United States Office of Pesticides «nd Toxic Sufactances
Environmental Protection Offica of Pesticide Programs (TS-766C)
Agency Washington, DC 2O460
540/FS-89-001
xvEPA Pesticide
Fact Sheet
Name of Chemical: METIRAM
Reason for Issuance: REGISTRATION STANDARD
Date Issued: October 3, 1988
Fact Sheet Number: 181
1. DESCRIPTION OF CHEMICAL
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
disulfides
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
2. USE PATTERNS AND FORMULATIONS
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
powder.
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
sprayers.
Application Rates: Terrestrial food crop: 0.3 - 6.4 Ib ai/A
Terrestrial nonfood crop: 1.2 - 2.4 Ib ai/A
3. SCIENCE FINDINGS
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
required
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.
4. TOLERANCE ASSESSMENT
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.
-------
5. SUMMARY OF REGULATORY POSITIONS
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.
6. LABELING REQUIREMENTS
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).
7. SUMMARY OF DATA GAPS
Product Chemistry All - Due within 6 months
• Technical Grade:
. Preliminary analysis of product samples
MLJP:
Analysis & certification of product ingredient
Oxidizing or reducing action
Flammability
Explodability
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
Toxicology
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
8. CONTACT PERSON AT EPA
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.
-------
&EPA
U.S. Environmental Protection Agency
Office of Pesticide Program (TS-757C)
PMSD, Information Services Branch
401 M Street, S.W.
Washington, D.C. 20460
Official Business
Penalty for Private Use $300
First Class Mail
Postage and Fees Paid
EPA
Permit No. G-35
------- |