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    FAO/PL:1967/M/11/1
    WHO/Food Add./68.30

    1967 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD

    THE MONOGRAPHS

    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Working Party of Experts and the WHO Expert
    Committee on Pesticide Residues, which met in Rome, 4 - 11 December,
    1967. (FAO/WHO, 1968)

    FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS
    WORLD HEALTH ORGANIZATION
    Rome, 1968

    MGK 264

    N-(2-ethylhexyl)-bicyclo-(2,2,1)hept-5-ene 2,3-dicarboximide

    IDENTITY

    Chemical name

    N-(2-ethylhexyl)-bicyclo-(2,2,1)hept-5-ene 2,3-dicarboximide

    N-(2-ethylhexyl)-5-norbornene-2,3-dicarboximide

    N-octyl bicycloheptene dicarboximide

    Synonyms

    Octacide 264, Van Dyke 264, ENT-8184

    Empirical Formula

    C17H25NO2

    Structural Formula

    CHEMICAL STRUCTURE 

    Relevant Physical and Chemical Properties

    MGK 264 is a colorless oily liquid and has a specific gravity of 1.050
     .010 at 20C, refractive index of 1.4985  .0010 at 25C, boiling
    point above 150C at 2 mm Hg., flash point above 177C, and solidifies
    at less than -20C. It is miscible with kerosene, white oils, benzol
    hydrocarbons, aliphatic alcohols, esters, ketones, halogenated
    hydrocarbons, and fluorinated hydrocarbon propellents.

    Composition of the Technical Products

    MGK 264 is practically pure
    N-(2-ethylhexyl)-5-norbornene-2,3-dicarboximide. It is formulated with
    pyrethrins and allethrin into oil-type sprays, emulsifiable
    concentrates, dusts and concentrates for pressurized and thermal
    aerosols. Baker (1963) reported the combination of MGK 264 and

    piperonyl butoxide was more effective in synergizing pyrethrins than
    either material alone. Consequently, formulations with MGK 264 usually
    contain 3.3 parts of MGK 264, 2 parts of piperonyl butoxide, and 1
    part of pyrethrins. Aerosols containing 0.5, 1, and 1.67 per cent of
    pyrethrins, piperonyl butoxide, and MGK 264, respectively, are used in
    food storage and processing areas at the rate of 1 fl oz/1,000 cu ft
    (1.04. ml/m3).

    EVALUATION FOR ACCEPTABLE DAILY INTAKES

    Biochemical aspects

    No data available.

    Acute toxicity

                                                              
                         LD50 mg/kg
    Animal      Route    body-weight     References
                                                              

    Rat         oral        3640         Shelanski et al., 1966

    Rat         oral        2800         Lehman, 1951

    Rabbit      dermal       470         Lehman, 1952
                                                              


    Short-term studies

    Rat. A three-generation reproduction study with two litters per
    generation, was conducted at dietary levels of 0, 35, 350 and 3500 ppm
    of MGK 264, using 10 males and 20 females per dose level in each
    generation. The animals were mated for the first time at about 100
    days of age. Second litter animals were used for assembling second
    generation groups. The rate of weight gain was affected in both sexes
    at the high dose level in the second filial generation, and weight
    gain was non-significantly affected in the high-level males of the
    first generation. There was no effect on food consumption in the first
    and third generations, but consumption was lower than that of controls
    in all test groups in the second generation. There was an apparent
    adverse effect on fertility of the first generation females at the
    high dose level, but in the second generation fertility was
    significantly low only at the lowest test level. There was apparently
    some effect on litter growth indices of the high dose animals in the

    first and third generations and of the high and intermediate level
    animals in the second generation. No gross or microscopic pathology
    was found in weanlings selected for autopsy from all litters produced
    (Shelanski et al., 1966).

    MGK 264 has been incorporated into the diet of rats at 5000 ppm for 17
    weeks without evidence of damage (Lehman, 1952).

    Swine. Groups of 3 males and 3 female dwarf pigs received 0, 25, 100
    and 300 ppm of MGK-264 in the diet for 2 years. No effect, at any
    level was seen on appearance, behaviour, rate of weight gain, urine,
    blood picture, serum glutamic-oxaloacetic transaminase activity, blood
    urea nitrogen and relative weights of spleen, kidneys and adrenals.
    Post-test gross and microscopic examination of major organs of the
    high level animals revealed no difference from controls (Harris,
    1963).

    Long-term studies

    Rat. Groups of 10 males and 10 females were fed 0, 62.5, 250 and
    1000 ppm for 2 years. Rate of body-weight gain, food consumption,
    morbidity and mortality and the results of periodic examinations of
    blood and urine were not different between the groups. Gross and
    microscopic examination of animals dying during the test and of all
    survivors at the end of two years showed no difference between the
    groups in distribution of tumours or lesions (Wisconsin Alumni
    Research Foundation, 1964)

    Comments

    Two year studies on rats and swine were carried out and not even
    relatively high doses caused toxicological effect, suggesting a low
    order of toxicity of the compound.

    In a three-generation study in rats doses of 36 mg/kg/day or less
    produced no effects upon growth or reproduction indices. No
    biochemical data are available. Also the effects of combinations with
    other agents, with which MGK 264 is used, are not known.

    TOXICOLOGICAL EVALUATION

    The toxicological data are inadequate to serve as a basis for an
    estimation of the acceptable daily intake for man.

    Further work required

    Biochemical studies on the qualitative and quantitative aspects of
    metabolism of the compound. Feeding studies in combination with other
    agents, with which it is combined in practice.

    EVALUATION FOR TOLERANCES

    USE PATTERN

    Pre-harvest treatments

    MGK 264 combined with pyrethrins and piperonyl butoxide is used as a
    cattle spray to control or repel horn flies, stable flies, horse
    flies, houseflies, mosquitoes, and gnats. An oil or water solution
    containing 2 per cent of MGK 264 is applied at the rate of 2 oz/animal
    (59 ml/animal).

    Post-harvest treatments

    MGK is primarily a synergist for pyrethrins and allethrin and is used
    in sprays, dusts, and aerosols for the control of household and stored
    product insects in institutions, restaurants, dairies, creameries,
    cheese factories, bakeries, canneries, meat packing plants, flour
    mills, peanut mills, grain bins, food warehouses, bottling plants,
    food markets, and other facilities where food and animal feed are
    stored, processed, handled, transported, or marketed. It has no direct
    application to food. Therefore, any MGK 264 residue in food is through
    exposure to the insecticide while it is being used as a premise
    treatment or by contact with treated surfaces.

    When used according to good agricultural practices in formulations for
    the control of insects in storage, processing, and marketing
    facilities, MGK 264 may leave residues as high an 10 ppm in foods
    exposed to the treatment. It is believed to be a rather stable
    compound although no supporting data are available.

    Other uses

    MGK 264 is used in sprays and aerosols for the control of flies,
    mosquitoes, gnats, fleas, roaches, and carpet beetles in homes and
    industrial buildings.

    RESIDUES RESULTING FROM SUPERVISED TRIALS

    In a test conducted by McLaughlin Gormley King in the United States
    (unpublished), dried apricots, dried peaches, and dried pears were
    exposed to 1, 5 and 10 treatments at 2- or 3-day intervals to aerosol
    formulations containing 0.5 per cent of pyrethrins, 1 per cent of
    piperonyl butoxide, 1.67 per cent of MGK 264, and 96.83 per cent of
    light petroleum distillate applied each time at the rate of 2.5 fl oz/
    1,000 cu ft (2.61 ml/m3). The residues on all three dried fruits
    after 1, 5, and 10 treatments, respectively, were 0.5 to 0.9 ppm, 0.92
    to 1.30 ppm, and 1.21 to 1.90 ppm of pyrethrins; 3.7 to 5.2 ppm, 4.5
    to 5.4 ppm, and 4.8 to 7.7 ppm of piperonyl butoxide; and 1.8 to 2.6
    ppm, 3.0 to 4.3 ppm, and 6.9 to 7.2 ppm of MGK 264. The MGK 264
    residue in dried apricots was not determined because of interference.

    A number of packaged foods were exposed to aerosol treatments using an
    oil formulation containing 0.5 per cent of pyrethrins, 1 per cent of
    piperonyl butoxide, and 1.67 per cent of MGK 264 applied at 1 fl
    oz/1,000 on ft (1.04 mg/m3) and at 10 times this rate. The MGK
    residues at the 1- and 10-fl oz (1.04- and 10.45-ml) dosages,
    respectively, were 0.006 and 0.57 ppm in sugar in cloth bags, 0.007
    and 0.014 ppm in sugar in paper bags, 0.016 and 0.094 ppm in beans in
    burlap bags, 0.007 and 0.148 ppm in flour in cloth bags, 0.000 and
    0.0317 ppm in salt in cloth bags, and 0.000 and 0.006 ppm in brown
    mustard in burlap spice bags (McLaughlin Gormley King (unpublished)).

    Flour in uncovered containers, in partially covered containers, and in
    paper bags was exposed to one and two space treatments of an oil
    formulation containing 0.4 per cent of pyrethrins, 0.5 per cent of
    piperonyl butoxide, and 0.5 per cent of MGK 264 applied at 2-, 4-, and
    16-fl oz/1,000 cu ft (2.09-, 4.18-, and 16.71-ml/m3).

    The top 1-1/2 inches (3.81 cm) of flour in the uncovered container had
    less than 1 ppm of pyrethrins, 1.5 ppm of piperonyl butoxide, and 1.5
    ppm of MGK 264. In the top 1/2 inch (1.27 cm) of flour in the
    partially covered container the maximum residue of each of these
    materials was 0.1 ppm. In the top 1/4 Inch (0.64 cm) of bagged flour;
    only a trace of the three materials was present (McLaughlin Gormley
    King (unpublished)).

    Spray containing 0.100 per cent of pyrethrins, 0.200 per cent of
    piperonyl butoxide, and 0.333 per cent of MGK 264 applied to surfaces
    at the rate of 1 gal/1,000 sq ft (40.7 mg/m2) leaves a residue, when
    fresh, of 3 mg of pyrethrins, 6 mg of piperonyl butoxide, and 10 mg of
    MGK 264 per square foot (107.6 mg/m2). If a cubic foot (0.028 m3) of
    flour resting on the treated surface absorbed all of the residue, it
    would contain 0.2 ppm of pyrethrins, 0.4 ppm of piperonyl butoxide,
    and 0.66 ppm of MGK 264 (McLaughlin Gormley King (unpublished)).

    Three fatty foods were exposed to aerosol treatments using 1 fl
    oz/1,000 cu ft (1.04 ml/m3) (recommended dosage) and 10 fl oz/1,000
    cu ft (10.45 ml/m3) of an oil concentrate containing 0.5 per cent of
    pyrethrins, 1 per cent of piperonyl butoxide and 1.67 per cent of MGK
    264. Packaged oleomargarine, bacon, and Brazil nuts exposed to the
    1-fl-oz (1.04-ml) treatment had no detectable residue of any of the
    three spray ingredients; those exposed to the 10-fl-oz (10.45-ml)
    treatment had 0 to 0.395 ppm of Pyrethrins I, 0 to 0.0587 ppm of
    Pyrethrins II, 0.0 ppm piperonyl butoxide, and 0 to 0.516 ppm of MGK
    264. The unwrapped food directly exposed to the 1-fl-oz (1.04-ml)
    treatment had 0.233 to 0.257 ppm of Pyrethrins I, 0.178 to 0.272 ppm
    of Pyrethrins II, 0.753 to 1.103 ppm of piperonyl butoxide, and 1.429
    to 2.575 ppm of MGK 264; those exposed to the 10-fl-oz (10.45-ml)
    treatment had 1.565 to 2.345 ppm of Pyrethrins I, 1.048 to 2.306 ppm
    of Pyrethrins II, 3.79 to 7.59 ppm of piperonyl butoxide, and 7.500 to
    16.35 ppm of MGK 264. The Brazil nuts in all cases had the highest
    residues (McLaughlin Gormley King (unpublished)).

    RESIDUES IN FOOD MOVING IN COMMERCE

    No information available.

    FATE OF RESIDUES

    No information available other than on the stability of the compound.

    METHODS OF RESIDUE ANALYSIS

    A gas chromatography method utilizing a modified electron capture cell
    and a paper chromatographic cleanup for removing interfering
    materials, waxes, and oils are described by Bruce (1967). The method
    is accurate to picogram quantities of MGK 264.

    NATIONAL TOLERANCES

              United States       Processed foods     10 ppm

    RECOMMENDATIONS FOR TOLERANCES

    No tolerances are recommended because no acceptable daily intake has
    been estimated, and no data are available on rate of disappearance of
    MGK 264 and its metabolites in foods after aging, processing, and
    cooking.

    FURTHER WORK

    Further work required before tolerances can be recommended

    Data on the following are required:

    Rate of disappearance of residues in food during storage, processing,
    marketing, and cooking.

    Levels of residues in/on food while in commercial channels.

    Total diet studies.

    REFERENCES PERTINENT TO EVALUATION FOR ACCEPTABLE DAILY INTAKES

    Harris, L.E. (1963) Unpublished report submitted by McLaughlin Gormley
    King Company

    Lehman, A.S. (1951) Quarterly Bulletin Ass. Food and Drug Off. U.S.,
    15, 122

    Lehman, A.J. (1952) ibid., 16, 3 : 47

    Shelanski, M.V., Gittes, H.R. and Benhayem, S. (1966) Toxicol. appl.
    Pharmacol., 9, 555.

    Wisconsin Alumni Research Foundation (1964) Unpublished report
    submitted by McLaughlin Gormley King Company.

    REFERENCES PERTINENT TO EVALUATION FOR TOLERANCES

    Baker, G.J. (1963) The "dual synergist system" of piperonyl butoxide
    and MGK 264. Pyrethrum Post 7 : 16-18.

    Bruce, W.N. (1967) Detector cell for measuring quantities of
    organophosphorus insecticides, pyrethrin synergists, and other
    compounds by gas chromatography. J. Agr. Food Chem. 15 : 178-186.
    


    See Also:
       Toxicological Abbreviations