Sponsored jointly by FAO and WHO


    The monographs

    Data and recommendations of the 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, 24 September - 3 October 1984

    Food and Agriculture Organization of the United Nations
    Rome 1985



         Parathion Methyl was evaluated by the Joint Meeting in 1968,
    1972, 1975, 1979 and 1980 (FAO/WHO 1969, 1973, 1976, 1980, 1981). A
    temporary ADI of 0-0.001 mg/kg bw was allocated in 1980. New data were
    presented to the JMPR in 1982, including mutagenicity data, a
    3-generation reproduction study and data from a two-year rat feeding
    study. However, since the available oncogenicity data did not permit a
    complete evaluation of the carcinogenic potential of parathion methyl
    the meeting extended the temporary ADI and requested additional data
    on the two-year feeding study in rats by 1984. Additional information
    is reviewed in this monograph addendum.



    Special Studies on Carcinogenicity


         Additional data on a 2-year feeding study in rats as requested by
    the Joint Meeting in 1982 (FAO/WHO 1983) were available. Historical
    data on the incidence of follicular and parafollicular thyroid
    adenomas as well as uterine adenocarcinomas in SPF Wistar TNO/W74 rats
    used in previous report (Bomhard et al., 1981) have been provided.

         Tumours of the same type in both thyroid lobes were counted as
    being one tumour. The incidence of thyroid carcinomas were also
    included. The historical control data were collected from 15
    experiments. The thyroid and uterine tumour incidence of the high dose
    group (50 ppm) is within the range of the historical controls. Only
    fifty percent of the control animals from Bomhard et al., 1981, study
    were examined histologically.

         Histological examination of the 2 and 10 ppm dose groups were
    performed and these data were presented as well. In both groups there
    were no pathomorphological indications of compound related effects on
    the organ systems evaluated. Type and location of benign and malignant
    tumours did not demonstrate an oncogenic effect from parathion methyl
    as they were randomly distributed and within the normal range for this
    strain of rat (Schilde and Bomhard, 1984).

    Acute Toxicity

         The acute toxicity of parathion methyl via oral and dermal routes
    is summarized in Table 1.

    TABLE 1:  Acute Toxicity of Parathion Methyl


    Species          Sex    Route        LD50         Reference

    Rat (fasted)     M      Oral       2.9 mg/kg      Heiman, 1982
                     F      Oral       3.2 mg/kg      Heiman, 1982

    Rat              M      Oral       10.8 mg/kg     Heiman, 1982
    (non-fasted)     F      Oral       9.3 mg/kg      Heiman, 1982

    Rabbit           M      Oral       10.0 mg/kg     Heiman, 1982
    (fasted)         F      Oral       19.4 mg/kg     Heiman, 1982

    Rat              M      Dermal     46.0 mg/kg     Heiman, 1982
                     F      Dermal     41.0 mg/kg     Heiman, 1982

    Special Study on Eye and Skin Irritation

         Instillation of 0.1 g of parathion methyl into the conjunctival
    sac of albino rabbits did not produce irritation.

         Application of 0.5g of parathion methyl (as a wet paste) to the
    skin of albino rabbits did not produce primary skin irritation
    (Pauluhn, 1983).

    Short-term Studies

    Rabbit - Dermal

         Groups of New Zealand white rabbits (6 males and 6 females per
    group) were administered parathion methyl (purity 96.3%) dermally at
    dose levels of 0, 50 and 250 mg/kg bw formulated in Cremophor E.I.,
    applied daily for 3 weeks (15 consecutive workdays). Material was left
    uncovered for 6 hours. The skin was then cleaned with soap and water.
    There was a dose-related inhibition of erythrocyle and brain
    cholinesterases in both dose groups. Plasma cholinesterase was also
    significantly depressed in the high dose group. These animals
    presented symptoms of cholinergic poisoning and 5 animals in this
    group died. The results of the remaining clinical chemistry,
    hematological evaluations and organ weight data did not demonstrate
    significant differences from controls. Microscopic examination
    revealed epithelial proliferation with hyperkeratosis of the treated

         Since a no effect level was not established a separate three-week
    dermal study was initiated using 0 and 10 mg/kg bw. No signs of dermal
    involvement or proliferative changes were noted and cholinesterase
    levels were comparable to controls (Mihail and Vogel, 1984).

    Rat - Inhalation

         Groups of Wister albino rats (10 males and 10 females per group)
    were exposed to parathion methyl aerosol concentrations of 0 (solvent
    only), 0.9, 2.6 and 9.7 mg per 120 m air. Animals were exposed for
    6 hours/day, 5 days/ week for 3 consecutive weeks. No mortality
    occurred. Plasma and brain cholinesterase levels were significantly
    depressed in high dose groups animals. They presented signs of
    cholinergic poisoning, reduced body weight gain and decreased organ
    weights. The mid dose group presented slight inhibition of plasma
    cholinesterase levels. Histopathological examinations were
    unremarkable between treated and control groups (Thyssen and Mohr,


         Parathion methyl was allocated a temporary ADI of 0-0.001 mg/kg
    by the 1980 JMPR. New data were presented at the 1982 JMPR including a
    two-year rat study but as this did not allow full evaluation of the
    carcinogenic potential of parathion methyl, or permit a no-effect
    level to be established, the temporary ADI was extended and additional
    data were requested from the two-year rat study by 1984.

         Re-evaluation of these data, the additional data requested and
    now provided, and carcinogenicity studies of parathion methyl in mouse
    and rat of the National Cancer Institute (1979) have indicated no
    evidence of carcinogenicity and have allowed the calculation of a
    no-effect dose in the two-year rat feeding study of 2 ppm in respect
    to terminal brain cholinesterase, plasma and erythrocyte
    cholinesterasis. This allowed the allocation of a full ADI, based
    partly on data in man (see 1975 JMPR).

    Level causing no toxicological effect

         Rat: 2 ppm in the diet equivalent to 0.1 mg/kg bw

         Man: 0.3 mg/kg bw/day

    Estimate of acceptable daily intake for man

         0 - 0.02 mg/kg bw



         Further observations in man.


    Bomhard, E., Loser, E., and Schilde, B. (1981) E605-Methyl
         (parathion-methyl) chronic toxicological study on rats (feeding
         experiment of two years). Report submitted to the World Health
         Organization by Bayer AG. (Unpublished)

    Bomhard, E. (1984). Ref: Parathion Methyl/report no. 9889: WHO
         requirements. Report submitted to the World Health Organization
         by Bayer AG. (Unpublished)

    Heinmann, K.G. (1982). E 120 (Parathion-Methyl)/Tests for acute oral
         and acute dermal toxicity. Report submitted to the World Health
         Organization by Bayer AG. (Unpublished)

    Mihail, F. and Vogel, O. (1984). E 120 (Parathion-Methyl)/Subacute
         dermal toxicity studies with rabbits. Report submitted to the
         World Health Organization by Bayer AG.(Unpublished)

    NCI, (1979). Bioassay of Methyl Parathion for possible carcinogenicity
         study. D.H.E.W. publication NCI-CG-TR-157. National Institutes of
         Health Bethesda M.D.

    Pauluhn, J. (1983). Parathion Methyl (E 120)/Study for
         irritant/corrosive effect on skin and eye (Rabbits). Report
         submitted to the World Health Organization by Bayer AG.

    Schilde, N. and Bomhard, E. (1984). E 605-methyl (Parathion Methyl)
         /Supplementary histopathological examination for the two year
         feeding study with rats (addendum to Rep. No. 9889). Report
         submitted to the World Health Organization by Bayer AG.

    Thyssen, J. and Mohr. U. (1982). E 120 (Parathion Methyl) /Subacute
         inhalation study with rats. Report submitted to the World Health
         Organization by Bayer AG. (Unpublished)

    See Also:
       Toxicological Abbreviations
       Parathion Methyl (Pesticide residues in food: 1982 evaluations)