WHO/Food Add./68.30



    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)

    Rome, 1968


    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


    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).


    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.


    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.



    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            -

    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 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

    (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).


    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).


    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).


    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). 


    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


    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


    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.


    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


    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:

    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 :

    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)