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 formulaOther 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 µg/ml or 1/µg/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 µg/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 µg/ml. A build-up of the metabolite tetrahydrophthalimide occurred in the blood which reached a maximum of about 25 µg/ml 30 hours after intragastric administration of captan. From then on it decreased to a level of 4.2 µg/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 µg/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 µg/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 Ackerson, G.W. and Mussehl, F.E. (1953) Toxicity of treated seed corn in rations for chicks. Unpub. rept. Departments of Biochemistry. Nutrition and Poultry Husbandry, University of Nebraska Archer, T.E. and Corbin, J.B. (1969) Detection of captan residues in prune fruits and blossoms by thin-layer chromatography. Bull. envir. Contam. Toxicol. 4:55-63 Arnold, D. (1967) Mutagenic study on captan. Swiss white mice. Unpub. rept. from Industrial Bio-test Laboratories submitted to California Chemical Company Association of Official Agricultural Chemists. (1965) Official methods of analysis of the Association of Official Agricultural Chemists. 10th ed. Washington D.C. 390:24.111 Batte, E.G. (1953) A study of the effect of feeding Orthocide(R) treated seed to hogs. Unpub. rept. submitted by Stauffer Chemical Company Bevenue, A. and Ogata, J.N. (1968) The examination of mixtures of captan and Phaltan by Chromatography. J. Chromatog. 36:529-31 Boyd, E.M. and Krijnen, C.J, (1968) Toxicity of captan and protein-deficient diet. J. clin, Pharmacol. 8:225-34 Chevron. (1959) Captan residues an processed citrus by-products. Chevron Report November 1959 Courtney, K.D. (1968) Teratological investigation of captan, imidan and thalidomide in Macaca mulatta. Unpub. rept. of the Bionetics Research Laboratories, submitted to Stauffer Chemical Company Crossley, J. (1967) The stability of captan in blood. Unpub. rept. prepared and submitted by Chevron Chemical Company Dye, D.F. (1969) Difolatan(R). Unpub. summary report prepared and submitted by Chevron Chemical Company Elsea, J.R. (1957) Captan technical 91%, pure DDT. Acute oral administration; acute potentiation. 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Unpub. rept. of Hazleton Laboratories submitted to Stauffer Chemical Company and to California Spray-Chemical Company Hansen, J. (1953) California Spray-Chemical Corporation (unpublished). Innes, J.R.M., Ulland, B.M., Valerio, M.G., Petrucelli, L., Fishbein, L., Hart, E.R., Pallota, A.J., Bates, R.R., Falk, H.L., Gart, J.J., Klein, M., Mitchell, I. and Peters, J. (1969) Bioassay of pesticides and industrial chemicals for tumorigenicity in mice: a preliminary note. J. Nat. Cancer Inst. 42: 1102-14 Johnson, D.F. (1954) A toxicity test of n-trichloromethylthiotetrahydrophthalimide. Southwestern Vet. 8: 55-57 Kay, J.H. and Calandra, J.C. (1961) Chronic oral toxicity of captan. Albino rate. Addendum report to Ortho Division, California Chemical Company prepared by Industrial Bio-test Laboratories Inc. Kennedy, G. (1966) Three generation reproduction study on captan - albino rats. Unpub. rept. of Industrial Bio-test Laboratories submitted to Chevron Chemical Company Kennedy, G., Fancher, O.E., and Calandra, J.C. (1968) An investigation of the teratogenic potential of captan, folpet, and Difolotan. Toxicol. appl. Pharmacol. 13:420-30 Kilgore, W.W. and White, E.R. (1967) Determination of difolatan residues in fruits by electron-capture gas chromatography. J. Agr. Fd Chem. 15: 1118-20 Kilgore, W.W., Winterlin, W. and White, R. (1967) Gas chromatographic determination of captan residues. J. Agr. Fd Chem. 151 1035-37 Kirby, A.H.M. Fungicides for deciduous top fruit: a survey in 1968. Wd Rev. Pest 1969 Control, 8: 45-58 Kittleson, A.R. (1952) Colorimetric determination of N-trichloromethylthiotetrahydro-phthalimide. Analyt. Chem. 24: 1173-75 Klayder, T.J. (1963) Captan in green vegetables. J. Assn Off, Anal. Chem. 46: 241-3 Leary, J.B. (1966) Difolatan: shay rat tests, Unpub. rept. of Chevron Chemical Company (cited by Crossley, 1967) Legator, M. 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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)