpublished Reports Nos. 7103-7105/76, 7100-7105/77,
    7123/77, 7103-7108/78, 7127-7128/78 (1976-1978).

    Caro, J.H., Freeman, H.P., Glotfelty, D.E., Turner, B.C., Edwards,
    W.H.  Dissipation of Soil-Incorporated Carbofuran in the Field.  J.
    Agric. Food Chem. 21, 1010-1015.

    Case, R.S., Wilson, N.H.  Cholinesterase Evaluation Conducted During a
    Two-Year Dietary Toxicity/Oncogenicity Study with Carbofuran in Rats.
    (1979) Unpublished Report submitted by FMC Corporation to the World
    Health Organization.

    Canada.  Information submitted by the CCPR Country Delegation, 1979.

    Denmark.  Information submitted by the CCPR Country Delegation, 1979.

    Finland.  Information submitted by the CCPR Country Delegation, 1979.

    Deuel, L.E., Jr.  Residue Levels of Propanil, Molinate, Carbofuran,
    Carbaryl and their Respective Metabolises in Rice Paddy Water. Diss.
    Abstr. Int. B 36, 1997-1998.

    FMC Corp. Unpublished Reports:

    No. MO-1355.  Determination of Carbofuran and Residues in Tomatoes.
    (1975).

    No. W-0063. Determination of Carbofuran and its Metabolites in Green
    Alfalfa from a Mixed Stand. (1976a).

    No. 1-0132.  Determination of Carbamate and Phenol Residues of
    Carbofuran in Green and Dry Canadian Alfalfa and Brome Grasses.
    (1976b).

    No. MC-1370.  Determination of Carbofuran and 3-hydroxycarbofuran in
    Sweet corn. (1976c).

    No. MC-1371, No. MC 1373.  Determination of Carbofuran and
    3-hydroxycarbofuran in Sweet Corn. (1976d).

    No. M-4049.  Carbofuran and 3-hydroxycarbofuran Residue Analysis in
    Mexican Egg plant. (1977a).

    No. M-4049.  Carbofuran and its Carbamate Metabolite Residues in
    Burley Tobacco. (1977b).

    No. W-0173.  Determination of Carbamate and Phenol Residues of
    Carbofuran in Tomatoes and Tomato Processing Products from Tomato
    Processing Studies. (1977c).

    No. M-3634.  Determination of Carbofuran Carbamate and Phenolic
    Metabolite Residues in Potato Tubers. (1978a).

    No. M.4364.  Determination of Carbofuran carbamate Residues in/on
    Argentinean garlic. (1979a).

    No. M.4326.  Determination of Carbofuran carbamate Residues in/on
    Soybeans. (1979b).

    No. M.4367.  Determination of Carbofuran Carbamate Residues in/on
    Burley Tobacco. (1979c).

    Getzin, L.W.  Persistence and Degradation of Carbofuran in Soil.
    Environ. Entomol. 2, 461-467.

    Gupta, R.C., Dewan, R.S.  Residues and Metabolism of Carbofuran in
    Soil. Pesticides 8, 36-39.

    Herbold B.  Salmonella/Microsome Test for Detection of Point Mutagenic
    Effects.  (1978) Unpublished Report from Institut Toxicologie
    submitted by Bayer, A.G.

    Hicks, B.W., Dorough, H.W., Davis, R.B.  Fat of Carbofuran in Laying
    Hens. J. Econ.Entomol. 63, 1108-1111.

    Hungary.  Information supplied by Country Representative to CCPR,
    1979.

    Knaak, J.B., Munger, D.M., McCarthy, J.F.  Metabolism of Carbofuran in
    Alfalfa and Bean Plant.  J. Agric. Food Chem. 18, 827-831.

    Marshall, T.C., Dorough, H.W.  Bio-availability in Rats of Bound and
    Conjugated Plant Carbamate Insecticide Residues.  J. Agric. Food Chem.
    25, 1003-1009.

    McDonald, L.A.  Effect of pH on Dissipation in Water. PVC Corporation,
    unpublished Report, June, 26, 1972.

    Metcalf, R.L., Fukuto, T.R., Collins, C., Borck, K., Abd El-Aziz, S.,
    Munoz, R, Casill, C.C.  Metabolism of
    2,2-Dimethyl-2,3-dihydrobenzofuranyl-7 N-Methyl-carbamate/Furadan, in
    Plants, Insects and Mammals.  J. Agric. Food Chem. 16, 300-325.

    Metcalf R.L., Reinbold, K.A., Sanborn, J.R., Childers, W.F., Bruce,
    W.N., Coats, J.  Comparative Biochemistry, Biodegradability and
    Toxicity of DDT and Carbofuran Analogues.  Final Report, Project No.
    B-070-ILL; University of Illinois, Water Resources Center, Report
    No.95. (1974).

    Philippines.  Information submitted by Country Representative,
    1979.

    South Africa.  Information submitted by Country Representative,
    1979.

    Stanovick, R.P.  Metabolism of Carbofuran in Soil. (1968) I.
    Quantitative and Qualitative Determination of Radioactive Carbofaran
    and its Metabolites in Soil. FMC Corporation, Report No. M.2303,
    (1968).

    Talekar N.S., Lee, E.M., Sun, L.T.  Absorption and Translocation of
    Soil and Foliar Applied 14C-Carbofuran and 14C-Phorate in Soybean and
    Mungbean Seeds.  J. Econ. Entomol. 70, 685-688.

    Talekar, N.S., Sun, L.T., Lee, E.M., Chen, J.S.  Persistence of Some
    Insecticides in Subtropical Soil.  J. Agric. Food Chem. 25, 384-352.

    Turner, B.C., Caro, J.H.  Uptake and Distribution of Carbofuran and
    its Metabolites in Field-Grown Corn Plants.  J. Environ. Qual. 2,
    245-247.

    Venkateswarlu, K, Gowda, T.K.S., Sethunathan, N.  Persistence and
    Biodegradation of Carbofuran in Flooded Soils, J. Agric. Food Chem.
    25, 533-536.
    


    See Also:
       Toxicological Abbreviations
       Carbofuran (ICSC)
       Carbofuran (Pesticide residues in food: 1980 evaluations)
       Carbofuran (Pesticide residues in food: 1996 evaluations Part II Toxicological)
       Carbofuran (JMPR Evaluations 2002 Part II Toxicological)