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

    MANCOZEB

    IDENTITY

    Chemical name

    Zinc ion coordination product with manganese
    ethylene-1,2-bisdithiocarbamate polymer.

    Empirical formula

    (C4H6N2S4Mn)a . (C4H4N2S4Zn)y

    Structural formula

    CHEMICAL STRUCTURE 

    The polymer contains 1.6 per cent zinc, i.e., 6 per cent of the units
    are in the form of the coordination complex.

    Other relevant chemical properties

    The addition of zinc chloride to a suspension of maneb yields a
    product mancozeb, superior to maneb. Mancozeb is essentially inert to
    oxidation by atmospheric oxidation, in contract with maneb. It is also
    essentially non-phytotoxic in contrast with maneb, zineb or mixtures
    of these which are harmful to a number of plants.

    The standard formulation is an 80 per cent wettable powder containing
    Mn++ 16 per cent and Zn++ 2 per cent.

    EVALUATION FOR ACCEPTABLE DAILY INTAKES

    Biochemical aspects

    For information see In animals.

    Acute toxicity

                                                  
                         LD50
    Animal   Route   (mg/kg b.w.)     Reference
                                                  

    Rat      Oral        8000         Larson, 1965
                                                  

    Special studies

    Rat. Groups of 15 males and 15 females were fed 0, 100, 300 and 1000
    ppm of the active product for three months, in a study comparing the
    thyroid effect of this compound with that of propylthiouracil in
    similar groups of rats at 300 ppm for three months or 1333 ppm for 5
    weeks. Oxygen consumption studies were conducted during the third
    month, and at the end of the study 131-I-uptake was determined for
    each animal, following which the thyroid gland was examined
    microscopically. At 1000 ppm, terminal body weights were adversely
    affected and PBI was depressed in the females; thyroid weight ratios
    were elevated and the metabolic rate was lowered in the males; and one
    animal of each sex showed significant thyroid hyperplasia, 131I-uptake
    was not affected. At 100 and 300 ppm, PBI was significantly increased
    in both sexes, but thyroid weights and histology and metabolic rates
    were unaffected. In the groups fed propylthiouracil, weight gain
    depression, increased thyroid weight ratios, lowered 131I-uptakes,
    lowered metabolic rates and severe thyroid hyperplasia were seen in
    both sexes. Propylthiouracil did not affect PBI (Larson, 1965).

    Short-term studies

    Rat. Groups of 10 males and 10 females were fed 0, 25, 50, 75 and
    100 ppm for 13 weeks. No effect of the compound was found on
    body-weight gain, survival, food consumption, peripheral blood
    picture, urinary constituents and weights and histologic appearance of
    major organs. (Larson, 1965).

    In a three-generation reproduction study, mating groups of 20 males
    and 20 females were maintained on diets containing 0, 25, 100 and 1000
    ppm of the compound. Two litters were produced per generation and
    filial generations were composed of second-litter animals. Parental
    generation animals were followed for 90 weeks (reported under
    "Long-term studies"); the first litters from each generation were
    given gross post-mortem examination after weaning, as were all
    breeding generations after weaning their second litters. The second
    litters of the second filial generation were given thorough
    histopathologic examinations at weaning age. At 1000 ppm, lowered
    fertility was seen in the first and second filial generations, without
    effect on gestation, lactation, viability of offspring or weaning
    weights. Uninterpretable, significant variations (both relative

    increases and decreases) in thyroid weight ratios were found in 8 of
    20 group means at 100 and 1000 ppm. Histological examination of the
    F3b animals disclosed no thyroid hyperplasia at any level, nor any
    other significant organ pathology, (Larson, 1965).

    Dog. Groups of 4 males and 4 females were fed 0, 25, 100 and 1000
    ppm of the active product for 2 years. PBI and 131I-uptake were
    determined at 6, 12 and 24 months: the only deviations from control
    values were seen at 24 months, in lower 131I-uptakes at 48 and 72
    hours in the 100 ppm group, and at 72 hours in the 1000 ppm group. No
    adverse effect was seen on behaviour, survival, rate of weight gain,
    food consumption, blood picture, urine, clinical indices of hepatic
    and renal function, organ weight ratios and the gross and histologic
    appearance of major organs. (Larson, 1965).

    Long-term studies

    Rat. Groups of 25 males and 25 females were fed 0, 25, 50, 100 and
    1000 ppm for 90 weeks. The only significant effect of the compound was
    hyperplasia of the thyroid acinar epithelium in some of the animals in
    the 1000 ppm group. This effect was not seen at lover levels, and no
    effect at any level was found on survival, body-weight gain, food
    consumption, blood picture, urine, metabolic rate (determined at 30
    weeks and one year for controls and 1000 ppm animals and for all
    groups at 21 months), organ weight ratios and microscopic appearance
    of major organs. (Larson, 1965).

    Comments

    In the long-term study in the rat a level of 100 ppm was without
    toxicological effect. In the two-year feeding study in the dog, a
    lower 131I-uptake was observed in the 100 ppm group and the 1000 ppm
    group at 24 months, but not at 6 and 12 months. This type of study has
    not been conducted on any of the other dithiocarbamates. No other
    effects were observed in this study.

    More information is needed on the chemical nature of the residues in
    or on the plant. While these data are being obtained, a temporary ADI
    is proposed.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

    Rat. 100 ppm in the diet, equivalent to 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 bisdithiocarbamates).

    This value is based on experiments carried out with mancozeb 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

    Mancozeb was introduced in 1961 as a material superior to maneb or a
    mixture of maneb and zineb in the protection of certain agricultural
    crops from plant pathogenic fungi.

    RESIDUES RESULTING FROM SUPERVISED TRIALS

    Using good agricultural practice of an appropriate spray
    concentration, number of applications and time interval before harvest
    the residue values indicated in Table I were found.

    FATE OF RESIDUES

    In plants

    The following have been identified as intermediate degradation
    products of mancozeb applied to plants : ethylene bis-isothiocyanate,
    ethylene thiourea, Jaffe's base [N-2(2-imidazolyl)-ethylene thiourea], 
    ethylene urea, 2-imidazoline, N-formyl ethylenediamine,
    ethylenediamine, elemental sulfur and sulfate ion. A preliminary
    measurement of ethylene thiourea from sugar beet tops after 17 days
    using a high level of mancozeb indicated a level of 2 per cent.

    In animals

    An experiment with C14 labelled mancozeb in the rat diet for seven
    days at 20 mg per rat per day (approx. 1000 ppm) indicated that the
    metabolism follows pathways similar to its degradation on plants. The
    distribution of carbon-14 made 24 hours after the final feeding of
    C14 labelled mancozeb in the rat diet was as follows : feces 70.90
    per cent, urine 15.5 per cent, cage washings 3.98 per cent and
    carcasses 1.45 per cent, total 91.83 per cent. Of the activity in the
    feces 47  4 per cent was estimated as mancozeb from the hot
    acid-CS2-evolved assay, ethylene bisisothiocyanate sulfide 7.5 per
    cent, ethylenethiourea 6.0 per cent and ethylene urea 2.0 per cent,
    total identified 62 per cent.


        TABLE I
                                                                                                   
    Crops               Time Interval    Treatment per     Applications       Residue (ppm)
                           (days)        acre (lb/acre)      (Number)       Mean         Range
                                                                                                   

    Almonds, hull            16                9                1           0.07        0.06-0.08
       "   , meat                                                          55.1        43.0 -78.5

    Apples                   56                4                8           1.5         1.2 -1.8

    Cranberries              55                6                4           0.99        0.85-1.12

    Plums and prunes         12                6                3           1.33        1.11-1.51

    Barley                   26                2                3           1.41        0.52-2.38

    Cotton (seed)            26                3                2           0.21        0.12-0.40

    Peanuts, nuts            21                2                6           0.04        0.01-0.09
       "   , hay                                                           54.0          43 - 64

    Sugar beets, roots       61                2                3           0.09        Nil -0.14
      "     "  , silage                                                     0.288

    Carrots                  15                2               15           0.26        0.08-0.49

    Celery                    5                2               10           1.01        0.38-1.88

    Cucumber                  7                2                5           0.38        0.21-0.52

    Lettuce and endive       14                2                8           0.10        0.025-0.19

    Melons                    7                3                8           0.85        0.05-1.86

    Tomatoes                  7                3                8           0.58        0.51-0.79
                                                                                                   
    

    The C14-components of the urine identified were as follows : ethylene
    thiourea 28 per cent, N-acetyl ethylediamine 19 per cent, ethylene
    urea 12 per cent, ethylene bisisothiocyanate sulfide 5.5 per cent,
    ethylenediamine 1.5 per cent, being 70 per cent of the total activity
    (Rohm and Haas, 1967).

    METHODS OF RESIDUE ANALYSIS

    The method of residue determination is the same for the other
    dithiocarbamate fungicides based on the determination of carbon
    disulfide released on acid treatment (Gordon, Schuckert and Bornak,
    1967) and is non-specific for mancozeb.

    NATIONAL TOLERANCES
                                                                                       
    Country          Tolerance, ppm         Crop
                                                                                   

    United States
      of America          65            peanut vine hay, sugar beet tops

                          28            raisins

                          25            straw of barley, oats, rye and wheat

                          20            bran of barley, oats, rye and wheat

                          15            bananas (2 ppm in pulp)

                          10            apples, celery, crab apples, fennel,
                                        pears, quinces, papayas

                           7            cranberries, cucumbers, grapes, summer
                                        squash, tomatoes (0 in pulp), edible
                                        melons (0 in pulp)

                           5            grains of barley, oats, rye and wheat

                           2            carrots and sugar beets

                           1            flour of barley, oats, rye and wheat

                           0.5          corn, cottonseed, kidney, liver,
                                        peanuts

    Canada                 1            sugar beets

    (continued)
                                                                                   
    Country          Tolerance, ppm         Crop
                                                                                   

    Canada                 2            apples, cucumbers, melons, squash
                                        tomatoes.

    Federal Republic       3            leaf vegetables, fruit vegetables,
      of Germany                        pulses, fruit including grapes.
                                                                                   
    
    RECOMMENDATIONS FOR TOLERANCES

    In light of the non-specificity of the available analytical method, it
    is not possible to make recommendations for tolerances of mancozeb per
    se at this time.

    FURTHER WORK

    Further work required before recommendations for tolerances can be
    made

    Development of an analytical method specific for mancozeb or, failing
    this, data indicating that a combined tolerance for all
    dithiocarbamate fungicides would be acceptable.

    REFERENCES PERTINENT TO EVALUATION FOR ACCEPTABLE DAILY INTAKES

    Larson, P.S. (1965) Unpublished report submitted by Rohm and Haas
    Company.

    REFERENCES PERTINENT TO EVALUATION FOR ACCEPTABLE DAILY INTAKES

    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.

    Rohm and Haas. (1967) Unpublished data submitted to FAO.
    


    See Also:
       Toxicological Abbreviations
       Mancozeb (ICSC)
       Mancozeb (AGP:1970/M/12/1)
       Mancozeb (WHO Pesticide Residues Series 4)
       Mancozeb (Pesticide residues in food: 1993 evaluations Part II Toxicology)