DICHLOFLUANID JMPR 1977 Explanation The Joint Meeting evaluated dichlofluanid in 1969 and 1974 (FAO/WHO, 1970, 1975). A temporary ADI was established in 1974, when further information was required on the absorption, distribution and excretion of dichlofluanid and on the pharmacokinetics of the dichlorofluoromethylthio moiety. Further information was recorded as desirable on the fate of the fluorine-containing moiety of the molecule in and on plants, on residues resulting from supervised trials on various specified crops, on residues in raw agricultural products moving in commerce and on the suitability of Becker's analytical method for regulatory purposes. Some of the required information has been provided, and is reviewed below. EVALUATION FOR ACCEPTABLE DAILY INTAKE Absorption, distribution, biotransformation and excretion Groups of rats received a single oral dose of 14C-dichlofluanid (0.1, 5 or 20 mg/kg b.w.) in order to establish the excretion rate and distribution over various organs. The 14C-label was incorporated in the dichlofluoromethylthio moiety and thus, activities reflect the sum of the unchanged compound and some of its metabolites. 40-60% of the dose was eliminated in urine and 20-30% in faeces, while 22% was exhaled within the first 48 hr. In 24 hr the elimination through bile following an intraduodenal injection (0.5 mg/kg b.w.) was 7% of the initial activity. From these data it was calculated that 70-80% of orally administered dichlofluanid was absorbed. The distribution over various organs was measured during the 10 days following oral administration of 5 mg dichlofluanid/kg b.w. In a period from 2 hr to 2 days after injection, about a ten-fold decrease in the amount of labelled substances in the whole body was observed. After 10 days a residue of 1% was measured. Similar decreases were found in pancreas, spleen, lungs, brain, testes, muscle, skin, perirenal fat, erythrocytes and plasma, while liver, kidneys and adrenals showed somewhat higher residues. A dissimilar pattern was found in the thyroid. The maximal concentration was reached after 1 day (compare e.g., plasma, 1.5 hr) and at each time of measurement a relative concentration about 50 times that in the whole body was observed (Weber et al., 1977). COMMENTS Adequate information on absorption, distribution, excretion and pharmacokinetics of the dichlorofluoromethylthic moiety has been provided. Within 2 days about a ten-fold decrease in the amount of labelled dichlofluanid was observed in most of the organs. After 10 days a residue of 1% of the dose was present. The consequence of relatively high residues of this organic fluorine compound in the thyroid was of some concern and should be further investigated. TOXICOLOGICAL EVALUATION Level causing no toxicological effect Rat: 1500 mg/kg in the diet, equivalent to 75 mg/kg bw Dog: 1000 mg/kg in the diet, equivalent to 25 mg/kg bw ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR HUMANS 0-0.3 mg/kg bw RESIDUES IN FOOD AND THEIR EVALUATION RESIDUES RESULTING FROM SUPERVISED TRIALS Some of the trials data requested in 1974, together with data on some other crops, were supplied (Table 1). Residues were below the following levels (mg/kg): 15 in blackberries, 7 in gooseberries and onion leaves, 2 in paprika, 1 in dried hops, 0.5 in wheat straw and 0.1 in wheat grain and onions (bulbs). In addition, residues resulting from supervised trials on eggplants and gherkins were at or below 1 mg/kg and on potatoes below 0.1 mg/kg. New residue data for currants, beans with pod, strawberries (under glass), cucumber, lettuce (under glass) and tomatoes were below the limits recommended by the 1974 Joint Meeting. No information was provided on residue levels in loganberries, mulberries, raspberries, leaf brassicas, melons, kohlrabi or barley. FATE OF RESIDUES In soil Different types of soil were field-treated with 15 kg dichlofluanid/ha; 2-3 months after application, residues of dichlofluanid + dimethylphenylsulphamide (DMSA) in the upper layers (0-10 cm depth) were below 0.1 mg/kg. Columns containing 30 cm layers of sand or sandy loam were treated with dichlofluanid at a rate corresponding to 2.5 kg/ha and leached to simulate a rainfall of 200 mm. Less than 1% of the applied dose (as dichlofluanid + DMSA) was found in the leachate (Bayer, 1975/77). In Japan, volcanic ash, diluvial and alluvial soils treated 1-3 times each with 2 mg dichlofluanid/kg soil, contained < 0.03-0.4 mg/kg 7-11 days after the last application; 27 days after the last of 4-5 applications, residues were < 0.03-1.4 mg/kg (Takase and Terada, 1976). In processing Field-treated strawberries with original levels of 8.6 and 5.1 mg dichlofluanid + DMSA/kg contained 1.9 and 1.5 mg/kg respectively after washing. After canning, residues declined to 1.3 and 1.0 mg/kg. 08 mg/kg was found in jam made from the strawberries (Wrieden, 1976). RESIDUES IN FOOD MOVING IN COMMERCE In 1976 a total of 449 samples of 19 fruits and vegetables (especially strawberries, currants and blackberries) moving in commerce were analysed for dichlofluanid (including DMSA calculated as the parent compound) in the Netherlands (Food Inspection Services, 1976). Only 15 of the samples, all of strawberries, currants or raspberries, had residues above 2mg/kg of which three samples of strawberries contained residues higher than 5 mg/kg (5.4, 14.5 and 20 mg/kg). In 189 samples, the residues were at or below 0.1 mg/kg. Residue levels (except in two samples of strawberries) were well below the limits recommended by the Joint Meeting. METHODS OF RESIDUE ANALYSIS A gas-chromatographic method has been developed which determines dichlofluanid + DMSA (Vogeler, 1975/77). After extraction with water/acetone and dichloromethane, dichlofluanid is saponified and the total DMSA determined by a flame photometric detector in the sulphur mode. The lower limit of determination is at or about 0.1 mg/kg expressed as dichlofluanid. The method is less suitable for regulatory purposes than the multi-residue method of Becker. The Becker method was studied collaboratively by 4 laboratories (Thier, 1977). 16 species of fruit and vegetables were spiked within a range of 0.01-15 mg dichlofluanid/kg and analysed. Recoveries were between 71 and 106% with an average of about 90%. The method of Becker is suitable for regulatory purposes. APPRAISAL Residue data requested by the 1974 Joint Meeting confirmed that the temporary maximum residue limits recommended then for beans, cucumbers, currants, lettuce, strawberries and tomatoes were appropriate. They also provided a basis for the new temporary limits recommended below. Dichlofluanid was shown not to be readily leached from soil. Residues in soil after field application were below 0.5 mg/kg after one month and below 0.1 mg/kg after 2-3 months. Residues in strawberries were reduced to about 20-30% of the original level by washing, 15-20% by canning and 10-15% by jam making. TABLE Residues of dichlofluanid + dimethylphenylsulphamide (DMSA) expressed as dichlofluanid on different crops from supervised trials Crop Country1/ Dose kg No. of Days after Residue (mg/kg) References a.i./ha applications last appl. blackberries D 2.0 5 0 11.6 - 47.0 Bayer, 1975/77 4 8.4 - 22.5 7 7.0 - 7.2 14 3.1 - 5.2 21/22 1.0 - 3.2 beans, green, D 1.3 5 0 1.6 -2.6 Bayer, 1975/77 with pods 4-7 0.4 -0.8 14-28 0.1 -0.3 cucumber D 1 8 0-10 <0.1 -0.1 Bayer, 1975/77 J 1.5-2 10 1-7 <0.1 2/ Nitokuno, 1971/74 cucumber, D 0.6-2 10 0-1 0.5 - 3.2 under glass 3-10 0.3 - 1.8 currants D 2.0 3 0 11.1 - 18.7 Bayer, 1975/77 (black) 4 7.0 - 8.9 7 3.6 - 3.9 14 2.7 - 2.8 21 0.6 - 0.9 eggplant J 4 1-2 0-1 <0.1 - 1.0 2/ Nitokuno, 1971/74 3-7 0.1 - 0.5 2/ gooseberries D 2.0 4 0 5.2 - 7.9 Bayers 1975/77 4 4.1 - 6.7 7 2.7 - 6.1 14-21 0.7 - 2.2 TABLE (Continued) Crop Country1/ Dose kg No. of Days after Residue (mg/kg) References a.i./ha applications last appl. gherkins, D 1.2 10 0-1 0.5 - 0.8 Bayer, 1975/77 under glass 3-10 0.3 - 0.6 hops J 5.0-5.8 3 21 0.42 Nitokuno, 1971/74 26 0.041 lettuce J 2 4-9 2-10 <0.1-0.1 2/ Nitokuno, 1971/74 lettuce, D 0.6 6 0 31 under glass 14-28 0.1-2.4 Bayer, 1975/77 onions, D 1.0 6 0 12.3 - 19.0 Bayer, 1975/77 leaves 4 3.7 - 7.9 7 3.0 - 6.9 14 1.8 - 3.4 21-28 0.3 - 2.1 bulbs D 0-28 <0.1 bulbs J 0.8-1.3 7-14 7-20 <0.1 Nitokuno, 1971/74 peppers, D 1 6 0-1 1.3 - 3.5 Bayer, 1975/77 sweet 3-14 <0.1 - 0.8 potatoes D 0.6 6 7 <0.1 Bayer, 1975/77 strawberries, J 2.5-3 2-4 1-10 0.3 - 4.6 2/ Nitokuno, 1971/74 under glass tomatoes D 1.2 6 0-7 0.3 - 1.0 Bayers 1975/77 J 1.5-4 1-10 0-7 <0.1 - 0.3 2/ Nitokuno, 1971/74 TABLE (Continued) Crop Country1/ Dose kg No. of Days after Residue (mg/kg) References a.i./ha applications last appl. tomatoes, D 1.2 6 0-7 0.1 - 0.5 Bayer, 1975/77 under glass wheat grain D 1 1 42 <0.1 - 0.1 Bayer, 1975/77 wheat 0 14.1 - 23.4 ears/straw 14 1.5 - 2.9 28-35 0.1 - 0.3 1/ D = Federal Republic of Germany J = Japan 2/ analysed for dichlofluanid only The gas-chromatographic multi-residue analytical method of Becker has been validated for regulatory purposes by collaborative study. A method for determining both dichlofluanid and dimethylphenylsulphamide (DMSA) by gas chromatography has been developed, but is less suitable for regulatory analysis. RECOMMENDATIONS The following temporary maximum residue limits are recommended in addition to those proposed in 1974. They refer to dichlofluanid only. Commodity Limit, mg/kg Pre-harvest interval (days) on which recommendation is based Blackberries 15 3-7 Gooseberries 7 0-7 Sweet peppers 2 1-3 Eggplants, hops (dried) 1 0-1 Wheat straw 0.5 28 Onions, bulb 0.1 0-28 Potatoes 0.1 0-21 Raw grain (barley, oats, rye, wheat) 0.1 42 FURTHER WORK OR INFORMATION REQUIRED (by July 1979) 1. Studies to elucidate the accumulation seen in the thyroid. 2. Results from current studies on the pathways of degradation, especially the fate of the fluorine-containing moiety of the molecule in or on plants. DESIRABLE 1. Further residue data on dichlofluanid residues (parent compound) resulting from supervised trials especially on melons and leaf brassicas. REFERENCES Bayer, A.G. 1975/77 Pflanzenschutzmittel-Rückstände, Dichlofluanid (Euparen); Leverkusen, Federal Republic of Germany (unpublished). Food Inspection Services; 1976 Information from the Netherlands on pesticides included in the priority lists. Dichlofluanid. Ref: CL 1977/15; Oct. 20, 1977. Nitokuno Institute; 1971/74 Analytical Test Results on Residues, Dichlofluanid (Euparen), Nihon Tokushu Noyaku Seizo K.K., Japan Takase, I. and Terada, H. 1976 Residues of Euparen and Morestan in Upland Soils after Multiple Treatment. Nihon Tokushu Noyaku Seizo K.K., Agric. Chemicals Inst., Japan; Report No. 1043; 30 March 1976. Thier, H.-P. 1977 Arbeitsgruppe zur Rückstandsanalytik der Pestizide in Lebensmitteln. Unpublished Vogeler, K. 1975-7 in Bayer A.G., 1975-77, reference above Weber, H., Patschke, K., Wegner, L.A. Dichlofluanid - 14C (EuparenR-Wirkstoff); Biokinetische Untersuchungen an Ratten. Bayer AG Bericht Nr. 7081. Submitted to the WHO (1977) (unpublished report) Wrieden, J. 1976 Untersuchungen von Fungizidrückständen (EUPAREN) in Erdbeeren nach deren Verarbeitung zu Marmelade und Obstkonserven. Diplomarbeit, Inst. f. spezielle Lebensmitteltechnologie, Univ. Hohenheim; Fed. Rep. Germany. FAO/WHO, 1970 1969 evaluations of some pesticide residues in food. FAO/PL:1969/M/17/1; WHO/Food Add./70.38. FAO/WHO 1975 1974 evaluations of some pesticide residues in food. AGP: 1974/M/11; WHO Pesticide Residues Series, No. 4.
See Also: Toxicological Abbreviations Dichlofluanid (FAO/PL:1969/M/17/1) Dichlofluanid (WHO Pesticide Residues Series 4) Dichlofluanid (Pesticide residues in food: 1979 evaluations) Dichlofluanid (Pesticide residues in food: 1981 evaluations) Dichlofluanid (Pesticide residues in food: 1982 evaluations) Dichlofluanid (Pesticide residues in food: 1983 evaluations)