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    MONOCROTOPHOS                                   JMPR 1972

    IDENTITY

    Chemical name

         Dimethyl-1-methyl-2-methyl carbamoyl-vinyl phosphate (E)-

    Synonyms

         "Azodrin", "Azodrin(R) Insecticide", "Nuvacron", SD9129

    Structural formula

    CHEMICAL STRUCTURE 1


    Physical and chemical properties of technical monocrotophos

         Physical state:     reddish-brown mixture of solid and liquid (at
                             25-30C)

         Odour:              that of a mild ester

         Melting point:      25-30C (technical)
                             54-55C (pure)

         Vapour pressure:    7 x 10-5 mm Hg (at 20C)

         Solubility:         soluble in water, acetone and alcohol; very
                             slightly soluble in mineral oils.

         Stability:          stable when stored in glass and polyethylene
                             containers. Technical grade has a half-life
                             of 2 500 days at 38C. Rate of hydrolysis in
                             solution is slow.
                             Half-life in solution (2 ppm) at pH 7.0 and
                             38C is 23 days; at pH 4.6 and 100C,
                             half-life is 80 minutes.

         Purity:

         Analysis of a typical sample of technical monocrotophos gave the
         following results:

                                                                     % w

         Monocrotophos                                                77

         Dimethyl-1-methyl-2-methylcarbamoyl-vinyl phosphate (Z)-      9

         N-methylacetoacetamide                                        2

         Dimethyl phosphate                                            5

         Others (less than 1% w each)                                  7

                                                                     100

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, distribution and excretion

    Following an oral dose of 1 mg/kg to male and female rats,
    monocrotophos was rapidly eliminated in the urine primarily as
    hydrolysis products (70% of the urinary excretion within six hours),
    unchanged monocrotophos (25%) and traces of the N-hydroxymethyl and
    desmethyl metabolites. In 24 hours the rate of excretion had
    diminished substantially, indicating rapid absorption and elimination
    (Menzer and Casida, 1965). Monocrotophos administered orally to a goat
    was found in the milk within one hour after treatment. Other
    metabolites were found in lesser quantity than the parent

    monocrotophos. Within 24 hours, the major quantity had cleared, and
    only minute residues were found (Menzer and Casida, 1965).
    Monocrotophos is a minor metabolite of dicrotophos (Bidrin(R)), its
    N,N-dimethyl crotonamide analogue, and treatment of rats with
    dicrotophos yielded small quantities of monocrotophos in the urine
    within two hours (Bull and Lindquist, 1964).

    Monocrotophos was fed to lactating dairy cows at a level of 45 ppm in
    the diet. Monocrotophos and two metabolites were found in milk. In
    urine further metabolites were observed (Potter, 1965).

    Biotransformation

    Monocrotophos injected into bean plants was metabolized to the
    N-hydroxy-methylamide (SD 12657) and the amide (SD 11319).
    Monocrotophos was more persistent in this plant study than
    dicrotophos-Bidrin(R), its N,N dimethyl analogue (Menzer and Casida,
    1965).

    In cotton, monocrotophos has been shown to be metabolized to the
    hydroxymethyl derivative (SD 12657) but not to the amide (SD 11319).
    The oxidative route of metabolism yielding substituted crotonamides
    was found to be slower than the metabolic route yielding substituted
    phosphoric acid esters (Lindquist and Bull, 1967). A major
    water-soluble metabolite observed in plants by these authors was
    identified as a glycoside of the N-hydroxymethyl (SD 12657) derivative
    (Shell Chemical Co., 1972).

    The metabolic fate of monocrotophos in mammals has been well
    documented (Menzer and Casida, 1965; Bull and Lindquist, 1964; 1967).
    These data are summarized in Figure 1.

    Effect on enzymes and other biochemical parameters

    As with other organo-phosphorus esters, monocrotophos acts on the
    organism as a direct cholinesterase inhibitor. The selectivity of
    inhibition of cholinesterase from various sources in the body suggests
    that blood cholinesterase activity is the most sensitive parameter for
    exposure; brain cholinesterase activity is depressed only at higher
    levels of exposure. Penetration into the brain may be the cause,
    rather than a difference in sensitivity, although in vitro studies
    have shown that monocrotophos has a somewhat greater affinity (k2) and
    activity (I50) against rat RBC cholinesterase (Reiffy 1969).
    Monocrotophos is metabolized to compounds which are less potent
    inhibitors of human plasma cholinesterase, as evidenced by in vitro
    pI50 values, i.e., monocrotophos (SD 9129) - 6.5; N-Methyl hydroxy
    monocrotophos - 5.9; N-desmethyl monocrotophos - 5.6 (Menzer and
    Casida, 1965).

    FIGURE 1

    TOXICOLOGICAL STUDIES

    Special studies on metabolites

    The acute toxicity of metabolites of monocrotophos in mouse and rat is
    summarized in Table 1.

    The acute toxicity of components of technical monocrotophos in rat is
    summarized in Table 2.

    TABLE 1  Acute toxicity of monocrotophos metabolites
                                                                             

    Metabolite                                   Reference
                                                                             

    N-methyl hydroxy monocrotophos (SD = 12657)

    Mouse          ip       LD50 = 12 mg/kg      (Menzer and Casida, 1965)

    Rat            oral     LD50 = 27 mg/kg      (Shellenberger, 1966a)

    N-desmethyl monocrotophos (SD 11319)

    Mouse          ip       LD50 = 3 mg/kg       (Menzer and Casida, 1965)

    Mouse          oral     LD50 = 5.5           (Shellenberger, 1966a)

    Glycoside of N-desmethyl monocrotophos (SD 13311)

    Rat (M)        oral     LD50 = 168 mg/kg     (Shell Chemical Co., 1966)

    N-methyl acetoacetamide

    Rat            oral     LD50 = >2 000 mg/kg  (Shellenberger, 1966a)
                                                                             

    TABLE 2  Acute toxicity of components of technical monocrotophos
                                                                                  

    Component                                  Species   Route     LD50 (mg/kg)
                                                                                  

    Dimethyl phosphate of
    3-hydroxy-N-methyl-trans-crotonamide       Rat       Oral      420

    Dimethyl phosphate of 2-chloro-3
    hydroxy-N-methyl-cis-crotonamide           Rat       Oral      14

    Dimethyl phosphate of 2-chloro-3
    hydroxy-N-methyl-trans-crotonamide         Rat       Oral      140
                                                                                  

    Short-term studies on the glycoside metabolite (SD 13311)

    Groups of rats (42 males and 42 females per group, except for the
    highest level which had 22 of each sex) were fed the glycoside
    metabolite of monocrotophos (a glycoside of the dimethyl phosphate of
    3-hydroxy-N-(hydroxymethyl)-cis-crotonamide) for 9 days at levels of
    0, 1, 3, 9, 18 and 90 ppm (the 1 ppm was fed for seven weeks and the
    dosage increased to 18 ppm for the final five weeks). Rats were fed a
    normal diet for four weeks after the feeding study ended. Slight
    growth effects were noted at 90 ppm from 7-12 weeks in both sexes.
    Blood cholinesterase was depressed at 9 ppm in both sexes. At 18 ppm,
    brain cholinesterase was depressed. Cholinesterase activity was not
    affected at 3 ppm. No effects were observed on blood parameters or
    gross and microscopic histology (Shell Chemical Co., 1966).

    Special studies on neurotoxicity

    Groups of adult White Leghorn hens (ten hens per group) were fed
    monocrotophos in the diet at levels of 0, 1, 10 and 100 ppm for four
    weeks. A single group of ten hens was fed TOCP in the diet at 1 000
    ppm for four weeks. At the end of the feeding interval, five birds
    from each group were sacrificed, and histological examinations of
    brain, spinal cord and sciatic nerve were performed. Physiological
    response, body-weight, food consumption and egg production data were
    collected. Monocrotophos at all dose levels produced a weight loss in
    hens. Egg production was not affected at 1 ppm but was inhibited at 10
    and 100 ppm. Mortality occurred at 100 ppm, and although several birds
    showed tremors 10-12 days after feeding started, all were able to
    stand and walk normally. TOCP fed birds developed typical signs of
    ataxia after 16-17 days. All survivors were unable to stand at the end
    of the treatment period. Histological examination of TOCP-treated hens
    showed severe demyelination in the posterior horns of the spinal cord.
    Examination of nervous tissue from monocrotophos fed and control hens
    showed slight evidence of demyelinated tracts, primarily in the
    anterior horns. No differences were noted in controls and hens
    undergoing monocrotophos treatments. Monocrotophos does not produce
    delayed neurological signs of poisoning when compared to the response
    induced by TOCP (Shellenberger, 1965b).

    Special studies on potentiation

    Male rats were given oral doses of a combination of monocrotophos and
    the following anticholinesterase compounds, with no signs of
    potentiation: dioxathion, dimethoate, carbaryl, disulfoton, EPN,
    Folex, malathion, parathion, schradan, demeton, azinphos-methyl,
    dicrotophos, crotoxyphos, coumaphos, dichlorvos, diazinon, naled,
    trichlorphon, ethion, mevinphos, carbophenothion and phosphamidon.
    Potentiation of the acute oral toxicity was observed with
    monocrotophos in combination with fenchlorphos (Shellenberger, 1965a).

    Special studies on reproduction

    Groups of rats (10 males and 20 females per group) were fed
    monocrotophos in the diet at 0, 2, 5, 12 and 30 ppm, and subsequently
    mated. The progeny of this mating were maintained on this dietary
    regime and mated. This was followed for three generations (Eisenlord
    and Loquram, 1965). In a separate study groups of rats (10 males and
    20 females per group) were fed monocrotophos at the same levels and
    subjected to a three-generation, two-litter per generation study
    (Eisenlord and Loquram, 1966).

    Effects due to monocrotophos were noted in both studies at levels of 5
    ppm and above. Appearance and behaviour was affected at 12 and 30 ppm,
    as manifested in stunted growth and emaciation. Thinned or missing
    hair on the flanks or head was seen in all monocrotophos groups among
    adult females and pups, but not in adult males or controls. The level
    of 30 ppm was lethal to pups and reduced pregnancies. Pup mortality
    was evidenced at 5 ppm in both studies and absent at 2 ppm. Weight of
    parents was adversely affected at 30 ppm. At 12 ppm, several parents
    were affected (F2 and F3 males in one study and F2 females and F3
    males in the second). No effects were noted on any parameter at 2 ppm.
    Gross and histopathological examinations showed no differences from
    the control values.

    Special studies on teratogenicity

    Groups of pregnant rabbits received oral daily doses of 0.7 and 2
    mg/kg monocrotophos from day 6 to 18 of gestation. On day 28 of
    pregnancy, the foetuses were removed and examined. No compound-related
    teratogenic effects were observed (Thorpe and Dix, 1972).

    Acute toxicity

    The results of acute toxicity studies in animals are summarized in
    Table 3.

    TABLE 3  Acute toxicity of monocrotophos in animals
                                                                             
    Species      Sex      Route    LD50        Reference
                                   (mg/kg)
                                                                             
    Rat          M        IP       5           Bull & Lindquist, 1967
                 M        Oral     14-23       Shellenberger & Newell, 1963
                                               Shellenberger, 1965b; 1966a
                 F        SC       7           Reiff, 1969
                 M        Oral     18          Gaines, 1969
                 F        Oral     20          Ibid.

    Mouse        M&F      IP       8           Menzer & Casida, 1965
                          Oral     15          Shellenberger & Newell, 1963

    Guinea Pig   M&F      SC       app.60      Hunter, 1964
                                                                             

    Signs of poisoning following monocrotophos are typical of other
    anticholinesterase organo-phosphates. Toxic signs occur rapidly and in
    animals include tremors, lacrimation, diarrhea, salivation, tonic and
    clonic convulsions and other signs of cholinergic stimulation. Deaths
    occur rapidly, usually within four hours, and animals surviving 24
    hours generally recover and appear normal.

    Atropine alone, but preferably in combination with reactivators (P2S
    or Toxogonin), was shown to be an effective antidote to monocrotophos
    poisoning in rodents (Hunter, 1964: Reiff, 1969).

    Short-term studies

    Japanese quail

    Groups of Japanese quail (12 males and 12 females per group) were fed
    monocrotophos at 0, 0.5, 5 and 50 ppm in the diet for three weeks.
    Mortality and weight loss occurred at 50 ppm. Food consumption was
    reduced at 5 ppm, while egg production was normal. Blood
    cholinesterase activity was depressed at all feeding levels, while
    brain cholinesterase activity was depressed at 5 ppm and above. At 5
    ppm in the diet of adult females, monocrotophos had no effect on the
    embryo heart beat or development of the chicks (Shellenberger, 1966b).

    Rat

    Groups of rats were fed monocrotophos in the diet at dosage levels of
    0 (42 males and 42 females), 0.5, 1.5 (30 males and 30 females/group),
    15 (42 males and 42 females), 45 and 135 ppm (12 males and 12
    females/group) for twelve weeks. Growth was depressed at 45 ppm.
    Cholinesterase depression was observed on haematology or gross and
    microscopic pathology (Shellenberger and Newell, 1964).

    Dog

    Groups of Beagle dogs were fed monocrotophos in the dry diet at levels
    of 0, 0.5, 1.5, 15 (four dogs of each sex/group), 45 and 135 ppm (two
    dogs of each sex/group) for 13 weeks. After 8 weeks, the dogs fed 135
    ppm were changed to 270 ppm for weeks 9-10, then to 540 ppm for weeks
    11-12, and to 1 080 ppm for the final week.

    Body-weights were reduced at dietary levels of 270 ppm. Organ weights
    were also affected in this high feeding level group. Cholinesterase
    depression was observed at 1.5 ppm in blood and brain. There were no
    compound-related effects on haematological values, blood biochemistry,
    organ weights or gross and microscopic pathology (Shellenberger and
    Newell, 1964).

    Groups of dogs were fed monocrotophos in the diet for two years at
    levels of 0 (four males and four females) 0.16, 1.6, 16 ppm (three
    males and three females/group) and for one year at 100 ppm (two males
    and two females). Moderate cholinergic stimulation was observed at 100
    ppm as tremors and salivation. Blood cholinesterase depression was
    noted at 16 and 100 ppm in both males and females. Marginal brain
    cholinesterase depression was also noted at a dose level of 1.6 ppm
    after 93 and 104 weeks. No effects were noted on growth, mortality,
    haematological parameters, urinalyses or physiological measurements.
    Gross and histopathological examination showed no compound-related
    effects (Johnston et al., 1967a).

    Long-term studies

    Rat

    Groups of rats were fed monocrotophos in the diet for two years at
    levels of 0 (40 males and 40 females), 1, 10 and 100 ppm (25 males and
    25 females/group). Growth of males and females at 100 ppm was
    depressed. Food consumption was also lower than controls at this
    level. RBC and plasma cholinesterase depression was observed at 10 and
    100 ppm in both males and females. Brain cholinesterase depression in
    males and females was significantly inhibited at all levels. At 100
    ppm, the weights of liver, gonad, thyroid and pituitary were reduced
    in females. Thyroid and pituitary/body-weight ratios were depressed at
    100 ppm. No effects were noted on survival, haematology or
    histopathological examination of organs and tissues (Johnston
    et al., 1967b).

    COMMENT

    Monocrotophos is rapidly absorbed, metabolized and eliminated by
    mammals. Plant and animal metabolites are similar.

    Potentiation was observed with fenchlorphos but not with other
    cholinesterase-inhibiting compounds. No delayed neurotoxic effects
    were observed.

    Short-term studies in rats and dogs indicate no-effect levels at 0.5
    ppm for cholinesterase depression.

    In long-term studies a no-effect level has not been demonstrated in
    the rat, the lowest dose tested (1 ppm) causing significant brain
    cholinesterase depression.

    In dog, two-year studies indicated a no-effect level of 0.16 ppm with
    regard to brain cholinesterase depression. An effect was observed at
    1.6 ppm.

    In estimating an ADI for this compound, it was noted that in rat a
    firm no-effect level was 0.5 ppm, with minimal effect level at 1 ppm.
    In dog a no-effect level of 0.5 ppm was also demonstrated but the
    minimal effect level was 1.5 ppm. Since the no-effect level is more
    closely defined in rat, the latter species was used as a basis for
    determining the ADI.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

         Rat: 0.5 ppm in the diet, equivalent to 0.025 mg/kg/day

         Dog: 0.5 ppm in the diet, equivalent to 0.0125 mg/kg/day

    ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR MAN

         0 - 0.0003 mg/kg body-weight

    RESIDUES IN FOOD AND THEIR EVALUATION

    USE PATTERN

    Monocrotophos is an organo-phosphorus insecticide, which finds its
    main use for foliar application to cotton (over 80% of monocrotophos
    applied). It is also recommended for application against foliage pests
    of maize, sugar cane, sugarbeet, vegetables, potatoes and certain
    fruits. It is particularly effective against Lepidoptera, Homoptera
    and certain Coleoptera, acting by both systemic and residual contact
    properties.

    Monocrotophos is known to be officially registered and/or approved for
    use in the following countries:

    Angola                   Yugoslavia
    Argentina                Mexico
    Australia                Mozambique
    Austria                  Nicaragua
    Brazil                   Pakistan
    Bulgaria                 Peru
    Chile                    Philippines
                             South Africa
    Colombia                 Spain
    Costa Rice               Sudan
    Ecuador                  Switzerland
    El Salvador              Thailand
    Egypt                    Trinidad
    France                   Turkey
    Greece                   Uruguay
    Guatemala                U.S.A.
    India                    Venezuela
    Israel                   Viet-Nam
    Italy                    Zambia

    USE RECOMMENDATIONS

    Typical maximum recommended application rates are: 1.0 kg a.i./ha for
    cotton, potatoes and fruit; 1.5 kg a.i./ha for maize; 0.8 kg a.i./ha
    for sugar cane; and 0.5 - 0.6 kg a.i./ha for vegetables and sugar
    beet.

    The recommended minimum period between treatment and harvest varies
    from country to country, but is generally about 7 - 15 days for
    vegetables and potatoes, 14 days for cotton, 21 days for tomatoes,
    maize and citrus and 28 - 30 days for other crops.

    Multiple applications of monocrotophos are often made, depending on
    pest incidence, and use recommendations allow for these treatments.

    The detailed use recommendations are given in Table 4.


    TABLE 4  APPLICATIONS OF MONOCROTOPHOS TO CROP FOLIAGE

                                                                             

    Crop                         Recommended          Recommended period
                                 application rates    between treatment
                                 (kg. a.i./ha)        and harvest (days)1
                                                                             

    Cotton                       0.25 -1.0            Australia      - 21
                                                      Mexico         - 14
                                                      S. Africa      - 30
                                                      Spain          - 30
                                                      U.S.A.         - 21

    Maize                        0.25 -1.5            Colombia       - 30
                                                      Uruguay        - 28

    Sugarcane                    0.25 -0.75           Uruguay        - 28
                                                      Venezuela      - 30
                                                      U.S.A.         - 30

    Carrots, turnips, onions     0.25 -0.5

    Potatoes                     0.25 -1.0            Colombia       - 30
                                                      Italy          - 21
                                                      S. Africa      - 14
                                                      Venezuela      - 14
                                                      U.S.A.         - 7

    Sugar beet                   0.25 - 0.80          Italy          - 21

    TABLE 4  (Cont'd.)

                                                                             

    Brussels sprouts,            0.2 -0.6             Yugoslavia     - 28
    cauliflower and cabbage                           Colombia       - 30
                                                      Peru           - 15
                                                      Venezuela      - 21
                                                      Vietnam        - 21

    Tomatoes                     0.25 -1.0

    Hops                         0.25 -0.5

    Soybeans                     0.25 -0.5            Colombia       - 30
                                                      Vietnam        - 21

    Peas and beans               0.5                  Colombia       - 30
                                                      Pom            - 15

    Apples, pears2               0.01 - 0.04% a.i.    Australia      - 28
                                                      Italy          - 30

    Citrus                       0.5 - 1.0            Venezuela      - 21

    Coffee                       0.25 - 0.8
                                                                             

    1  Monocrotophos is not recommended for post-harvest use on agricultural
       commodities.

    2  Monocrotophos is recommended for use on apples and pears in Australia,
       and Italy only.


    RESIDUES RESULTING FROM SUPERVISED TRIALS

    Residue data are available from supervised trials carried out in 24
    countries on food crops grown under various conditions, using various
    rates of application and pre-harvest intervals.

    In most trials, dosage rates, number of applications and pre-harvest
    intervals were observed, in accordance with label recommendations, and
    the data from these trials are summarized in Table 5. Residues of
    monocrotophos in grain crops and root vegetables are usually below, or
    close to, the limit of determination of the analytical method, while
    leafy vegetables and fruit often contain detectable residues.

        TABLE 5  Residues of monocrotophos in crops following recommended foliage treatments

                                                                                                 

                        Maximum          Minimum
                        recommended      preharvest     Trials      Results       Range of
    Crop                rate             interval                                 residues (ppm)
                        (kg a.i./ha)     (days)         (no.)       (no.)
                                                                                                 

    Cotton (seed)       1.0              14             11          14            <0.02-0.08

    Cotton (oil)        1.0              14             5           6             <0.02-0.04

    Sugarcane           0.75             30             4           5             <0.05

    Potatoes            1.0              7              14          27            <0.08-0.20

    Maize grain         1.5              14             14          25            <0.01-0.05

    Tomatoes            1.0              21             10          17            <0.01-0.51

    Brussels sprouts    0.6              15             4           8             <0.05-0.21

    Cauliflower         0.6              15             6           8             <0.01-0.14

    Cabbage             0.6              21             9           23            <0.02-0.19

    Carrots             0.5              14             2           5             <0.01-0.04

    Turnips             0.5              10             1           3             <0.05

    Onions              0.5              10             3           6             <0.02-0.09

    Sugar beet          0.8              14             8           25            <0.01-<0.05

    Peas                0.5              15             2           2             <0.07-0.60

    Beans               0.5              21             3           6             <0.01-0.22

    Soybeans            0.5              14             7           12            <0.01-0.03

    Coffee              0.8              42             2           2             <0.01-0.08

    Hops                0.5              28             1           2             0.3 - 0.41

    Citrus fruit        1.0              21             11          26            <0.01-0.45

    Apples              1.0              28             7           20            <0.05-1.0

    Pears               1.0              28             5           10            <0.01-0.76
                                                                                                 
        Cotton

    Since the major outlet for monocrotophos is as a foliage insecticide
    on cotton, numerous studies have been undertaken to examine the extent
    of residues of monocrotophos in cottonseed and oil, if any, likely to
    arise from recommended treatments.

         Cottonseed

         Monocrotophos is recommended for application to cotton foliage at
         a maximum dosage rate of 1 kg a.i./ha, applications being made at
         5-7 day intervals, where pest incidence dictates, with a final
         treatment to harvest interval of 14 days. Trials in which these
         recommendations were followed showed that residues of
         monocrotophos in cottonseed were below the limit of determination
         of the analytical method employed (<0.02 - <0.07 ppm) with the
         exception of one sample which contained an apparent residue of
         monocrotophos of 0.08 ppm. This sample had an unusually long
         pre-harvest interval of 94 days, and the untreated corresponding
         sample contained 0.05 ppm monocrotophos.

         Cottonseed oil

         Following recommended treatments of cotton with monocrotophos,
         residues (max. 0.04 ppm) have only been detected occasionally in
         the oil. A tendency was observed for residues to be lower in the
         crude oil when they were detected in the corresponding seed.

         Cotton foliage

         On foliage, residue levels of monocrotophos were proportional to
         the dosage rates at short pre-harvest intervals. The half-life on
         foliage was between less than three days to six days. In U.S.A.,
         where monocrotophos is widely used on cotton, no grazing of
         livestock or feeding of treated trash is permitted since the
         residue levels range from 8 to >100 ppm.

    Potatoes

    The data developed relative to the use of monocrotophos on potatoes
    showed that, when treated at the recommended rate of 0.25 - 1.0 kg
    a.i./ha, with a minimum pre-harvest interval of seven days, residues
    of monocrotophos were consistently less than the limit of
    determination of the analytical method employed (<0.01 - <0.08 ppm).

    Sugarcane

    Analyses of sugarcane which had been repeatedly treated at 0.5 - 1.0
    kg a.i./ha, and products from the sugarcane, showed that the residue
    levels of monocrotophos were consistently less than the limit of
    determination of the analytical method (<0.05 ppm) when a pre-harvest
    interval of 30 days was observed.

    Maize

    The results of a considerable number of studies, carried out to
    determine the residues of monocrotophos in maize are given below:

         Grain

         No residues of monocrotophos (<0.01 - <0.05 ppm) have been
         found in maize grain treated according to label recommendations
         (max. dosage of 1.5 kg a.i./ha, pre-harvest interval of 14 days).
         Residues in maize grain have been detected only in trials where
         very short pre-harvest intervals have been used.

         Husks and cobs

         Extensive data show no significant residues of monocrotophos in
         samples of husks and cobs from maize plants which had received
         applications of monocrotophos. Residues of monocrotophos which
         occur at short pre-harvest intervals (1-3 days) decrease rapidly.
         At intervals of 14 days or longer they had decreased to an
         average level of 0.04 ppm (range 0.005 - 0.40 ppm) from
         treatments up to the maximum recommended dose rate of 1.5 kg
         a.i./ha.

         Silage

         Following recommended treatments of monocrotophos to maize,
         residues of monocrotophos in maize silage ranged from less than
         0.01 ppm to 1.4 ppm (mean of 0.15 ppm).

         Stover

         Residues of monocrotophos in maize stover, following recommended
         treatments, ranged from less than 0.01 ppm to 0.06 ppm (mean of
         0.02 ppm). Levels of 13 - 17 ppm present in stover one day after
         application rapidly decreased to 0.20 - 0.06 ppm 23 days later.

    Tomatoes

    Following recommended applications of monocrotophos (maximum rate of
    1.0 kg a.i./ha, pre-harvest interval of 21 days) to tomatoes, residues
    of monocrotophos ranged from less than 0.01 ppm to 0.51 ppm (mean of
    0.11 ppm).

    Brussels sprouts

    Following recommended applications (dosage rate up to 0.6 kg a.i./ha,
    pre-harvest interval of 15 days) of monocrotophos to Brussels sprouts,
    residues of monocrotophos ranged from less than 0.05 ppm to 0.21 ppm,
    with an arithmetic mean of 0.10 ppm.

    Cauliflower

    Residues of monocrotophos in samples of cauliflower, which had
    received recommended applications of monocrotophos (up to 0.6 kg
    a.i./ha, pre-harvest interval of 15 days) ranged from less than 0.01
    ppm to 0.14 ppm (arithmetic mean of 0.03 ppm).

    Cabbage

    The results of studies carried out to determine the residues of
    monocrotophos in cabbage, following recommended treatments (dosage
    rate up to 0.6 kg a.i./ha, four applications and pre-harvest interval
    of 21 days), were evaluated. Residues of monocrotophos in cabbage from
    these trials ranged from less than 0.02 ppm to 0.19 ppm.

    Carrots

    Following recommended applications (maximum dosage rate of 0.5 kg
    a.i./ha, pre-harvest interval of 14 days), maximum residues of
    monocrotophos found in carrots were 0.04 ppm; generally no residues
    (less than 0.01 ppm) were detected. Corresponding levels in the carrot
    tops were 0.65 - 1.6 ppm (mean of 1.1. ppm).

    Turnips

    No residues of monocrotophos (less than 0.05 ppm) have been detected
    in turnips, even when the turnips were harvested immediately after
    application.

    Onions

    Onions, treated with monocrotophos at recommended applications
    (maximum dosage rate of 0.5 kg a.i./ha, pre-harvest interval of ten
    days) did not contain residues exceeding 0.09 ppm monocrotophos (mean
    value of 0.03 ppm).

    Sugar beet

    Residues of monocrotophos in sugar beet roots did not exceed the limit
    of determination of the analytical method employed (0.01 - 0.05 ppm),
    following treatment at a maximum dosage rate of 0.8 kg a.i./ha. The
    data cover applications made within 14 days of lifting, although in
    practice applications as late as this are unusual. Corresponding
    residues of monocrotophos in sugar beet leaves ranged from less than
    0.01 ppm to 0.55 ppm.

    Peas

    Following application of monocrotophos to peas, at dosage rates up to
    0.5 kg a.i./ha with pre-harvest intervals of 15 days or longer, the
    only positive residue detected was 0.06 ppm, all the other samples
    being below the limit of determination of the analytical methods
    (<0.01 - <0.07 ppm).

    Beans

    Residues of monocrotophos in beans, following recommended treatments
    (up to 0.5 kg a.i./ha, pre-harvest interval of 21 days), ranged from
    less than 0.01 ppm to 0.22 ppm.

    Soybeans

    Residues of monocrotophos in soybeans did not exceed 0.03 ppm,
    following treatment of monocrotophos according to label
    recommendations (maximum dosage rate of 0.5 kg a.i./ha, pre-harvest
    interval of 14 days). Maximum residue of monocrotophos in soybean
    foliage was 0.87 ppm (mean of 0.22 ppm).

    Coffee

    Residues of 0.08 ppm in raw coffee beans, following a recommended
    treatment of monocrotophos, were reduced to below the limit of
    determination of the analytical method (less than 0.01 ppm) on
    processing.

    Hops

    In a field trial carried out in Germany, with monocrotophos at 0.5 kg
    a.i./ha and a minimum of 28 days pre-harvest interval, residues of
    monocrotophos in dried hops ranged from 0.3 to 0.41 ppm.

    Citrus fruit

    Residues of monocrotophos in citrus fruit treated with monocrotophos
    at label recommendations (up to 1.0 kg a.i./ha, pre-harvest interval
    of 21 days) ranged from less than 0.01 ppm to 0.45 ppm (mean of 0.08
    ppm).

    Apples

    Monocrotophos is recommended for use on apple trees in Australia and
    Italy only, at dosage rates equivalent to 0.04% a.i. in the spray,
    with a final treatment to harvest interval of four weeks. Data from
    trials carried out in these countries were examined. Residues of
    monocrotophos in apples treated according to this recommendation range
    from <0.01 ppm to 1.5 ppm. These upper figures, however, derive from
    experiments in which the spray was applied by hand, which usually
    requires a somewhat higher volume; it is considered that in practical
    conditions of use, 1.0 ppm would be the highest level reported.

    Pears

    Monocrotophos is only recommended for application to pears in 
    Australia and Italy. Maximum recommended dosage rate is 0.04% a.i. in
    the spray with a final treatment to harvest interval of 28 days in

    Australia and 30 days in Italy. Residues of monocrotophos treated
    according to these recommendations ranged from 0.08 ppm to 0.76 ppm
    (mean - 0.41 ppm) in pears from these two countries.

    FATE OF RESIDUES

    General comments

    Residues of breakdown products do not occur in food commodities to a
    significant extent.

    Extensive studies with monocrotophos have shown that degradation can
    occur by hydrolytic and/or oxidative mechanisms. From the experimental
    work it appears that the primary metabolic pathway is hydrolysis,
    yielding metabolic products which are non-cholinesterase inhibiting
    and of low toxicity. Evidence of secondary metabolic pathways
    involving oxidation reactions have been found in that small quantities
    of the N-methylol analogue of monocrotophos, its glycoside and the
    unsubstituted amide analogue were detected in the radiotracer studies.
    Residues of cholinesterase inhibiting breakdown products have been
    detected in crops only rarely, following recommended treatments, and
    then at levels close to the limit of determination of the analytical
    method employed. Likewise in meat and milk from animals fed
    monocrotophos in their diet, at levels far exceeding those likely to
    be encountered in practice, only extremely low levels of breakdown
    products have been detected, if at all.

    In animals

    Studies have been conducted with monocrotophos fed to cattle and goats
    to determine whether residues in feed give rise to residues in meat
    and milk.

    32P monocrotophos was fed continuously to two lactating cows at a
    level equivalent to 45 ppm in their total diet (Shell Development Co.,
    undated). This level is approximately 20 times that which would occur
    in practice, assuming a maximum of 50% of monocrotophos-treated
    feedstuff in the total diet. Levels of monocrotophos found in the milk
    from the two cows were 0.01 ppm and 0.008 ppm. Average levels of
    dimethyl phosphate and of N-hydroxy methyl monocrotophos were 0.002
    ppm and 0.001 ppm, respectively (Ibid.). No residues of glycosides of
    the N-hydroxy methyl compound were detected. After 14 days of this
    feeding regime, the two cows were slaughtered and residues determined
    on the red meat and liver. These results are given in Table 6.

    TABLE 6  Residues of monocrotophos and its breakdown products
             present in meat from cows fed monocrotophos

                                                                             

                               Residues present (ppm)
                                                                             

    Sample                         dimethyl         N-hydroxy methyl
    analysed      monocrotophos    phosphate        monocrotophos

    Red meat      0.02, 0.04       0.005, 0.008     0.003, 0.0084

    Liver         0.11, 0.13       0.05, 0.06       0.02, 0.04
                                                                             


    32P monocrotophos was administered orally to goats (Menzer and
    Casida, 1965) at a single dose of 1 mg/kg body-weight. Within 72 hours
    of the application, only 1.4% of the applied radioactivity was present
    in the goats' milk. The authors suggested that, in animals,
    monocrotophos degradation took place by oxidative N-demethylation to
    N-hydroxy methyl monocrotophos and unsubstituted amide. Residues of
    these compounds and monocrotophos in samples of the milk from the
    treated goats up to 24 hours after treatment are given in Table 7.

        TABLE 7  Residues of monocrotophos and its breakdown products found
             in milk from goats administered monocrotophos
                                                                                              
                        Residues present in goats' milk (ppm)

    Hours after                          N-hydroxy methyl    unsubstituted     total organo-
    administration      monocrotophos    monocrotophos       amide             extractable
                                                                                              
    1                   0.045            0.0001              <0.0001           0.067
    2                   0.032            0.0086              0.0007            0.061
    4                   0.034            0.0086              0.0015            0.074
    6                   0.023            0.011               0.0013            0.057
    8                   0.012            0.0099              0.0007            0.042
    12                  0.007            0.0044              0.0006            0.025
    16                  0.006            0.0020              0.0001            0.012
    20                  0.012            0.0009              0.0003            0.022
    24                  0.001            0.0007              <0.0001           0.007
                                                                                              
    
    As indicated in Table 7, residues of monocrotophos fell from a maximum
    value of 0.0451 ppm one hour after administration to 0.0014 ppm 23
    hours later. Maximum levels of N-hydroxy methyl monocrotophos, and the
    unsubstituted amide, detected were 0.0105 ppm (after six hours) and
    0.0015 ppm (after four hours), respectively. These levels had
    decreased by a fifteen-fold factor 24 hours after application.

    To determine whether residues in animal feeds could give residues of
    the conjugate of N-hydroxy methyl monocrotophos in meat and milk, two
    Guernsey cows were fed for ten days with the conjugate at a level of
    20 ppm in the total diet (this level is more than 2 000 times that
    which may be encountered in practice). The results showed that the
    combined residues of the conjugate and its hydrolysis products,
    N-hydroxy methyl monocrotophos and the unsubstituted amide, in milk,
    were all below 0.01 ppm. At the end of the ten day study the cows were
    slaughtered and their tissues analysed. The results are given in Table
    8.

    TABLE 8  Residues of monocrotophos breakdown products found in tissues
             of cows fed monocrotophos conjugate

                                                                             

    Tissues        Residues present (ppm)
    analysed
                   conjugate of N-hydroxy    N-hydroxy methyl monocrotophos
                   methyl monocrotophos      plus unsubstituted amide
                                                                             

    fat            <0.01                     0.02, 0.04

    kidney         0.02, 0.01                <0.01, 0.01

    meat           <0.01, <0.01              0.01, 0.01

    liver          <0.01, 0.01               <0.01,  0.01
                                                                             

    In plants

    In order to elucidate the mode of breakdown in leaves, 32P
    monocrotophos was applied to cotton plants, both in the glasshouse and
    in the field, either as a foliar spray, a stem banding treatment, a
    seed dressing or by petiole injection (Lindquist and Bull, 1967). For
    the foliar treatment, monocrotophos was applied at a rate of
    40 mg/cotton leaf. In the field studies, 85% of the applied
    radioactivity was lost during the first two days, presumably through
    volatilization. Breakdown was shown to take place on both the surface
    and the inside of the treated leaves. Principal breakdown products
    found were O-desmethyl monocrotophos, dimethyl phosphate and N-hydroxy
    methyl monocrotophos. When monocrotophos was applied as a stem bending
    treatment, the recovered radioactivity after 21 days was unchanged
    monocrotophos, probably because the lanolin in the formulation had a
    stabilizing effect. Following the application of monocrotophos as a
    seed treatment (not a recommended application) at a rate of 0.5 mg
    monocrotophos/cotton seed, 50% of the radioactivity recovered after
    one week was unchanged monocrotophos. O-desmethyl monocrotophos was
    present in all samples, indicating the cleavage of a methyl-phosphate

    bond. Dimethyl phosphate (formed by hydrolysis of the vinyl phosphate
    bond) was recovered in increasing amounts with time. The N-hydroxy
    methyl monocrotophos was only detected at 21 days after treatment,
    while an unknown compound, later identified as a glycoside of
    N-hydroxy methyl monocrotophos (Shell Development Co., undated), was
    the major metabolite at 14 and 21 days.

    Petiole injection of monocrotophos at 70 mg monocrotophos/cotton leaf
    indicated half-lives of monocrotophos in cotton leaves of eight days
    in the glasshouse and seven days in the field. Small amounts of the
    N-hydroxy methyl monocrotophos and its conjugate were detected. No
    residues of the unsubstituted amide (N-desmethyl monocrotophos) were
    detected in cotton plants. The authors proposed the pathways shown in
    Figure 2 for the degradation of monocrotophos.

    Menzer and Casida (1965) injected 32P-monocrotophos into bean plants
    at a level of 43.5 ppm and found trace amounts of the N-hydroxy methyl
    monocrotophos (0.14% of monocrotophos applied) and the unsubstituted
    amide (0.10% of monocrotophos applied) eight days after injection.
    However, 20 and 32 days after application monocrotophos was the only
    compound detected.

    In studies with 14C-labelled monocrotophos (Shell Research Ltd.,
    undated) on the foliage of maize, cabbage and apples, and on apple
    fruit, the breakdown products present were the unsubstituted amide,
    N-hydroxy methyl monocrotophos, (both in the free and conjugated
    forms), O-desmethyl-monocrotophos acid and traces of
    N-methylacetoacetamide and 3-hydroxy-N-methyl butyramide.

    Since, of the breakdown products detected in plants following
    application of monocrotophos, only the unsubstituted amide
    (N-desmethyl monocrotophos) and the free and bound N-hydroxy methyl
    monocrotophos can cause cholinesterase inhibition, analytical methods
    (Ibid.) were developed for the determination of these compounds.

    Samples from field trials were analysed using these methods.

    Results from trials with sugar beet, potatoes, Brussels sprouts,
    cauliflower, maize, pears, peas, onions and soybeans (Ibid.) showed
    that residues of the unsubstituted amide and the N-hydroxyl methyl
    monocrotophos (free and conjugated) could not be detected, nor could
    monocrotophos.


    FIGURE 2

    Further data, obtained in cases where monocrotophos residues were
    above detectable levels, are shown in Table 9.

    It will thus be seen that, in practice, where crops have been treated
    with monocrotophos in the field, residues of cholinesterase inhibiting
    degradation product in the edible parts did not reach detectable
    levels. The only exception was a single sample of carrots in which a
    residue of conjugated methylol at a level near to the level of
    determination of the analytical method was reported.

    In soils

    Although monocrotophos is not used as a soil-applied pesticide, a
    series of tests were conducted to determine the half-life of
    monocrotophos in soil (Shell Chemical Co., undated). In Ripperdam
    sandy loam and Sacramento clay loam, the half-lives of monocrotophos
    were 18 and 6 days, respectively. In an early experiment (Shell
    Research Ltd., undated), where monocrotophos was applied to soil at
    rates of 0.25 or 0.5 kg a.i./ha, initial residues, immediately after
    application, of 5.6 - 6.6 ppm monocrotophos had fallen to below the
    limit of determination of the analytical method employed (less than
    0.04 ppm) five months later.

    In storage and processing

    Studies to determine the effects of storage on residues of
    monocrotophos in apples (Shell Research Ltd., undated) have shown that
    these residues are not significantly reduced on storage at 15 - 20C
    for 24 days, or at 5 - 10C for two to three months. Long-term
    deep-freeze storage trials have shown that monocrotophos residues are
    stable in broccoli and soybean foliage for 11-19 months, although
    exceptionally 90% of monocrotophos residues were lost from cabbage
    after 14 months deep-freeze storage (Shell Development Co., undated).

    Numerous studies on the effect of domestic and commercial processing
    on residues of monocrotophos in food crops have been carried out.
    Domestic processes, such as washing, peeling and cooking, reduce the
    levels of residues of monocrotophos in fruit and vegetables by between
    35% and 95%. Commercial processes often have greater effects on
    residues of monocrotophos. This canning can reduce typical levels by
    over 90%, while the preparation of processed coffee beans, refined
    cottonseed and soybean oil, and dried citrus pulp reduced typical
    residues to below the limits of the analytical methods employed.


        TABLE 9  Residues of monocrotophos breakdown products found in crops1

                                                                                                             

                                  Preharvest                   Residues present (ppm)
    Crop           Country        Interval       Crop          monocrotophos     amide plus      conjugated
                                                 part                            methylol        methylol
                                                                                                             

                                  21             roots         <0.01             <0.01           <0.05
    Sugar beet     Italy          21             leaves        0.14              <0.01           -

                                  31             roots         <0.01             <0.03           <0.05
    Sugar beet     France         31             leaves        0.10              <0.03           -
                                  31             roots         <0.01             <0.03           -
                                  31             leaves        0.04              0.06            -

    Maize          Italy          14             husk +        0.10              0.20            -
                                                 straw         0.10              0.30            -

                                  13             grain         <0.01             <0.01           <0.05
    Maize          S. Africa      13             husk          0.90              0.10            <0.10
                                  13             straw         1.0               0.50            <0.20

                                  3              whole         0.39              <0.05           -
    Cabbage        S. Africa      13             whole         0.22              <0.05           <0.10
                                  3              whole         0.50              <0.05           -
                                  13             whole         0.38              <0.05           <0.10

                                  28             whole         <0.02             <0.04           -
    Onions         U.K.           14             whole         0.14              <0.04           -
                                  7              whole         0.17              <0.04           -

                                  6              whole         0.06              <0.012          -
    Tomatoes       S. Africa      20             whole         0.08              <0.012          -
                                  6              whole         0.34              <0.012          -

                                  49             whole         <0.01             <0.02           <0.05
    Tomatoes       S. Africa      28             whole         0.03              <0.02           -
                                  49             whole         0.01              <0.02           <0.05
                                  28             whole         0.10              <0.02           <0.05

    TABLE 9  (Cont'd.)

                                                                                                             

                                  Preharvest                   Residues present (ppm)
    Crop           Country        Interval       Crop          monocrotophos     amide plus      conjugated
                                                 part                            methylol        methylol
                                                                                                             


                                  67             whole         0.18              <0.05           <0.05
    Apples         Australia      37             whole         0.51              <0.05           <0.05
                                  8              whole         1.8               <0.05           0.06

    Apples         Italy          30             whole         1.0               <0.04           <0.03

    Pears          Italy          39             whole         0.15              <0.04           <0.05

                                  14             roots         0.06              <0.02           0.10
    Carrots        S. Africa      21             roots         0.04              <0.02           <0.05
                                  28             roots         <0.01             <0.02           <0.05

                                                                                                             

    1  Data from Shell Research Ltd.
    2  Analysed only for unsubstituted amide.
    
    Analyses of fruit with monocrotophos residues have demonstrated that
    residues are mainly in the peel. Thus peeling removed 66% of residues
    present in oranges, 35 - 70% in apples (Shell Research Ltd.; Shell
    Chemical Co., undated) and 80 - 95% in grapefruit (Ibid.). In another
    study to determine the levels of monocrotophos present in different
    parts of apples, it was shown that 57 - 64% of the residues were
    present in the pulp, 5% in the waxy surface layer, the remainder being
    in the peel. The removal of the outer leaves of cabbages reduced the
    monocrotophos levels by 95%, of cauliflower by 90% and of Brussels
    sprouts by over 75% (Shell Research Ltd., undated).

    Cold water washing can also reduce residues. Thus washing tomatoes
    reduced residues of monocrotophos by up to 35% (Shell Development Co.;
    Shell Chemical Co., undated). Domestic cooking reduced levels by
    60 - 70% in green beans and 80 - 85% in Brussels sprouts (Shell
    Research Ltd., undated).

    The effect of the various steps in the commercial canning of beans
    (Fahey et al., 1969) and tomatoes (Fahey et al., 1971) has been
    studied. Cold water washing of beans effected a 27% reduction and
    blanching a 40% reduction. Residues in the canned beans were only 2%
    of the residues in the fresh beans. The processes of cold washing and
    lye peeling reduced residues in tomatoes by 63% and 87%, respectively.
    An 85% reduction in residues of monocrotophos was achieved in tomato
    juice and a 91% reduction in whole tomatoes by canning. The process of
    juicing oranges reduced the levels of monocrotophos from 0.8 ppm in
    the pulp to 0.10 ppm and below (Shell Research Ltd., undated).

    Commercial processing of raw coffee beans by removing the berry flesh
    mechanically, followed by fermentation, and sun-drying to a moisture
    level of 10%, reduced residues of 0.08 ppm monocrotophos in the raw
    beans to below the limit of determination of the analytical method
    (less than 0.01 ppm) in the processed beans (Ibid.).

    The preparation of refined soybean oil reduced residues of 0.13 ppm
    monocrotophos in beans to less than 0.01 ppm in the finished oil
    (Shell Chemical Co., undated). Similarly, residues of 0.03 ppm in
    kernels were reduced to less than 0.01 ppm in processed corn meal and
    oil (Ibid.).

    With cottonseed oil (Shell Research Ltd., unpublished) it has been
    shown that 1 ppm monocrotophos added to the crude oil was reduced to
    below the limit of determination of the analytical method (<0.01 ppm)
    by the alkali refining step.

    Experiments to determine the residues of monocrotophos likely to occur
    in beer prepared from monocrotophos-treated hops have demonstrated
    that residues of 1.8 ppm monocrotophos in hops were reduced to levels
    at or below the limit of determination of the analytical method (0.02
    ppm) in filtered and unfiltered beer (Ciba-Geigy Ltd., undated).

    During the commercial preparation of citrus pulp cattle feed (Westlake
    et al., 1970) from monocrotophos-treated oranges, residues were
    reduced to below the limit of determination (less than 0.03 ppm), with
    over 50% being lost during grinding and liming and the remainder
    during drying.

    The following sections summarize these effects in terms of individual
    crops, in order to give an estimate of upper levels to be expected in
    foods when they are ready to eat.

    Cottonseed and soybean oils

    Since the process of alkali refining destroys residues in crude
    cottonseed oil at levels well above those in practice, refined
    cottonseed oil products will not contain detectable residues of
    monocrotophos. The same conclusion may be drawn for soybean oil.

    Brassicas

    In the case of Brussels sprouts, removal of outer leaves followed by
    cooking reduced typical levels by 95%. Thus sprouts with initial
    residues of 0.2 ppm (proposed tolerance levels) would not be expected
    to contain more than 0.01 ppm when cooked and ready to be eaten.

    In the case of cauliflower, removal of outer leaves alone reduced
    residue levels some 10-fold so that even without cooking, levels in
    trimmed cauliflower at an initial level of 0.5 ppm (proposed
    tolerance) would be reduced to 0.05 ppm. In the case of cabbage, where
    removal of outer leaves reduced residues 20-fold, cabbage with
    residues at the proposed tolerance level of 0.05 ppm would not be
    expected to contain more than 0.03 ppm when trimmed ready for cooking.

    Fresh tomatoes

    Fresh tomatoes with 0.5 ppm monocrotophos residues (proposed
    tolerance) would lose, according to available data, an average 25% of
    their residues, leading to a little less than 0.4 ppm at the point of
    consumption.

    Commercially processed tomatoes

    The combined effects of washing and lye peeling reduced residues to
    approximately 5% of their initial value so that residues in tomatoes
    ready for canning would not exceed 0.01 ppm, a level which would be
    further reduced by canning itself.

    Similar considerations apply to canned tomato juice, and neither of
    these finished products would contain detectable residues of
    monocrotophos.

    Beans

    Domestic cooking of beans with monocrotophos residues at the tolerance
    level of 0.2 ppm would reduce these to approximately 0.1 ppm.
    Commercial canning would reduce these levels to below 0.01 ppm,
    whereas freezing, which involves washing and blanching, would reduce
    levels to 0.1 ppm.

    Coffee

    Coffee beans with initial residue at the tolerance level of 0.1 ppm
    would be unlikely to contain detectable residues (< 0.01 ppm) after
    fermentation and drying. For this reason, subsequent processes such as
    roasting and brewing were not studied.

    Hops

    Hops with residues at the tolerance level do not give rise to
    detectable residues in beer.

    Citrus fruit

    Residues in citrus fruit were reduced to an average of 30% of their
    initial value on peeling, so that the raw fruit after peeling would
    not contain residues above 0.15 ppm, where initial residues were at
    the tolerance level of 0.5 ppm.

    Juicing reduced levels of around 0.8 ppm in the pulp of oranges to
    0.10 ppm in the juice.

    Potatoes, maize grain and root vegetables

    With the exception of carrots, where two samples out of five were
    reported to contain low residues, these crops, treated as recommended,
    have not contained measurable residues so that work to demonstrate the
    effects of processing on reducing residues could not meaningfully be
    undertaken.

    Sugarcane and sugar beet

    In the case of sugarcane the absence of detectable residues has been
    demonstrated not only in the raw commodity but also in the
    manufactured products. In neither crop were residues detected
    following recommended treatments.

    METHODS OF RESIDUE ANALYSIS

    Residues of monocrotophos can be determined by specific methods
    utilizing either gas-liquid chromatographic procedures or a
    cholinesterase inhibition method.

    Gas chromatographic methods

    Gas chromatographic methods of analysis for monocrotophos are the
    methods of choice, based on accuracy, specificity, sensitivity and
    speed.

    Monocrotophos can be determined by the general procedure using the
    flame photometric detector (Beroza and Bowman, 1968; Brody and Chaney,
    1966). Specific methods for monocrotophos using this detector have
    been developed (Shell Research Ltd., undated; Bowman and Beroza, 1967)
    and allow analyses of crops down to a limit of determination of 0.01
    ppm. The following procedure (Shell Research, Ltd., undated) has
    proved satisfactory in analysing crops: samples are extracted by
    maceration with chloroform, low water content crops are first dampened
    with water. Co-extracted natural products are removed using a column
    adsorption chromatographic clean-up technique. The
    monocrotophos-containing extract is analysed using the flame
    photometric detector (FPD). Using this procedure, mean recoveries are
    75 - 120% from crops at the 0.05 - 0.20 ppm level.

    The thermionic detector has also been employed in the analyses of
    crops for residues of monocrotophos (Shell Chemical Co., undated). In
    this method, the sample is extracted with dichloromethane followed by
    clean-up using a series of solvent exchanges and washings, prior to
    injection of an aliquot of the extract onto the GLC instrument. Mean
    recoveries with this method are 80 - 120% for crops, with a limit of
    determination of 0.03 - 0.05 ppm.

    Enzymatic inhibition

    Specific enzymatic methods for the detection and determination of
    monocrotophos in crops and milk have been developed (Shell Development
    Co., undated). The samples for analysis are extracted with chloroform,
    followed by a solvent exchange to hexane and concentration of the
    extract. Column chromatography using a gradient column elution
    technique with hexane/dichloromethane removes co-extractives. The
    separated monocrotophos is transferred to water and determined by
    enzyme inhibition spectrophotometric methods. Using this procedure,
    the limit of determination of monocrotophos is about 0.10 ppm in crops
    and 0.01 ppm in milk. Recoveries are in the range of 70 - 125%.

    Methods for analyses of monocrotophos breakdown products

    The analytical data for the N-methylol and for the unsubstituted amide
    reported in this summary were developed using the method described for
    monocrotophos (Shell Research Ltd., undated). The conjugate of the
    N-methylol was determined using the method, which depends on
    converting the conjugate to the sec-butyl thio-ether of the methylol
    and subsequent determination by T.L.C. and enzyme inhibition (Ibid.).

    A further method, using the thermionic detector (Griang and Beckman,
    1968) has been developed for analysing crops for residues of
    O-desmethyl monocrotophos, N-hydroxy methyl monocrotophos and its
    conjugate.

    NATIONAL TOLERANCES

    Officially approved tolerances for monocrotophos have been established
    in some countries and examples of these are given in Table 10.

    TABLE 10

    Examples of national tolerances as reported to the meeting

    Country              Crop(s)                            Tolerance
    (ppm)

    Australia           Cottonseed, potatoes          0.1
                        Apples, pears                 1.0

    Italy               Apples, pears                 0.5

    South Africa        All treated crops             0.1

    U.S.A.              Cottonseed, potatoes,
                        sugarcane                     0.1

    Venezuela           Cottonseed, rice, maize,
                        potatoes, sugarcane,
                        vegetables, citrus fruit      0.1

    Yugoslavia          All treated crops             0.1

    APPRAISAL

    Monocrotophos is an organophosphorus insecticide which finds its main
    use for foliar application to cotton. It is also recommended for
    application against foliage pests of maize, sugarcane, sugar beet,
    vegetables, potatoes and certain fruits. It possesses both systemic
    and residual contact properties.

    Approved uses involve the application of from 0.25 - 1.0 kg a.i./ha.
    The recommended pre-harvest interval varies according to crop and
    country, ranging from seven days on potatoes to 30 days on fruit and
    vegetables.

    Extensive studies have shown that degradation of monocrotophos
    residues on and in plants can occur by hydrolytic and/or oxidative
    mechanisms. The products of hydrolysis are non-cholinesterase
    inhibiting and of low toxicity. Only insignificant amounts of
    secondary metabolites have been found during radiotracer studies.

    Volatilization appears to be the major factor in the rapid loss of
    residues following application. Monocrotophos itself is the principal
    residue found on most plants even 7 - 28 days after application.
    Metabolism studies suggest that ruminants receiving
    monocrotophos-treated feedstuff metabolize the residue to metabolites
    similar to those found on plants. There appears to be no tendency for
    residues to accumulate in animals receiving contaminated rations. Only
    low levels of monocrotophos and trace amounts of breakdown products
    were detected in red meat, liver and milk of cattle receiving
    feedstuffs containing monocrotophos at levels many times the maximum
    likely to occur in practice.

    Residue data, obtained from supervised trials in 24 different
    countries clearly demonstrated the level of residues to be expected
    under widely differing conditions on a wide range of crops. Except for
    samples of leafy materials collected within one or two days of
    application of heavy dosages of monocrotophos, residues in excess of
    1.0 ppm were seldom encountered.

    No substantial residue occurs in any fraction of the cotton plant used
    for food, even when unprocessed.

    As cotton foliage retains significant residues for more than three
    weeks following application of approved rates of monocrotophos,
    feeding of treated cotton foliage to cattle should be avoided.

    Domestic processes, such as washing, peeling and cooking reduce the
    levels of monocrotophos residues in fruit and vegetables by between
    35% and 95%. Commercial processes often have greater effects on
    reducing residues of monocrotophos. The peeling of citrus fruits
    removes 60 - 73% of the total residue. Beer produced from treated hops
    was shown to contain no detectable residues. The absence of residue
    has been demonstrated in sugarcane and in sugar products manufactured
    therefrom.

    For determining monocrotophos residues, either gas-liquid
    chromatography or cholinesterase inhibition methods are used, with the
    former being the methods of choice from the aspect of accuracy,
    specificity, sensitivity and speed. The limit of determination is 0.01
    ppm. Using GLC methods recoveries of 75 - 120% were obtained from crop
    material containing 0.05 - 0.2 ppm. Several of the available methods
    appear suitable for regulatory purposes, but the method of Bowman and
    Beroza (1967) is recommended.

    RECOMMENDATIONS

    The following recommended tolerances for animal products reflect a
    value at or just above the limit of determination. The time interval
    between application and harvest which has been used in determining the
    maximum residue limits is appropriate to the agricultural practices in
    numerous countries.

    TOLERANCES

                                                                             

                                                      Interval between
    Foodstuff                     Tolerance           treatment and
                                  (ppm)               harvest (days)
                                                                             

    Cottonseed                    0.1                 14

    Cottonseed oil (raw)          0.05*               14

    Potatoes                      0.05*               7

    Maize (grain)                 0.05*               14

    Tomatoes                      0.5                 21

    Brussels sprouts              0.2                 15

    Cabbage, cauliflower          0.2                 21

    Carrots, turnips              0.05*               14

    Onions                        0.1                 10

    Sugar beet                    0.05*               14

    Peas                          0.1                 15

    Beans                         0.2                 21

    Soybeans                      0.05*               14

    Coffee (raw beans)            0.1                 42

    Hops (dried)                  1                   30

    Citrus fruit                  0.2                 28

    Apples and pears              1 (temporary        28
                                      1975)

    Meat and edible offal of
    cattle, sheep, goats,
    pigs and poultry              0.02*               from feeding
    Milk                          0.002*              treated plant
    Milk products                 0.02*               products
    Eggs (shell free)             0.02*                 "
                                                                             

    *  at or about the limit of determination

    FURTHER WORK OR INFORMATION

    DESIRABLE

    1.   Studies on human exposure.

    2.   Information on the incidence of residues in apples and pears.

    REFERENCES

    Beroza, M. and Bowman, M.C. (1968) Chromatography of pesticide
    residues containing phosphorus or sulphur with the flame photometric
    detector. Environ. Sci., Technol., 2: 450.

    Bowman, M.C. and Beroza, M. (1967) Chromatographic analysis of azodrin
    and Bidrin. J. Agr. Fd. Chem., 15: 465

    Brody, S.S. and Chaney, J.E. (1966) Flame photometric detector. J.
    Gas. Chromat., 4: 42.

    Bull, D.L. and Lindquist, D.A. (1964) Metabolism of 3-hydroxy-N,
    N-dimethyl-crotonamide dimethylphosphate by cotton plants, insects and
    rats. J. Agr. Fd. Chem., 12: 310-317.

    Bull, D.L. and Lindquist, D.A. (1967) Metabolism of
    3-hydroxy-N-methyl-cis-crotonamide dimethyl phosphate (azodrin) by
    insects and rats. J. Agr. Fd. Chem., 14: 105-109.

    Gaines, T.B. (1969) Acute toxicity of pesticides. Tox. Appl.
    Pharmacol., 14: 515-534.

    Ciba-Geigy Ltd. (undated) Reports on monocrotophos nos. 86 - 88,
    90 - 93, 97, 111, 116 - 131. (unpublished)

    Einsenlord, G. and Loquram, G.S. (1965) Results of short route
    reproduction study of rats fed diets containing SD 9129 insecticide
    over three generations. Data from the Hine Laboratory submitted by the
    Shell Chemical Company. (unpublished)

    Einsenlord, G. and Loquram, G.S. (1966) Results of long route
    reproduction study of rats fed diets containing SD 9129 insecticide
    over three generations. Data from the Hine laboratory submitted by the
    Shell Chemical Co. (unpublished)

    Fahey, J.E., Gould, G.E. and Nelson, P.E. (1969) Removal of gardona
    and azodrin from vegetable crops by commercial preparative methods. J.
    Agr. Fd. Chem., 17: 1204.

    Fahey, J.E., Gould, G.E. and Nelson, P.E. (1971) Removal of azodrin
    residues from tomatoes by commercial preparative methods. J. Agr. Fd.
    Chem., 19: 81.

    Griang, B.Y. and Beckman, H.F. (1968) Determination of bidrin, azodrin
    and their metabolites with the thermionic detector. J. Agr. Fd. Chem.,
    16: 899.

    Hunter, C.G. (1964) The efficacy of atropine and oxime therapy as an
    antidote to poisoning by SD 9129 in guinea pigs. Report Tunstall
    Laboratory submitted by the Shell Chemical Co. (unpublished)

    Johnston, C.D., Thompson, W.M. and Donoso, J. (1967a) Azodrin safety
    evaluation by a chronic feeding study in the dog for two years. Data
    from Woodard Research Corporation submitted by Shell Chemical Co.
    (unpublished)

    Johnston, C.D., Thompson, W.M. and Donoso, J. (1967b) Azodrin safety
    evaluation by a chronic feeding study in the rat for two years. Data
    from Woodard Research Corporation submitted by Shell Chemical Co.
    (unpublished)

    Lindquist, D.A. and Bull, D.L. (1967) Fate of
    3-hydroxy-N- methyl-cis-crotonamide dimethyl phosphate in cotton
    plants. J. Agr. Fd. Chem., 15: 267-272.

    Menzer, R.L. and Casida, J.E. (1965) Nature of toxic metabolites
    formed in mammals, insects and plants from 3-(dimethoxy
    phosphinyloxy)-N,N-dimethyl-cis-crotonamide and its N-methyl
    analogue. J. Agr. Fd. Chem., 13: 102-112.

    Potter, J.C. (1965) Cattle feeding studies with 32P-labelled azodrin.
    Data submitted by Shell Chemical Co. (unpublished)

    Reiff, B. (1969) Pharmacological studies into the toxic actions of
    cholinesterase inhibitors: (a) The effect of antidotes on the
    subcutaneous toxicity of azodrin in the rat. Report of Tunstall
    Laboratory submitted by Shell Chemical Co. (unpublished)

    Shellenberger, T.E. (1965a) Potentiation studies - rats. Data from
    Stanford Research Institute submitted by Shell Chemical Co.
    (unpublished)

    Shellenberger, T.E. (1965b) Demyelination study - hens. Data from
    Stanford Research Institute submitted by Shell Chemical Co.
    (unpublished)

    Shellenberger, T.E. (1966a) Acute toxicity of azodrin and metabolites.
    Data from Stanford Research Institute submitted by Shell Chemical Co.
    (unpublished)

    Shellenberger, T.E. (1966b) Cholinesterase inhibition and
    toxicological evaluations of two organophosphate pesticides in
    Japanese quail. Tox. Appl. Pharm. 8: 22.

    Shellenberger, T.E. and Newell, G.W. (1963) Acute oral toxicity. Data
    from Stanford Research Institute submitted by Shell Chemical Co.
    (unpublished)

    Shellenberger, T.E. and Newell, G.W. (1964) Subacute toxicity and
    cholinesterase study of Shell compound SD 9129 - rat and dog. Data
    from Stanford Research Institute submitted by Shell Chemical Co.
    (unpublished)

    Shell Chemical Co. (1966) Subacute toxicity and cholinesterase study
    of Shell compound SD 13311 in rats. Data from Stanford Research
    Institute submitted by Shell Chemical Co. (unpublished)

    Shell Chemical Co. (1972) Identification of unknown 4. Report Shell
    Chemical Co. (unpublished)

    Shell Chemical Co. (undated) Reports on monocrotophos nos 50 - 67, 69
    - 74, 76, 77, 79 - 81, 89, 101, 115, 132 - 136, 139 - 151, 153, 172,
    176, 182 - 184. (unpublished)

    Shell Development Co. (undated) Reports on monocrotophos nos. 68, 75,
    78, 82 - 85, 100, 110, 112, 114, 137, 138, 152, 155, 171, 173 - 175,
    177 - 181. (unpublished)

    Shell Research Ltd. (undated) Reports on monocrotophos nos. 1 - 49,
    94, 95, 98, 99, 154, 156 -170. (unpublished)

    Thorpe, E. and Dix, M. (1972) Toxicity studies on azodrin:
    Teratological studies in rabbits. Summary submitted by Shell Chemical
    Co. (unpublished)

    Westlake, W.E., Gunther, F.A. and Jeppson, L.R. (1970) Persistence of
    azodrin residues on and in Valencia oranges and in
    laboratory-processed citrus pulp cattle feed. J. Agr. Fd. Chem., 18:
    864.

    Young, J.R. and Bowman, M.C. (1967) Azodrin for corn earworm and fall
    armyworm control and its persistence in sweet corn. J. Econ. Ent., 60:
    1282.
    


    See Also:
       Toxicological Abbreviations
       Monocrotophos (HSG 80, 1993)
       Monocrotophos (ICSC)
       Monocrotophos (WHO Pesticide Residues Series 5)
       Monocrotophos (Pesticide residues in food: 1991 evaluations Part II Toxicology)
       Monocrotophos (Pesticide residues in food: 1993 evaluations Part II Toxicology)
       Monocrotophos (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)