FENTHION            JMPR 1975


         Fenthion was last evaluated by the 1971 FAO/WHO Joint Meeting
    (FAO/WHO, 1972). Concerning residues in food and their evaluation,
    only information on the frequency and level of fenthion residues in
    food commodities in commerce were listed as desirable. No such data
    have become available.

         New information on the toxicology, composition of technical
    fenthion and on national tolerances and pre-harvest intervals has been
    supplied and is listed in the following monograph addendum.



    Effects on enzymes and other biochemical parameters

         When fenthion was administered at doses of 0.5 mg/kg orally to
    rats, and 1-8 mg/kg intravenously to cats, significant inhibition of
    and effects on heart rate and blood pressure were observed. However,
    an intravenous dose of 0.3 mg/kg to cats produced no significant
    changes in blood pressure, heart rate or other physiological
    parameters (Wills et al., 1975).


    Special studies on reproduction


         In a five generation reproduction study (2 litters per
    generation) two groups of Charles River CD 1 mice consisting of 14
    females, 10 males; and 22 females, 10 males, received 0 and 60 ppm
    fenthion respectively in their drinking water. In the parameters
    studied (reproductive performance, lactation, viability and growth
    rate of pups) the principal effect was a significant increase in pup
    mortality especially in the 2nd, 3rd and 4th generations. The highest
    mortality appeared to be in the first postnatal week. No
    histopathological changes were noted in the liver or kidney. There was
    no evidence of teratogenic potentials (Budreau and Singh, 1973b).

    Special studies on teratogenicity


         Pregnant Charles River CD 1 mice were injected intraperitoneally
    with single doses of 40, 80 and 160 mg/kg body weight at various time
    periods during organ ogenesis. Foetuses were removed by caesarean
    section on days 16 and 18 and viscera and skeletal structure examined
    for abnormalities. The frequency of resorptions and festal deaths was
    not affected. Foetal weights were reduced significantly. Although the
    number and type of abnormalities were increased when compared to the
    control group, this did not appear to be dose-related. There was no
    apparent teratogenic effect, however, the incidence of resorptions was
    increased when fenthion was injected intraperitoneally for three
    consecutive days (day 9, 10, 11 of gestation) at 20 mg/kg (Budreau and
    Singh, 1973a).

         Fenthion was administered orally to groups of female rats for one
    generation (two litters) at dosage levels of 5 mg/kg body weight and
    10 mg/kg body weight from both day 1 through day 7 and day 8 through
    day 10 of gestation. Animals were sacrificed on day 21, foetuses were
    removed by caesarean section and examined for internal and external
    abnormalities. No malformations were observed. The incidence of
    resorptions was increased and weight of foetuses reduced. The second
    progeny from these females were not affected. In a further study rats
    were given fenthion at a dosage level of 5 mg/kg body weight from day
    1 through day 13 of gestation, There was no evidence of teratogenesis.
    However, the incidences of foetal resorption and abortion were
    increased. During the lactation period there was an increased
    mortality and a decrease in the body weight gain of the pups. By day
    45 postpartum surviving new born had recovered normal weight
    (Fytizas-Danielidou, 1971).

    Acute toxicity

    Mouse (F) I.P. 200-240 mg/kg Budreau and Singh 1973

    Observations in man

         The potential dermal and respiratory exposure to fenthion during
    field application by hand gun power spray equipment, back-pack hand
    pressure sprayer and hand granular dispersal for mosquito control was
    studied over two work seasons (Fytizas-Danielidou, 1971). Human
    workers exposed to 3.6-12.3 mg/h (dermal) or <0.02-0.09 mg/h
    (inhalation), equivalent to 0.5-1.5 mg/kg/day (dermal) and 0.01-0.05
    mg/kg/day (inhalation), showed a decrease in plasma, but not
    erythrocyte, cholinesterase activity (Wolfe et al., 1974).


         Although additional data have been made available relating to
    reproduction, teratology and potential human exposure to fenthion,
    adequate two-year feeding studies and data to elucidate the mechanism
    of action of prolonged cholinesterase inhibition as required by the
    1971 Joint Meeting, have not been provided. Sufficient data was
    available to extend the existing temporary acceptable daily intake.


    Level causing no toxicological effect:

         Rat: 3 ppm in the list equivalent to 0.15 mg/kg bw

         Dog: 2 ppm in the diet equivalent to 0.05 mg/kg bw

    Estimate of temporary acceptable daily intake for man

         0 - 0.0005 mg/kg bw

    TABLE 1. Composition of technical fenthion (Bayer AG, 1975)


    O,O-dimethyl O-(3-methyl-4-methylthiophenyl)
    phosphorothioate                                      min.    96%

    O,S-dimethyl O-(3-methyl-4-methylthiophenyl)
    phosphorothioate                                      max.    1.0%

    O-methyl O-(3-methyl-4-methylthiophenyl)
    phosphorothioate                                      max.    0.5%

    3-methyl-4-methylthiophenylphenol                     max.    0.5%

    bis-O,O-diethylphosphorothioic anhydride              max.    0.5%

    O,O-dimethyl O-(3-methyl-4,6-di(methylthio)phenyl
    phosphorothioate                                      max.    1.5%

    1-methylthio-2-methyl-4-methoxybenzene                max.    0.5%

    O,O,O-trimethyl phosphorothioate                      max.    0.1%

    water                                                 max.    0.1%

    TABLE 2.  National tolerances for fenthion reported to the Meeting
              (changes and additions since the 1971 evaluation)


                                                     Tolerance   Pre-harvest
    Country                   Commodity              (mg/kg)     interval (days)

    Australia          General                                          14

                       Milk and milk products
                       (fat basis)                      0.2

                       Cereals, fruit,                  2.0

                       Meat of cattle                   1.0             1

    Brazil             Fruit                            1.0             14

                       All other crops                                  10

    Federal Republic   Cherries                                         14
    of Germany
                       Pome fruit                                       21

                       Fruit generally                  1.0

    Hungary            General                          1.0             21

    Israel             Apples, apricots,
                       peaches                          2.0

                       cucurbits, olives
                       olive-oil, onions,
                       pears                            1.0

    Japan              Rice                             0.05         14 - 30

                       Potatoes                         0.05            7

    Poland             Apples, plums                                    28

    TABLE 2. (continued)


                                                     Tolerance   Pre-harvest
    Country                   Commodity              (mg/kg)     interval (days)

    South Africa       General                          2.0

                       Apples, apricots,
                       coffee, cucurbits,
                       guavas, peaches, pears,                          10
                       plums, pome fruit

    Spain              Cereals, citrus fruit,
                       fruit, olives, rice                              30

    USA                Rice                             0.1             30
                       Rice straw                       0.5

    Yugoslavia         General                          0.5
                       Fruit, olives                                    21


         New information has been provided concerning the composition of
    technical grade fenthion. The minimum content of O,O-dimethyl
    O-(3-methyl-4-methylthiophenyl) phosphorothioate is 96% as already
    reported (FAO/WHO, 1972) but in recent production the impurity
    O,O-dimethyl O-(3-methyl-4,6-di(methylthio)phenyl) phosphorothioate
    has decreased from 5-7% to 1.5%. New national tolerances have been
    established for several commodities for which no residue data or only
    limited data were available to the 1971 Meeting. The appropriate
    residue data should therefore be supplied to the Joint Meeting.

         Limited residue data on fruit and vegetables moving in commerce
    have been received. With one exception (0.5 mg/kg apples) residues in
    142 samples (including 125 samples of apples) were below 0.02 mg/kg in
    apples, cabbage, cherries, cucumbers, kohlrabi, lettuce, peaches and
    pears. The samples were from food inspections in Hungary (1974) and
    the Netherlands (1975).


    REQUIRED (by 30 June 1978, in addition to the information listed in
    FAO/WHO 1972a, p.43 and before additional maximum residue limits can
    be recommended)

         1.   Residue data from supervised trials in accordance with good
              agricultural practice on other citrus fruit (especially
              lemons), coffee, cucurbits, onions and potatoes, and
              additional residue data on sugar beet roots and tops.


         See FAO/WHO 1972a, p.43


    Bayer AG. (1975) Pflanzenschutz-Anwendungstechnik, Leverkusen, 1975 

    Budreau, C.H. and Singh, R.P. (1973a) Teratogenicity and
    Embryotoxicity of Demeton and Fenthion in CF 1 Mouse Embryos. Tox.
    Appl. Pharm., 24, 325-332.

    Budreau, C.H. and Singh, R.P. (1973b) Effect of Fenthion and
    Dimethoate on Reproduction in the Mouse. Tox. Appl. Pharm., 26,

    Fytizas-Danielidou, R. (1971) Effects des pesticides sur la
    reproduction des rats blancs. I. Lebaycide. Fakulteit van de
    Landbouwwetenschappen. 23. Internationaal Symposium over Fytofarmacie,
    4 Mei, 1971.

    Wills, J.H., Groblewski, G.E. and Coulston, F. (1975) Status report to
    Bayer AG. West Germany from Institute of Comparative and Human
    Toxicology, Albany Medical College, Albany, New York submitted to WHO
    by Bayer AG.

    Wolfe, H.R., Armstrong, J.F. and Durham, W.F. (1974) Exposure of
    Mosquito Control Workers to Fenthion. Mosquito News, 34, 263-267.

    See Also:
       Toxicological Abbreviations
       Fenthion (ICSC)
       Fenthion (WHO Pesticide Residues Series 1)
       Fenthion (Pesticide residues in food: 1977 evaluations)
       Fenthion (Pesticide residues in food: 1978 evaluations)
       Fenthion (Pesticide residues in food: 1979 evaluations)
       Fenthion (Pesticide residues in food: 1980 evaluations)
       Fenthion (Pesticide residues in food: 1983 evaluations)
       Fenthion (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
       Fenthion (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
       Fenthion (Pesticide residues in food: 1997 evaluations Part II Toxicological & Environmental)