FOLPET     JMPR 1973


         This fungicide was evaluated by the 1969 FAO/WHO Meeting on
    Pesticide Residues (FAO/WHO, 1969) and a temporary acceptable daily
    intake for man of 0-0.16 mg/kg estimated. Further studies were
    requested on the metabolism of folpet, particularly the
    trichloromethylthio-moiety, and on the effects of the compound on
    reproductive physiology. Long-term studies of sufficient duration to
    test for carcinogenic effects were also considered to be needed.
    Further data.made available are summarized in this monograph addendum.


    Biochemical aspects

         In blood, the sulfonamide bond is hydrolyzed rapidly (Dye, 1969)
    yielding phthalimide, which is further hydrolyzed to phthalic acid,
    and a trichlormethylthio-moiety which is identical to that produced
    during the biodegradation of captan and probably metabolized by the
    same pathways (see monograph on captan).


    Special studies on mutagenicity

    Mouse. A dominant lethal mutagenic study was conducted using groups
    of 12 male mice, aged 70-80 days, which were administered 0, 5 or 10
    mg folpet/kg bw intraperitoneally. Each male mouse was then placed
    with three untreated virgin females. These were removed after a week
    and replaced by another three females. This was repeated for six
    consecutive weeks. Females were killed a week after removal from the
    male and the numbers of implantation sites, deciduomata and late death
    resorption sites and embryos counted. The percentage of mated females
    which became pregnant was slightly but not significantly lower in the
    10 mg/kg group than in controls. The number of deciduomata was
    slightly high during weeks two and three in the 5 mg/kg group but not
    in the 10 mg/kg group, and during the fifth week in the 10 ppm group.
    The findings in test animals otherwise compared well with those of
    controls (Calandra, 1971).

    Drosophila. Folpet was administered either by injection into male
    drosophila or by leg feeding to larvae. The results showed that no
    mutagenic changes could be produced in the system although a very weak
    effect could not be excluded (Kramers and Knaap, 1973).

    Special studies on teratogenicity

         Groups of 2-13 pregnant hamsters were administered a single dose
    of between 400 and 1000 mg folpet/kg bw on days seven or eight of
    gestation or were dosed daily from the sixth to the tenth day with a

    total of between 1000 and 2500 mg folpet/kg bw. They were killed and
    examined on the fifteenth day of gestation. At the highest dosage
    levels maternal mortality was increased and some abnormal fetuses were
    produced but the lower dosage levels produced no indication of
    teratogenic activity (Robens, 1970).

    Acute toxicity

         0, one and two mice died in groups of two mice which received
    respectively 15, 20 and 50 mg/kg of folpet by intraperitoneal
    injection. The LD50 appeared to be in the region of 20 mg/kg/day.


         The structure of folpet is similar to that of captan. Hydrolysis
    of the compound takes place rapidly the phthalimide residue being
    metabolized to phthalic acid. The trichloromethylthio-moiety is
    presumably metabolized by the same pathways as for captan.

         Previous studies have demonstrated a fetotoxic effect with folpet
    but no evidence of teratogenic activity was found with folpet or
    phthalimide. Negative results were seen in a dominant lethal test
    using mice and in a test for mutagenicity in which drosophila were
    exposed to high dosage levels.

         The LD50 of folpet by the intraperitoneal route was about 20
    mg/kg compared with > 10 000 mg/kg by the oral route; further
    investigation of the intraperitoneal toxicity would be of interest.

         In view of the similarity of folpet to captan, the present
    knowledge of the manner in which the trichloromethylthio-moiety is
    metabolized and the adequate long-term studies available on captan
    (see monograph on captan) an estimate can be made of an acceptable
    daily intake by man.


    Level causing no toxicological effect

         Rat:   3200 ppm in diet equivalent to 160 mg/kg bw

         Dog:   1000 mg/kg bw per day

    Estimate of acceptable daily intake for man

         0-0.1 mg/kg



    1. Investigation of the fetotoxic action of folpet.

    2. Investigation of the intraperitoneal toxicity.

    3. Information on the nature, level and fate of residues following
    washing, blanching, storage, and thermal processing of treated crops.

    4. Residue data obtained by the newer methods of analysis on the main
    commodities for which tolerances have been recommended.

    5. Information on the fate of folpet in the soil.

    6. Further data on the levels of degradation products in relation to
    residues of the parent compound.

    7. Results of metabolism studies currently planned.


    Calandra, J.C. (1971) Mutagenic study with folpet in albino mice.
    Unpublished report of Ind. Bio-Test Labs submitted by Chevron Chemical

    Dye, D.F. (1969) Folpet. Unpublished summary report submitted to FAO
    and WHO by Chevron Chemical Co.

    Kramers, P.G.N. and Knaap, A.G.A.C. (1973) Mutagenicity tests with
    captan and folpet in Drosophila melanogaster. Mutation Research, 21:

    Robens, J.F. (1970) Teratogenic activity of several phthalimide
    derivatives in the golden hamster. Toxicol. Appl. Pharmacol., 16:


    See Also:
       Toxicological Abbreviations
       Folpet (HSG 72, 1992)
       Folpet (ICSC)
       Folpet (FAO/PL:1969/M/17/1)
       Folpet (WHO Pesticide Residues Series 4)
       Folpet (Pesticide residues in food: 1984 evaluations)
       Folpet (Pesticide residues in food: 1986 evaluations Part II Toxicology)
       Folpet (Pesticide residues in food: 1990 evaluations Toxicology)
       Folpet (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)