IPCS INCHEM Home


    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)