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
PARATHION
This pesticide was evaluated toxicologically by the 1965 Joint Meeting
of the FAO Committee on Pesticides in Agriculture and the WHO Expert
Committee on Pesticide Residues (FAO/WHO, 1965). Additional
toxicological information, together with information for evaluation
for tolerances, is summarized and discussed in the following monograph
addendum.
EVALUATION FOR ACCEPTABLE DAILY INTAKES
Biochemical aspects
The liver tissue of rats, mice and several avian and piscine species
has been found to produce a potent cholinesterase-inhibiting compound
in vitro on incubation with parathion. Rat and mouse liver
homogenates were found more efficient than those of avian and piscine
species tested in both inactivation of paraoxon and in formation of
p-nitrophenol from paraoxon (Murphy, 1966)
In investigation of in vitro metabolism of parathion by rat tissue
homogenate fractions, although many tissues were found to form
paraoxon on incubation with parathion, the greatest activity per gram
of tissue was found in the liver. The microsomes were not found to be
the most active liver fraction in the normal rat. The hepatic
microsomal activity in male rats was found to be increased 65-130 per
cent per unit weight of liver tissue by pre-treatment of the animals
with phenobarbital or 3,4-benzopyrene (Neal, 1967).
Acute toxicity
In the female mouse, the LD50 of paraoxon by oral, intraperitoneal,
subcutaneous and intravenous routes, respectively, are: 12.8, 2.29,
0.6 and 0.59 mg/kg body weight (Natoff, 1967).
Short-term studies
Rat. Twenty female rats were fed 0.05, 0.5 or 5.0 ppm for a maximum
of 84 days. The only effects were on cholinesterase, which was
depressed in erythrocytes at 0.5 and 5.0 ppm to 46 and 20 per cent
respectively of control values by the 12th week (maximum depression
occurring during the 4th week), and slightly depressed at 5.0 ppm in
the plasma. Brain cholinesterase was unaffected (Edson, 1964).
A three-generation reproduction study at 0, 10 and 30 ppm parathion
using 10 male and 20 female rats per level for each generation, and
comprising two litters per generation, revealed a reduced percentage
of offspring surviving to weaning in all generations at 30 ppm. A
doubtful reduction in mean weanling weights was also observed at 30
ppm. The 10 ppm level had no apparent effect. Parameters studied
included number of litters per group, number of stillbirths, number of
live births, litter size, foetal resorption, foetal birth weights,
percentage survival to weaning and weanling weights. Abnormalities
attributable to parathion were absent in all groups. Similarly,
pathology and organ weights of all groups of weanlings sacrificed fell
within normal limits for the species (Johnston, 1966).
Comments
The animal work is comprehensive, though because of species
differences it is difficult to adopt a maximum no-effect level in the
diet as a basis for arriving at an ADI. The evaluation is therefore
based on the findings in man.
The reproduction studies in the rat gave reassuring results.
TOXICOLOGICAL EVALUATION
Level causing no significant toxicological effect
Man: 0.05 mg/kg body-weight per day.
Estimate of acceptable daily intake for man
0-0.005 mg/kg body-weight.
EVALUATION FOR TOLERANCES
USE PATTERN
In 1966 the world production of parathion was approximately 15,000
tons (U.S.A. production 8,800 tons) whereas methyl-parathion
production was 35,000 tons (U.S.A. production 16,200 tons).
Pre-harvest treatments
Parathion is a wide spectrum insecticide which is used on food crops
as well as on fruits and vegetables and tea. It is applied in sprays
or dusts, the usual application rate being 0.2 - 1 kg/ha, depending
upon the crop, pest and climate. The following table gives a review of
application rates and minimum intervals between use and harvest.
Crop Country Application Pre-harvest
rate interval
Wheat Australia 560 g/ha 6 months
Field crops Austria 200 g/ha 3 weeks
Unspecified Canada 280 g/ha 15 days
Cereals Ecuador 490 g/ha -
(cont'd)
Crop Country Application Pre-harvest
rate interval
Field crops Germany 200 g/ha 2 weeks
Young crops India 80 g/ha 4 weeks
Field crops Iraq 30 days
Rice Japan 253-846 g/ha -
Cereals Norway 100-200 g/ha 2 weeks
Barley, oats,
wheat U.S.A. 1680 g/ha 15 days
Rice fields U.S.A. 112 g/ha 1 day
Tolerances such as those accepted in the U.S.A. result in a daily
intake, based on total diet studies, of 0.001 mg/person, corresponding
to 0.00002 mg/kg, well below the ADI of 0.005 mg/kg bodyweight.
(Duggan et al, 1967)
Under greenhouse conditions the interval between use and harvest is
usually 1.5 as high as given in the above tables.
Pre-harvest treatments
Parathion is not used against insects on stored crops.
Other uses
Parathion has very limited use as a household insecticide and in the
public health field.
RESIDUES RESULTING FROM SUPERVISED TRIALS
Residues in crops after soil treatment
Crop Location Maximum Interval after Range of
dosage application residues,
(lbs. /A) ppm
sugar beets Washington 4 6 months 0.1 (whole beet)
(soil, pre-plant)
Residues in crops after soil treatment (cont'd)
Crop Location Maximum Interval after Range of
dosage application residues,
(lbs. /A) ppm
potatoes Washington 4 1/2-5 months 0.2 - 0.06 (tubers)
Idaho (soil, pre-plant)
( Schulz, personal communication )
Residues in crops after foliage application
Parathion applied on plants disappears quickly, but more slowly than
methyl-parathion (Maier-Bode, 1965)
Crop days after Residues
application in ppm
fruits 7 0-0.5
14 0-0.3
vegetables 14 0.02-0.17
carrots 14 7.0
56 0.8
grain
(except rice) 1 0.7
rice 9 0.1
field crops 7 0.03-0.06
14 0.02
The biological half-life of parathion residues is about two to three
times greater than methylparathion. The high residue level and
persistence of parathion in carrots is due to accumulation in
oil-cells (Maier-Bode, 1965).
RESIDUES IN FOOD AT TIME OF CONSUMPTION
Total diet studies in U.S.A in 1965-1966 showed that only very low
residues (0-0.001 ppm) were present in vegetables and fruits as
consumed (Duggan, et al 1967). In 1963-1964, parathion residues in
food in commerce were 0.03-0.83 ppm (Williams, 1964).
FATE OF RESIDUES
In plants
In the cytoplasm of leaves, parathion is metabolized by a fermentative
route, probably beginning with a transformation to paraoxon (II). If
parathion is dissolved in lipoids - on peel or oil-cells - it very
slowly migrates into the aqueous tissues where it is metabolized
(Maier-Bode, 1965).
Terminal residues from parathion deposits on bean leaves are
isoparathion, paranitrophenol, paraoxon, an intermediate between
parathion and isoparathion and a more polar metabolite than
p-nitrophenol (El Refai, 1966).
In animals
Davison (1955) showed that Mg++ and diphosphopyridine nucleotide are
required to oxidize the phosphorothioate to a potent antiesterase. In
subsequent studies Cook and Pugh, (1957) showed that ultra-violet
light could also trigger the activation or conversion of parathion to
its more potent analog.
The metabolism of parathion has been studied by Dahm, et al (1950) in
cows. They observed that large intake levels (0.3 mg/kg/day) produced
no toxicological symptoms. Using the Averell and Norris essay they did
not find parathion, p-nitrophenol, paraoxon, amino-parathion,
aminoparaoxon, or aminophenol in the milk, blood or urine. Levels of
glucuronic acid in the urine from treated cows were higher than those
in normal cows. It was concluded that the urinary product was
p-aminophenyl-glucuronide. Cook (1957) showed that parathion is very
rapidly reduced to aminoparathion in the rumen fluid of a cow. Ahmed,
Casida and Nichols (1958), using 32P-labelled parathion in the cow,
noted that the parathion level in the rumen fell rapidly, most of it
being converted to aminoparathion and a hydrolysis product.
The urinary products were, principally, 0,0-diethyl
phosphorothioate, the remainder being diethyl phosphate. This showed
the differences in the metabolic routes. O'Brien (1960) has
illustrated the postulated metabolic pathways of parathion for cows.
In the case of rats (Ahmed et al., 1958) and men (Lieben, 1953) the
metabolic pattern is quite different from that of the cow, the
aminophenol is not a major excretory product. Further studies have
been conducted using other species of animals (Metcalf and March,
1953; Jensen, 1952) resulting in different percentages of the
metabolites recovered from each.
In storage and processing
After 10 weeks storage of rice bran and rice bran oil at 30 to 40°C
parathion residues were still 70 per cent of the original amount
(Goto, 1959). During cold-storage (10 to 15°C) of fruits and fruit
products, no degradation could be found within six months (Maier-Bode,
1965; Koivistoinen, 1959). Parathion residues in fruits disappear
during treatment with heat; sterilization by heat and juice extraction
by steam eliminate residues fairly well whilst short cooking (jams)
only partly eliminates residues (Maier-Bode, 1965; Koivistoinen, 1959;
Dürr, 1954).
METHODS OF RESIDUE ANALYSIS
Most residue analyses in the past have used the colorimetric method of
Averell and Norris, 1948, which has been worked out to a detection
limit of 0.05 ppm. This method includes metabolites which contain the
nitrophenyl group, but it is not specific for parathion. Lamar et al.,
1966, described a GLC-method using an EC-detector and a clean-up
procedure. This method was improved by industry (Bayer, private
communication). Storherr and coworkers, 1964, introduced the
thermionic detector for determination of parathion residues. PC and
TLC are also used. (Shen Chin Chang, 1952; Abbott, 1965; Getz, 1963).
NATIONAL TOLERANCES
The following tolerances for parathion have been established:
Product Country Tolerance in ppm
(methyl + ethyl)
General Austria 1
Cereals Brazil 1
A variety of registered
crops Canada 1 (ethyl only)
Vegetables, fruits Germany (BRD) 0.5
Apples, pears, quinces
citrus fruits Germany (DDR) 1
General Netherlands 0.5
Fruits Switzerland 0.75
A variety of registered
crops U.S.A 1
RECOMMENDATIONS FOR TOLERANCES
Temporary tolerances
In the light of the evidence presented above, the Joint Meeting
recommends the following temporary tolerances:
Commodity temporary tolerance
vegetables 0.7 ppm
(except carrots)
fruits (fresh) 0.5 "
peaches, apricots, citrus 1.0 "
In the absence of data it was not possible to recommend tolerances for
cereals.
FURTHER WORK
Further work required before 30 June 1970
Data on :
Residues resulting from pre-harvest treatment of cereals and the fate
of parathion in storage and processing.
Residues in cotton seed oil and cotton cake.
Residues found in total diet studies.
Further work desirable
Data on :
Occurrence of the oxygen analog in plants
Metabolism of the amino analog, e.g. in ruminants.
Further information on the presence of residues in food commodities
moving in commerce.
REFERENCES PERTINENT TO EVALUATION FOR ACCEPTABLE DAILY INTAKES
Edson, E.F. (1964) Food and Cosmetics Toxicology, 2, 311
Johnston, C.D. (1966) Unpublished report submitted by Monsanto
Chemical Company
Murphy, S.D. (1966) Proc. Soc. exper. Biol. Med., 123, 392
Natoff, I.L. (1967) J. Pharm. Pharmacol., 19, 612
Neal, R.A. (1967) Biochem. J., 103, 183
REFERENCES PERTINENT TO EVALUATE FOR TOLERANCES
Abbott, D.C., Crosby, N.T., Thomson, J. (1965) Use of thin-layer and
semipreparative gas-liquid chromatography in the detection,
determination and identification of organophosphorus pesticide
residues. Proc. Soc. Anal. Chem. Conf : 121-133.
Ahmed, M.K., Casida, J.E., Nichols, R.E. (1958) Bovine metabolism of
organophosphorus insecticides: significance of rumen fluid with
particular reference to parathion. J. Agr. Food Chem. 6 : 740-746.
Averell, P.R., Norris, M.V. (1948) Estimation of small amounts of
0,0-diethyl-0-(p-nitrophenyl) thiophosphate. Anal. Chem. 20:
753-756.
Chang, S.C. (1952) The speed of toxic action on the pea aphid of
several insecticides. J. Econ. Ent. 45 : 370-372.
Cook, J.W. (1957) In vitro destruction of some organophosphate
insecticides by bovine rumen fluid. J. Agr. Food Chem. 5: 859-863.
Cook, J.W., Pugh, N.D. (1957) A quantitative study of
cholinesterase-inhibiting decomposition products of parathion formed
by ultraviolet light. J. Assoc. Offic. Agr. Chem. 40 : 277-281.
Dahm, P.A., Fountaine. F.C., Pankaskie, J.E., Smith, R.C., Atkeson,
F.W. (1950) The effects of feeding parathion to dairy cows. J. Dairy
Sci. 33 : 747-757.
Davison, A.N. (1955) The conversion of schradan (OMPA) and parathion
into inhibitors of cholinesterase by mammalian liver. Biochem. J.
61 : 203-209.
Duggan, R.E., Weatherwax, J.R. (1967) Dietary intake of pesticide
chemicals. Science 157 : 1006-1010.
Dürr, H.J.R. (1954) Parathion spray residue on apples and canned
peaches. Fmg. in S. Afr. 29 : 231-232.
El-Refai, A., Hopkins, T.L. (1966) Parathion absorption, translocation
and conversion to paraoxon in bean plants. J. Agr. Food Chem. 14 :
588-592.
FAO/WHO. (1965) Evaluation of the toxicity of pesticide residues in
food. FAO Mtg. Rept. PL/1965/10/1; WHO/Food Add./27.65.
Getz, M.E. (1963) The determination of organophosphate pesticides and
their residues by paper chromatography. Res. Rev. 2: 9-25.
Goto, S., Mukai, I., Sato, R. (1959) Parathion residues in rice
grains. Botyu-Kagaku 24 : 30-34.
Jensen, J.A. (1952) Studies on fate of parathion in rabbits, using
radioactive isotope techniques. Arch. Ind. Hyg. 6: 326-331.
Koivistoinen, P., Raine, P. (1959) Occurence and disappearance of
parathion and malathion residues in vegetables and fruits. J. Sci.
Agric. Soc. Finland 31 : 294-302.
Lamar, W.L., Goerlitz, O.F., Law, L.R. (1966) Determination of organic
insecticides in water by electron capture gas chromatography. Adv. in
Chem. Ser. 60 : 187-199.
Lieben, J., Waldmann, R.K., Krause, L. (1953) Urinary excretion of
paranitrophenol following exposure to parathion. Arch. Ind. Hyg.
Occupat. Med. 7 : 93-98.
Maier-Bode, H. (1965) Pflanzenschutzmittel-Rückstände, Stuttgart,
Ulmer. 455 p.
Metcalf, R.L., March, R.B. (1953) The isomerization of organic
thionophosphate insecticides. J. Econ. Ent. 46 : 288-294.
O'Brien, R.D. (1960) Toxic phosphorus esters : chemistry, metabolism
and biological effects. New York, Academic Press. 434 p.
Storherr, R.W., Getz, M.E., Watts, R.R., Friedman, S.J., Erwin, F.,
Giuffrida, L., Ives, F. (1964) Identification and analysis of five
organophosphate pesticides : Recoveries from crops fortified at
different levels. J. Assoc. Off. Agr. Chem. 47 : 1087-1093.
Williams, S. (1964) Pesticide residues in total diet samples.
J. Assoc. Off. Agr. Chem. 47 : 815-821.
See Also:
Toxicological Abbreviations
Parathion (HSG 74, 1992)
Parathion (ICSC)
Parathion (FAO Meeting Report PL/1965/10/1)
Parathion (FAO/PL:1969/M/17/1)
Parathion (AGP:1970/M/12/1)
Parathion (Pesticide residues in food: 1984 evaluations)
Parathion (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
Parathion (IARC Summary & Evaluation, Volume 30, 1983)