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    FAO/PL:1969/M/17/1

    WHO/FOOD ADD./70.38

    1969 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD

    THE MONOGRAPHS

    Issued jointly by FAO and WHO

    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
    Group on Pesticide Residues, which met in Rome, 8 - 15 December 1969.

    FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS

    WORLD HEALTH ORGANIZATION

    Rome, 1970

    CAPTAN

    IDENTITY

    Chemical name

    N-(trichloromethylthio)-3a,4,7,7a-tetrahydrophthalimide (IUPAC)

    Synonyms

    N-(trichloromethylthio) cyclohex-4-one-1,2-dicarboxyimide

    Structural formula

    CHEMICAL STRUCTURE 

    Other relevant chemical properties

    The technical product is claimed to contain 96 percent captan; the
    remainder consists of common salt (sodium chloride), water and
    unreacted tetrahydrophthalimide. The pure crystal ins product, m.p.
    178 C, is reported to have a vapour pressure of less than 1  10-6
    torr at 25 C, but that of the technical product is stated to be much
    higher. Solubility in water at normal temperatures is extremely low;
    it is less than 10 percent in common organic solvents. Captan is
    stable, except under alkaline conditions, at normal temperature; it
    will decompose at temperatures in the region of 100 C, very slowly in
    dry or rapidly in moist atmospheres (Klayder, 1963). In alkaline
    solution, 1.0N NaOH, captan yields 2.8 equivalents of chloride ion.
    Cooking, especially in water would lead to rapid decomposition of
    residues to water-soluble products.

    Formulated products include wettable powders containing 50 to 83
    percent a.i. and dusts, those for field use containing a few percent
    a.i. and those for seed treatment 75 Percent.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    This pesticide was evaluated for acceptable daily intake by the 1965
    Joint FAO/WHO Meeting on Pesticide Residues (FAO/WHO, 1965). Since
    that time additional information has become available, especially on
    the metabolism and on the effect upon reproduction. Therefore, the
    previously published monograph has been revised and is now reproduced
    in its entirety.

    BIOCHEMICAL ASPECTS

    Absorption, distribution and excretion

    Captan is rapidly decomposed in both human and rabbit blood at room
    temperature. Decomposition appears to be according to first order
    kinetics although some concentration dependency is evident, possibly
    due to the low solubility of captan in aqueous media. At initial
    concentrations of 100 g/ml or 1/g/ml in human blood the half-life of
    captan was calculated as 0.9 minutes or 0.2 minutes respectively. In
    rabbit blood at an initial concentration of 1 g/ml, the half-life is
    0.3 minutes (Crossley, 1967).

    Captan, as an aqueous slurry, was administered by intragastric
    intubation to female rabbits at levels of 0 mg/kg body-weight (two
    rabbits) or 500 mg/kg body-weight (five rabbits). Blood was drawn
    directly from the heart at intervals up to 56 hours and analysed for
    captan and its metabolite tetrahydrophthalimide. No captan was
    detected in the blood at any time after administration of the dose,
    using an analytical method sensitive to 0.025 g/ml. A build-up of the
    metabolite tetrahydrophthalimide occurred in the blood which reached a
    maximum of about 25 g/ml 30 hours after intragastric administration
    of captan. From then on it decreased to a level of 4.2 g/ml after 56
    hours; the estimated half-life being 6 hours (Crossley, 1967).

    Recent information on the metabolism of captan has been inferred from
    work on captafol, a compound which differs from captan only in the
    nature of the chlorinated group attached to the sulphur atom (see the
    monograph on captafol). Rats were fed celery which had been treated
    with captafol to give levels of 60 or 600 ppm. The stomach content of
    the animals was analysed at several intervals and both
    tetrahydrophthalimide and tetrahydrophthalic acid were detected
    (Leary, 1966).

    Rats, dogs and monkeys wore fed carbon14-carbonyl labelled captafol.
    The radioactivity rapidly entered the blood and tetrahydrophthalimide
    was detected in the blood, faeces and urine. Tetrahydrophthalamic acid
    as well as other more water soluble metabolites were the principal
    radioactive compounds present in the blood and urine. Because of the
    similarity in structure it has been assumed that captan would be
    metabolized in a similar fashion with respect to the
    tetrahydrophthalic acid portion of its molecule (Dye, 1969).

    Feeding studies with captan demonstrated that captan is not stored in
    the eggs or flesh of poultry nor in the tissues of pigs (Weir, 1957;
    Link et al., 1956).

    Effect on enzymes and other biochemical parameters

    In the presence of compounds such as cysteine which contain sulfhydryl
    groups, all the three chlorine atoms in captan are liberated an
    chloride ions, and four sulfhydryl groups disappear for every molecule
    of captan that reacts. In general captan initially reacts with two
    molecules of a simple thiol to give tetrahydrophthalimide, the
    disulfide derived from the thiol, thiophosgene and one chloride ion.
    The thiophosgene reacts with two additional molecules of the thiol, to
    give ultimately two more chloride ions, carbon disulfide and the
    sulfide derived from the thiol. In the case where cysteine is the
    thiol the reaction is slightly more complicated resulting in the
    formation of a substituted thiazolidinethione. The presence of all
    these compounds from the metabolism of captan, has been confirmed
    chemically (Owens, 1969).

    TOXICOLOGICAL STUDIES

    Special studies on reproduction

    Rat

    A three-generation reproduction study was conducted with rats which
    received technical captan in their diet in concentrations of 0, 100,
    500, and 1000 ppm. Groups of 16 female animals were used and two
    litters were produced in each generation. No significant differences
    were found between control and captan treated rats with respect to
    fertility, gestation, viability or lactation indices, or in the
    weaning weights in the first two generations. No effects were observed
    in the third generation except for a slightly lowered lactation index
    for the group receiving 1000 ppm of captan. Histopathological
    examination of tissues from 10 pups receiving 1000 ppm in the third
    generation revealed no damage (Kennedy, 1966; Kennedy, et al., 1968).

    Special studies on teratogenicity

    Chicken

    A group of 5 male and 18 female White Leghorn chickens were fed a diet
    containing 0 or 2,300 ppm (equivalent to 75 mg/kg body-weight)
    technical captan for 6 weeks. The birds were observed for body-weight
    effects, food consumption, behavioural reaction, and egg production.
    Eggs collected during days 29 through 39 were incubated to determine
    the extent of hatchability and the presence of any effects on the
    chicks. No adverse effects were noted (Palazzolo, 1966).

    Captan was injected in dimethylsulfoxide solution into either the yolk
    or air cell of fresh fertile White Leghorn eggs in amounts sufficient
    to produce concentrations of 3 to 20 ppm in the eggs. The eggs were
    incubated and non-viable embryos and hatched chicks were examined for
    gross abnormalities. In a total of 1,292 eggs, the incidence of
    malformations was 7.8 percent compared to an incidence of less than 2

    percent in solvent-injected and uninjected control eggs. Malformations
    of the feet and legs followed a specific pattern. Micromelia, amelia,
    and phocomelia accounted for most of the deformities (Verrett, at al.,
    1969).

    Hamster

    Groups, each comprising 20 pregnant female hamsters ware fed diets
    containing concentrations of captan sufficient to enable the animals
    to receive an average daily intake of 0, 125, 250, or 1000
    mg/kg/body-weight of captan from days 1 through 15 of gestation. At
    day 159 all females were sacrificed, the young were surgically removed
    and the foetal development and structural formation of each was
    examined. The incidence of abnormal effects was not greater in any
    test group than in the controls. The dose level of 1000
    mg/kg/body-weight of captan resulted in a significant increase in
    foetal resorption (Kennedy, at al., 1968).

    Monkey

    Groups of seven pregnant Rhesus monkeys were given daily oral doses of
    6.35, 12.5 or 25 mg/kg body-weight of captan on days 22 through 32 of
    gestation. (Thalidomide was used as a positive control at dosage
    levels of 5 mg/kg/body-weight/day in six animals and at 10
    mg/kg/body-weight/day in four animals). Foetuses were recovered on
    approximately day 84 of gestation by Caesarian section and examined
    for organ and skeletal defects. Foetal mortality occurred in three of
    seven monkeys at the 25 mg/kg level. The foetal mortality in the
    parent colony not fed captan was 13.2 percent on 439 conceptions.
    There was no abnormality among any foetus in either of the three dose
    levels of captan (Courtney, 1968).

    Groups of seven pregnant monkeys (Rhesus and stumptail) were given
    captan orally at levels of 10, 25 or 75 mg/kg body-weight daily on
    days 21 through 34 of gestation. One abortion occurred at the 75 mg/kg
    level but there were no malformations. (Thalidomide was given as a
    positive control an in the previous experiment (Vondruska, 1969).

    Rabbit

    Four pregnant New Zealand White rabbits were given daily oral doses of
    80 mg/kg bodyweight of captan during days 7 through 12 of gestation.
    Captan produced no embryotoxicity in the litters of rabbits (Fabro at
    al., 1965).

    A group of six pregnant Dutch Belted rabbits was given 75
    mg/kg/body-weight/day of technical captan, orally on days 6 through 16
    of gestation. Three other groups each containing five to seven New
    Zealand White rabbits were given 18.75, 37.5 or 75
    mg/kg/body-weight/day of technical captan orally on days 6 through 18
    of gestation. A control group and a positive control group (75 mg/kg
    thalidomide) wore also maintained. No malformed foetuses occurred in

    any group treated with captan. An increased incidence of foetal
    resorption occurred in the New Zealand White rabbits given 75 mg/kg of
    captan. Another group of nine pregnant Dutch Belted rabbits were given
    75 mg/kg/body-weight/day of technical tetrahydrophthalimide, a
    metabolite of captan, on days 6 through 16 of gestation. A slight rise
    in the occurrence of resorption sites occurred. No skeletal
    abnormality was observed (Kennedy, et al., 1968).

    Groups of 9 pregnant New Zealand white rabbits were given captan at
    dose-levels of 37.5, 75 or 150 mg/kg body-weight/day from days 6
    through 16 of gestation. Thalidomide was used as a positive control at
    levels of 75 and 150 mg/kg body-weight and produced the expected
    teratological response. Captan at 75 mg/kg caused 9 malformed young
    from 75 implantations of 9 pregnant does. At the dose level of 37.5
    mg/kg captan produced one malformed foetus from 49 implantation sites
    (McLaughlin at al., 1969).

    Rat

    Groups of five to ten pregnant female rats were given oral doses of 0,
    50, 100, or 250 mg/kg/body-weight day of technical captan from days 6
    through 15 of gestation or 0, 500, 1000 or 2000 mg/kg/body-weight/day
    from days 8 through 10. Examination of 371 foetuses obtained from the
    captan-treated rats revealed no significant increase in the number of
    abnormalities. Three and two grossly malformed foetuses were found
    from the rats treated with 1000 and 2000 mg/kg/body-weight/day of
    captan respectively; compared with one in the corn oil control and
    none in the lower doses of captan (Kennedy, et al., 1968).

    Special studies on mutagenicity

    Mouse

    Single intraperitoneal injections of technical captan at doses of 0,
    3.5 and 7.0 mg/kg body-weight were administered to an unspecified
    number of male mice. Another group of male mice was given 100 mg/kg
    body-weight of methyl methanesulfonate as a positive control. The
    treated male groups were mated with three groups of untreated females
    on each of three consecutive weeks post-treatment. The results
    demonstrated that dominant lethal mutations were not induced by
    treatment with captan (Arnold, 1967).

    The mutagenic activity of captan was evaluated in bacteria, in the
    heteroploid human embryo lung call line, and in a cell line derived
    from the kidney of the rat-kangaroo. In bacteria, captan increased the
    mutation rate both in streptomycin-dependent E. coli and a
    thymine-dependent E. coli strain. Captan inhibited both growth and
    mitosis of heteroploid embryonic lung cells in concentrations of less
    than 5 g/ml. In the studies with the rat-kangaroo cell line the
    chromosome breaks and mitotic inhibition were proportional to the
    concentration of captan over the range of 1 to 10 g/ml (Legator, et
    al., 1969).

    Special studies on carcinogenicity

    Mouse

    Groups of 18 mice of each sex from two hybrid strains were given
    captan from 7 days of age for 18 months. The dose of 215 mg/kg
    body-weight was given to the mice daily by gavage from the seventh day
    of age to the time of weaning at four weeks of age; thereafter, the
    chemical was added to the diet in the corresponding amount of 560 ppm.
    There was no significant increase in tumours in the group fed captan
    compared with the controls (Innes, et al., 1969).

    Acute toxicity

                                                               
    Animal    Route    LD50 mg/kg      References
                       body-weight
                                                               

    Rat       oral     9,000            Elsea, 1957

    Rat       oral     12,500           Boyd and Krijnen, 1968

    Rat       oral     480 (low
                       protein diet)

    Mouse     i.p.     10               Arnold, 1967
                                                               


    Short-term studies

    Chicken

    An unspecified number of chicks were fed a diet containing 320 ppm of
    captan for 28 days. In another experiment a group of 30 chicks was fed
    the same dosage for 74 days along with a control group of 10 chicks.
    No gross abnormalities were found in the birds in either experiment
    (Ackerson and Mussehl, 1953; Link et al., 1956).

    Groups of 15 hens were fed diets containing 0, 100, 1000, or 10,000
    ppm of technical captan for 90 days. The hens receiving 100 and 1000
    ppm of captan displayed normal food consumption, egg production, and
    survival. In those receiving 10,000 ppm there was food-refusal, weight
    loss, and decreased egg production. There were no gross effects
    observed at autopsy in any cup. Analysis of the eggs and of the
    tissues of the hens revealed no stored captan (Weir, 1957).

    Dog

    Groups of four dogs, each comprising two male and two female animals,
    were started on a dose regime of 0, 10, 25 and 50 mg/kg body-weight of
    captan. At the beginning of week 10 the dose level of the dogs
    receiving 25 mg/kg was increased to 100 mg/kg. At week 18 these dose
    levels were again increased to 100 mg/kg and 300 mg/kg respectively.
    The captan was administered by gelatin capsule normally six days a
    week for 66 weeks. Liver and kidney weights were slightly increased in
    the dogs which received 300 mg/kg body-weight. There was no evidence
    of systemic toxicity and no gross or histopathological changes in
    tissues due to treatment at any dose-level, nor were there any
    significant changes in haematological or biochemical findings
    (Fogleman, 1955).

    Pig

    Eight half-grown pigs were fed for three months on corn treated with
    captan to provide a level of 540 ppm. The treatment did not affect the
    rate of food consumption, rate of growth or general health of the
    animals when compared to the effect on an equal number of control
    animals. There was no gross abnormality observed in any animal on the
    captan diet (Batter 1953).

    Four groups, comprising 10 weanling pigs each of about 14 kg in
    weight, were fed rations containing 0, 420, 820, 1,680 ppm of captan
    for 119 days. No gross pathological effects that could be attributed
    to captan were observed (Meads and Warner, 1954).

    Three pigs were fed 500 ppm and two pigs were fed 4000 ppm of captan
    in the diet for 22-25 weeks. The animals displayed no abnormal
    symptoms, but no further observations were made (Johnson, 1954).

    Seven pigs were fed 480 ppm of captan in their diet for 14 weeks,
    three other animals served as controls. The test animals displayed
    normal weight gain. Gross examination of all organs revealed no
    pathological changes and histopathological study of the liver and
    kidneys revealed no abnormalities. Erythrocyte and lenkocyte counts
    were not significantly different between test and control groups. No
    residual captan (i.e. <0.1 ppm) was found in the tissues of the
    animals (Link at al., 1956).

    Rat

    Five groups, each containing 11 male and 11 female rats, were fed
    diets containing either technical or recrystallized captan at dose
    levels up to 0, 5000 or 10,000 ppm for 13 weeks. All experimental
    groups were started at a level of 500 ppm of captan and the dose
    levels were gradually increased until the 5000 ppm level was reached
    after four weeks and the 10,000 ppm level after seven weeks. Both dose
    levels caused growth retardation; however, there was no difference
    between comparable groups of rate receiving the technical and
    recrystallized material (Gray, 1954).

    Long-term studies

    Rat

    Groups, each containing 10 male and 10 female rats, were fed diets
    containing 0, 1000 and 5000 ppm of technical captan for two years.
    Another group of 20 rats received 10,000 ppm of technical captan for
    24 weeks. This group was then divided in half, one half being fed
    recrystallized captan for 30 weeks; the other half continued on the
    technical compound for 30 weeks. The female animals in the group
    receiving 1000 ppm of captan had a reduction in weight gain for the
    last 16 weeks of the experiment. Female rats receiving 5000 ppm of
    technical captan also displayed reduced weight gain, and both sexes on
    diets containing 10,000 ppm of either technical or recrystallized
    captan had marked growth depression. At autopsy, indication of
    testicular atrophy was found in some animals fed 10,000 ppm. Otherwise
    the organ-weight, blood picture, tumour frequency and histological
    studies were not significantly different from those in controls (Weir,
    1956).

    A group of 30 male and 30 female rats was fed dietary levels of 1000
    ppm of captan for 17 months. Body-weight gains, food consumption,
    survival rate and tumour incidence were comparable to a control group
    (Kay, 1961).

    COMMENT

    The acute short-term and long-term studies on captan provide adequate
    information to determine no-effect levels. Information of the fate of
    the trichloromethylthio moiety in the metabolism of captan is still
    incomplete. The observation that the acute toxicity of the compound to
    rats is many times higher when the animals are fed a low protein diet
    is of some concern. The special studies are extensive and cover a
    range of animal species. Possible teratogenic effects in rabbits and
    indications of embryotoxic effects in monkeys were observed, and
    therefore only a temporary acceptable daily intake was established.
    However, the biochemical requirements referred to in the previous
    monograph on captan (FAO/WHO, 1965) have now been partially fulfilled
    and therefore it was considered justified to establish a slightly
    higher acceptable daily intake.

    TOXICOLOGICAL EVALUATION

    Level causing no significant toxicological effect

    Dog: 100 mg/kg body-weight/day

    Monkey: 12.5 mg/kg body-weight/day

    Rat: 1000 ppm in the diet, equivalent to 50 mg/kg body-weight/day

    Estimate of temporary acceptable daily intake for man

    0-0.125 mg/kg body-weight

    RESIDUES IN FOOD AND THEIR EVALUATION

    USE PATTERN

    Pre-harvest treatments

    Captan is a non-systemic fungicide with no insecticidal or acaricidal
    activity. According to a survey (Kirby, 1969) of world-wide fungicide
    use on top fruit, captan was first choice for control of scab on
    apple, pear and peach, bitter rot and black rot on apple, sooty blotch
    and leaf spot on pear, brown rot on cherry, peach and plum, and leaf
    spot on sweet cherry. Other fruits on which its use is recommended
    include apricots and grapes, and it is only now being superseded for
    control of botrytis (gray mould) on strawberries. Captan is approved
    in the U.K. for the control of stem rot of tomato. It is also used on
    citrus and many vegetables.

    In the U.K. in 1967, captan was used on about 11,000 hectares of
    apples and 2,500 hectares of pears, with a small usage on plum, cherry
    and peach. Probably about 1000 hectares of apples received captan for
    control of storage rots, i.e. were sprayed in August-September. The
    rate of use is 0.1 percent a.i. high volume, or about 3 kg a.i. per
    ha. West Germany recommends 2 kg a.i. per ha for control of apple scab
    or vine downy mildew.

    Captan is of no value for control of rusts or powdery mildews.

    Post-harvest treatments

    Captan is used for rot control in stored potatoes and as a dip for
    fruit and vegetables. It is also used as a pre-packing spray for
    packing boxes. Prunes dipped in suspensions of the 50 percent w.p. at
    0.12, 0.24 and 0.48 percent a.i. bore 3.6, 4.8 and 11 ppm and 2.3, 6.1
    and 11.1 ppm captan before and after dehydration, respectively (Archer
    and Corbin, 1969).

    Other uses

    Captan is used as a seed dressing, particularly on peas. It has been
    proposed for ringworm control on animals; milk obtained 24 hours after
    a cow had been sprayed contained less captan than could be detected
    (<1 ppm) (Hansen, 1953). Captan is also used on turf and ornamentals,
    especially roses, and as a soil fungicide.

    RESIDUES RESULTING FROM SUPERVISED TRIALS

                                                                  
                          Interval      Rate            Residue
    Crop                  days          % a.i.            ppm
                                                                  

    Apple                    1          0.12            4 to 36

                            42          0.12            0.3 to 0.5

                            94          0.12            0.2

    Apricot (fresh)          0          0.12            16 to 17.5

                             7          0.12            11

                            21          0.12            6 to 9

                            42          0.12            4 to 5

    Apricot (dried)          7          0.12            8

                            40          0.12            <1

    Cherry                   0          0.24            10 to 53

                             7          0.24            6

                            14          0.24            4

                             0          0.12            4 to 22

                             7          0.12            3

                            14          0.12            1

    Citrus                   1          0.12            9 to 13

    Fig                      0          0.12            1.7

                             2          0.12            0.2

    Peach                    0          0.12            2 to 6

                             5          0.12            3

                            14          0.12            8

                             0          0.24            3 to 7

                             3          0.24            8 to 11

    (cont'd)
                                                                  
                          Interval      Rate            Residue
    Crop                  days          % a.i.            ppm
                                                                  
    Peach                   14          0.24            1 to 12

    Pear                     1          0.12            1 to 28

                             9          0.12            8 to 12

    Plum             (Post-harvest)     1.2 to 4.8      4 to 11 (green)

                            do.         do.             3 to 11 (dehydrated)

    Sweet potato             0          0.24            2

                             0          0.48            25

    Hops                   119          0.24            0.1 to 1.5

    Rhubarb                  0          0.12            6 to 14

    Grape                    1          0.12            12 to 34

                            57          0.12            4

                             1          4.6 kg per ha   0.1 to 0.4

                            90          4.6 kg per ha   0.1 to 0.5

    Strawberry               0          5.75 kg per ha  6.5

                             2          do.             3 to 7

                             5          do.             3 to 5

                             8          do.             1 to 5

    Blueberry                0          0.24            0.8 to 1.6

    Cranberry                0          4.6 kg per ha   4 to 7

                            83          do.             1.5 to 2.5

    Raspberry                7          2.9 kg per ha   0.7

                            12          do.             11

    Raisin (before wash)     0          1.15 kg per ha  27 to 35

           (after wash)      0          do.             1 to 2

    (cont'd)
                                                                  
                          Interval      Rate            Residue
    Crop                  days          % a.i.            ppm
                                                                  


    Cucumber                 1          0.12            5.6 to 6.3

                             7          0.12            0.3 to 2.5

    Lettuce                  0          0.18            0.2 to 6

                             5          0.18            1

                            10          0.18            0.7 to 5

    Green beans              0          0.24            2 to 7

    Pepper                   1          0.12            6 to 8

                             7          0.12            1 to 9

    Spinach                  3          0.12            75

                            10          0.12            15

    Tomato                   0          0.24            6 to 12

                             3          0.24            10

                            20          0.24            <1
                                                                  


    Further information on residues is available from the literature. One
    late-season application of captan at 0.1 percent to apples and pears
    gave deposits of about 1 ppm, falling to undetectable levels at
    harvest (Martin and Pickard, 1955). Strawberries sprayed five times,
    from early bloom to one day before picking, with 1.5 kg per ha captan
    on each occasion bore 6.0 ppm captan; fruit picked three days later
    bore 4.7 ppm and fruit picked eight days after the final spray bore
    2.9 ppm; fruit from plots sprayed with 2.2 kg per ha in another year
    bore similar but smaller residues (Fahey et al. 1962). Strawberries
    sprayed twice in early bloom with captan at 0.4 percent a.i. (9.2 kg
    a.i. per ha) had 6 ppm on the first fruits to ripen and less than 2
    ppm on fruits picked eight days later (Sillibourne 1966). In Finland,
    0.15% a.i. sprayed on to lettuce led to 57 ppm after three days:
    washing reduced this to 2 ppm (State Inst. Agric. Chem., Helsinki,
    1969).

    FATE OF RESIDUES

    Captan does not appear to undergo any chemical change on plant
    surfaces, and only a very small amount appears to enter plant tissues.
    Potatoes dipped in a captan slurry had 29 ppm on the skin and only 0.3
    ppm in the pulp seven days later; no residue could be detected in the
    pulp after baking or boiling (Chevron Chemical Company, Pesticide
    Petition No. 15, 1955, direct communication).

    Residues of up to 8 ppm on Valencia oranges were reduced by the normal
    commercial washing procedure to 0.2 ppm. When 10 ppm captan was added
    to washed oranges before processing to pulp, no captan could be
    detected in the pulp or molasses (Chevron, 1959).

    METHODS OF RESIDUE ANALYSIS

    The method of Kittleson (1952) for the calorimetric determination of
    captan residues forms the basis of the recommended procedure
    (Association of Official Agricultural Chemists, 1965) which is
    suitable for regulatory purposes at the present time. The cleaned-up
    extract of fruit or green vegetables is heated with resorcinol and the
    optical density of the resultant solution in acetic acid is measured
    at 425 nm. Ospenson et al. (1964) have reviewed the uses of this
    procedure, which is inaccurate below about 0.5 ppm of captan, and a
    similar but less sensitive method using pyridine as the colour-forming
    reagent.

    More recently, interest has been shown in chromatographic methods for
    captan. Kilgore et al. (1967) proposed a gas chromatographic method
    for the examination of apricots, peaches, tomatoes and cottonseed.
    Using a silicone column with electron-capture detection, the detection
    limit was about 0.01 ppm with recoveries averaging 92 percent; under
    similar chromatographic conditions captan was clearly separated from
    difolatan (Kilgore and White, 1967). Several stationary phases were
    studied by Bevenue and Ogata 1968) who found the cyanosilicone GE
    XE-60 most suitable for captan residue analysis since it gave the best
    separation from folpet. These three allied compounds, captan, folpet
    and difolatan, were examined by Pomerantz and Ross (1968) who devised
    gas and thin-layer chromatographic systems for the separation,
    identification and determination of the parent compounds and some of
    their possible degradation products. Archer and Corbin (1969) have
    suggested a thin-layer chromatographic procedure for detecting captan
    residues in prune fruits and blossoms. These chromatographic methods
    should form the basis of a suitable regulatory procedure for the
    determination of residues of captan in fruit, and it is recommended
    that such a method should be established.

    NATIONAL TOLERANCES
                                                                               
        Country                     Crop                  Tolerance (ppm)
                                                                           

    Benelux                Tree fruits, vegetables              15

    Canada                 Tree fruits, vegetables, nuts,       40
                           small fruits, root crops,
                           melons, leafy vegetables

    Germany (Fed. Rep.)    Fruits                               15

    United States of       Beetgreens, cherry, lettuce,        100
    America                spinach

                           Stone fruits, grapes, mangoes        50
                           celery, leeks, onions (green),
                           shallots
                           Apple, pear, avocado, small          25
                           fruits, cucurbits, onions
                           (dry), tomato, garlic, egg
                           plant
                           Beet (roots), cottonseed, 12          2
                           vegetables
                           Beans (dry and succulent),           25 (interim)
                           citrus pineapple potato
                           Almond (kernels)                      2 (interim)
                           Almond (hulls)                      100 (interim)
                                                                           
    
    APPRAISAL

    Captan is a non-systemic fungicide that has attained very wide use on
    fruit, vegetables, ornamentals, turf and seeds; it is probably
    recommended for more diseases on deciduous top fruit than any other
    fungicide. It provides no control of powdery mildews and little of
    rusts. The technical product is stated to contain 95 percent captan,
    the main impurities being water, common salt, and unreacted
    tetrahydrophthalimide.

    Solubility in water is very low and residues remain as superficial
    deposits; these are partly removed by washing with water, especially
    from non-waxy crops such as strawberry. Dry captan is stable to heat
    and U.V. radiation, but aqueous suspensions are quickly decomposed at
    100 C or in alkaline media. Hydrogen sulphide is evolved and all
    other breakdown products remain in solution. The instability of the
    -N-S-bond leads to release of tetrahydrophthalimide and deamination
    products. Cooking and other processing methods lead to rapid
    decomposition of captan residues. Persistence on crop surfaces is
    relatively long.

    RECOMMENDATIONS FOR TOLERANCES, TEMPORARY TOLERANCES OR PRACTICAL 
    RESIDUE LIMITS

    TEMPORARY TOLERANCES (effective to June 1973)

                                                     
    Apples and cherries                     40 ppm

    Pears                                   30 ppm

    Apricots                                20 ppm

    Citrus, peaches, plums, rhubarb,
    tomatoes                                15 ppm

    Strawberries, cranberries,
    raspberries, cucumbers,
    lettuce, green beans, peppers           10 ppm

    Raisins (dried vine fruits)             5 ppm
                                                     

    Insufficient data were available to enable tolerances to be suggested
    for blueberries, figs, hops, sweet potatoes or spinach.

    FURTHER WORK OR INFORMATION

    REQUIRED (before 30 June 1973)

    1. Further teratogenicity studies in non-human primates.

    2. Further studies on metabolism especially on the
       trichloromethylthiomoiety.

    3. Residue data for other crops, including blueberries, figs, hops,
       sweet potatoes and spinach.

    4. Residue data from countries other than the U.S.A.

    DESIRABLE

    1. The effects of feeding a low protein diet on the chronic toxicity
       of captan.

    2. The development and evaluation of a GLC method, distinguishing
       captan from captafol and folpet, suitable for regulatory purposes.

    REFERENCES

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    in rations for chicks. Unpub. rept. Departments of Biochemistry.
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    Archer, T.E. and Corbin, J.B. (1969) Detection of captan residues in
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    Contam. Toxicol. 4:55-63

    Arnold, D. (1967) Mutagenic study on captan. Swiss white mice. Unpub.
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    Association of Official Agricultural Chemists. (1965) Official methods
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    Batte, E.G. (1953) A study of the effect of feeding Orthocide(R)
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    Bevenue, A. and Ogata, J.N. (1968) The examination of mixtures of
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    Boyd, E.M. and Krijnen, C.J, (1968) Toxicity of captan and
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    Chevron. (1959) Captan residues an processed citrus by-products.
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    Courtney, K.D. (1968) Teratological investigation of captan, imidan
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    Crossley, J. (1967) The stability of captan in blood. Unpub. rept.
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    Dye, D.F. (1969) Difolatan(R). Unpub. summary report prepared and
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    See Also:
       Toxicological Abbreviations
       Captan (HSG 50, 1990)
       Captan (ICSC)
       Captan (PIM 098)
       Captan (WHO Pesticide Residues Series 3)
       Captan (WHO Pesticide Residues Series 4)
       Captan (Pesticide residues in food: 1977 evaluations)
       Captan (Pesticide residues in food: 1978 evaluations)
       Captan (Pesticide residues in food: 1980 evaluations)
       Captan (Pesticide residues in food: 1982 evaluations)
       Captan (Pesticide residues in food: 1984 evaluations)
       Captan (Pesticide residues in food: 1984 evaluations)
       Captan (Pesticide residues in food: 1990 evaluations Toxicology)
       Captan (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
       Captan (IARC Summary & Evaluation, Volume 30, 1983)