United States             Office of Pesticides «nd Toxic Sufactances
                    Environmental Protection      Offica of Pesticide Programs  (TS-766C)
                    Agency                 Washington, DC  2O460
xvEPA       Pesticide
                    Fact  Sheet
                   Name of Chemical:   METIRAM
                   Reason for Issuance:  REGISTRATION STANDARD
                   Date Issued:  October 3,  1988
                   Fact Sheet Number:  181

        Chemical Name:  -Mixture of 5.2 Parts by Weight (83.9%) of
                      Ammoniates of  [ethylenebis  (dithiocarbamate)]
                      zinc with 1 part by weight  (16.1%) ethylenebis
                    - [dithiocarbamic acid],  bimolecular and
                      trimolecular cyclic anhydrosulfides and

        Common Name:  Metiram

        Principal Trade Names:  Polyram™, Polyram-Combi™

        EPA  (Shaughnessy) Code:  014601

        Chemical Abstracts Service (CAS) Number:  9006-42-2

        Year of Initial Registration: late 1940's

        Pesticide Type:  Fungicide

        Chemical Family:  Ethylene bisdithiocarbamate (EBDC)

        U.S. and Foreign Producers:  FMC and BASF


        Registered uses:   Terrestrial food crop uses on apples, asparagus,
                         celery,  corn (sweet), cotton,  cucumber, peanuts,
                         pecans,  potatoes (including seed pieces), sugar beets,
                         and tomatoes; Terrestrial nonfood crop uses on tobacco
                         (field and transplants) and roses

        Predominant uses:   Apples and potatoes

        Pests controlled:   Foliar fungal diseases of selected fruit, nut,
                         vegetable, field and ornamental crops.

  Types of Formulations:   Formulation intermediate,  dust,  and wettable

  Types and Method of     Foliar application to fruits,  vegetables and     ~
   Application:           nuts by aerial equipment,  as well as ground equipment.
                          For ground equipment metiram suspensions typically
                          made from a wettable powder, would be applied
                          by means of air blast sprayers or in the case of
                          some row crops by means of tractor mounted boom

  Application Rates:       Terrestrial food crop: 0.3 - 6.4 Ib ai/A
                          Terrestrial nonfood crop:  1.2  -  2.4 Ib ai/A


a.  Chemical Characteristics

        Physical state:   solid
        Color:  Light yellow
        Odor:  odorless
        Vapor Pressure:  <1 x 10~7 mbar at 20 C
        Molecular Formula:  (Ci6H33Nlls16Zn3)

    Toxicology Characteristics

        Acute Toxicity:   All studies required

        Major Routes of Exposure: Dermal, Inhalation and oral by ingestion       "
                                  of food residues

        Subchronic Toxicity:  Inhalation study is adequate, other studies

        Oncogenicity:  Studies required

        Chronic feeding:   Studies required

        Metabolism:  Studies in rats indicate that the polymer is
                     hydrolyzed and readily absorbed and eliminated in
                     the urine and feces.  ETU was one of the metabolites
                     in the urine and bile of rats.

        Reproduction:  Study required

        Teratogenicity & Developmental Toxicity: Studies required

        Mutagenicity:  Considering only the acceptable studies, the
            majority of mutagenicity studies on metiram were negative.
            However, the in vitro sister chromatid exchange assay  in
            Chinese hamster ovary cells was positive  and  is considered
            a sensitive test for chromosomal effects. ' According to the
            present data, metiram is considered positive  for chromosomal         |

            damage.  A gene mutation assay is required.

    Physiological and Biochemical Characteristics

        Metabolism and Persistence in Plants and Animals:

            Metabolism of metiram is not completely understood.  Additional
            data are being required in plants and livestock.  ETU is a
            major metabolite of concern.

    Environmental Characteristics

         Presently only the "hydrolysis and photodegradation in soil and
    in water data requirements on both metiram and ETU were fully satisfied.
    Metiram has a very limited solubility in water.  Metiram in water
    solution degrades primarily to ETU and other transient degradates.
    ETU is also a soil degradate of metiram and its formation on soil is
    enhanced by sunlight.  ETU is stable in water at pH 5-9 and under
    sunlight and the degradation of ETU on soil is not enhanced by sunlight
    radiation.  ETU is the degradate of major environmental concern.
    There are indications that ETU may leach and enter groundwater.  However,
    additional data are required to complete the groundwater assessment.

    Ecological Characteristics

       0 Metiram has been found to be slightly toxic to birds.  Formulated
    metiram showed that LC50 values for mallard duck and bobwhite quail
    are both greater than 3712 ppm.

       0 Based on an acute contact honeybee toxicity study, there is
    sufficient information to characterize metiram as practically nontoxic
    to honeybees.


     Tolerances, expressed as zinc ethylene bisdithiocarbamate, have been
established for residues of metiram in a variety of raw agricultural commodities
(40 CFR 180.217 and 180.319).

    The toxicology data for metiram are insufficient to determine an
Acceptable Daily Intake (ADI) or whether the toxicity observed in the
studies is due to metiram or ETU.  A three generation rat reproduction
study has been used to calculate a Provisional ADI (PADI).  Because a
NOEL was not reached in the three generation study, an uncertainty factor
of 1000 was employed.  The PADI for metiram is 0.0003 mg/kg/day.

    The theoretical maximum residue contribution (TMRC), based on the
assumption that 100 percent of each crop is treated and contains residues
at the tolerance level, is 0.009 or approximately 3000 percent of the PADI.
Based on a more realistic dietary assessment,  using anticipated field
residues and estimate of percent crop treated, the estimated average
consumption for the U.S. population is 0.00038 mg/kg/day or 122 percent
of the PADI.


     The Agency initiated a Special Review for metiram along with the                  *
other EBDC's in June 1987 because of concern about the oncogenic risk to               I
consumers from dietary exposure to ETU from food treated with these pesticides,
and the risks of teratogenicity and adverse thyroid effects to applicators
and mixer/loaders from exposure to ETU.

o  ETU has been classified as a 62 oncogen (probable human carcinogen).

o  The Agency will not consider establishment of new food use tolerances
   for metiram because the current residue chemistry and toxicology data
   are not sufficient to assess existing tolerances and the toxicology
   data base is insufficient to determine an ADI and does not allow a
   decision as to whether observed toxicity is due to metiram or ETU.

0  The Agency will consider the need for establishment of tolerances for
   ETU and any intermediate metabolites when data are sufficient to permit
   such decisions.

0  The Agency will not establish any food/feed additive regulations pursuant
   to Section 409 of the Federal Food, Drug and Cosmetic Act (FFDCA) and is
   deferring action on previously established food/feed additive regulations.

0  Protective clothing labeling for metiram products, as required as a result
   of the 1982 Decision Document,  must be updated.

0  The Agency is requiring reentry data for metiram.  In order to remain in
   compliance with FIFRA, an interim 24-hour reentry interval requirement              (
   must be placed on the label of all metiram end-use products registered
   for agricultural uses, until the required data are submitted and evaluated
   and any change in this reentry interval is announced.

0  The Agency has screened and reviewed the environmental fate data to
   determine if metiram/ETU and/or its degradate(s) have the potential to
   leach into ground water.  The Agency has decided that in addition to
   environmental fate data requirements, a small-scale retrospective
   ground water monitoring study is also required to define the extent of
   the ground water problem.

o  While the data gaps are being filled, currently registered manufacturing-use
   products (MP's) and end-use products (EP's) containing metiram as the
   sole active ingredient may be sold, distributed, formulated and used,
   subject to the terms and conditions specified in this Standard.
   However, new uses will not be registered.  Registrants must provide
   or agree to develop additional data, as specified in the Data Appendices
   of the Registration Standard, in order to maintain existing registrations.


     All metiram products must bear appropriate labeling as specified in
40 CFR 156.10.  Appendix II of the Registration Standard contains information
on labeling requirements.

     In addition to the above,  in order to remain in compliance with FIFRA,
the Agency is requiring:

     0 Protective clothing requirements
     0 Environmental hazard precautions
     0 Worker safety rules
     0 Reentry interval
     0 Grazing restrictions for apples, pecans, corn (sweet), cotton, peanuts,
       sugar beets and potato (seed pieces).


    Product Chemistry  All - Due within 6 months

   • Technical Grade:
   . Preliminary analysis of product samples

    Analysis & certification of product ingredient
    Oxidizing or reducing action
    Storage stability
    Corrosion characteristics

    Toxicology - The last studies are due 12/90

    Acute testing
    Dermal sensitization
    90-Day feeding (rodent and nonrodent)
    21-Day subchronic dermal
    Chronic toxicity (rodent and nonrodent)
    Oncogenicity (rat and mouse)
    Teratology (rabbit and rat)
    Reproduction (rat)
    Mutagenicity (point gene mutation)

    Residue Chemistry - Data due 10/88 and 4/89

    Nature of the Residue in Plants and Livestock
    Analytical Methods
    Magnitude of Residue for Variety of Commodities

    Environmental Fate - Last studies are due 7/90

    Leaching and adsorption/desorption
    Field dissipation
    Degradation soil
    Degradation (soil long-term)
    Small-scale retrospective ground water monitoring
    Confined rotational crops
    Fish accumulation

    Reentry Protection  - Data due 7/89

    Reentry Studies on Foliar and Soil Dissipation

    Wildlife and Aquatic Organisms - Last data are due in 12 months

    Avian oral toxicity
    Freshwater fish toxicity
    Acute freshwater invertebrates
    Estuarine and marine organism toxicity

    ETU Data Requirements


    Chronic (rodent and non-rodent) Data due 5/90
    Reproduction  Data due 12/90

    Environmental Fate - Last studies due 7/90

    Aerobic and anaerobic soil metabolism
    Aerobic aquatic
    Lab volatility
    Degradation (soil)
    Aquatic (sediment)
    Degradation (soil long-term)
    Small-scale retrospective ground water monitoring study
    Fish accumulation


    Lois A. Rossi
    Product Manager (21)
    Fungicide-Herbicide Branch
    Registration Division (TS-767C)
    Office of Pesticide Programs
    Environmental Protection Agency
    401 M St., SW
    Washington, D.C.  20460

    Office location and phone number:
    Room 227, Crystal Mall #2
    1921 Jefferson Davis Highway
    Arlington, VA
    (703) 557-1900

9.  DISCLAIMER:  The information in this Pesticide Fact Sheet is a summary
only and may not be used to satisfy data requirements for pesticide regis-
tration and reregistration.   The complete Registration Standard for the
pesticide may be obtained from the National Technical Information Service.
Contact the Product Manager listed above for further information.

   U.S. Environmental Protection Agency
   Office of Pesticide Program (TS-757C)
   PMSD, Information Services Branch
   401 M Street, S.W.
   Washington, D.C. 20460

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