PROPINEB JMPR 1977 IDENTITY Chemical name zinc propylenebisdithiocarbamate Synonyms (R) Antracol Methylzineb Mezineb LH 30/Z Bay 46 131 Structural formula S S | | (-Zn-S-C-NH-CH2-CH-NH-C-S-)X | CH3 Empirical formula (C5H8N2Zn)X Other information on identity and properties Composition Satisfactory information was available to the Meeting Appearance White to yellowish powdery practically odourless Molecular Weight 289.8 (for the theoretical monomeric compound) Melting point The technical product undergoes degradation, accompanied by brown discoloration, above about 160°C; at about 300°C, the organic components of the product sublime, leaving a very small inorganic remainder of ZnS. Solubility Practically insoluble in all usual solvents Stability Unstable in strongly alkaline and strongly acid conditions EVALUATION FOR ACCEPTABLE DAILY INTAKE Propineb, a propylene analogue of zineb, has moderate acute toxicity. It degrades to propylene thicurea (PTU). Orally administered propineb is readily excreted via urine and faeces. Propineb has a goitrogenic effect. Following oral administration, high tissue concentration in, and enlargement of the thyroid and pituitary glande occurred. These effects are reversible. A dominant lethal test in mice was negative. Reproduction studies in rats show no adverse effect at 20 and 60 ppm, but muscular damage (myasthenia) and reduced fertility occurred at 200 ppm. In a teratogenicity study, a teratogenic effect was produced only at a dose which was highly toxic and lethal to the dams. In a long-term study, a significent increase in the incidence of thyroid benign tumours and skeletal muscle degeneration was observed at dietary level of 1000 ppm and above. Significant thyroid enlargement occurred in the males at dietary levels of 100 ppm and above. In another two-year feeding experiment with rats at a level of 100 ppm, serum protein-bound iodine (PBI) was lowered. Two studies in dog were carried out (four months and two years). No adverse effects were seen at 3000 ppm. In a study with rats for two years, a dose-dependent reduction of growth and significant increase in liver and kidney weights were noted at 100 ppm and above. In a four-week study with hens, no effects were seen at 1000 ppm and a dose-dependent increase in thyroid weight occurred at 2000-8000 ppm. No neurotoxicity was observed. Because of the concern of the Meeting regarding the potential for thyrotoxicity and tumorigenicity of PTU (known to occur with ETU), the Meeting recommended a temporary ADI for humans. TOXICOLOGICAL EVALUATION Level causing no toxicological effect Rat: 10 mg/kg in the diet, equivalent to 0.5 mg/kg bw Dog: 3000 mg/kg In the diet, equivalent to 75 mg/kg bw ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR HUMANS 0-0.005 mg/kg bw RESIDUES IN FOOD AND THEIR EVALUATION USE PATTERN Propineb is a propylenebisclithiocarbamate fungicide notable for its rapidity of action and its long-lasting activity. It has a broad spectrum of activity and is especially used as a protective treatment for the control of numerous fungal disease pathogens belonging to the classes and groups of Oomyoetes, Ascomycetes, Basidiomycetes and Fungi imperfecti. Propineb is marketed in more than 70 countries and hence is used worldwide. TABLE 1. Application rates of propineb on various crops Application rate Recommended Number of pre-harvest Crop Formulation (in kg a.i./ha) applications interval (days) Bananas WP 1.4 - 2.1 6 - 14 7 Pome fruit (apples, pears) WP 1.4 - 2.8 8 - 12 7 - 10 Cherries WP 1.4 - 2.8 2 - 3 7 Plums, damsons WP 1.4 - 2.8 2 - 5 7 Peaches WP 1.4 - 2.8 2 - 3 7 - 10 Currants(fresh) WP 2.1 - 2.8 2 - 3 14 Gooseberries WP 2.1 - 2.8 2 - 3 14 Citrus fruit WP 2.1 - 4.2 3 - 6 14 Grapes WP 1.75 - 2.8 4 - 10 21 - 28 DP 1.4 6 - 8 21 - 28 Beans WP 1.0 - 2.1 3 - 5 7 Cucurbits WP 0.84 -1.4 2 - 4 4 - 7 Celery WP 0.84 -1.4 2 - 4 7 - 14 Tomatoes WP 0.84 -1.75 4 - 8 4 Onions WP 1.4 - 2.1 2 - 3 7 - 10 Potatoes WP 1.05 - 2.8 4 - 8 7 Cereals WP 1.4 - 2.1 1 - 3 28 - 35 Rice WP 1.4 - 2.1 1 - 3 21 Groundnuts WP 1.4 - 2.1 4 - 6 14 Coffee WP 2.3 4 4 - 7 Tobacco WP 2.1 - 2.8 10 - 16 7 DP 3.0 - 4.0 10 - 16 7 Hops WP 1.5 - 5.6 10 - 16 7 Post-harvest treatments Dose Number of Crop Formulation (in g. a.i./ha) applications Currants (fresh) WP 2.1 -2.4 2 WP= Wettable powder DP= Dust TABLE 2. Residues of propineb in crops after application of 70% WP formulation (Supervised Trials: Bayer, 1977) Application rate No. of Days after Residue (mg/kg) Crop kg/ha applications application range mean Apples 2.1 12 0 n.d. - 5.4 (3) 3.2 4 1.5 - 2.7 (3) 2.2 7 1.7 - 2.4 (3) 2.0 10 1.1 - 2.2 (3) 1.5 14 0.9 - 2.3 (3) 1.6 Bananas 2.35 - 3.53 4 1 n.d. (6) n.d. Pulp 3 n.d. (6) n.d. 7 n.d. (6) n.d 14 n.d. (6) n.d 21 n.d. (6) n.d. Peel 1 n.d. - 0.5 (6) 0.2 3 n.d. - 0.4 (6) <0.2 7 n.d. - 0.55 (6) 0.2 14 n.d. - 1.35 (6) 0.3 21 n.d. - 0.35 (6) <0.2 Total 1) 2.1 - 3.15 12 0 - 3 n.d.- <0.2 (20) <0.2 7 n.d.- <0.2 (6) <0.2 12 n.d.- <0.2 (3) <0.2 Beans 1.05 2 - 3 0 0.9 - 1.0 (2) 1.0 3 0.2 - 0.8 (2) 0.5 7 n.d. - 0.3 (3) 0.1 14 n.d. (3) n.d 21 n.d. (3) n.d. Celeriac 1.05 2 - 4 0 n.d. (3) n.d Edible root 14 n.d. - 0.2 (6) <0.1 21 n.d. (6) n.d 28 n.d. (3) n.d 35 n.d. (3) n.d TABLE 2. (Continued) Application rate No. of Days after Residue (mg/kg) Crop kg/ha applications application range mean Celeriac 1.05 2 - 4 0 16.5 - 25.7 (3) 21.7 leaf 14 0.2 - 0.4 (3) 0.3 21 0.2 - 0.3 (3) 0.2 28 0.1 - 0.3 (3) 0.1 35 n.d. - 0.2 (3) <0.1 Cherries 2.8 3 0 2.2 - 14.0 (5) 7.4 7 0.6 - 2.3 (5) 1.7 14 0.2 - 0.5 (5) 0.3 21 0.1 - 0.3 (5) 0.2 28 n.d. -<0.1 (3) <0.1 Citrus 2.52 -4.2 2 - 4 78/79 0.08- 0.17 (2) 0.13 (Satsuma Orange) 124/228 0.07 (2) 0.07 Pulp Peel 78/79 0.09-0.18 (2) 0.14 124/128 0.06-0.31 (2) 0.19 Juice 78/79 < 0.05 (1) 0.05 Coffee 21 g/shrub 4 6 n.d. (1) n.d. (beans, hulled) Cucumber 1.4 3 7 n.d. (1) n.d. 6X 0.1 g/plant 6 3 n.d. - <0.3 (2) n.d. Blackcurrants 2.8 2 - 3 0 11.8 - 38.6 (3) 25.2 7 4.35 - 17.4 (4) 11.7 11-14 1.2 - 13.4 (6) 8.7 21 0.65 -10.3 (5) 6.3 28 0.25-10.7 (5) 5.0 38-39 0.4 - 1.1 (2) 0.75 TABLE 2. (Continued) Application rate No. of Days after Residue (mg/kg) Crop kg/ha applications application range mean Red currants 2.8 2 - 3 0 7.2 - 34.2 (3) 20.8 7 2.15 - 22.6 (4) 10.2 11-14 1.9 - 16.4 (10) 6.3 21 0.4 - 9.9 (7) 3.8 28 0.3 - 7.6 (7) 3.5 39 0.3 - 1.2 (2) 0.75 Grapes 2.1 - 3.5 6 - 10 0 4.3 - 25.45 (9) 15.2 14/15 2.05 -11.2 (9) 7.6 28 0.95 -8.2 (9) 5.0 35 0.6 - 5.3 (7) 3.1 42-78 n.d. - 6.15 (15) 3.2 Hops 1.5 - 5.6 9 - 20 0 - 6 76.5 - 475 (3) 253 7 - 9 86 - 309 (4) 175 14 14 (1) 14 Sweet melon Pulp 1.4 3 7 n.d. (1) n.d. Peel 7 0.2 (1) 0.2 Onions 2.52 10 - 14 7 0.03 (2) <0.03 7 - 13 12 0.03 - 0.06 (2) 0.05 7 - 13 20 0.03 (2) 0.03 Peaches 2.1 - 2.8 3 0 2.45 - 30.5 (3) 16.9 4 - 7 0.2 - 9.9 (4) 4.9 14 0.4 - 3.8 (3) 2.4 21 1.3 (2) 1.3 28 0.85 - 5.0 (2) 2.9 Plums 2.8 3 0 1.0 - 1.4 (3) 1.2 7 1.0 - 1.8 (3) 1.3 14 0.65 - 0.7 (3) 0.7 21 0.35 - 0.55 (3) 0.4 28 0.25 - 0.4 (3) 0.3 TABLE 2. (Continued) Application rate No. of Days after Residue (mg/kg) Crop kg/ha applications application range mean Potatoes 1.26 6 7 n.d. (3) n.d. 22 n.d. (1) n.d. 51-60 n.d. (2) n.d. Tobacco 0.2 - 0.4 7 - 17 2 - 7 90 - ca.4000 (28) 625 1.3 - 4.6 11 - 18 3 - 5 64.9 - 465 (3) 224 12 45.4 (1) 45.4 17 158.5 (1) 158.5 Tomatoes 1.4 6 0 0.2 - 0.55 (3) 0.5 Greenhouse 3 0.3 - 0.65 (3) 0.5 4 0.4 - 0.8 (3) 0.6 7 0.3 - 0.75 (3) 0.45 Field-grown 1.75 5 0/1 2.2 - 3.35 (2) 2.8 3 1.65 - 2.3 (2) 2.0 7 0.4 - 1.8 (2) 1.1 Wheat 1.575 - 2.1 1 - 4 0 37.5 - 53.0 (3) 43.3 Ears 7 7.15 - 10.35 (3) 8.45 Grains 26 0.3 (1) 0.3 38-42 n.d. - 0.15 (6) 0.1 47-68 n.d. - 0.5 (9) 0.1 Straw 42-68 0.85 - 1.6 (6) 1.1 1) The peel was analyzed, and the residue found was converted to whole fruit. Pre-harvest treatments Propineb is formulated as a wettable powder and as a dust, with the wettable powder formulation being used predominantly. The major uses of propineb are in viticulture, fruit-growing and vegetable-growing. It is used also on a wide range of other crops including tobacco, hops, rice, groundnuts and coffee. The application rates for the different crops are listed in Table 1. The large variation in the numbers of applications per season is accounted for not only by the many different diseases on each crop but also by the very large differences in infection conditions from one region to another and also from year to year. RESIDUES RESULTING FROM SUPERVISED TRIALS Data on residues of propineb (determined as evolved CS but expressed as propineb) in various crops following supervised treatments with the wettable powder are shown in Table 2. The figures in brackets represent the number of analytical results reported (Bayer, 1977). Other uses Propineb is also recommended for use on ornamentals (WP formulation). FATE OF RESIDUES In plants The distribution and metabolism of (14C) propineb was studied on apples and grapes after a single application in 1972/73 (Vogeler et al., 1977a), and on grapes after three applications in 1976 (Vogeler et al., 1977b), under field conditions. Degradation of (14C) propylenethiourea (PTU) on apples was also studied (Vogeler et al., 1977a). The studies were model experiments under field conditions to investigate metabolism and not designed to make quantitative determinations of metabolite residues after commercial application of propineb. Whereas propineb remains mainly on the fruit surface, some of the metabolites formed can penetrate, at least partially, into the pulp. Degradation of propineb results in the formation of a metabolite which has not yet been identified, and also the following known metabolites: propyleneurea (PU), PTU, 4-methylimidazoline, and the methyl compounds of DIDT (5,6-dihydro-3H-imidazo (2,1-C)-1,2,4-dithiyole-3-thione) and Jaffé's base (3-(2imidazolin-2-yl)-2-imidazolidinethione. In the 1976 study involving three applications to grapes, the metabolites were found to be present in the grapes in the following percentages at harvest: Methyl Propineb 4-methyl- Unidentified compound PU PTU Methyl imidazoline metabolite of Jaffé's compound base of DIDT 41 1.7 7 4.6 4.3 9 9 In the studies conducted in 1972-73, the unidentified metabolite occurred in a larger amount than in the 1976 study. The methyl compounds of DIDT and Jaffé's base were detected only in the 1976 study. 4-methylimidazoline is formed in the isolation step as a result of a transformation of the unidentified metabolite, which is not stable as a free base. It is presumed that this compound is also formed from this metabolite in the plant. Degradation of PTU on apples proceeds rapidly and as it results in the formation of the same unidentified metabolitel it is assumed that propineb is degraded mainly via PTU. The residue level of PTO is governed mainly by the formation of PTU from propineb and the further degradation of PTU. In soil In field studies, propineb was found to undergo relatively fast degradation with half-lives in the range 2-8 clays, while in similar studies conducted in Japan, a halflife of about 20 days was recorded after five applications (Bayer, 1977). The half-lives in laboratory degradation studies were 1 and 9 days while under experimental conditions in Japan they were less than 1 day (Bayer, 1977). In leaching studies conducted with propineb in which 200 mm of water (simulating rainfall) vas passed through 300 mm-high soil columns in 2 days no propineb was found in the leachate (Bayer, 1977). In metabolic studies conducted with (14C) propineb in two standard soils it was degraded to PU to the extent of more than 50% of the amount applied (Vogeler, 1976). In addition, formation of CO2 was noted. Small amounts (about 4%) of PTU were found. Other metabolites occurred only 2 in amounts equivalent to less than 4% of the applied propineb; they were not identified. Degradation of (14C) PTU also resulted in the formation mainly of PU and CO2. At the end of the study period, PTU was no lonjer detectable. Pr)m the comparison of-the results of the degradation studies with propineb mid PTU, it is concluded that degradation of propineb proceeds mainly via PTU. The behaviour of (14C) propineb in field lysimeters with cores of undisturbed soil was studied over a period of 22 months by Mittelstaedt and Führ (1977). The total radioactivity showed a loss of 43% in follow soil with no plant cover and a loss of 26% in soil covered with grass. This loss may be attributed largely to the degradation of propineb CO2, because laboratory studies revealed that 39% of the applied propineb was degraded to C02 after 74 days. The radioactivity still present in the field soil after 22 months was retained largely in the upper 5 cm layer. Of this radioactivity, only about 10% was extractable. Heavy absorption or incorporation in the organic matter of the soil probably prevented further translocation or leaching. Of the radioactivity originally applied, 1.8% was recovered in the leachate of the soil with no plant cover and 0.3% was recovered in that of the covered soil. From the results of an additional laboratory study (Vogeler, 1977), it is assumed that the radioactivity in the leachates was accounted for by PU and other polar compounds. METHODS OF RESIDUE ANALYSIS Propineb residues can be determined by the well-known CS2 evoluation methods such as that on Keppel (1969), in which stannous chloride used as a reducing agent. A modified procedure based on the Keppel method has recently been proposed (Thier, 1977). Propylene thiourea can be determined by gas chromatography, without derivatization, by an adaptation of the method of Otto et al. (1977). The sample is extracted with methanol and the methanol evaporated. The remaining water phase is shaken out with n-hexane and cleaned up on an aluminium oxide column. The aqueous eluate is concentrated and shaken out with dichloromethane. After evaporation of the dichloromethane, the residue is dissolved in methanol and PTU directly determined by gas chromatography. NATIONAL TOLERANCES REPORTED TO THE MEETING The following national tolerance and pre-harvest intervals were reported to the Meeting. Country Crop Tolerance, Pre-harvest mg/kg interval days Australia General 3 Austria General 14 Vegetables, fruit crops 2.0 (dithiocarbamates calculated totally Other crops 0.05 as carbon disulphide) Belgium Cereals 0.2 calculated as CS2 Fruit, vegetables, excl. potatoes and citrus 2.0 as CS2 Potatoes 0.5 as CS2 Field-grown: Grapes, hops 42 Leek, onions celery, asparagus - 28 shallot, beans, cereals, spinach Gherkins 10 All other crops 14 Field-grown and under glass: Lettuce, endive from 1.3 - 1.11 28 Under glass: Lettuce, endive from 1.11 - 1.3 42 Radish, spinach 28 Tomatoes, gherkins, cucumbers 3 Country Crop Tolerance, Pre-harvest mg/kg interval days German Democratic Republic (GDR) Field crops - Potatoes 7 Top fruit and vegetables 10 Small fruit, leafy vegetables 21 Fruit-producing vegetables 4 Grapes 14 Crops for production of baby foods and dietary foods 28 Crops for production of drugs 21 Forage crops, grassland (pastures) 7 Pome fruit, small fruit, strawberries, stone fruit, nut crops, root vegetables, leafy vegetables, 3.0 calculated as brassicas, legumes carbon disulphide (pulse crops), fruit-producing vegetables Citrus fruit, cereals, milled grain products, potatoes, onions, vegetable and animal fats, 0.1 calculated as meat, fish, eggs, carbon disulphide, milk, baby foods Country Crop Tolerance, Pre-harvest mg/kg interval days Germany Federal Republic of (FRG) Potatoes 7 Pome fruit 10 Stone fruit, small fruit 21 Grapes 42 Tomatoes (field-grown and under glass) 4 Celery 28 Hops, tobacco 7 Vegetables, excl. cucumbers and tomatoes 2.0 dithiocarbamates, Fruit crops 2.0 thiuram disulphides Cucumbers and tomatoes 1.0 calculated totally Other food crops 0.05 as carbon disulphide Hungary General 3.0 Tomatoes (processing) 8 Peppers (processing) 10 Fruit crops and grapes 30 All other crops 21 Israel General unrestricted Italy General 7 Mexico Avocado, cocoa, lemons, mandarin oranges, bergamot oranges, 7 mango, apples, pears, potatoes Netherlands Potatoes, cereals 0.5 as CS2 All other crops 2.0 as CS2 New Zealand General 7 Country Crop Tolerance, Pre-harvest mg/kg interval days Norway General 14 Portugal General 7 South Africa General 3.0 Wine grapes 28 Table grapes 28-42 Tomatoes, potatoes 3 Boysenberries, youngberries 14 Spain General 10 Sweden General 30 Switzerland Grapes 3.0 21 Vegetables, excl. lettuce 21 Yugoslavia Tobacco 7* Grapes 42* All other crops 14* * (official recommendation) APPRAISAL Propineb is a broad specturm propylenebisdithiocarbamate fungicide which is marketed world-wide. Major uses are pre-harvest treatments of fruits and vegetables and in viticulture. The wide variation in application frequency (1 to 16 applications) is due to the different natures and extent of the fungi against which it is aimed. Residues data were provided from supervised trials of propineb applications to a range of crops. Residues observed, expressed as propineb, varied from up to 10 mg/kg on grapes and blackcurrants to less than 0.05 mg/kg (limit of determination) in banana pulp. The distribution and metabolism of propineb residues in apples and grapes have been studied, together with the associated propylenethiorurea (PTU) in apples. Whereas the parent propineb and PTU remain mainly on the surface, some other metabolites (of which several are described) can penetrate at least partially into the flesh of the fruit. PTO degrades rapidly to yield the same metabolites (some as yet unidentified) as does propineb, suggesting that the degradation of propineb may proceed via PTU. Field studies of propineb degradation in soil have shown half-lives ranging from 2 to 20 days depending on conditions. Over 50% was converted to propyleneurea (PU) during similar studies using 0-14 labelled propineb or PTU. Residue analysis is carried out by CS evolution procedures based on that of Keppel (1969). A gas-chromatographic method for ETU (Otto et al., 1977) has been adapted for the determination of PTU residues. RECOMMENDATIONS As the analytical method depends on CS2 evoluation, temporary maximum residue limits identical to those of the other dithiocarbamates are recommended (see "Dithiocarbamate fungicides"). The limits are for CS2. FURTHER WORK OR INFORMATION REQUIRED (by July 1980) 1. A study of the mechanism of action of propineb on the thyroid. 2. Further work to elucidate the mode of action of PTU and its long-lerm toxicity. 3. Information regarding the fate of residues during food processing, including cooking. REFERENCES Bayer, (1971) Data submitted by Bayer AG (unpublished). Keppel G.E. (1969) Modification of the Carbon Disulfide evolution Method for Dithiooarbamate Residues. J. Ass. Off. Anal. Chem. 52, 162-167. Mittelstaedt, W. and Führ, F. (1977) Verhalten von Propineb in bewachsenem und unbewachsenem Boden. Landwirtroh. Forsoh., in press. Otto, S., Keller, W. and Drescher, N. (1977) A new gas chromatographic determination of ethylenethiourea residuee. J. Environ, So. Hlth., B 12 (3): 179-191. Thier, H.P. (1977) Veröffentlichungen aus den Arbeitsgruppen sur RUckstandsanalytik der Pestizide in Lebensmitteln. 5. Mitteilung: Nalytik von DithiocarbamatRückstäden. Lebensmittelchem. gerichtl. Chem. 3-1, 25-27. Vogeler, K. (1976) Zum Metabolismus von Propineb, Zineby Propylenthioharnstoff und Athylenthioharnstoff im Boden nach BBA-Plerkblatt Nr. 36. Bayer AG, Pflanzenschutz-Anwendungstechnik, unpublished report RA 726, September, 1976. Vogeler, K. (1977) Leachine-Laborversuche mit (140) Propineb Bayer AG; Pflanzenschutz-Anwendunstechnik, unpublished report RA-573, July 20, 1977. Vogeler K., Drezer Ph., Papp, R.l Steffan, E., Ullerneyer, H. Verteilung und Metabolismum von Propineb in Apfeln und Weintrauben sowie der Abbauprodukte Propylenthioharnstoff und Athylenthioharnstoff in Apfeln. Pflanzenschutz-Nachrichten Bayer 30, 72-97. Vogeler K., Rapp, A., Steffan, H., Ullemeyer, H. Der Metabolismus von Propineb in Weintrauben nach dreimaliger Applikation von. Antracol im Freiland. Bayer AG, Pflanzenschutz-Anwendungstechnik, unpublished report RA-363, April 28, 1977b.
See Also: Toxicological Abbreviations Propineb (Pesticide residues in food: 1984 evaluations) Propineb (Pesticide residues in food: 1985 evaluations Part II Toxicology) Propineb (Pesticide residues in food: 1993 evaluations Part II Toxicology)