Sponsored jointly by FAO and WHO


    Joint meeting of the
    FAO Panel of Experts on Pesticide Residues
    in Food and the Environment
    and the
    WHO Expert Group on Pesticide Residues
    Rome, 6-15 October 1980



    Parathion-methyl was evaluated by the Joint Meeting in 1968, 1972,
    1975, and in 1979 (FAO/WHO 1969, 1973, and 1976; FAO, 1980).  In
    1979, based on the consideration that parathion-methyl was neither
    teratogenic nor embryotoxic in rats and that previously requested
    long-term studies were in progress, the Meeting extended the
    temporary Acceptable Daily Intake.

    Further information on the toxicological hazards associated with
    the use of parathion-methyl under actual field conditions in India
    and short-term studies were made available to the Meeting.  These
    data are reviewed in this monograph addendum.



    Special studies on potentiation

    In an effort to evaluate the possible acute interaction of
    parathion-methyl and other toxic insecticides, acute studies with
    DDT and parathion-methyl in rats were performed.  Male rate were
    orally administered fractions of the LD50 of each material.  The
    ratio of LD50 value calculated to that observed in the study
    suggested a less than additive effect when the two insecticides are
    administered simultaneously (i.e., the acute toxicity was less than
    anticipated based on preliminary toxicity data with each material
    alone) (Kimmerle, 1975 ).  An additional trial in male rats
    administered parathion-methyl and parathion-ethyl (parathion)
    showed the combined toxic effects to be additive (Flucke and
    Kimmerle, 1977).

    Special studies an carcinogenicity


    In a dose range-finding study, groups of mice (5 male and 5 female,
    B6C3F1, mice/group) were fed parathion-methyl at dosage levels of
    0, 20, 40, 60, 80, 100, 125, 250 or 500 mg/kg for 7 weeks.  After
    1 week of control diet (following parathion-methyl dosing) the
    animals were sacrificed and tissues of some of the upper dosage
    groups were examined microscopically.  The criterion of 10% weight
    loss was chosen to develop the dosage levels of the chronic study
    (the data were not reported in detail enough to determine whether
    the 10% weight loss would be the criterion for the high or low
    dosage groups in the chronic study).

    Mortality was noted in the study; the high dose group had no
    survivors and the 250 mg/kg group had only 1 female of 10 mice
    surviving the 7-week trial.  Mean body weights were not
    substantially reduced (maximum was 6% at week 7).  From these data
    the initial dosage levels for the chronic study were chosen as 0,
    62.5 or 125 mg/kg.

    Groups of mice, 50 male and 50 female (20 of each sex were used as
    controls) B6C3F1 mice/group, were fed parathion methyl for 102
    weeks. All animals were 6 weeks of age at the inception of the
    study and were fed parathion-methyl diets 7 days per week.  Animals
    were housed in groups of five under clean, but not SPF conditions,
    and were in rooms where other chemicals were administered to mice
    in chronic studies. The animals were weighed every two weeks during
    the initial phase of the study and monthly for the remainder of the
    study.  At the conclusion of the study all animals were sacrificed
    and necropsied. Histopathologic evaluations were made on all major
    tissues and organs and on all lesions, noted on gross examination.

    There was a substantial decrease in growth of male mice, such that
    the dosage levels had to be reduced at 38 weeks from 125 and 62.5
    mg/kg to 50 and 20 mg/kg respectively.  Thereafter, the males grew
    normally. The 125 mg/kg dose in females was responsible for a
    slight weight loss over the entire course of the study.  There were
    no differences in mortality with respect to control groups. 
    Sufficient survivors were available for an adequate study on the
    development of neoplastic and non-neoplastic lesions.

    On pathologic examination, a variety of lesions were observed in
    both treated and control animals.  The incidence and type of each
    neoplasm was not attributable to the presence of parathion-methyl
    in the diet. All lesions encountered were attributed to the common
    ageing process in this strain of mice.  Statistical evaluation of
    the data concurred with the gross and pathological findings.  It
    was concluded that under the conditions of this bioassay,
    parathion-methyl was not carcinogenic to the B6C3F1 mouse.  These
    conclusions were confirmed by a Data Evaluation/Risk Assessment
    Subgroup of the Clearinghouse on Environmental Carcinogens (NCI,


    In a dose range-finding study, groups of rats ( 5 female and 5
    male, F344 (Fischer) rats), were fed parathion-methyl in the diet
    at dosage levels of 0, 10, 20, 30, 40, or 50 mg/kg for 7 weeks.  At
    the conclusion of the dietary trial, all animals were maintained on
    control diets for one week and sacrificed.  Growth had been
    measured twice a week for the 8-week trial.  Abnormalities noted on
    gross and microscopic analyses of tissues and organs and a 10%
    growth reduction were chosen as requisites for the dosage levels to
    be used in the chronic study.

    There was no mortality in the male rats and survival of the females 
    mixed.  There were no serious lesions noted on sacrifice and based

    on growth the dosage levels of 0, 20 or 40 mg/kg were chosen for the
    chronic study.

    Groups of rats (50 male and 50 female (20 of each sex were used as
    controls, F344 (Fischer) rats per group) were fed parathion-methyl
    in the diet, 7 days per week for 105 weeks at dosage levels of 0,
    20 or 40 mg/kg.  Groups of rats were housed together (4 of each sex
    per cage) in a clean room where several other chemicals were being
    studied.  The animals were not maintained under SPF conditions. 
    Body weight data were recorded periodically over the course of the
    study as were chemical analyses of the dietary content.  At the
    conclusion of the study, all animals were sacrificed for gross and
    microscopic analyses of tissues and organs.

    There was no substantial effect of parathion-methyl on growth,
    although the 40 mg/kg dosage level decreased female growth and
    increased the mortality rate of females.  Survival of females was
    significantly reduced at 40 mg/kg.

    A variety of neoplastic and non-neoplastic lesions were noted in
    rats over the course of the study.  Each type of neoplasm had been
    noted previously in this strain of rat.  The incidence by type and
    site and by test group and sex was reported to be unaffected by
    parathion-methyl in the diet.  Based on the chronic bioassay data,
    there was no evidence that parathion-methyl was carcinogenic to
    this strain of rat. The conclusion was confirmed by the Data
    Evaluation/Risk Assessment Subgroup of the Clearinghouse on
    Environmental Carcinogens (NCI, 1979).


    In three supervised trials in India, groups of agricultural
    workers, either wearing protective clothing or clothing normal to
    the area, were examined before, during and after exposure to three
    different formulations of parathion-methyl applied by hand in
    different agricultural situations indigenous to India.  Two
    concentrations of parathion-methyl as an emulsifiable concentrate
    in water and one trial with parathion-methyl as a 2% dust were used
    in these trials.  The duration of exposure for the individuals
    participating was four hours per day for four successive days. 
    Pre-exposure, exposure, and post-exposure examinations with respect
    to physical determinations, cholinesterase measurements and
    haematological parameters ware performed on the individuals.

    As might be expected from this type of experiment, the most
    significant data reported were cholinesterase depression levels
    reflective of exposure.  In the trial with the high concentration
    parathion-methyl emulsifiable concentrate, there was no substantial
    difference with respect to cholinesterase depression in the
    individuals wearing protective clothing from those wearing normal
    clothing.  Cholinesterase depression data suggested that exposure

    had, indeed, occurred although cholinesterase depression levels 
    rarely exceeded the 25% level that would be indicative of excessive

    In the trial where a lower concentration of the parathion-methyl
    emulsifiable concentrate was used, none of the workers showed any
    substantial inhibition of cholinesterase activity during the course
    of the experiments.  Differences in the two trials with
    emulsifiable concentrates were probably reflective of the
    differences in concentration of the technical material and in the
    crop upon which the technical material was sprayed (in the higher
    concentration the crop was a high span of cotton that presumably
    increased the exposure from drift).

    In the third trial, a 2% dust formulation of parathion-methyl did
    not induce cholinesterase activity in any of the exposed workers
    regardless of whether protective clothing was used.

    In none of the above trials were there any of the variations in
    haematological parameters or significant side effects noted with
    some other insecticides (Anonymous, 1976).



    Parathion-methyl was previously evaluated by the Joint Meeting in
    1968, 1972, 1975 and 1979 (FAO/WHO, 1969b, 1973b, 1976b, 1980b) and
    a temporary ADI of 0-0.001 mg/kg bw/day was allocated.  Some data
    were submitted to the meeting and reviewed.  An extensive study of
    agricultural field workers exposed to different formulations of
    parathion-methyl under agricultural conditions in India showed
    that, following good agricultural practices, occupational exposure
    would not result in significant adverse short-term effects.  While
    these data were sufficient to relieve concerns about the short-term
    hazards associated with short-term occupational exposure, the
    meeting decided to extend the temporary ADI and request that
    reproduction and long-term studies be made available.

    Level causing no toxicological effect

    Man: 0.3 mg/kg bw/day.

    Estimate of temporary acceptable daily intake for man

    0-0.001 mg/kg bw/day.


    Required (by 1982)

    1. Reproduction study in species appropriate to such a test.
    2. Results of adequate long-term study reported to be in progress.


    Anonymous. Studies on the Toxic Hazards of Methyl-Parathion
    Preparations to Human Workers When Engaged in Agricultural Pest
    Control Operations Under Indian Field Conditions. (1976)
    Unpublished report from the Haffkine Institute for Training
    Research and Testing (Bombay) submitted by Bayer (India) Limited to
    the World Health Organization.

    Flucke, W. and Kimmerle, G. Studies on Acute Toxicity of
    Simultaneously Administered Parathion-Methyl (Parathion-M) and
    Parathion-ethyl (Parathion-A). (1977) Unpublished report from Bayer
    AG Institut für Toxicologie submitted to the World Health
    Organization by Bayer, AG.

    Kimmerle, G. Acute Toxicity of DDT in Combination with
    Parathion-Methyl and Penithrothion to Rats. (1975) Unpublished
    report from Bayer AG Institut für Toxicologie submitted to the
    World Health Organization by Bayer, AG.

    NCI. Bioassay of Methyl Parathion for Possible Carcinogenicity.
    National Cancer Institute, Carcinogenesis Technical Report Series
    #157. D.H.E.W. Publication No. (NIH 79-1713). Report of a study
    performed at the Fredrick Cancer Research Center, Fredrick, MD, and
    prepared by Tracor Jitco, Inc. for the National Cancer Institute.


    See Also:
       Toxicological Abbreviations
       Parathion-methyl (FAO/PL:1968/M/9/1)
       Parathion-methyl (WHO Pesticide Residues Series 2)
       Parathion-methyl (WHO Pesticide Residues Series 5)
       Parathion-methyl (Pesticide residues in food: 1978 evaluations)
       Parathion-methyl (Pesticide residues in food: 1979 evaluations)
       Parathion-methyl (Pesticide residues in food: 1984 evaluations)
       Parathion-methyl (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)