FAO/PL:1967/M/11/1 WHO/Food Add./68.30 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 MANEB 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. IDENTITY Other relevant chemical properties Commercial formulations include a wettable concentrate with a minimum of 70 per cent maneb and a dust containing about 5 per cent maneb. EVALUATION FOR ACCEPTABLE DAILY INTAKES Biochemical aspects Maneb was not stored in the tissues of rats fed up to 2500 ppm for 2 years, or in tissues of dogs given daily doses of up to 75 mg/kg for 1 year (Clayton et al., 1957). Acute toxicity LD50 mg/kg Animal Route body-weight Reference Rat oral 6750 Clayton et al., 1957 Short-term studies Rat. Administration of single oral doses of 1500 mg/kg body-weight/day for 10 days to six male rats caused weight loss, weakness of hind limbs and one death after eight doses (Clayton et al., 1957). Groups of 5 male and 5 female rats were fed 0, 100, 1000 and 10,000 ppm maneb for 90 days. No clinical signs or pathological changes were found at 1000 ppm in females, or at 100 ppm in males and females. Higher dose levels caused weight loss, weakness, stiffness of hind limbs, and 10,000 ppm caused 80 per cent mortality. Thyroid hyperplasia was seen at 10,000 ppm and, to a lesser extent, in males at 1000 ppm. The remaining animals appeared normal (Clayton et al., 1957). A three-generation reproduction study with two litters per generation, was done using 16 male and 16 female rats per dose level for each generation, at 0, 125 and 250 ppm maneb. Test animals were maintained for 3 months post-weaning before the first matings. No effect was seen on fertility, gestation, viability, lactation or litter size. No gross or histological abnormalities, as compared with controls, were found in animals selected for examination from the third filial generation (Sherman & Zapp, 1966). Comments In long-term studies in the rat a level of 250 ppm was without toxicological effect. The same level was without effect in the three-generation reproduction study. In the one-year study in dogs, the only effect seen at the dose level of 20 mg/kg daily, was a loss in body-weight in one animal. The chemical nature of the residues of maneb 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 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. Estimate of temporary acceptable daily intake for man 0 - 0.025 mg/kg body-weight (alone or in combination with other ethylene bis-dithiocarbamates.) This value is based on experiments carried out with maneb 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 Maneb in primarily used as a pre-harvest spray to protect agricultural crops, both fruit and plants, from invasion by fungal plant pathogens. Initially being relatively insoluble, spraying and dusting involves the whole plant. Residues are reduced by weathering, metabolism by the plant, and washing and trimming the product. During the weathering and metabolism by the plant a number of products result, such as ethylene thiuram monosulfide, ethylenethiuram disulfide and ethylenethiourea. RESIDUES IN FOOD AT TIME OF CONSUMPTION A recent survey of 5 composite basic 2-week diets for males, 14 to 19 years, identified 6 dithiocarbamates, including maneb with values ranging from 0.4 to 0.8 ppm (Duggan, Barry & Johnson, 1966) FATE OF RESIDUES General considerations The manganese salt has a low water solubility and is stable in a dry, inert atmosphere. However, degradation slowly occurs on exposure to air and moisture to a variety of compounds. Ethylene thiuram monosulfide (ETM) and ethylene thiuram disulfide (ETD) (Morehart & Crossan, 1965) as well aa ethylene thiourea and 2 unidentified products (Fishbein & Fawkes, 1965) by chromatography. The former authors suggested from their metabolism studies with fungal spores that toxicity is due mainly to ETD. However, this is a dynamic system and possibly the ETM could not be detected. In a modified zineb preparation, ETM could be detected and its action on rat liver mitochondria examined (Kovacs & Caumo, 1966). METHODS OF RESIDUE ANALYSIS To date the residue is estimated by measuring the carban disulfide released on acid treatment and recent modifications to suit different crops are outlined (Gordon, Schuckert & Bornak, 1967). However, the method is non-specific. RESIDUES RESULTING FROM SUPERVISED TRIALS Crop Rate Number Pre-harvest Residue of of interval (ppm) Reference application applications (days) (lb/acre) almonds 9 - 129 (0.01-0.12) 0.05 (meat) Rohn & Haas (1964) (12.4-26.4) 20 (husks) " bananas 2*** post harvest < 0.1 (pulp) " 3.0 (peels) " 4 5 0 13.0* du Pont (1958) broccoli 4 5 1 4.5** " 4 7 14 1.4 " celery 1.5 7 7 7.4 " cherries 6 1 14 (2.9-3.4) 3.3 Rohm & Haas (1964) chicken muscle (feed contained 45 ppm) nil " cranberries 6 4 55 (0.35-0.61) 0.48 " egg albumen (feed contained 45 ppm) nil " /yolk lettuce 2 3 23 25 du Pont (1958) (stripped) lima beans 2 5 0 0.04 " 2 5 7 nil " peaches 2 3 15 8.4 " RESIDUES RESULTING FROM SUPERVISED TRIALS (cont'd) Crop Rate Number Pre-harvest Residue of of interval (ppm) Reference application applications (days) (lb/acre) sugar beet 2.5 2 65 (0.70-1.10) 0.43 Rohm & Haas (1964) enslage Residue (ppm) Trimmed/washed Commercially processed * 4.0 0.28 ** 2.7 <0.25 *** lb/gal. NATIONAL TOLERANCES Country Tolerance Crop Canada 2 ppm bananas (edible pulp) 7 ppm apples, beans (dry), carrots, corn, cranberries, cucumbers, eggplant, figs, grapes, melons, onions, peppers, pumpkins, squash, tomatoes, turnips (roots). 10 ppm apricots, beans (fresh), broccoli, Brussels sprouts, cabbage, cauliflower, celery, Chinese cabbage, collards, endive, kale, kohlrabi, lettuce, mustard greens, nectarines, peaches, rhubarb, spinach and turnip tops. USA essentially the same as for Canada except potatoes (0.1 ppm) and sugar beet tops 45 ppm (not to be applied within 10 days of harvest and tops not to be fed to livestock). West Germany 3 ppm leafy vegetables, fruit, pulses. RECOMMENDATIONS FOR TOLERANCES Although some progress has been reported neither the chemical nature nor the mode of action of the residues of maneb 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 maneb in or on the plant to include the identification and mode of action of any critical intermediates, and on the development of specific methods of analysis. The data on this subject to required prior to 30 June 1971. REFERENCES PERTINENT TO EVALUATION FOR ACCEPTABLE DAILY INTAKES Clayton, J.W., Hood, D.R., Barnes, J.R. & Borgmann, A.R. (1957) Unpublished report submitted by E.I. du Pont de Nemours & Co. Sherman, H. & Zapp, J.A. (1966) Unpublished report submitted by E.I. du Pont de Nemours and Co. REFERENCES PERTINENT TO EVALUATION FOR TOLERANCES Duggan, R.E., Barry, H.C., & Johnson, L.Y. (1966) Pesticide residues in total diet samples. Science, 151: 101-104. du Pont, E.I. (1958) Submission to Canada Dept. of Health and Welfare, Food and Drug Directorate. FAO/WHO (1966) Evaluation of the toxicity of pesticide residues in food. FAO Meeting Rpt. PL.1965/10/1; WHO Add./27.65. Fischbein, L., & Fawkes, J. (1965) Thin layer chromatography of metallic derivatives of ethylenebis (dithiocarbamic acid) and their degradation products. J. Chromatog., 19: 364-369. 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. Kovacs, A., & Caumo, B. (1966) Systemicity of zinc ethylenebisdithiocarbamate. Atti. Simp. Int. Agrochim., 6: 263-269 (1967, Chem. Abstr. 67: 90012 r). Morehart, A.L., & Crossan, D.F. (1965) Studies on the ethylenebis dithiocarbamate fungicides. Exp. Stn. Bull. 357, Agric. Exp. Stn. Univ. Delaware, Newark, Del. 26 p. Rohm and Haas. (1964) Submission to Canada Dept. of Health and Welfare, Food and Drug Directorate.
See Also: Toxicological Abbreviations Maneb (ICSC) Maneb (FAO Meeting Report PL/1965/10/1) Maneb (Pesticide residues in food: 1993 evaluations Part II Toxicology) Maneb (IARC Summary & Evaluation, Volume 12, 1976)