CAPTAFOL JMPR 1976 Explanation This fungicide was evaluated by the Joint Meetings in 1969, 1973 and 1974 (FAO/WHO 1970b, 1974b and 1975b). The 1973 Joint Meeting considered the following information desirable. 1. Studies to investigate the metabolism of the tetrachloroethylthio-moiety of captafol. 2. Data on effects of washing, peeling, and blanching on residue levels in various crops. 3. Data on residue levels in commodities moving in commerce. 4. Additional data and information on agricultural practices in user countries with respect to asparagus, beans, cabbage, celery, citrus fruit, coffee, grapes, lettuce, pineapple, strawberries and tea. No new data were obtained on question 1 and only limited data on questions 2 and 3. Information was received on both uses and residues resulting therefrom on pineapple but not on any other crops mentioned in question 4. However some information was provided on extensions of the use pattern in some countries on pea nuts, potatoes, tomatoes and wheat, and on the resulting residues. A further evaluation of captafol for acceptable daily intake is planned for 1978, for the reasons given in the Report of the present Meeting (FAO/WHO, 1977a). RESIDUES IN FOOD AND THEIR EVALUATION USE PATTERN Information on recently introduced uses of captafol is given in Table 1. RESIDUES RESULTING FROM SUPERVISED TRIALS Residue data became available from supervised trials on pineapple and on some crops not included in the 1973 monograph, namely peanuts, potatoes, tomatoes and wheat. A summary of the data is provided in Tables 2-4. TABLE 1. Use pattern. Information not included in the monographs of the 1969, 1973 and 1974 Joint Meetings Application Recommended pre-harvest Target No. of Mode of interval In use Crop Country organism treatments kg a.i./ha treatment (days) since peanuts U.S.A. 5-10 1.5 spraying 14 1973 pineapple South heart rot 4 times 8 spraying (200 21 1973/ Africa monthly g a.i./100 l) 1974 potatoes South early & 7-11 max. 1.6 spraying at 7 3 1972 Africa late day intervals blight U.S.A. early & 1971 late blight tomatoes South early & 4-5 max. 4.8 spraying at 7 3 1972 Africa late day intervals blight (160 g a.i./ 100 1). wheat Netherlands mildew and 1 1 one or two sprayings 42 1975 ripening mixed with from development diseases other of the ear until the fungicides until the beginning of flowering Feekes scale 10.1 - 10.5.1. Peanuts (Chevron 1975) Thirteen experiments were carried out in 1973 and 1974: 4 in Florida, 3 in Texas, 2 in Georgia, 2 in Alabama, 1 in Oklahoma and 1 in North Carolina. In all the experiments the fungicide was applied at the recommended rate i.e. 1.5 kg a.i./ha. Multiple applications were made 6-10 times, using ground or air equipment. The peanuts were dug 9-27 days and combined 16-28 days after the last application. Residues were determined on whole pods, hulls, shelled nuts, oil, meal, peanut butter, roasted beans and vines at various stages of dryness. The maximum residues observed after application of 1.5 kg a.i./ha were: maximum residue commodity in mg/kg whole mature pods 0.46 hulls 1.3 shelled nuts <0.01 oil (hexane extracted or hydrolic pressed) <0.01 peanut meal <0.01 peanut butter <0.01 Details are given in Table 2. In the Table the residues of captafol in shelled nuts, peanut meal, peanut oil and peanut butter are omitted since the maximum residue values found were all at or about the limit of determination. FATE OF RESIDUES In animals A feeding study was carried out in which 6 mature lactating Holstein cows, all at a medium stage of lactation, received either 5.7 or 11.4 mg 14C-captafol orally for 30 days. These levels correspond to 0.5 and 1 ppm respectively in the total diet. The latter levels are considerably higher than those which would occur from the inclusion of peanut hulls or potatoes at normal proportions in the total diet. TABLE 2. Residues of captafol in peanuts in U.S.A. (Chevron, 1975) Interval after application 14-17 days Application Residue, mg/kg Residue, mg/kg moisture moisture Year rate formulation whole content whole content no kg a.i./ha pods hulls vines vines % pods hulls vines vines % 1973 10 1.5 wp 0.04-0.07a 0.57-0.64a 20-23a 75a 13-14a 14a 1973 10 3 wp <0.01-0.27 76-90 75 1973 10 1.5 wp 0.06-0.14 1.1 - 1.3 184-230 21.5 1973 9 1.5 wp 0.25-0.46 1.1 - 1.3 194-211 21.8 1973 9 3.0 wp 1.1 - 1.4 568-588 20.4 1973 7 1.5 wp <0.01-0.02 0.45-0.50 117-176 9.9 1973 7 3 wp <0.01-0.02 100-203 13.7 1973 11 1.5 wp <0.01 <0.01 24-30 16.6 1973 8 1.5 wp 0.02-0.11 0.48-0.97 82-97 1973 8 3.0 wp 0.04-0.08 32-33 1974 8 1.5 wp 0.09-0.15 1.3 - 1.4 75-102 14.5 1974 10 1.5 110-122b 78b 0.36-0.39b 39-52b 38b 1973 5 1.2 0.02-0.02 0.03-0.08 1973 5 2.4 0.02-0.03 0.13-0.16 1973 11 1.2 <0.01-0.01 0.49-0.88 101-109 1973 11 2.4 0.01-0.01 1.25-1.27 85.5-107 1974 7 1.5 0.18-0.23 1974 10 1.5 0.36-0.39 42-50 days 51-54 days 4 1.2 wp <0.01-0.02 0.06-0.11 4 2.4 wp <0.01 0.25-0.51 5 1.0 wp 0.03-0.04 0.17-0.24 36-82.9 5 2.0 wp 0.01-0.03 0.26-0.45 122-133 1973 10 1.5 wp 7.6-11.0a 12.2a 1974 10 1.15 wp 39-41b 13.5b a Results from a single trial b Results from a single trial TABLE 3. Residues of captafol in pineapple, potatoes and tomatoes Residues, mg/kg, at interval (days) Application after application rate formulation Crop Country no kg a.i./ha 0 1-3 7 13/14 27/28 89 Pineapple South 41 200g/100 l wp Africa whole fruit 15.7 22.8 1.6 5.1 2.5 rind 35.5 55.6 23.8 8.6 6.25 pulp <0.3 <0.3 <0.3 <0.3 <0.3 Potatoes South 11 1.6 kg/ha wp <0.05 Africa Tomatoes South 4 2.4 wp 4.7 4.1, 2.4 2.5 Africa 2.9 1 monthly TABLE 4. Residues of captofol in wheat Residues, mg/kg, at interval (days) after Application application, average (range) Wheat no rate formulation fraction Country Year kg a.i./ha 38 42/43 48 66 Ref. grain Netherlands 1974 1 0.75 wpa (<0.05-<0.05) ICI 1974 1 1.00 wpa (<0.05-<0.05) 1975 grain 1975 1 1.0 wpa 0.03 ICI (0.01-0.09) 1975 straw 3.6 (1.5-4.8) grain 1975 1 1.0 wpa 0.1 ICI (0.07-0.14) 1975 straw 1.8 (0.7-2.9) grain 1975 1 1.0 wpa <0.01 ICI straw <0.01 1975 grain 1975 1 1.0 wpa <0.01 ICI straw 1.3 1975 grain 1975 1 1.0 wpb <0.01 ICT straw <0.1 1975 grain 1975 1 1.0 wpb 0.05 CIBA- straw 1.0 wpb 0.22 Geigy (0.16-0.31) 1975 grain 1975 1 1.0 wpb 0.05 Ciba- Geigy straw 0.74 1975 (0.51-0.87 a mixture with ethirimol b mixture with CGA 30599 For peanut hulls, the maximum used in the diet is 20%, in most instances only 10% in a maize/soybean base diet. For peanut meal the maximum amount in the diet could be about 25%, with the normally used maximum being 10%. The maximum residue level found in peanut hulls, after 6-11 spray applications at the recommended rate of 1.5 kg a.i./ha was 1.3 mg/kg, thus leading to a maximum of 0.26 mg/kg in the diet. The peanut meal, with maximum levels of 0.03 mg/kg will not contribute significant captafol residues. The feeding levels chosen are 5-10 times higher than the amounts in the total diet derived from potatoes, when these constitute no more than 20% of the total diet and residues are approximating the proposed maximum residue limit of 0.5 mg/kg. 20% potatoes is the maximum ratio recommended, normally the proportion is lower. An excellent recovery of captafol was obtained in this study, the range being 84-101%. By far the major route of excretion was the urine, with faeces accounting for a lesser but significant quantity. In the same feeding study Bio-Test Laboratories (1970) showed that captafol was rapidly excreted from cows receiving daily oral doses of 14C captafol. The major excretion route was the urine, the remainder (about 10%) being excreted in the faeces. No captafol was found in either the milk or tissues at any time. The total concentration of captafol and its main metabolites containing 14C in whole milk at any time was also insignificant (< 0.01 mg/kg). Radioactivity was monitored in samples of milk, tissue, urine and faeces. The average counting efficiency was 70% in the milk samples, 58% in blood and 54% in tissue. The limit of detection of radioactivity in this study was set at 20% above background. From the data the following limits of detection of captafol and its 14C- metabolites may be calculated. milk 0.0004 mg/kg Captafol + 14C-containing metabolites calculated as captafol fat 0.004 mg/kg " " blood 0.002 mg/kg " " other tissues 0.002 mg/kg " " (Chevron 1970) Milk At the lower feeding rate of 5.7 mg 14C-captafol the levels of 14C calculated as captafol equivalents found in the daily pooled milk varied between 0.001 and 0.003 mg/kg. Two days after the last dosing no residues could be detected in the milk. At the feeding rate of 11.4 mg captafol the corresponding levels ranged from 0.002 to 0.006 mg/kg. The levels of 14C in the milk of treated cows followed a rapid equilibration and elimination pattern. Within 24 hours of the first dose the radioactivity in the milk reached a level which was not exceeded during the entire 30 days dosing period. Once the administration of captafol was stopped the 14C concentration in the milk dropped quickly; two days later no measurable amounts of 14C were found. (Chevron, 1970) Tissues 14C captafol residues (mg/kg total metabolites calculated as captafol) were measured in tissues obtained from cows, 24 hours and 8 days after the last dose of 14C captafol. In the former group the levels of radioactivity did not exceed 0.01 mg/kg of total metabolites except in liver and kidney. Since it was shown that over 90% of the administered dose was excreted in the urine it is not surprising that the concentration of 14C was somewhat higher in these organs (Table 5). Blood Only traces of radioactivity were found in the blood, the highest value being 0.005 mg/kg. In storage, processing and cooking Only limited data were obtained on the effect of household washing on captafol residues. In an experiment on leeks (ten Broeke and Dornseiffen 1973) it was shown that normal household washing removed 62-84% of the residue (Table 6). NATIONAL TOLERANCES REPORTED TO THE MEETING Since the 1969 and 1973 evaluations of captafol (WHO/FAO 1970b, 1974b) the national tolerances for several commodities have been amended and new tolerances for other commodities established. APPRAISAL This fungicide was evaluated by the Joint Meetings in 1969, 1973, and 1974 (FAO/WHO, 1970b, 1974b, 1975b). Only limited information was obtained on the questions listed as desirable in the 1973 evaluation. Of the crops on which captafol is authorised or recommended in various countries and on which further information was desired, additional data became available only on residues and use on pineapple. No information was obtained about uses on asparagus, beans, cabbage, celery, citrus fruit, coffee, grapes, lettuce, strawberries or tea and the maximum residue limits concurrent with these uses. TABLE 5. 14C residues in cow tissues Total metabolites calculated as captafol, mg/kg Feeding level 5.7 mg 14C captafol/day 11.4 mg 14C captafol/day Time Tissues Cow no. 1 2 3 4 5 6 brain 0.001 0.003 0.006 0.003 heart 0.002 0.001 0.005 0.006 day muscle 0.002 0.004 0.006 0.008 30 fat 0.001 0.000 0.001 0.001 liver 0.005 0.005 0.010 0.019 kidney 0.007 0.006 0.014 0.021 brain 0.001 0.003 heart 0.001 0.002 day muscle 0.002 0.004 38 fat 0.000 0.001 liver 0.002 0.004 kidney 0.002 0.003 TABLE 6. Effect of washing on captafol residues in leeks (ten Broeke and Dornseiffen, 1973) Application Residues, mg/kg, at interval(days) after application, mean (range) Country rate formulation 7 14/14 20/21 Crop & year no kg a.i./ha unwashed washed unwashed washed unwashed washed Leek Netherlands 6 1.2 EC 384 g/l 1972 var.Olifant 4.7 1.8 3.2 0.4 1.7 0.3 (3.0-6.2) (1.0-2.4) (1.6-5.1) (n.d.-0.9) (1.1-3.4) (0.3-0.4) var.Iglo 2.6 0.5 1.4 0.2 1.5 0.2 (2.0-3.4) (0.2-0.9) (0.6-2.5) (0.2-0.3) (0.7-4.0) (0.1-0.6) TABLE 7. National tolerances reported to the Meeting Maximum residue limit Country Commodity mg/kg Australia apricots, nectarines, peaches 15 cherries (sour) 5 other fruit & vegetables 2 cucumbers, melons 2 cherries (sweet) 2 Belgium fruit & vegetables, except 3 potatoes Canada peaches 15 cherries (sour) 10 tomatoes 5 cherries (sweet), cucumbers, 2 melons Fed.Rep. of leaves of celeriac, leek, Germany lettuce 7-5 fruit of vegetables (incl. tomatoes, cucumbers, gherkins, eggplant) 5 fruit 5 other commodities of plant origin 0.2 Japan cabbage, radish (leaves & roots), sweet potatoes, tea 1 apples, japanese pear 5 Netherlands (1 tolerance under consideration; it may be expected that the revised tolerances will come into force in 1977) peaches 151 cherries (sour 101 other fruits 51 leek 8 fruits of vegetables, i.e. bell peppers, eggplant, cucumbers, melons, tomatoes 51 other vegetables 3 raw grain 0.2 other food commodities 0.05* South Africa pineapple 10 potatoes, tomatoes 5 TABLE 7. (Cont'd.) Maximum residue limit Country Commodity mg/kg U.S.A. cherries (sour) 50 apricots, peaches 30 tomatoes 15 cranberries 8 melons 5 cherries (sweet), cucumbers, nectarines, peanut hulls, plums 2 citrus fruits, potatoes 0.5 apples 0.25 corn (incl.sweet corn) kernels & cob, husk removed, macadamia nuts, onions, pineapple 0.1** peanuts (meals with hulls removed 0.05** taro corn 0.02** * at or about the limit of determination. ** negligible residues. The information obtained on residues on pineapple includes a use which was not evaluated at former Meetings. For this crop an amendment of the earlier established maximum residue limit is recommended. Since no additional information was obtained on other use patterns covered in earlier monographs, except some data on residues on tomatoes, the limits previously recommended are retained. Some information was provided on extensions of the use pattern in some countries and on residues occurring in crops at harvest as a consequence of these applications. These new data allow additional maximum residue limits to be recommended for peanuts and wheat. Limited information was obtained on the effect of washing, cooking and processing. In a supervised trial on leeks it was shown that 62-84% of the residue remaining on the crop as marketed was removed by normal household washing. RECOMMENDATIONS The following temporary maximum residue limits are recommended in addition to or amending those previously recommended. Pre-harvest intervals Limits on which recommendations Commodity mg/kg are based(days) Pineapple(whole fruit) 10 21 Peanut hulls 2 14 Peanuts 0.5 14 Wheat 0.2 42 Peanut kernels 0.05 14 FURTHER WORK OR INFORMATION REQUIRED (by 1978) 1. Further studies to assist evaluation of histopathological changes in the kidneys and liver of rats. 2. Studies to investigate the lymphocyte-neutrophil shift noted in previous experiments. DESIRABLE 1. Further studies to investigate the metabolism of the tetrachloroethylthio moiety of captafol. 2. Considerably more information from countries where captafol is used to clearly indicate use patterns and resulting residues. 3. Further data on the effects of washing, peeling and blanching on residue levels in various crops. 4. Information, including information from studies now in progress, on new methods for the analysis of the parent compound together with the main metabolites in products of animal origin. 5. Results of on-going studies to show the level and nature of captafol residue in meat, milk, poultry and eggs. 6. Results of studies now in progress to show the fate of captafol residues in citrus and citrus pulp. REFERENCES Bio-Test Lab. Milk and meat residue studies in dairy cows. 1970 Report provided to Chevron no. IBT 78909. ten Broeke, R. & Dothseiffen, J.W. Residues of captafol 1973 on leek. Unpublished report no. 169 Food Inspection Service, Amsterdam (in Netherlands language). Chevron The fate of difoletan in lactating cows. 1970 Unpublished Report Chevron Chemical Company no. 72114. Chevron Difoletan residues in peanuts. Unpublished Report 1975 provided to Joint Meeting 1976. Ciba-Geigy Residues in winter wheat (grain and straw) after 1975 treatment with RTilt 60 w.p. ICI Residues in cereals, trials in Holland 1974. 1974 Unpublished report provided by the Netherlands to 1974 Joint Meeting 1976. ICI Residue summary ethirimol/captafol in cereals. 1975 Unpublished report no. BPA/YV/132/09.01.76 provided by the Netherlands to Joint Meeting 1976 Olthof, P.D.A., & Lagemaat, L. Residues of difoletan in leek. 1971 Unpublished Report no. 3886. Central Institute for Nutrition and Food Research, the Netherlands. de Vos, R.N., & Pot, W. Residues of difoletan in pears. Unpublished 1971 Report no. 3340. Central Institute for Nutrition and Food Research, the Netherlands.
See Also: Toxicological Abbreviations Captafol (HSG 49, 1990) Captafol (ICSC) Captafol (PIM 097) Captafol (FAO/PL:1969/M/17/1) Captafol (WHO Pesticide Residues Series 3) Captafol (WHO Pesticide Residues Series 4) Captafol (Pesticide residues in food: 1977 evaluations) Captafol (IARC Summary & Evaluation, Volume 53, 1991)