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    CARBARYL     JMPR 1973

    EXPLANATION

         Carbaryl was evaluated by Joint Meetings in 1966, 1967, 1968,
    1969, and 1970 (FAO/WHO, 1967b, 1968b, 1969b, 1970b, 1971b). At the
    1969 Meeting it was decided that all temporary tolerances for carbaryl
    should be reviewed in 1973 and the previously proposed tolerance for
    whole milk was withdrawn until data on the levels of water-soluble
    metabolites could be evaluated. In the course of the numerous
    re-evaluations of carbaryl, many recommendations for tolerances were
    altered and in 1969 the original broad crop categories were expanded
    into subgroups or individual crops. This has led to some confusion and
    in particular certain crops (such as root crops), originally covered
    by the broad categories (such as vegetables), were inadvertently
    omitted from subsequent recommendations. Therefore, such oversights
    are corrected and a complete listing of current tolerance
    recommendations is provided in this monograph addendum. Also, the
    results of additional experimental work on certain commodities not
    previously considered became available and are summarized therein.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    Biochemical aspects

         In rats it was observed that absorption of carbaryl probably
    occurs in the stomach or anterior portions of the small intestine
    (Casper and Pekas, 1971). Carbaryl absorbed through the stomach was
    found to be unchanged in the blood (Casper, 1972). Carbaryl absorbed
    through the intestine underwent transformation to alpha-naphthol and
    was conjugated as a glucuronide (Pekas, 1971; Pekas and Paulson,
    1970). In insects, as well as mammals, it was observed that metabolism
    occurred during penetration from the gut (Shah and Guthrie, 1971).
    Studies on metabolites from the rat have confirmed the identity of
    5,6-dihydro-5,6-dihydroxycarbaryl glucuronide (Sullivan et al., 1972;
    Richey et al., 1972). Andrawes et al. (1972) found alpha-naphthol
    conjugated as a sulfate to be the predominant metabolite in eggs after
    continuous dosing of hens. In insects, a new metabolite was isolated,
    characterized and suggested to be 2-hydroxy-carbaryl (Moriyama et al.,
    1972). Using human lung cell cultures, rat liver and plant cell
    cultures, carbaryl was found to be metabolized to hydroxylated
    products and subsequently conjugated. The initial report of a new
    metabolite, the N-O-conjugate of carbaryl (Locke, 1972a and b), has
    not been confirmed by these authors (Personal communication). An in
    vitro study using human liver and rat liver preparations suggested
    that human liver produced minor carbaryl metabolites, not previously
    seen with rat tissue (Strother, 1972). These products were not
    identified, although the major metabolites were common to both
    systems. Several studies have been reported on the biological
    interaction of carbaryl with endogenous materials. Pinolene, a beta
    pinene polymer, has been shown to extend the residual life of carbaryl

    in certain crops. The probability that this activity is physical
    rather than biological is strong (Blazques et al., 1970). Oral
    administration of gossypol was found to stimulate liver microsomal
    oxidative activity and concomitantly the ability to dealkylate
    carbaryl (Abou-Donia and Dieckert, 1971). Similarly, methylmercury and
    chlordane were observed to have the same increased effect on the
    metabolism of carbaryl (Lucier et al., 1972). Compounds which were
    found to decrease MAO activity reduced the excretion of carbaryl from
    rats (Dorough et al., 1972). Atropine reduced the acute toxicity of
    carbaryl and seven other carbamates administered subcutaneously to
    male mice. Oximes were slightly effective in reducing the acute
    toxicity of seven carbamates and were slightly therapeutic in
    combination with atropine. With carbaryl, obidoxime and P2S were
    synergistic and were antagonistic to the therapeutic effects of
    atropine. This reverse effect was noted only with carbaryl (Natoff and
    Reiff, 1973).

         Stenberg (1970) reported that 0.7 mg/kg administered orally for
    3-1/2 months induced tension and stimulation of the thyroid activity
    (increase of PSI, thyroid weight increase, and proliferation of
    colloid content of RNA). The effects diminished at six months.
    Rappoport (1969) administered carbaryl for three months at 50
    mg/kg/day and found changes in the thyroid gland using the electron
    microscope.

         Carbaryl at 7.6 and 38 mg/kg administered orally to rabbits for
    11 months led to disturbances in carbohydrate and protein metabolism
    and other biochemical changes in the liver. When administered at 0.76
    and 0.38 mg/kg doses, a retention of bromsulphalein in blood was
    observed; a decrease in protein and an increase in alpha and 
    globulin content. Tissue cholinesterase was depressed at all doses
    (Kagan et al., 1970). In subacute test, carbaryl decreased the
    glycolytic activity in brain (Jakushko, 1971) and other tissues
    (Hajkina, 1970).

         With the aid of microelectronic techniques, Homenko (1971)
    examined the effect of carbaryl on the membrane potential of motor
    neurons of the spinal cord in rats. Carbaryl administered orally at
    doses of 8.5 mg/kg and above caused increases in the potential,
    depending on the dose and duration of treatment.

    TOXICOLOGICAL STUDIES

    Special studies on mutagenicity

         The mutagenic potential of carbaryl was demonstrated in tests
    with Drosophilia melanogaster. It was suggested that there was a
    slight mutagenic tendency in these tests (Hogue, 1972; Brzheskiy,
    1972).

    Special studies on neurotoxicity

         Carbaryl has been reported to exert a possible sympathomimetic
    effect in addition to its parasympathomimetic properties (Santolucito
    et al., 1972). This property of carbaryl may explain apparent
    discrepancies in behavioural studies (Sideroff and Santolucito, 1972).

    Special studies on reproduction

         Previous work in the Rhesus monkey (FAO/WHO, 1970) indicated that
    carbaryl may interfere with reproduction in this species. Eleven
    female monkeys were treated with carbaryl at the rate of 0, 2, 6.3,
    and 20 mg/kg. One of these monkeys delivered a baby while four
    controls conceived and delivered normal babies. In a recent, as yet
    uncompleted, experiment, groups of 16 pregnant Rhesus monkeys were
    administered carbaryl orally, by stomach tube, twice daily from day 18
    to day 40 of gestation at a dose of 0, 0.2, 2 and 20 mg/kg. An interim
    report on this study indicates that carbaryl at levels up to and
    including 20 mg/kg/day does not have an effect on the reproduction
    parameters measured. Of 15 control monkeys, there were 12 live births,
    two abortions and one still-born. Of the 11 monkeys receiving the
    vehicle as a control, there were 10 live births and one abortion. In
    the group receiving the low dose (0.2 mg/kg), there were 11 live
    births and two abortions. In the group receiving the intermediate dose
    (2.0 mg/kg), there were 11 live births and one abortion, while in the
    group receiving the highest dose (2.0 mg/kg) there were 10 live births
    and three abortions. Although the study is not complete, the initial
    indications of a reproductive hazard in Rhesus monkeys, based upon
    previous data, is unfounded. The abortions and still births occurring
    in the current study have been reported to be within the normal limits
    for the Rhesus colony and the results to date indicate that carbaryl
    does not induce abortion in these monkeys (Dougherty et al., 1973).
    Weil et al. (1972a and b) reported on a reproduction study in progress
    where carbaryl was administered to rats orally by gavage or in the
    diet (with and without corn oil as a vehicle). Rats were divided into
    three groups; one group (five subgroups, 15 male and 25 female)
    received daily intubation (five days per week) of carbaryl suspended
    in corn oil at doses of 0, 3, 7, 25 and 100 mg/kg; one group (five
    subgroups) received dietary concentrations of 0, 7, 25, 100 and 200
    mg/kg/day, five days per week; one group (two subgroups) received
    carbaryl in dietary concentrations of 0 and 100 mg/kg/day, five days
    per week, with corn oil (4 ml/kg/day) as a carrier. Data were reported
    for the F1a generation. There were significant effects on reproduction
    in only the intubated groups receiving 100 mg/kg, where fertility was
    reduced and mortality was observed. Signs of poisoning were evident at
    levels of 7 mg/kg and above. There were some effects reported on the
    F1b generation, where a reduction in the number of litters was
    reported in the intubated group receiving 100 mg/kg/day. No effects
    were noted in rats receiving 200 mg/kg/day in the diet. A similar
    study was reported for guinea-pigs. Guinea-pigs receiving 200 mg/kg by
    gavage or 300 mg/kg in the diet administered during gestation or
    organogenesis showed no effect on reproduction (Weil et al., 1972b).
    Benson et al. (1967 report cited in Weil et al., 1972a) gave groups of

    20 hybrid female mice diets containing carbaryl at concentrations of
    10 and 30 mg/kg/day from day 6 after mating. No effects were noted in
    parents and no teratological changes were noted in the pups.

         Collins et al. (1970) reported reproduction on a study where
    carbaryl was fed to rats at levels of 0, 2000, 5000 and 10 000 ppm for
    three generations. Carbaryl at 10 000 ppm inhibited reproduction. At
    2000 ppm and above only a dose-related decrease in pup weight was
    observed. No effects on reproduction parameters were observed at 2000
    ppm. Gerbils fed carbaryl at 0, 2000, 6000 and 10 000 ppm in the diet
    for three generations showed no effects on reproduction at 2000 ppm.
    At 6000 and 10 000 ppm the survival index and the average number of
    young weaned per litter were reduced.

         Following i.v. administration of 14C-carbaryl to mature dogs,
    small amounts of radio-activity were detected 30 or 60 minutes after
    injection in the testes, vas deferens and prostate gland. In mice,
    oral administration of carbaryl (0.9 mg/kg) resulted in 14C in
    testes, prostate gland, seminal vesicle (seminal plasma) and the
    epididymis. Carbaryl administered orally for five days to mice at a
    dosage of 38 or 68 mg/kg had little effect on the reproductive organs
    in male mice (gonad weight or sex accessory gland weight). The doses
    had no effect on testosterone metabolism in the prostate gland,
    although androgen hydroxylase activity in liver microsomes was
    stimulated (16 alpha-hydroxyl testosterone activity was stimulated).
    Carbaryl had a far less affinity for reproductive organs than DDT.
    Regardless of species, carbaryl did not seem to possess any particular
    affinity for organs of reproduction (Thomas et al., 1973; Dieringer et
    al., 1973).

         Peroral administration to rats resulted in reproductive effects
    on both males and females, impaired oogenesis and spermatogenesis.
    When fed to successive generations, carbaryl at 2 mg/kg in the diet
    also resulted in ovarian and testicular problems. especially noted in
    the second, third and fourth generations (Shtenberg and Orlova, 1970).

         Carbaryl was fed for 90 or 138 days to female rats at levels of 5
    or 10 mg/kg. The rate of fertilization was reduced at 5 mg/kg with a
    normal number of corpora lutea observed. The litters were larger with
    no teratogenic effects noted. At 10 mg/kg, a greater rate of reduction
    of fecundity was observed (Trifonovia et al., 1970 - Abstract only).

         Carbaryl has been reported to interfere with oogenesis and the
    oestrous cycle and was said to exert a direct gonadatoxic effect
    (Mandzhgaladze and Vashakidze, 1972). Dosing was reported to be at
    1/200) -> 1/1000 of the LD50 level for an unspecified time. (Details
    of this report were unavailable.)

         Carbaryl was fed to hens at 0, 250 and 500 ppm in the diet for 36
    weeks and to their progeny for four weeks at 0 and 500 ppm, either
    alone or in combination with malathion. Growth was affected in both
    parents and chicks, but reproduction and egg characteristics were not

    affected. A study at 500 ppm in males showed no effects on fertility
    over a four-week period (Lillie, 1973).

         In hens fed carbaryl at 500 ppm for 36 weeks, no effects on hens
    or progeny were observed, except a slight weight loss and growth
    depression. Administration of carbaryl to male leghorns resulted in no
    effect on reproduction (Lillie, 1973).

         Carbaryl introduced in albino rats perorally at doses of 2 and 5
    mg/kg over six months resulted in unfavourable effects on ovaries and
    testes and gonadotropic function of the hypophysis. Progressive
    atrophic, dystrophic and necrotic changes in the testes and the
    ovaries were shown histologically and histochemically (Stenberg and
    Otovan, 1971).

         Vashakidze (1970) reported on gonadotropic, embryotoxic and
    mutagenic effects of carbaryl following oral administration.

         Structural changes were reported in the gonads and
    spermatogenesis was impaired in the late period of meiosis. These
    changes were clearly expressed in subacute tests.

         Carbaryl affected reproductive capability of the treated animals
    and caused sterility in subthreshold doses - 2 and 1 mg/kg in a six-
    month experiment. An increased quantity of undeveloped and dead
    embryos was noted in a chronic test at a dose of 1.3 mg/kg.

         The results of the cytogenetic investigations show that carbaryl
    causes the chromosomes to stick together frequently during a
    continuous introduction of small doses (0.5 mg/kg). The effect of
    carbaryl is characterized also by changes of the ovogenesis: affected
    cycle; and injury of the cells of the follicular apparatus. The effect
    on ovogenesis was dependent on the dose and the duration of treatment.
    Carbaryl also caused embryo mortality.

         A threshold dose of the specific effects of carbaryl on the
    gonads of female albino rats is 10 mg/kg, in subacute test - 1 mg/kg,
    and in chronic test - 0.5 mg/kg.

         Sensitivity of the embryo to carbaryl appeared during the second
    half of pregnancy (10-18 days).

         In a six-month oral administration study (0.3-10 mg/kg), the
    average weight of the semen decreased at doses of 4 and 2 mg/kg, with
    changes noted in spermatogenesis. A dose of 0.5 mg/kg causes no effect
    on spermatogenesis.

    Comments

         When carbaryl was evaluated by a previous meeting (FAO/WHO, 1970)
    adverse effects on reproductive physiology in several animal species
    and an increased urinary amino acid to creatinine ratio in man were
    regarded as matters for concern. Several studies were reviewed by the

    present Meeting relating to the effect of carbaryl on reproduction. No
    effect on reproduction was seen in Rhesus monkeys. Studies in several
    species of animals showed that administration by gavage is more likely
    to affect reproduction than administration in the diet. Further work
    was reported which indicated disturbance in the thyroid gland
    following short-term treatment. In longer-term studies, disturbances
    of carbohydrate and protein metabolism, liver function and endocrine
    function and effects on gonads were observed. Behavioural changes have
    been reported indicating possible sympathomimetic effects on
    peripheral systems. New data with respect to the effects of carbaryl
    on renal function have not been reported.

         In the light of all the data available, the Meeting felt
    justified in establishing a permanent ADI.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

         Rat:  200 ppm in the diet equivalent to 10 mg/kg bw

         Man:  0.06 mg/kg/day

    Estimate of acceptable daily intake for man

         0-0.01 mg/kg bw

    RESIDUES IN FOOD AND THEIR EVALUATION

    Use pattern

    Pre-harvest treatments

         Carbaryl has been in general use around the world since 1959 for
    control of insect pests which attack agricultural crops as well as
    certain other non-agricultural pests. Approximately one-half of the
    carbaryl produced annually in the United States of America is used
    within the country. The balance is exported and, in 1972, foreign
    sales were distributed as follows: cotton 40%, vegetables 150/, rice
    10%, potatoes 10%, fruit 5%, livestock 5%, and miscellaneous 15%.
    Within the United States of America, the most important uses are (in
    decreasing order): soybeans, corn (sweet and field), ornamentals and
    turf, forest and shade tree, cotton, deciduous tree, fruit, peanuts,
    poultry, and vegetables. The registered uses and recommended rates are
    given in more detail in Table 16 under National Tolerances. The
    versatility of carbaryl, as indicated by its registration of 85 crops
    for control of 160 different insect pests, accounts in part for the
    broad usage. Reliable performance against target pests and the low
    hazard to man and the environment have also been important factors in
    moulding the pattern of use for carbaryl.

         The strongest influence on the use patterns of carbaryl in recent
    years has been a marked reduction in the general use of certain
    low-cost organochlorine insecticides.

    Post-harvest treatments

         None.

    Residues resulting from supervised trials

    Root crop vegetables

         The available data on residues found when small plots of carrots,
    turnips, beets, radishes and parsnips were treated one or more times
    at the maximum recommended rate of 2 lb ai/acre is shown in Table 1
    (Union Carbide, 1973).

    TABLE 1. CARBARYL RESIDUES (ppm) IN ROOT CROP VEGETABLES

                                                                       

                                              Days after last treatment

    Crop         lb ai/acre   Number of       0          3          7
                              treatments
                                                                       

    Carrot           2            11          1.7        -          -

                     2             4          0.1        -          2

                     2             1          0.5        -          -

    Turnip           2             1          0.8        -          -

                     2             2          0.6        -          -

                     2             6          10.3       1.3        0.9

                     2             2          1.2        0.9        0.5

    Beet             2             7          6.5        0.3        0.4

                     2             1          1.1        -          -

                     2             2          0.6        -          -

    Radish           2             6          11.0       -          -

    Parsnip          2             3          1.2        -          -

                                                                       

         The pre-harvest use limitation Is three days except for carrots,
    where no limit exists.

    Peanuts, soybeans, sorghum grain and cowpeas

         The results of supervised trials on both small experimental plots
    and large commercial fields are shown in Tables 2, 3, 4 and 5 (Union
    Carbide, 1973). Although applications of carbaryl to these crops are
    often made close to harvest, an interval of at least one week would
    usually precede harvest. There are no pre-harvest limitations on
    peanuts, soybeans, or cowpeas; a limit of 21 days is set for sorghum
    grain.

    TABLE 2. CARBARYL RESIDUES (ppm) IN PEANUTS: NUT PLUS HULL

                                                                            
                                  Number of Days after last application
    lb ai/acre   Number of                                                   
                 applications     0        41a      48a      73b     80b
                                                                            

    1.5          1                0.33     -        -        -       -

    1.0          1                -        -        0.26     -       0.72

    1.0          2                -        0.40     -        0.98    -

    2.0          1                -        -        0.21     -       0.72

    2.0          2                -        0.18     -        1.6     -

    1.0          1                -        -        0.26     -       -

    1.0          2                -        0.46     -        2.0     -

    2.0          1                -        -        0.18     -       0.63

    2.0          2                -        0.28     -        0.96    -
                                                                            

    a Normal digging time.

    b Normal picking time - after drying.

    TABLE 3. CARBARYL RESIDUES (ppm) IN SOYBEANS (DRY MATURE SEED)

                                                                            
    lb ai/acre     Number of           Days after last application
                   applications                                              
                                       38        85           99
                                                                            

    1              2                   0.96      -            -

    2              3                   -         0.07         -

    1.5            1                   -         -            0.08

    2              1                   -         -            0.05

                                                                            

    TABLE 4. CARBARYL RESIDUES (ppm) IN SORGHUM GRAIN

                                                                            

    lb ai/acre   Number of       Days after last application
                 applications                                                
                                 0         3         7-8       11-16
                                                                            

    4            3               40        30        -         -

    2            4               7.2       4.1       2.9       -

    2            3               22        14        15        24

    2            2               7.0       1.9       1.1       1.3

    2            1               45        -         39        11

    2            1               35        -         9.7       -

    2            1               20        -         5.0       -

    2            1               3.9       -         2.3       1.3

    2            1               -         -         5.0       1.0

    2            1               -         -         4.5       0.8

    2            1               -         -         5.0       -

    1.5          2               44        -         39        8.8

    1            3               16        1.0       0.6       0.7

    TABLE 4. (Cont'd.)

                                                                            

    lb ai/acre   Number of       Days after last application
                 applications                                                
                                 0         3         7-8       11-16
                                                                            

    1            1               11        -         4.1       1.8

    1            1               5.9       -         2.0       1.0

    1            1               2.9       -         0.6       -
                                                                             

    Maximum, ppm                 45        30        39        24

    Average, ppm                 20        10        9         5
                                                                             


    TABLE 5. CARBARYL RESIDUES (ppm) IN COWPEA HULLS AND PEAS

                                                                            
    lb ai/lacre    Number of      Days after last application
                   applications                                              
                                  0         1         3         7
                                                                            

    Hull + pea
    sample

    2.8                 3         -       8.1     6.3     4.5
    2                   8         2.3     -       1.5     1.0
    2                   2         4.0     -       0.6     1.6
    2                   2         3.4     -       -       -
    2                   1         26      24      4.8     3.1
    2                   3         12      -       4.5     0.9
    1.5                 1         2.5     -       1.3     -
    1.3                 1         3.1     -       1.6     -

    Hull only
    2                   1         4.2
    1                   1         3.4

    Pea only
    2.8                 3         -       0.7     0.8     0.6
    2                   1         0.9     -       -       -
    1                   1         0.8     -       -       -
    2                   2         0.4     -       0.5     0.7
                                                                            

    Sugar beets

         Good agricultural practice for the use of carbaryl on sugar beets
    requires 2 lb ai/acre maximum with one or two applications up to 14
    days before harvest. The results from small plot replicated trials are
    shown in Table 6 (Union Carbide, 1973).

    Forage crops

         Forage crops on which carbaryl is used include alfalfa, clovers,
    cowpea foliage, corn forage, grasses, peanut hay, sorghum forage and
    soybean foliage. A maximum dosage of 1.5 lb ai/acre (2 lb ai/acre on
    cowpeas and sorghum) is permitted with no pre-harvest limitation.
    Although applications of carbaryl to these forage crops are often made
    close to harvest, an interval of one week would precede harvest in
    most cases.

         The average and maximum residues determined in field trials on
    these crops are summarized in Table 7 (Union Carbide, 1973).

    Cucurbits

         Residues resulting from replicated small plot and field
    treatments are given in Table 8 (Union Carbide, 1973). Good
    agricultural practice calls for a maximum dosage of 1 lb ai/acre
    repeated as needed at 7-10 day intervals with no harvest limitation.

    Fate of residues

    General comments

         The nature of the terminal residues of carbaryl in plants and
    animals was summarized in the 1969 review (FAO/WHO, 1970b). Since
    then, new information has become available on the distribution of
    metabolites in plant tissues and on the transfer of residues to meat,
    milk and eggs.

    In plants

         The metabolism and distribution of 14C-radio-labelled carbaryl
    in a variety of plants has been examined (Andrawes and Chancey, 1970;
    Chancey and Andrawes, 1971a, 1971b, 1972a, 1972b, 1973). These results
    are summarized in Tables 9, 10 and 11. The conditions for extraction
    of total 14C-materials and subsequent hydrolysis of the water-soluble
    components were not optimized for each individual crop and the methods
    described by Wiggins and Weiden (1969a and b) were applied without
    modification to determine the metabolic profile of carbaryl in various
    plant species. Thus, metabolic data obtained should be regarded as
    qualitative. With this limitation, it is concluded that the metabolic
    pathway of carbaryl is qualitatively similar in all plant species
    studied and that the metabolic profile in foliage is generally similar
    to that in fruit (Andrawes, 1973).



    
    TABLE 6.  CARBARYL RESIDUES (PPM) IN SUGAR BEETS

                                                                                                          

                                         Days after last treatment
                                                                                                           
                Number of    Tops                                      Roots
    lb ai/.cre  treatments                                                                                 
                             0       7       14      21      28        0       7       14      21      28
                                                                                                          

    2           1            17      4.5     1.5     0.6     0.2       0.09    0.03    0.03    0.03    0.03

    2           1            6.5     1.3     0.7     -       0.1       0.02    0.02    0.04    -       0.03

    2           2            86      2.9     0.3     -       -         0.04    0.05    0.03    -       -

    2           2            7.8     18      0.6     0.1     -         0.02    0.02    0.02    -       -

    4           1            170     15      3.6     0.7     0.5       0.11    0.03    0.05    0.02    0.03

    4           1            26      1.5     0.5     -       0.1       0.03    0.03    0.04    -       0.02

    4           2            160     5.8     0.4     -       -         0.05    0.11    0.08    -       -

    4           2            15      8.5     1.4     0.5     -         0.05    0.03    0.03    0.03    -

    1           1            12      5       -       0.5     -         -       -       -       -       -

    2           4            8       5       -       -       -         -       -       -       -       -

    1.5         1            10      -       1.4     -       -         -       -       -       -       -
                                                                                                          

    



    TABLE 7. CARBARYL RESIDUES (ppm) IN FORAGE CROPS

                                                                  

                            Days after last application
    Forage crop         Average                 Maximum
                                                                   

                        0       3       7       0       3       7
                                                                  

    Alfalfa             40      23      9       190     33      27

    Clover              32      24      8       77      60      16

    Corn forage         16      6       4       33      9       9

    Cowpea foliage      26      14      10      72      42      17

    Grass               45      26      12      98      60      26

    Peanut hay          24      11      3       63      19      8

    Sorghum forage      51      21      13      144     70      62

    Soybean foliage     48      20      9       136     38      19
                                                                  

    TABLE 8. CARBARYL RESIDUES (ppm) IN CUCURBITS

                                                                            

                      lb ai/acre   Number of        Days after last spray
                                   treatments                                
                                                 0       1-2     3       7
                                                                            

    Cucumbers             1            2         3.7     -       -       -
                          1            6         1.5     -       -       -
                          1            5         6.9     -       -       -
                          1            4-7       4.6     -       1.6     1.6
                          2            3-4       1.6     1.7     1.0     0.6
                          1            1         3.4     2.5     1.9     1.1

    Summer squash         1            6         1.2     -       -       -
                          1            2         1.7     1.3     -       -
                          2            3-4       1.2     1.3     1.4     0.5

    Winter squash         2            7         5.7     -       -       -
                          2            6         1.8     -       -       -

    Cantaloupe            1            9         5.4     -       -       -

    Table 8 (cont'd)
                                                                            
                      lb ai/acre   Number of     Days after last spray
                                   treatments                                
                                                 0       1-2     3       7
                                                                            

                          1            7         3.8     -       -       -
                          2            3         3.4     -       -       -
                          2            6         2.1     -       -       -
                          2            9         1.7     -       -       -

    Water melon           2            7         5.7     -       -       -
                          2            6         1.8     -       -       -
                                                                            

    TABLE 9. TRANSLOCATION OF 1-NAPHTHYL-14C-CARBARYL FROM FOLIAGE TO FRUIT

                                                                           

    Plant     Holding       Method of               Time       % of applied
              conditions    application             (days)     translocated
                                                                           

    Tomato    Greenhouse    7 surface treatments    50         0.4

    Wheat     Greenhouse    Leaf blade surface      21         <0.1
              Greenhouse    Stem injection          21         2.5

    Potato    Field         Stem injection          21         0.6
                                                    42         1.4

    Peanut    Field         Stem injection          21         0.5
                                                                           

    In animals

         Radio-tracer studies have shown that carbaryl is rapidly
    metabolized and is generally excreted almost entirely within 24-96
    hours after consumption. Elimination takes place mainly through the
    urine, faeces, and respiratory gas and, to a lesser extent, through
    the milk of dairy animals and eggs of poultry. The faecal route of
    elimination is quite minor (<10%) in species other than the dog.
    Long-term feeding of l-naphthyl-14C-carbaryl to laying chickens and
    lactating cows showed only 0.15% and 0.22% of the administered dose to
    appear in the eggs (Andrawes et al., 1972) and milk (Dorough, 1971)
    respectively. The metabolic pathway of carbaryl in intact animals is
    summarized in Fig. 1. Not all metabolites shown are formed by all
    species studied. The major portion of urinary metabolites consists of
    the water-soluble sulfate and glucuronide conjugates of the primary
    products. The metabolites 1-methoxy-5-(methylearbamoyloxy)-2-naphthyl
    sulfate and a conjugate of 5-methoxy-1,6-naphthalenediol were only
    observed in milk of cows treated with l-naphthyl-14C-carbaryl
    (Andrawes, 1973).



        TABLE 10. RELATIVE DISTRIBUTION OF METABOLIC PRODUCTS IN THE FOLIAGE (AS PERCENTAGE OF TOTAL RADIO-ACTIVITY IN INTERNAL EXTRACT) IN
              DIFFERENT PLANT SPECIES 21 DAYS AFTER APPLICATION OF 1-NAPHTHYL-14C-CARBARYL
                                                                                                                                       

                                                 Wheat                         Alfalfa                               Tomato
    Metabolite          Ricea   Corna                              Beanb                    Peanutb    Potatob
    
                        S,Gh    S,Gh     S,Ghb   I,Ghb   S, Gha    S,F      S,Fb   S,Ghb    S,F        S,F        S,Gha   I,Gha   S,Fb

                                                                                                                                       

    Free carbaryl       18.5    19.5     71.2    20.7    1.6       7.2      3.7    19.4     2.3        0.8        7.5     1.9     3.7

    Combined carbaryl   4.0     1.1      1.6     0.9     13.3      1.7      6.1    7.1      6.4        13.7       5.6     5.1     3.0

    I-naphthol          1.8     1.4      0.8     2.5     1.0       1.5      1.8    0.8      14.5       4.2        6.3     3.5     4.2

    4-hydroxy           2.0     4.2      18.2    2.6     11.7      2.5      3.6    2.0      9.1        3.3        10.8    7.3     6.4

    5-hydroxy           2.9     6.9      6.8     1.5     14.6      2.9      2.5    1.6      5.7        3.1        2.7     1.9     2.4

    Hydroxymethyl
    (methylol)          4.0     7.7      3.6     1.9     8.5       13.9     7.0    8.5      9.7        11.4       19.9    8.0     15.7

    5,6-dihydrodiol     2.1     1.4      1.5     ND      1.4       1.1      ND     4.1      ND         ND         ND      4.9     ND

    Unknowns            1.1     1.9      1.9     ND      2.7       ND       0.3    4.8      2.7        ND         4.0     3.4     2.8

    Origin of TLC       6.2     12.5     11.0    8.1     15.0      4.6      14.7   21.6     7.2        19.2       14.2    23.9    7.1

    Unhydrolysed        9.7     6.4      3.1     2.0     ND        17.6     18.5   8.8      9.6        11.7       7.1     10.0    13.6

    Unextracted         47.9    37.1     34.3    59.8    32.0      40.8     41.1   21.5     32.8       32.6       21.9    30.1    41.2

    7-hydroxy           ND      ND       ND      ND      ND        6.2      1.5    ND       ND         ND         ND      NO      ND
                                                                                                                                       

    a Seedlings.
    b Mature plants.

    Abbreviations: S -surface application;  I - injection into stem;  Gh - greenhouse;  F - field;  ND - none detected.
    
        TABLE 11. RELATIVE DISTRIBUTION OF METABOLIC PRODUCTS (AS PERCENTAGE OF TOTAL RADIO-ACTIVITY
              IN INTERNAL EXTRACT) IN TOMATO FRUIT AND WHEAT HEAD 21 DAYS APTER APPLICATION OF
              1-NAPHTHYL-14C-CARBARYL
                                                                                                        

                             Tomato-surfacea     Tomato-injectedb    Tomatoc            Wheat-Steme
    Metabolite                                                       surface    Wheatd
                             Ripe     Green      Ripe     Green      field      leaf     Chaff     Seed
                                                                                                        

    Free carbaryl            6.9      12.8       ND       0.6        4.0        9.1      6.1       4.1

    Combined carbaryl        2.5      1.8        1.6      1.5        3.2        3.0      1.5       3.8

    1-naphthol               1.2      8.8        0.6      2.4        8.2        1.4      0,9       5.2

    4-hydroxy                9.9      7.0        9.0      12.2       0.4        8.9      7,4       7.7

    5-hydroxy                6.3      8.1        1.5      3.3        0.3        4.4      4.4       3.1

    Methylol                 19.5     13.7       32.1     27.8       27.3       2.6      4.7       6.5

    5,6-dihydrodiol          4.1      1.2        ND       3.6        ND         ND       0.5       ND

    Unknowns                 0.9      0.7        5.1      4.0        ND         ND       ND        ND

    Origin of TLC            11.2     18.3       8.6      9.0        22.7       11.9     11.0      8.0

    Unhydrolysed             31.7     18.3       31.9     26.3       22.5       11.1     6.0       10.3

    Unextracted              5.8      9.3        9.6      9.3        11.1       47.4     57.0      51.3

    7-hydroxy                ND       ND         ND       ND         ND         ND       ND        ND
                                                                                                        

    a Carbaryl applied to the surface of the fruit in the greenhouse.
    b Carbaryl injected into the fruit in the greenhouse.
    c Carbaryl applied to the surface of the fruit in the field.
    d Carbaryl applied to the leaf blade of mature wheat, the head (chaff plus seeds) was analysed.
    e Carbaryl injected into the stem of maturing wheat plants in the greenhouse.
    

    FIGURE 1

    Potential transfer of residues to meat, milk and eggs

    (a) In dairy animals

         After oral administration of single does of
    1-naphthyl-14C-carbaryl at levels of 0.25 and 3.05 mg/kg,
    approximately 0.35% of each dose was detected in the milk (Dorough,
    1970). Maximum concentrations were found in samples taken six hours
    after dosing which, following the two treatments, were 0.063 and
    0.95 ppm, respectively.

         In another study, 1-naphthyl-14C-carbaryl was fed to lactating
    cows at levels of 0.15, 0.43 and 1.35 mg/kg bw (equivalent to 10, 30
    and 100 ppm in the feed) for 14 days (Dorough, 1971). Equilibrium
    between intake and elimination was reached within two days of
    initiation of the treatment. At each feeding level, approximately 0.2%
    of the dose was secreted in the milk. The concentration of total
    14C-carbaryl equivalents in the milk was 1/400 of that in the diet.
    Most of the 14C-residues (about 90%) were in the aqueous phase. Milk
    metabolites and their concentrations after feeding 100 ppm of
    l-naphthyl-14C-carbaryl for 14 days are shown in Table 12.

         Continuous feeding of l-naphthyl-14C-carbaryl to cows and a
    single oral dose of the same material demonstrated that carbaryl
    residues do not accumulate in the body tissues (Dorough, 1971).
    Furthermore, a good correlation existed between the level of pesticide
    fed and that which appeared in the tissues. The distribution of
    residues in different tissues and organs of cows receiving carbaryl in
    their feed is shown in Table 13, while Table 14 shows the nature of
    residues found in various samples.

    (b) In poultry and eggs

         Following administration of l-naphthyl-14C-carbaryl to hens,
    total 14C-residues reached a maximum and dissipated at a much faster
    rate in egg white than in egg yolk. In a single dose of 10 mg/kg
    (Paulson and Foil, 1969), maximum concentration of 14C-residues in
    egg white was 0.12 ppm at one day and dropped to trace amounts on the
    second day after treatment. The yolk residues reached a maximum at the
    fifth day (0.36 ppm) and had dissipated by the ninth (0.03 ppm). Under
    continuous feeding conditions, the total residue in the yolk or white
    at each sampling time was dosage related (Andrawes et al., 1972).
    Concentration of 14C-carbaryl equivalents (ppm) reached a maximum
    (0.10 ppm from 70 ppm in feed; 0.025 ppm from 21 ppm in feed) in the
    white after 2-6 days and in the yolk (1.0 ppm from 70 ppm in feed;
    0.30 ppm from 21 ppm in feed) after 6-9 days of dosing and remained
    level until the end of the treatment period. At plateau levels, the
    level of 14C-carbaryl equivalents in the white was one-tenth that in
    the yolk; however, the total equivalents were in a ratio of 5:1
    between yolk and white. The ratio of the concentration of carbaryl in
    whole eggs (white and yolk) to that in the diet was 0.006 at

    equilibration. After discontinuation of dosing, residues in the whites
    had a half-life of less than one day; for yolk residues the half-life
    was approximately 2-3 days. The nature of the metabolites found in
    eggs is shown in Table 15.

    TABLE 12. CHEMICAL NATURE OF CARBARYL METABOLITES IN COW'S MILK AND THEIR
              AVERAGE CONCENTRATIONS AFTER FEEDING WITH 1-NAPHTHYL-14C-
              CARBARYL AT LEVEL EQUIVALENT TO 100 ppm IN THE DIET FOR 14 DAYSa

                                                                            
    Metabolites                                  ppm in            % of
                                                 milk              total
                                                                            

    Carbaryl                                     17                6

    3,4-dihydro-3,4-dihydroxy-l
    naphthyl methylearbamate                     13                5

    5,(3-dihydro-5,6-dihydroxy-l
    naphthyl methylcarbamate                     94                34

    5-hydroxy-l-naphthyl methyl
    carbamate                                    3                 1

    5,6-dihydro-5,6-dihydroxy-l
    naphthol                                     9                 3

    l-naphthyl sulfate                           72                26

    1-methoxy-5-(methylearbamoyloxy)-
    2-naphthyl sulfate                           63                23

    5-methoxy-1,6-naphthalenediol                7                 2
                                                                            

    a Reference - Dorough, 1971.

    TABLE 13. TOTAL CARBARYL-14C EQUIVALENTS IN TISSUES OF COWS FED
              CARBARYL-NAPHTHYL-14C FOR 14 DAYS AT RATES OF 10, 30 AND
              100 ppm IN THE DIETa

                                                                            
                        ppm carbaryl-14C equivalents at feeding level of
    Tissues                                                                  
                        10 ppm         30 ppm         100 ppm
                                                                            

    Kidney              0.095          0.531          1.003

    Liver               0.033          0.100          0.411

    Lung                0.020          0.064          0.207

    TABLE 13. (Cont'd.)

                                                                            
                        ppm carbaryl-14C equivalents at feeding level of
    Tissues                                                                  
                        10 ppm         30 ppm         100 ppm
                                                                            

    Muscle              0.009          0.031          0.104

    Heart               0.012          0.038          0.095

    Fat                 0.000          0.015          0.025

    Blood               0.008          0.036          0.141
                                                                            

    a Cows were slaughtered 18 hours after the last dose was given.

    
    TABLE 14. RADIO-ACTIVE RESIDUES IN TISSUES OF A COW AFTER BEING FED 100 ppm CARBARYL-14C
              IN THE DIET FOR 14 DAYSa

                                                                                               

                                                 % of total radio-activity in sample
    Metabolites                                                                                 
                                       Kidney    Liver     Lung      Muscle    Heart     Blood
                                                                                               

    Carbaryl                           3.3       9.2       2.1       17.0      3.7       0

    5,6-dihydrodihydroxy carbaryl      4.5       3.0       8.8       38.6      31.3      22.0

    5,6-dihydrodihydroxy naphthol      1.8       4.1       0         0         4.9       2.0

    Naphthyl sulfate                   29.3      4.1       27.3      0         4.0       51.8

    Water-soluble unknowns             43.2      32.9      47.5      30.6      41.8      7.1

    Unextractable unknowns             17.9      46.7      14.3      13.8      14.3      17.1
                                                                                               

    a cows were slaughtered at 18 hours after the last dose was given.
    
         The distribution of carbaryl residues was determined in hen
    tissues after continuous treatment with either 7, 21 or 70 ppm of
    l-naphthyl-14C-carbaryl in the diet (Andrawes et al., 1972). Tissue
    residues were directly proportional to the concentration of carbaryl
    in the diet. The highest residues were found in the blood and tissues
    of high blood content (liver, kidney, lung and spleen); body fat,

    
    TABLE 15. METABOLIC PRODUCTS FOUND IN THE EGGS OF HENS FED 1-NAPHTHYL-14C-CARBARYL
              FOR 14 DAYS AT A LEVEL EQUIVALENT TO 70 ppm IN THE DIETa

                                                                                           
                                                                 % of the recovered
                                                                 radio-activity
    Chromatographic   Identity                                                             
    fractions                                                    Yolk(Y)   White(W)   Y + W
                                                                                           

    F1                1-naphthol                                 17.74     6.25       15.76

    F2                Carbaryl                                   4.59      0.73       3.92

    F3                1-naphthyl(hydroxymethyl)-carbamate        4.88      0.15       4.06

    S1                -                                          2.15      3.46       2.38

    S2                Unknown A                                  3.07      8.42       3.99

    S3                Unknown B                                  6.97      46.32      13.70

    S4                1-naphthol conjugate                       2.73      5.63       3.23

    S5                1-naphthyl sulfate                         44.05     15.59      39.14

    S6                1-naphthol conjugate                       5.03      5.68       5.14

    S7                Unknown B conjugate                        8.79      7.77       8.62

                                                                                           

    Average total g of 14C-carbaryl equivalents per eggb       19.7      3.4        19.7

    Average ppm of 14C-carbaryl equivalentsb                    0.4       0.1        0.4
                                                                                           

    a Reference -Paulson and Feil, 1969.

    b Based on eggs collected after equilibration was established; i.e. between the ninth
      and the fourteenth day of dosing.
    
    brain and muscles contained the lowest residues. For example, the
    distribution of 14C-carbaryl equivalents one day after treatment for
    14 days with 70 ppm in the diet was as follows (in ppm): liver 0.41,
    kidney 0.485, thigh 0.03, leg 0.032, breast 0.031, skin 0.043, fat
    0.026, gizzard 0.04, heart 0.049, and brain 0.017. The half-life of
    total body residues was calculated to be five days.

    Comparison of plant and animal metabolites

         For the most part, the primary metabolic pathway of carbaryl
    metabolism in plants is similar to that found in animals. Recognizable
    divergences between plant and animal metabolites are as follows: (1)
    conjugation of the primary metabolites in plants yields glycosides
    (Casida and Lykken, 1969; Fukuto, 1972; Kuhr, 1968) as compared to
    glucuronides, sulfates and pre-mercapturic acids in animals (Dorough,
    1970; Fukuto, 1972; Ryan, 1971); (2) the metabolite 7-hydroxy-l-
    naphthyl methylearbamate has been detected only in certain plants
    (Wiggins et al., 1970) but not in animals; (3) animal metabolites
    which are not reported for plants include:
    3,4-dihydro-3,4-dihydroxy-1-naphthyl methylearbamate,
    3,4-dihydro-3,4-dihydroxy-1-naphthol, 5,6-dihydroxy-l-naphthyl
    methylearbamate, 5,6-dihydroxy-1-naphthol,
    1-methoxy-5(methylearbamoyloxy)-2-naphthol, and
    5-methoxy-1,6-naphthalenediol (Dorough, 1970).

         The efficiency and rate of excretion of carbaryl plant
    metabolites when fed to rats have been investigated. It was found that
    a mixture of radio-labelled water-soluble plant metabolites were
    totally eliminated within 96 hours (Dorough and Wiggins, 1969). No
    change in the metabolic profile was observed in the excretion
    products. In a study conducted on the feeding of plant mare containing
    radio-activity designated as unextracted LIC-residues, it was found
    that this/these material(s) is/are poorly absorbed by the rat and
    is/are excreted primarily through the faeces (Tallent, 1970; Andrawes,
    1973).

    In storage and processing

         No information has been received on the disappearance of residues
    during storage and processing of cocoa beans and derived products or
    of cereals. However, data on the behaviour of carbaryl residues on
    other commodities make it appear probable that: (1) storage would have
    little effect on residues; (2) washing, heating, cooking or baking
    would likely reduce levels by a substantial amount.

         Carbaryl residue degradation and removal during commercial and
    home preparative procedures have been determined for green beans
    (Elkins et al., 1968), tomatoes (Farrow et al., 1968), spinach (Lamb
    et al., 1968), broccoli (Farrow et al., 1969), and spinach and
    apricots (Elkins et al., 1972). In general, washing (cold water),
    peeling (tomatoes), blanching and cooking were very effective in
    removing 50-99% of initial residues. Combinations of these operations
    were more effective than single steps. Commercial canning of spinach
    and apricots destroyed 44% and 12% of initial residues respectively.
    Preprocessing storage of green beans at 45F and tomatoes at 55F, and
    storage of canned spinach and apricots at ambient temperatures and
    100F had little effect on residues except for canned spinach at 100F
    where a 23% reduction was noted.

    Evidence of residues in food in commerce or at consumption

         Results of the fifth year (June 1968-April 1969) and sixth year
    (June 1969-April 1970) total diet studies of the United States Food
    and Drug Administration showed a continuation of the downward trend in
    detectable carbaryl residues (Corneliussen, 1970; Corneliussen, 1972).
    Carbaryl was detected in three composites in the period 1968-1969. Two
    results (in legume vegetables) were below the method sensitivity level
    of 0.2 ppm. One fruit composite had 0.3 ppm. Carbaryl was not detected
    in any of the diet composites during the 1969-1970 period.

    Methods of residue analysis

    In spite of vigorous research in recent years to develop a residue
    method for carbaryl utilizing gas chromatography, the current method
    of choice for regulatory purposes remains the colorimetric procedure
    described in the official AOAC method (Official Methods of Analysis
    of the AOAC, 11th ed., 1970, p. 493). This method has recently been
    extended by the Union Carbide Co. to include determination of the
    major carbaryl plant metabolites (total toxic residues). Procedures
    have been developed to determine free carbaryl, combined carbaryl, and
    the conjugated metabolites 1-naphthol and methylol carbaryl. Of the
    known plant metabolites, methylol carbaryl and naphthol are closest in
    toxicity to the parent carbaryl. Methylol carbaryl is also either the
    major metabolite or a significant metabolite in the plants
    investigated. No method yet exists for determining the animal
    metabolites such as 5,6-dihydro-5,6-dibydroxy-1-naphthyl methyl
    carbamate or water-soluble unknowns (Union Carbide, 1973).

    National tolerances

    TABLE 16. SUMMARY OF USA CARBARYL TOLERANCES AND LIMITATIONS

                                                                         
                             Tolerance      Dosage         Pre-harvest
    Use                      ppm            lb ai/acre     limit, days
                                                                         

    Alfalfa                  100            1.6            None
    Almonds, shelled         1              8              None
    Almond hulls             40             8              None
    Apples                   10             12             1 day
    Apricots                 10             8              3 days
    Asparagus                10             2              1 day
    Bananas                  10             1.1            None
    Beans                    10             2.125          None
    Beets, roots             5              2              3 days
    Beets, tops              12             2              14 days
    Blackberries             12             2              7 days
    Blueberries              10             2              None
    Boysenberries            12             2              7 days
    Broccoli                 10             2              3 days

    TABLE 16. (cont'd)
                                                                         
                             Tolerance      Dosage         Pre-harvest
    Use                      ppm            lb ai/acre     limit, days
                                                                         

    Brussels sprouts         10             2              3 days
    Cabbage                  10             2              3 days
    Cabbage (Chinese)        10             2              14 days
    Carrots                  10             2              None
    Cauliflower              10             2              3 days
    Cherries                 10             6              1 day
    Citrus                   10             1.25/100 gal   5 days
    Clover                   100            1.5            None
    Collards                 12             2              14 days
    Corn forage              100            2              None
    Corn kernels             5              3              None
    Cotton seed              5              2.5            None
    Cotton, forage           100            2.5            None
    Cowpeas                  5              2              None
    Cowpea forage            100            2              None
    Cranberries              10             4              1 day
    Cucumbers                10             1              None
    Dandelion                12             2              14 days
    Dewberries               12             2              7 days
    Eggplant                 10             4              None
    Endive (escarole)        10             2              14 days
    Filberts, shelled        1              5              None
    Grapes                   10             3              None
    Grapefruit               10             1.25/100 gal   5 days
    Grass and hay            100            1.5            None
    Horseradish              5              2              3 days
    Kale                     12             2              14 days
    Kohlrabi                 10             2              3 days
    Lettuce (head)           10             2              3 days
    Lettuce (leaf)           10             2              14 days
    Loganberries             12             2              7 days
    Melons                   10             1              None
    Mustard greens           12             2              14 days
    Nectarines               10             8              3 days
    Okra                     10             2              None
    Olives                   10             8              None
    Parsley                  12             2              14 days
    Parsnips                 5              2              3 days
    Peaches                  10             8              1 day
    Peanuts, nut and hull    5              1.5            None
    Peanut hay               100            1.5            None
    Pears                    10             12             1 day
    Peas and pods            10             2.6            None
    Peavine forage           100            2.6            None
    Pecans, shelled          1              3              None
    Peppers                  10             4              None
    Plums                    10             6              1 day

    TABLE 16. (cont'd)
                                                                         
                             Tolerance      Dosage         Pre-harvest
    Use                      ppm            lb ai/acre     limit, days
                                                                         

    Potatoes                 0.5 interim    2              None
    Prunes                   10             6              1 day
    Pumpkins                 10             1              None
    Radishes                 5              2              3 days
    Raspberries              12             2              7 days
    Rice                     5              2              14 days
    Rice straw               100            2              14 days
    Rutabagas                5              2              3 days
    Salsify roots            5              2              3 days
    Salsify tops             10             2              14 days
    Sorghum grain            10             2              21 days
    Sorghum forage           100            2              None
    Soybeans                 5              1.5            None
    Soybean hay              100            1.5            None
    Spinach                  12             2              14 days
    Squash                   10             1              None
    Strawberries             10             2              1 day
    Sugar beet and tops      100            2              14 days
    Swiss chard              12             2              14 days
    Tobacco                  NF             0.6-24         None
    Tomatoes                 10             4              None
    Turnips                  5              2              3 days
    Turnip tops              12                            14 days
    Walnuts, nuts            10             5              None
    Poultry, meat and fat    5              0.25a        7 days
    Poultry eggs             0.5 interim    0.25a        7 days
                                                                         

    a Denotes lb ai/100 birds.


    Appraisal

         Carbaryl is extensively used around the world for control of
    insect pests on a wide variety of agricultural crops, ornamentals,
    turf, forests, livestock and poultry. Uses are increasing as it is
    often selected as a replacement for the persistent organochlorine
    insecticides.

         Data available on residues in root crop vegetables (except
    potatoes) from supervised trials at recommended rates and pre-harvest
    intervals indicated that residues should not exceed 2 ppm if good
    agricultural practice is followed.

         The results of supervised trials on peanuts (groundnuts),
    soybeans, sorgbum grain and cowpeas show that residues of up to 2 ppm
    could occur on peanuts, up to 1 ppm on soybeans and cowpeas, and up to

    24 ppm (rarely) on sorghum grain. On sorghum grain, a tolerance of 10
    ppm would be sufficient to provide for the more nearly average residue
    of 5 ppm.

         Residues on sugar beet roots did not exceed 0.1 ppm at harvest in
    supervised trials. Sugar beet tops had residues up to 3.6 ppm in the
    same tests.

         Field trials on the forage crops, alfalfa, clovers, corn forage,
    cowpea foliage, grasses, peanut hay, sorghum forage and soybean
    foliage, resulted in maximum residues ranging from 33 to 190 ppm when
    treated the same day as harvest. Average residues ranged from 16 to
    51 ppm.

         The existing temporary tolerance of 3 ppm on cucurbits appears
    questionable since data from supervised trials indicate that residues
    greater than 5 ppm could occur in these crops with no pre-harvest
    limitation. The recommendation was changed from 10 ppm to 3 ppm : in
    1969 without giving supportive data.

         In accord with the policy of expressing tolerances to one
    significant digit (Report of the 1970 Joint FAO/WHO Meeting, 1971,
    Wld Hlth Org. techn. Rep. Ser., No. 474, Section 2.13), the figure
    for rice (rough) should be changed from 2.5 ppm to 3 ppm. It is
    emphasized that this should not be construed as a change in the
    tolerance but merely a numerical adjustment.

         No information has been received on the disappearance of residues
    during storage and processing of cocoa beans and derived products or
    of cereals into cereal products. However, data on the behaviour of
    carbaryl residues on other commodities make it appear probable that:
    (1) storage would have little effect on residues; (2) washing,
    heating, cooking or baking would likely reduce levels by a substantial
    amount. Since the requirements for data on the disappearance of
    residues during storage and processing of cocoa beans and of cereals
    into cereal products were initiated in 1968 and no interested party
    has responded, it seems reasonable to discontinue these requirements.

         Feeding experiments with hens using radio-labelled carbaryl have
    shown that residues in whole eggs are dose related, the ratio of
    concentration (in eggs) to concentration in diet being 0.006. At a
    diet level of 70 ppm of carbaryl, an average level of 0.4 ppm in eggs
    (yolk plus white) was reached at equilibrium. After discontinuance of
    feedingy residues decreased rapidly, the half-life in yolk being 2-3
    days. A tolerance in eggs (shell free) of 0.5 ppm is recommended to
    accommodate occasional residues in feed. The regulatory method of
    analysis recommended can account for approximately 70% of the residues
    (carbaryl, metabolites and their conjugates) in eggs.

         Feeding studies with lactating cows using radio-labelled carbaryl
    have shown that about 90% of the 14C-residues are found in the
    aqueous phase and that at each feeding level approximately 0.2% of the
    dose was secreted in the milk. The major metabolites found were

    l-naphthyl sulfate (26%), 5,6-dihydro-5,6-dihydroxy-l-naphthyl
    methylcarbamate (34%), and l-methoxy-5-(methylearbamoyloxy)-2-naphthyI
    sulfate. Unchanged carbaryl was only 6% of the total residue. Since no
    method of analysis is available for these compounds, no
    recommendations for a tolerance can be made; however, the recommended
    tolerance of 100 ppm on forage crops would give assurance that
    residues in whole milk would not exceed 0.2 ppm. Since it is very
    unlikely that any dairy animal would ever consume as much as 100 ppm
    of unchanged carbaryl daily, actual milk residues would be negligibly
    small.

         Cows fed 100 ppm of 14C-carbaryl in the diet had 1 ppm carbaryl
    equivalents in the kidney, 0.4 ppm in the liver, and 0.1 ppm in the
    muscle (including heart). In kidney, 43% of the total radio-activity
    was water-soluble unknowns, 30% was naphthyl sulfate, 18% was
    unextractable, and 3% was carbaryl. In liver, 47% was unextractable,
    33% was water-soluble unknowns, and 9% was carbaryl. In muscle, 39%
    was 5,6-dihydrodihydroxycarbaryl, 31% was water-soluble unknowns, 14%
    was unextractable, and 17% was carbaryl. On the basis of these
    results, it would appear that only 13-30% of meat residues are in a
    form that can be measured by the present analytical method. It is
    therefore recommended that the tolerance for meat of cattle, goat and
    sheep be reduced from 1 ppm to 0.2 ppm.

         An analytical method suitable for regulatory use on crops, meat,
    poultry and eggs has been developed.

    RECOMMENDATIONS

    Tolerances

         The temporary tolerances previously recommended are replaced by
    the following tolerances. The values represent the sum of free
    carbaryl, combined carbaryl, conjugated naphthol and conjugated
    methylol carbaryl expressed as total toxic residues of carbaryl.

         Changes from 1970 recommendations are underlined; single
    underline - new entry, double underline - re-entry of omitted
    commodity or change in value based on new data.

                                                                     ppm

    Animal Feedstuffs (green) (alfalfa, clover, corn
      forage, cowpea foliage, grasses, peanut hay,
      sorghum forage, soybean foliage, sugar beet tops,
      bean and pea vines                                             100

    Apricots, blackberries, boysenberries, nectarines,
      peaches, raspberries, asparagus, okra, leafy
      vegetables (except brassica), nuts (whole),
      olives (fresh), sorghum grain, cherries, plums                 10

    Blueberries, citrus fruit, cranberries, strawberries           7

    Apples, bananas (pulp), grapes, beans, peas
      (including pod), brassicas, tomatoes, peppers,
      aubergines, pears, poultry skin                              5

    Cucurbits (including melons), rice (rough)                     3

    Root crop vegetables (beets, carrots, radishes,
      rutabegas, parsnips), peanuts (groundnuts, whole)            2

    Cotton seed (whole), sweet corn, (kernels), nuts
      (shelled), olives  (processed), soybeans (dry
      mature seed), cowpeas                                        1

    Poultry (total) (edible portions), eggs (shell free)           0.5

    Potatoes, meat of cattle, sheep and goat, sugar beets              0.2

    FURTHER WORK OR INFORMATION

    Required (before a limit for residues in milk can be recommended)

    1.   A method suitable for regulatory purposes, for the determination
         of total residues of carbaryl in milk.

    Desirable

    1.   Further studies to elucidate the effects of carbaryl on renal
         function.

    2.   Further studies to resolve the differences in observations of
         different investigators on reproductive physiology, especially
         with regard to nouro-endocrine and behavioural changes.

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    See Also:
       Toxicological Abbreviations
       Carbaryl (EHC 153, 1994)
       Carbaryl (HSG 78, 1993)
       Carbaryl (ICSC)
       Carbaryl (PIM 147)
       Carbaryl (FAO Meeting Report PL/1965/10/1)
       Carbaryl (FAO/PL:CP/15)
       Carbaryl (FAO/PL:1967/M/11/1)
       Carbaryl (FAO/PL:1968/M/9/1)
       Carbaryl (FAO/PL:1969/M/17/1)
       Carbaryl (AGP:1970/M/12/1)
       Carbaryl (WHO Pesticide Residues Series 5)
       Carbaryl (Pesticide residues in food: 1976 evaluations)
       Carbaryl (Pesticide residues in food: 1977 evaluations)
       Carbaryl (Pesticide residues in food: 1979 evaluations)
       Carbaryl (Pesticide residues in food: 1984 evaluations)
       Carbaryl (Pesticide residues in food: 1996 evaluations Part II Toxicological)
       Carbaryl (JMPR Evaluations 2001 Part II Toxicological)
       Carbaryl (IARC Summary & Evaluation, Volume 12, 1976)