PARATHION-METHYL JMPR 1975
Explanation
Parathion-methyl was evaluated by the Joint Meeting in 1968
(FAO/WHO, 1969) and in 1972 (FAO/WHO, 1973).
Arising out of the list of requirements published in the report
of the 1972 Joint Meeting (FAO/WHO, 1973) some information became
available on residue levels from supervised trials in various areas,
on residues in food in commerce and on national tolerances and
pre-harvest intervals.
At the 1972 Joint Meeting, the data on which the temporary ADI
were based were re-evaluated and the temporary ADI was extended for a
further three years. The following additional studies have been
received and are discussed in this monograph addendum.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
BIOCHEMICAL ASPECTS
Metabolism
The metabolism of methyl parathion and parathion was studied in
sunfish and mice. Fish and mouse liver homogenates catalyzed
glutathione (GSH)-dependant metabolism of methyl parathion and methyl
paraoxon but not of parathion or paraoxon. Hydrolysis of methyl
paraoxon by fish liver homogenates exceeded that for parathion by
five-fold, while methyl paraoxon hydrolysis in mice was half of that
of paraoxon (Benke et al., 1974).
In vitro metabolism of methyl parathion and parathion has been
studied in male and female rats of several ages to determine the
mechanism responsible for the variations in toxicity. Oxidative
formation of the oxygen analogues, oxidative aryl cleavage,
glutathione-dependent dealkylation and dearylation were assayed in
liver homogenates. Rates of enzymatic detoxification of the
corresponding oxygen analogues by A-esterase, glutathion-S-aryl, and
S-alkyl-transferase and inactivation by binding were also studied.
Changes in LD50 values with age for methyl parathion and parathion
correlated better with changes in rates of reactions which represented
detoxification pathways for methyl paraoxon and paraoxon than for
reactions which represented direct metabolism of the parent
insecticides. Both male and female rats became much less sensitive to
the acute lethal effects of methyl paraoxon and paraoxon with
increasing age (Benke & Murphy, 1975).
TOXICOLOGICAL STUDIES
Special studies on comparative toxicity
The comparative toxicity, anticholinesterase action and
metabolism of methyl parathion and parathion were studied in sunfish
and mice to determine the basis for the low toxicity of methyl
parathion in sunfish (LD50>2500 mg/kg) and the LD50 value in mice
(13.5 mg/kg). Times of death were much shorter for both compounds in
mice than in fish. Low sensitivity of fish cholinesterases to paraoxon
as compared to mice accounted for the 10-fold lower toxicity of
parathion in fish LD50, 110 mg/kg). By contrast, sunfish had similar
cholinesterase sensitivities to methyl paraoxon and paraoxon (Benke et
al., 1974).
Special studies on potentiation
Intraperitoneal pre-treatment with triorthotolyl phosphate (TOTP)
has been shown to have a potentiation action on the toxicity of
paraoxon in the rat (Lauwerys & Murphy, 1969) and in the mouse (Lynch
& Coon, 1972). A 2.5-fold potentiation of methyl paraoxon toxicity was
shown in a study in the rat in which TOTP (125 mg/kg) had no
significant effects on rates of liver and plasma hydrolysis of
paraoxon and methyl paraoxon by A-esterases, or on GSH-dependent liver
enzymes (Benke & Murphy, 1974). It was indicated that TOTP could be
used as a specific inhibitor of the binding pathway of detoxification
of paraoxon and methyl paraoxon and perhaps other oxygen analogues of
organophosphorus insecticides (Cohen & Murphy, 1972).
Acute toxicity
LD50
Animal Route mg/kg bw References
Mouse (M) Intraperitoneal 11.0 Benke et al., 1974
Mouse (M) Intraperitoneal 6.4 Kamienski & Murphy,
1971
Rat Intraperitoneal 7.0 DuBois & Kinoshita,
1968
Rat (M) Oral 14.0 Gaines, 1969
Rat (F) Oral 24.0 Gaines, 1969
Observations in man
In further studies (Rider et al., 1968, 1969a, 1969b)
parathion-methyl was administered orally to groups of five test
subjects at dosage levels ranging from 14 to 20 mg/day increasing in
increments of 1 mg/day for a period of approximately 30 days. No
significant changes were observed in plasma and red blood cell
cholinesterase levels. When administered at levels of 28 and 30 mg/kg
a significant depression of 37% in red blood cell cholinesterase was
noted (Rider et al., 1971).
COMMENTS
The teratogenicity and reproduction studies requested by the 1968
and 1972 Joint Meetings have not been provided. Data pertaining to
long-term studies are not available. Information on further studies in
man, however, has become available. These short-term studies indicate
that man can tolerate the ingestion of up to 20 mg of parathion-methyl
daily for short periods without effect.
As studies required by previous Joint Meetings have not been
submitted no definitive acceptable daily intake can be estimated.
However, studies to provide the required information are presently
under way. Thus the temporary acceptable daily intake based on the
data in man was extended.
TOXICOLOGICAL EVALUATION
Level causing no toxicological effect
Man: 0.3 mg/kg bw.
ESTIMATED TEMPORARY ACCEPTABLE DAILY INTAKE FOR MAN
0-0.001 mg/kg bw.
RESIDUES IN FOOD AND THEIR EVALUATION
RESIDUES RESULTING FROM SUPERVISED TRIALS
Residue data from, supervised trials carried out in various areas
were required. New data were obtained from supervised trials on
fruits: apples, peaches and pears; on vegetables: cucumber
(glasshouse), kale, onions, tomatoes (glasshouse); on field crops:
sugar beet and on tea. The data are summarized in Table 1.
The references given in Table 1 are all to unpublished reports of
Bayer, 1975. The analytical methods used in the trials were as
follows.
TABLE 1. Residue of parathion-methyl resulting from supervised trials
Application Residues in mg/kg, at intervals (days) after application
Rate
Crop Country Year No. kg a.i./ha Formulation 0 1 3/4 7 14/16 20/21 Ref.
FRUITS
Apple
Abate Fetel Italy 1964 7 1.4-1.8 k/ha E.C. 40% 0.11 1
Boskoop Belgium 1965 2 0.32 g/tree E.C. 50% 0.32 0.31 0.25 0.09 0.06 0.04 2
Court Pendu Belgium 1965 2 0.32 g/tree E.C. 50% 0.78 0.22 0.23 0.12 0.07 0.04 3
Golden Delicious Belgium 1965 2 0.32 g/tree E.C. 50% 0.33 0.12 0.14 0.10 0.05 0.02 4
Golden Delicious Belgium 1965 3 0.32 g/tree E.C. 50% 0.4 0.4 0.24 0.17 0.14 5
King David Italy 1964 7 0.4-1.2 k/ha E.C. 50% <0.05 6
10 18 20 25 29
Peach
Amsden Italy 1965 3 7-10 g/tree wp 80% <0.05 7
Redhaven Italy 1964 3 10-12 g/tree E.C. 50% 0.11 8
Veechi 74 Italy 1964 3 10-12 g/tree E.C. 50% 0.05 9
Pears
Santa Maria Italy 1964 5 0.5 kg/ha E.C. 40% 0.05 10
Santa Maria Italy 1964 5 0.5 kg/ha E.C. 40% 0.12 11
Santa Maria Italy 1964 5 0.5 kg/ha E.C. 40% <0.05 12
Williams Italy 1964 3 1.25-1.5 kg/ha E.C. 40% 0.08 13
TABLE 1. (Cont'd.)
Application Residues in mg/kg, at intervals (days) after application
Rate
Crop Country Year No. kg a.i./ha Formulation 0/1 3/4 7/8 9/10 14/15 41/44
VEGETABLES
Cucumbers Belgium 1966 1 0.45 kg/ha dust 2% 14
(glasshouse)
Total fruit 0.14 0.05 0.05 <0.01
peel 0.64 0.26 0.12
pulp 0.04 0.02 0.04
Kale Belgium 1965 1 0.2 g/plant gran 10% <0.01 15
plant-foot
treatment
Red cabbage Belgium 1965 1 0.2 g/plant gran 10% <0.01 16
plant-foot
treatment
Hop Belgium 1965 1 0.5 g/plant E.C. 50% 17
leaf 0.12 n.d. n.d.
cones 0.17 n.d. n.d.
Onions Belgium 1965 1 0.25 g/m gran 10% n.d. 18
row-
treatment
0.125 g/m gran 10% n.d.
row-
treatment
Tomatoes Belgium 1966 1 0.6 kg/ha dust 2% 0.10 0.075 0.035 0.01 24
(glasshouse)
TABLE 1. (Cont'd.)
Application Residues in mg/kg, at intervals (days) after application
Rate
Crop Country Year No. kg a.i./ha Formulation 0 1 3/4 7 14/16 20/21 Ref.
FIELD CROPS
Sugar beet
Total plant Finland 1969 1 0.3 kg/ha dust 15% 0.5 0.15 0.04 0.04 19
5 6 7 13/14 20/21
TEA
fermented* East 1964 1 1.2 kg/ha E.C. 50% <0.2 20
Pakistan 2 1.2 kg/ha E.C. 50% <0.2
3 1.2 kg/ha E.C. 50% <0.2
4 1.2 kg/ha E.C. 50% <0.2
East 1964 1 0.6 kg/ha E.C. 50% <0.2 21
Pakistan 2 0.6 kg/ha E.C. 50% <0.2
3 0.6 kg/ha E.C. 50% <0.2
4 0.6 kg/ha E.C. 50% <0.2
East 1964 1 0.3 kg/ha E.C. 50% <0.2 22
Pakistan 2 0.3 kg/ha E.C. 50% <0.2
3 0.3 kg/ha E.C. 50% <0.2
4 0.3 kg/ha E.C. 50% 0.2
East 1964 1 0.3 kg/ha E.C. 50% <0.2 <0.2 23
Pakistan 1 0.6 kg/ha E.C. 50% <0.2 0.25
1 1.2 kg/ha E.C. 50% <0.2 <0.2
* Leaves are dried 18-20 hours, two hours fermentation, and afterwards 45 minutes dried at 82°C.
REFERENCES
1-13: calorimetric method, Gunther and Blinn, Adv. Chem. Ser., 1,
72, (1949). Limit of detection 0.05 mg/kg
14-18 and 24: calorimetric method Averell and Norris, Anal. Chem.,
20, 750 (1958). Limit of detection 0.01 mg/kg
20-23: GLC method (Bayer). Limit of detection 0.2 mg/kg
RESIDUES IN FOOD IN COMMERCE OR AT CONSUMPTION
Data obtained from a food inspection survey in Hungary are summarized
in Table 2. (Commodities of which fewer than 10 samples were taken
have been omitted.)
TABLE 2. Residues in food inspection samples in Hungary
No. of samples with residues
No. of in range (mg/kg)
samples
Commodity analysed <l.d.1 l.d.-0.25 >0.25-0.5
Apples 129 123 5 1
Apricots 16 8 6 2
Cabbage 40 24 16 -
Parsley 14 14 - -
Peaches 37 30 5 2
Potatoes 61 52 9 -
Strawberries 20 18 2 -
1 l.d. = limit of detection, varying from 0.01-0.05 mg/kg.
Note: national tolerance = 0.5 mg/kg.
NATIONAL TOLERANCES AND PRE-HARVEST INTERVALS REPORTED TO
THE MEETING
Officially recommended pre-harvest intervals and national
tolerances reported to the Meeting are shown in Tables 3 and 4
respectively.
TABLE 3. Officially recommended pre-harvest intervals
Country Crops Days
Australia Fruit, vegetables, field crops 21
Belgium Fruit, vegetables, field crops 21
Leafy vegetables glasshouse
(period 1/3 - 1/11) 28
Brazil All crops 15
Denmark All crops 14
Federal Republic field crops such as alfalfa,
of Germany clover, lupine, grain,
potatoes, rape, sugar beet 35
Grapes 35
Fruits: pome- and stone-fruit,
small fruits except
strawberries 28
Vegetables: cabbage, leafy
vegetables (glasshouse) 21
Leafy vegetables (outdoors),
carrots, celery, beans,
peas, leek, onions, radish,
horse-radish 14
Cucumbers, tomatoes (both
outdoors and under glass) 14
Democratic Field crops 14
Republic of Fruit, vegetables 10
Germany Crops used for production of
baby food, diet foods etc. 21-302
Finland All crops 21
Soil drenches 35
France All crops 15
Italy All crops 20
Yugoslavia Fruit, vegetables, field crops,
grapes 21
Morocco All crops 15
TABLE 3. (Cont'd.)
Country Crops Days
New Zealand Oil containing concentrates 21
All other formulations 14
Netherlands1 Pome- and stone-fruit, berries
(all outdoors) 21
Fruit (glasshouse) 28
Spray and dust smokes 10
Vegetables, except leaf celery,
parsley, bread beans,
pole-beans 21
Peas for canning 10
Bell peppers, cucumbers, melons,
tomatoes (all under glass) 3
Leafy vegetables (glasshouse)
except leaf celery and
parsley,
smokes only, period 1/3-1/11 10
period 1/1-1/3 21
Austria All crops 21
Poland Fruits, field crops, vegetables 21
Sweden All crops 28
Switzerland Fruit, vegetables, field crops 21
Spain All crops except cotton 21
Hungary All crops 14
United States of Fruits, field crops 15-212
America Vegetables 7-212
1 Including mixtures with parathion.
2 Depending on dosage rates and/or formulations used.
TABLE 4. National tolerances reported to the meeting
Tolerance
Country Crops mg/kg
Australia Fruit, vegetables, grain 1
Belgium1 Fruit, vegetables, except 0.5
potatoes
Brazil Fruits or vegetables, cabbage 0.2
Vegetables such as lettuce,
endive, spinach, chard, 1
cresses, chicory, parsley, etc.
Cottonseed-oil 0.05
Fresh fodder 1
Federal Republic Fruit and vegetables 0.15
of Germany
Democratic Republic Fruit and vegetables 0.5
of Germany Meat, fish, eggs, fat (of
animal and plant origin),
milk 0.0042
Potatoes, onions 0.0042
Baby food 0.0042
France Fruit and vegetables 0.15
India Raw cereals 0.2
Milled cereal products 0.005
Fruit 0.2
Vegetables 1
Israel Fruits, cabbage, cucumbers,
egg-plant, melons, squash,
water-melons 0.2
Other vegetables 1
Cottonseed-oil 0.05
Italy Fruit and vegetables
(except potatoes) 1
New Zealand Fruit and vegetables 0.5
Netherlands Fruit and vegetables 0.5
parathion-methyl
and -ethyl
together
TABLE 4. (Cont'd.)
Tolerance
Country Crops mg/kg
Poland Fruit 0.5
Switzerland Fruit and vegetables 0.5
parathion-methyl
and -ethyl
together
Hungary All crops 0.5
United States of Alfalfa hay 5
America Alfalfa (fresh) 1.25
parathion-methyl apples, apricots, artichokes,
and -ethyl avocados, barley, beans,
together beets (with or without tops)
or beet greens alone,
blackberries, blueberries
(huckleberries), boysenberries,
broccoli, Brussels sprouts,
cabbage, carrots, cauliflower,
celery, cherries, citrus fruits,
clover, collards, corn, corn
forage, cranberries, cucumbers,
currants, dates, dewberries,
eggplants, endive (escarole),
figs, garlic, gooseberries,
grapes, grass for forage,
guavas, hops, kale, kohlrabi,
lettuce, loganberries, mangoes,
melons, mustard greens,
nectarines, oats, okra, olives,
onions, parsnips (with or
without tops) or parsnip greens
alone, peaches, pea forage,
peanuts, pears, peas, peppers,
pineapples, plums (fresh
prunes), pumpkins, quinces,
radishes (with or without
tops) or radish tops,
raspberries, rice, rutabagas
(with or without tops) or
rutabaga tops, soybean hay,
spinach, squash, strawberries,
summer squash, Swiss chard,
TABLE 4. (Cont'd.)
Tolerance
Country Crops mg/kg
tomatoes, turnips (with or
without tops) or turnip
greens, vetch, wheat,
young-berries 1
Cottonseed 0.75
Sunflowerseed 0.2
Soybeans 0.1
1 Total residues of parathion-methyl and parathion.
2 At or about the limit of detection.
APPRAISAL
Residue data from supervised trials in areas other than those
included in the 1968 Evaluations (FAO/PL: 1968/M/9/1) have become
available. Such data were required by the 1972 JMPR (FAO/WHO, 1973).
Data were available from supervised trials on apples, peaches,
pears, cucumbers (glasshouse), red cabbage, curly kale, onions,
tomatoes (glasshouse), sugar beets and tea (fermented).
Although most of the data were not obtained recently, they still
provide useful additional information. The methods of analysis used
are reliable and sufficiently sensitive.
Taking into account the very broad field of application of
parathion-methyl in many areas of the world the amount of information
available is still unsatisfactory.
Because of the lack of such data, the Meeting was not able to
propose any changes in the tolerance figures already established at
the 1968 Meeting and only a few additional maximum residue limits can
be proposed.
Extensive information was obtained on pre-harvest intervals
officially recommended in various areas, on national tolerances and on
rates of application on several crops.
Only limited data were obtained on residues in food moving in
commerce. It has however to be recognized that in many countries in
routine surveys on residue levels no differentiation is made between
parathion(-ethyl) and parathion-methyl residues.
The new data available at the 1975 Meeting confirm some of the
temporary tolerances established at the 1968 Meeting. Additional data
from supervised trials on tomatoes, together with the data available
at the 1968 Meeting make it possible to recommend a temporary maximum
residue limit for parathion-methyl on tomatoes. Temporary maximum
residue limits for parathion-methyl or hops (dry cones), sugar beets
and tea (fermented) are also recommended in the light of the new data
on these commodities.
RECOMMENDATIONS
The temporary tolerances established by the 1968 Meeting for
fruit, cucumbers and cole crops (brassicas) could be confirmed as
temporary maximum residue limits in the light of the additional data
from supervised trials on apples, peaches, pears, cucumbers
(glasshouse), red cabbage and curly kale. The following additional
temporary maximum residue limits are also recommended. They refer to
parathion-methyl and its oxygen analogue, expressed as
parathion-methyl.
TEMPORARY MAXIMUM RESIDUE LIMITS
Pre-harvest interval
Limit, on which
Commodity mg/kg recommendation is
based, days
Tea (fermented
and dried) 0.2 14-21
Tomatoes 0.2 3 (glasshouse)
Sugar beet 0.05 21
Hops (dry cones) 0.05*
*At or about limit of determination.
FURTHER WORK OR INFORMATION
REQUIRED (by 30 June 1978)
1. Oral studies on teratogenesis and on reproduction in species
appropriate to such tests.
DESIRABLE
1. Adequate long-term studies in at least one mammalian
species.
2. Information on current use patterns in various countries on
crops for which no recommendations are made and on residue levels
resulting from such uses.
REFERENCES
Bayer. (1975) Unpublished reports of Bayer Leverkusen (Federal
Republic of Germany). 1:162/68; 2:183/65; 3:18/65; 4:182/65; 5:181/65;
6:161/68; 7:172/68; 8:170/68; 9:169/64; 10:168/68; 11:167/68;
12:165/68; 13:164/68; 14:203/66; 15:180/65; 16:179/68; 17:178/68;
18:175/65, 176/65; 19:265/69; 20-22:19a, 19b, 19c/66; 23:19d/66;
24:201/66
Benke, G. M., Cheever, J. L., Mirer, F. E. & Murphy, S. D. (1974)
Comparative toxicity, anticholinesterase action, and metabolism of
methyl parathion and parathion in sunfish and mice. Toxicol. Appl.
Pharmacol., 28:97-109.
Benke, G. M. & Murphy, S. D. (1974) Effect of TOTP pre-treatment on
paraoxon and methyl paraoxon detoxification in rats. Res. Com. Chem.
Path. Pharmacol., 8:665-672.
Benke, G. M. & Murphy, S. D. (1975) The influence of age on the
toxicity and metabolism of methyl parathion and parathion in male and
female rats. Toxicol. Appl. Pharmacol., 31:254-269.
Cohen, S. D. & Murphy, S. D. (1972) Inactivation of malaoxon by mouse
liver. Proc. Soc. Exp. Biol. Med., 139:1385-1389.
DuBois, K. P. & Kinoshita, F. K. (1968) Influence of hepatic
microsomal enzymes by phenobarbital on toxicity of organic phosphate
insecticides. Proc. Soc. Exp. Biol. Med., 129:699-702.
Gaines, T. (1969) Acute toxicity of pesticides. Toxicol. Appl.
Pharmacol., 14:515-534.
Kamienski, F. & Murphy, S. D. (1971) Biphasic effects of
methylene-dioxyphenyl synergists on the action of hexobarital and
organophosphate insecticides in mice. Toxicol. Appl. Pharmacol.,
18:883-894.
Lauwerys, R. R. & Murphy, S. D. (1969) Interaction between paraoxon
and tri-o-tolyl phosphate in rats. Toxicol. Appl. Pharmacol., 14:
348-357.
Lynch, W. T. & Coon, J. M. (1972) Effect of tri-o-tolyl phosphate
pre-treatment on the toxicity and metabolism of parathion and paraoxon
in mice. Toxicol. Appl. Pharmacol., 21:153-165.
Rider, J. A., Moeller, H. C., Puletti, E. J. & Swader, J. I. (1968)
Studies on the anticholinesterase effects of methyl parathion,
guthion, dichlorvos, and gardona in human subjects. Federation
Proceedings, 27 (2):597.
Rider, J. A., Moeller, H. C., Puletti, E. J. & Swader, J. I. (1969a)
Toxicity of parathion, systox, octamethyl pyrophosphoramide, and
methyl parathion in man. Tox. Appl. Pharm., 14:603-611.
Rider, J. A. & Puletti, E. J. (1969b) Studies on the
anticholinesterase effects of gardona, methyl parathion, and guthion
in human subjects. Federation Proceedings, 28 (2):479.
Rider, J. A., Swader, J. I. & Puletti, E. J. (1971) Anticholinesterase
toxicity studies with methyl parathion, guthion and phosdrin in human
subjects. Federation Proceedings, 30 (2):443.
See Also:
Toxicological Abbreviations
Parathion-methyl (FAO/PL:1968/M/9/1)
Parathion-methyl (WHO Pesticide Residues Series 2)
Parathion-methyl (Pesticide residues in food: 1978 evaluations)
Parathion-methyl (Pesticide residues in food: 1979 evaluations)
Parathion-methyl (Pesticide residues in food: 1980 evaluations)
Parathion-methyl (Pesticide residues in food: 1984 evaluations)
Parathion-methyl (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)