1967 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD THE MONOGRAPHS 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 Committee on Pesticide Residues, which met in Rome, 4 - 11 December, 1967. (FAO/WHO, 1968) FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS WORLD HEALTH ORGANIZATION Rome, 1968 ZIRAM This pesticide was evaluated toxicologically by the 1965 Joint Meeting of the FAO Committee on Pesticides in Agriculture and the WHO Expert Committee on Pesticide Residues (FAO/WHO, 1965). Additional toxicological information, together with information for evaluation for tolerances, is summarized and discussed in the following monograph addendum. EVALUATION FOR ACCEPTABLE DAILY INTAKES Short-term studies Rat. In a reproduction study, rats were given ziram in doses of 10 and 50 mg/kg/day and zineb in doses of 50 and 100 mg/kg/day orally for 2-6 months. Sterility, resorption of fetuses and anomalous tails in new born rats were observed at the high levels. The lower doses did not cause any significant changes, compared with a control group (Ryazanova, 1967). Long-term studies Rat. Weanling rats in groups of 25 males and 25 females were fed diets containing 25, 250 and 2500 ppm of ziram for 2 years. Growth was reduced at the highest concentration only; life-span was normal in all groups. Neurological changes were observed in the animals receiving 2500 ppm but not at the lower levels. In some of the males the testes were atrophied and there was a slight indication of thyroid hyperplasia, notably in the 2500 ppm group. There was no increase in tumour incidence in the treated animals (Hodge et al., 1956). Comments on experimental studies reported Although ziram was only found in trace amounts in tissues of rats and dogs fed the compound, storage of metabolites should be investigated as part of the metabolic studies needed on the dithiocarbamates. In long-term studies in the rat a level of 250 ppm was without toxicological effect. From the one-year study in the dog the daily dose of 5 mg/kg body- weight was without toxicological effect. The chemical nature of the residues of ziram in or on the plant has not been ascertained. Studies are needed on the metabolism of the dithiocarbamates. While these data are being obtained a temporary ADI, based on the long-term studies in the rat, is proposed. TOXICOLOGICAL EVALUATION Level causing no toxicological effect Rat. 250 ppm in the diet, equivalent to 12.5 mg/kg body-weight per day. Dog. 5 mg/kg body-weight per day. Estimate of temporary acceptable daily intake for man 0 - 0.025 mg/kg body-weight (alone or in combination with other dimethyl-dithiocarbamates). This value is based on experiments carried out with ziram and does not take account of chemical alterations after application. Further work required Studies of the compound in plants to determine the chemical nature of the residues, followed by appropriate toxicological studies. Results of the above work should be made available not later than 30 June 1971 after which a re-evaluation of this compound will be made. The re-evaluation may be made at an earlier meeting should relevant information become available. EVALUATION FOR TOLERANCES USE PATTERN Pre-harvest treatments Ziram is used primarily as a pre-harvest spray to protect a number of agricultural products from plant pathogens. RESIDUES RESULTING FROM SUPERVISED TRIALS Twelve applications of equal parts ziram and ferbam at 2 lb/acre to celery and allowing 7 days for weathering resulted in a residue of 10 ppm (trimmed) and 4.1 ppm (trimmed and washed). Spraying snap beans with one application at 1 1/2 lb/gal/acre and a 6 day time interval before sampling resulted in a residue of 3.2 ppm. RESIDUES IN FOOD AT TIME OF CONSUMPTION A recent survey of five composite basic 2-week diets for males 14-19 years old showed the presence of 6 dithiocarbamates with values ranging from 0.4 to 0.8 ppm (Duggan, Barry and Johnson, 1966). No residues were found in a more recent survey based upon the analyses of prepared foods (Duggan and Weatherwax, 1967), possibly because the residues decomposed rapidly as the foods were being prepared. NATIONAL TOLERANCES Country Tolerance, ppm Crop Reference Canada 7 apples, apricots, beans, beets, blackberries, FDD, Canada black-eyed peas, blueberries, broccoli, (1967) Brussels sprouts, cabbage, carrots, cauliflower, celery, cherries, collards, cranberries, cucumbers, eggplants, gooseberries, grapes, kale, kohlrabi, lettuce, loganberries, melons, mustard greens, nectarines, onions, peaches, peanuts, pears, peas, peppers, pumpkins, quinces, radishes, raspberries, rutabagas, spinach, squash, strawberries, summer squash, tomatoes turnips; U.S. 7 apples, apricots, beans, blackberries, blueberries, broccoli, cabbage, cantaloupe, carrots, celery, cherries, citrus fruits, cranberries, cucumbers, gooseberries, grapes, lettuce, loganberries, peaches, pears, peppers, plums, potatoes, prunes, raspberries, squash, strawberries; West Germany 3 leafy vegetables, fruits and pulses; METHODS OF RESIDUE ANALYSIS Residues have been determined by releasing either the dimethylamine (Barr, Clerk and Jacks, 1957) or the carbon disulfide (Pease, 1957) on acid treatment of the sample and measuring the intensity of a coloured copper complex formed. Since the colour formation is critical an improved modification has been outlined (Cullen, 1964). Better recoveries from a variety of crops have resulted from changes in the order of the acid decomposition procedure (Gordon, Schuckert and Bornak, 1967). Methods using polarographic techniques have also been developed (Nangniot, 1966; Vogeler, 1967). RECOMMENDATIONS FOR TOLERANCES Although some progress has been reported, neither the chemical nature nor the mode of action of the residues of ziram, in or on the plant have been ascertained and there is no specific method of analysis available. Accordingly, no tolerance figures can be recommended. FURTHER WORK Further work required Further work is required on the metabolism of ziram in or on the plant to include the identification and mode of action of any critical intermediates. The data on this subject is required prior to 30 June 1971. REFERENCES PERTINENT TO EVALUATION FOR ACCEPTABLE DAILY INTAKES Hodge, H.C., Maynard, E.A., Downs, W.L., Coye, R.D. & Steadman, L.T. (1956) J. Pharmacol. exp. Ther., 118, 174 Ryazanova, R.A. (1967) Gigiena i sanitaria, 2, 26 REFERENCES PERTINENT TO EVALUATION OF TOLERANCES Barr, H.E., Clark, P.J., Jacks, H. (1957) Determination of tetramethylthiuram disulfide and dimethyldithiocarbamate sprays on apples. New Zealand J. Sci. Tech. Sect. B, 38: 425-532. Cullen, T.E. (1964) Spectrophotometric determination of dithiocarbamate residues in food crops. Anal. Chem. 36: 221-224. Duggan, R.E., Barry, H.C., Johnson, L.Y. (1966) Pesticide residues in total diet samples. Science 151: 101-104. Duggan, R.E., Weatherwax, J.R. (1967) Dietary intake of pesticide chemicals, Science 157: 1006-1010. FDD/Canada. (1967) Food and Drug Directorate, Canada. T. I. L. 290, 15 September Gordon, C.F., Schuckert, R.J., Bornak, W.E. (1967) Improved method for the determination of ethylenebisdithiocarbamate residues in plants, fruits and vegetables. J. Assoc. Off. Anal. Chem. 50: 1102-1108. Nangniot, P. (1966) L'application des methodes electrochimiques a l'etude des residus des pesticides. Medel. Landbouwhogeschool Opzoekingstat. Staat Gent 31: 447-473 Pease, H.L. (1957) Determination of dithiocarbamate fungicide residues. J. Assoc. Off. Agric. Chem. 40; 1113-1118. Vogeler, Von K. (1967) Kolorimetrische und polarographische bestimmungen von ruckstanden in und auf pflanzen nach anwedung von Antracol. Pflanzenschutz-Nachrichte Bayer.
See Also: Toxicological Abbreviations Ziram (ICSC) Ziram (FAO Meeting Report PL/1965/10/1) Ziram (Pesticide residues in food: 1996 evaluations Part II Toxicological) Ziram (IARC Summary & Evaluation, Volume 53, 1991)