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
Relevant Physical and Chemical Properties
MGK 264 is a colorless oily liquid and has a specific gravity of 1.050
± .010 at 20°C, refractive index of 1.4985 ± .0010 at 25°C, boiling
point above 150°C at 2 mm Hg., flash point above 177°C, and solidifies
at less than -20°C. 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