vvEPA
United StatM
Environmantal Pfo tact ion
Agency
Office of
Pecticidat and Toxic Subetancee
Washington DC 20460
October 1988
540/RS-89-Q02
PMieidM
Guidance for the
Reregistration of
Pesticide Products
Containing METIRAM
as the Active Ingredient
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OMB Control No. 2070-0057
Expires 11/89
GUIDANCE FOR THE
REREGISTRATION OF PESTICIDE PRODUCTS
CONTAINING
METIRAM
AS THE ACTIVE INGREDIENT
CASE NUMBER 0644
CAS (Docket) Number 9006-42-2
EPA CHEMICAL CODE 014601
OCTOBER 1988
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
WASHINGTON, D.C. 20460
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TABLE OF CONTENTS
GLOSSARY OF TERMS AND ABBEVIATIONS
I. Introduction
II. Chemical(s) Covered by this Standard 4
A. Description of Chemical
B. Use Profile
C. Background
III. Agency Assessment 11
A. Summary
B. Preliminary Risk Assessment
» C. Other Science Findings
D. Tolerance Reassessment
IV. Regulatory Position and Rationale 34
A. Regulatory Positions
B. Criteria for Registration
C. Acceptable Ranges and Limits
D. Required Labeling
V. Products Subject to this Standard 43
VI. Requirement for Submission of Generic Data 45
A. What are generic data?
B. Who must submit generic data?
C. What generic data must be submitted?
D. How to comply with DCI requirements
E. Registrant Requests Regarding Data Requirements
and Agency Responses
F. Test Protocols and Standards
G. Procedures for requesting a change in test
protocol
H. Procedures for requesting extensions of time
I. Data format and reporting requirements
J. Existing Ssocks provisions upon suspension
or cancellation
VII. Requirement for Submission of Product-Specific 'Data 51
VIII. Requirement for Submission of Revised Labeling ... 52
IX. Instructions for Submission 52
A. Manufacturing use products (sole active)
B. Manufacturing use products (multiple active)
C. End use products
D. End-Use Products Containing the Subject Active
Ingredient As One of Multiple Active Ingredients
E. Intrastate products
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APPENDICES
I . DATA APPENDICES ~. . . 57
Guide to Tables
Table A
Table B
II. LABELING APPENDICES 94
Submary of label requirements and table
40 CFR 156.10 Labeling Requirements
Physical/Chemical Hazards Labeling Statements
Storage Instructions
Pesticide Disposal Instructions
Container Disposal Instructions
III. BIBLIOGRAPHY APPENDICES 119
Guide to Bibliography
Bibliography
IV. FORMS APPENDICES 124
EPA Form 8580-1 FIFRA §3(c)(2)(B) Summary Sheet
EPA Form 8580-3 Generic Data Exemption Statement
EPA Form 85-80-4 Product Specific Data Report
EPA Form 8580-6 Certification of Attempt to Enter Into an
Agreement with Other Registrants for Development
of Data
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GLOSSARY OF TERMS AND ABBREVIATIONS
The following terms are used throughout this Registration
Standard and are defined here for the convenience of the reader.
ADI: (Acceptable Daily Intake) An acceptable daily intake of
pesticide residue based on a complete data base.
ai: Active ingredient
CAS: Chemical Abstract Service (number)
EEC: (Estimated Environmental Concentration) Estimated pesticide
concentration in the environment (terrestrial or aquatic
ecosystem).
i
EP: End-use Product
EPA: The Environmental Protection Agency, also "the Agency"
FIFRA: The Federal Insecticide, Fungicide, and Rodenticide Act
HOT: Highest dose tested
LC5Q: (median lethal concentration): a statistically derived
concentration of a substance that can be expected to cause
death in 50 percent of test animals, expressed as weight
or volume of test substance per volume of air or water
or per weight of feed (e.g., mg/L or ppm).
LD5Q: (median lethal dose): a statistically derived single dose
that can be expected to cause death in 50 percent of animals
when administered by the route indicated, expressed as
weight of substance per unit weight of test animal (e.g.,
mg/kg).
LEL: Lowest Effect Level
MOS: Margin of Safety -
MPI: Maximum Permissible Intake
MRID: Master Record Identification (number)—EPA's system of
tracking studies used in support of registrations
MP: Manufacturing-use product
NPDES: National Pollution Discharge Elimination System
NOEL: No Observed Effect Level—the maximum dose used in a
test which produces no observed adverse effects.
111
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OPP: The Office of Pesticide Programs (EPA)
OM: Organic matter (used to describe soils)
ppm: Parts per million
PADI: (Provisional Acceptable Daily Intake) An acceptable daily
intake of pesticide residue based on a limited data base.
PAI: Pure active ingredient
Technical: Active ingredient as manufactured
TMRC: (Theoretical Maximum Residue Contribution)
IV
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I. INTRODUCTION
EPA has established the Registration Standards program
in order to provide an orderly mechanism by which pesticide
products containing the same active ingredient can be reviewed
and standards set for compliance with FIFRA. The standards
are applicable to reregistration and future applications for
registration of products containing the same active ingredient.
Each registrant of a product containing an active ingredient
subject to this Standard who wishes to continue to sell or
distribute that product must bring his product and labeling
into compliance with FIFRA, as instructed by this Standard.
The Registration Standards program involves a thorough
review of the scientific data base underlying a pesticide's
registration. The purpose of the Agency's review is to
reasses*s the potential hazards arising from the currently
registered uses of the pesticide; to determine the need for
additional data on health and environmental effects; and to
determine whether the pesticide meets the "no unreasonable
adverse effects" criteria of FIFRA. In its review EPA identifies;
1. Studies that are acceptable to support the data
requirements for the currently registered uses of the pesticide.
2. Additional studies necessary to support continued
registration. The additional studies may not have been
required when the product was initially registered or may be
needed to replace studies that are now considered inadequate.
3. Labeling revisions needed to ensure that the product
is not misbranded and that the labeling is adequate to protect
man and the environment.
The detailed scientific review and use index which are
not contained in this document, but is available upon request1,
focuses on the pesticide active ingredient. The scientific
review primarily discusses the Agency's evaluation of and
conclusions from available data in its files pertaining to
the pesticide active ingredient. However, during the review
of these data the Agency is also looking for potential hazards
that may be associated with the end use products that contain
the active ingredient. The Agency will apply the provisions
of this Registration Standard to end use products if necessary
to protect man and the environment.
1The scientific reviews and use index are available from the
National Technical Information Service, 5285 Port Royal Road,
Springfield, Va. 22161 or from the Order Desk (703) 487-4650
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EPA's reassessment results in the development of a
regulatory position, contained in this Registration Standard,
on the pesticide and each of its registered uses. See
Section IV - Regulatory Position and Rationale. Based on its
regulatory position, the Agency may prescribe a variety of
steps to be taken by registrants to maintain their registrations
in compliance with FIFRA. These steps may include:
1. Submission of data in support of product registration;
2. Modification of product labels;
3. Modifications to the manufacturing process of the
pesticide to reduce the levels of impurities or contaminants;
4. t Restriction of the use of the pesticide to certified
applicators or other specially trained individuals;
5. Modification of uses or formulation types; or
6. Specification of packaging limitations.
Failure to comply with the data submission requirements
may result in the issuance of a Notice of Intent to Suspend.
Failure to comply with the other requirements in this Standard
may result is the issuance of a Notice of Intent to Cancel.
In addition, in cases in which hazards to man or the
environment are identified, the Agency may initiate a special
review of the pesticide in accordance with 40 CFR Part 154
to examine in depth the risks and benefits of use of the
pesticide. If the Agency determines that the risks of the
pesticide's use outweigh the benefits of use, the Agency
may propose additional regulatory actions, such as cancellation
of uses of the pesticide which have been determined to cause
unreasonable adverse effects on the environment.
EPA has authority under the Data Call-in (DCI) provisions
of FIFRA sec. 3(c)(2)(B) to require that registrants submit
data to answer our questions regarding the chemical, toxicological,
and environmental characteristics and fate of a pesticide.
This Registration Standard lists the data EPA believer are
necessary to resolve our concerns about this pesticide.
These data are listed in the Tables A, and B in Appendix I.
Failure to comply with the DCI requirements enumerated in
this Registration Standard may result in issuance by EPA of a
Notice of Intent to Suspend the affected product registrations.
Registrants are reminded that FIFRA sec. 6(a)(2) requires
them to submit factual information concerning possible unreason-
able adverse effects of a pesticide at any time that they
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become aware of such information. Registrants must notify
the Agency of any information, including interim or preliminary
results of studies, if that information suggests possible
adverse effects on man or the environment. This requirement
is independent of the specific time requirements imposed by
EPA for submission of completed studies called in by the
Agency and continues as long as the products are registered
under FIFRA.
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I I . CHEMICAL ( S ) COVERED BY THIS STANDARD
A- Description of chemical (s )
The following chemical(s) are covered by this Registration
Standard:
Common name: Metiram
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 anhydrosulf ides and
disulf ides
CAS Number: 9006-42-2
OPP ' (Shaughnessy) Numbers: 014601
Empirical Formula:
Trade names: Polyram®, Polram-Comi® , Carbatene® and Zinc
Metiram®
Description of physical characteristics of chemical
Color: Yellow
Melting Point: Approximately 140°C
B . Use ^Profile
Type of Pesticide: Fungicide (with minor insecticidal
value) .
Pests Controlled (in general): Foliar fungal diseases of
selected fruit, nut, vegetable, field and ornamental
crops.
Registered Uses: Terrestrial food crop uses on apples,
asparagus, celery, corn (sweet), cotton, cucumber,
peanuts, pecans, potatoes (including seed- pieces),
sugar beets, and tomato; Terrestrial nonfood crop uses
on tobacco (field and transplants) and roses.
Predominant Use(s): Apple foliage and potato foliage and
seed piece treatment
Mode of Activity: Inhibition of certain fungal enzyme systems
Formulation Types Registered:
Formulating intermediate - 80% percent active ingredient
End-use products - dusts, wettable powders
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Method(s) of Application: All formulations may be applied
by aerial equipment and ground equipment except the
single active ingredient (3.5%) and 10% formulations
used as seed piece treatments.
Application Rates - Terrestrial Food Crop: 0.3-6.4 Ib ai/A
Terrestrial Nonfood Crop: 1.2-2.4 Ib ai/A
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C.. Background
Metiram is one of six chemicals classified as ethylene bisdi-
thiocarbamate (EBDC) fungicides. These broad spectrum fungi-
cides are used to prevent crop damage by fungi and to protect
harvested products from deterioration. The chemical structure
of metiram and the other EBDC's (amobam, maneb, nabam, mancozeb,
and zineb) and their metabolite, ethylenethiourea (ETU) are
depicted in Figure 1.
The chemistry of the EBDC's is complicated by their instability
and their propensity to form polymers. The solubilities
of several of the EBDC's in water and other solvents vary from
insoluble to completely soluble. The EBDC's are generally
unstable in the presence of moisture and oxygen, as well as
in bio!6gical systems. A common contaminant, degradation
product, and metabolite of all EBDC's is ETU, an odorless
white crystalline solid that is soluble in water but insoluble
in common organic solvents. EBDC residues, in or on foods,
are known to convert readily to ETU during commercial processing
or home cooking.
In 1977, the Agency initiated a Special Review (formerly
referred to as Rebuttable Presumption Against Registration
[RPAR]) of the EBDC's. The Special Review process is designed
to help the Agency determine whether to initiate procedures to
cancel, deny or reclassify registration of a pesticide product
because uses of that product may cause unreasonable adverse
effects on the environment, in accordance with sections 3(c)(6)
and 6 of FIFRA. This process is set forth in 40 CFR 154,
which describes various risk criteria and provides that a
Special Review may arise if the Agency determines that any
of these criteria have been met.
The EBDC Special Review was based on the presumption that the
EBDC's and the metabolite, ETU, posed three kinds of risk to
human health or the environment: oncogenicity, teratogenicity,
and acute toxicity to aquatic organisms. Three additional
areas of concern were also identified: thyroid toxicity,
mutagenicity, and skin sensitization. Skin sensitization was
subsequently determined not to meet a Special Review criterion.
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The Agency evaluated these potential risks in depth, taking
into account uncertainties associated with the risk estimates,
considering the significant benefits of the EBDC's and weighing
various regulatory options. In 1982, the Agency issued its
Decision Document on all EBDC's reporting on the results of
the evaluation. This evaluation resulted in the following
conclusions.
1. The potential risk of acute toxicity to aquatic organisms
resulting from use of mancozeb on commercially grown
wild rice would be mitigated through present cultivating
practices and the addition of a statement to the label
warning users of a hazard to fish.
2. Potential risks of teratogenicity and thyroid toxicity
to commercial and agricultural applicators would be
adequately reduced by requiring protective clothing.
3. Potential dietary exposure resulting from consumption
of home grown produce could be reduced by highlighting
preharvest intervals on labels of noncommercial (home
use) products used by home gardeners.
4. The issues of whether EBDC's or ETU pose a potential risk
of oncogenicity, mutagenicity, teratogenicity, and thyroid
effects to man were subject to many uncertainties. Avail-
able data on oncogenicity and mutagenicity were not adequate
to resolve key scientific issues such as the mechanism of
action of EBDC's and ETU. Additional data on the EBDC's
and ETU were needed for the Agency to determine their muta-
genic potential and to assess human exposure and oncogenic
risk. Some data would be required at termination of the
Special Review while further data needs, with particular
emphasis on chronic studies, dietary residues and exposure,
would be identified during a later reregistration review.
Data needs identified at that time included:
a. Metabolism studies designed to define the in vivo
conversion of the various EBDC's to ETU and other
metabolites.
b. Dermal absorption studies designed to demonstrate the
dermal penetration of each of the EBDC's and ETU.
c. Five mutagenicity studies on each of the six registered
EBDC's.
d. Mammalian cell transformation assays on each of the
six EBDC's and ETU.
With the issuance of the Decision Document, the Agency concluded
the Special Review and returned the EBDC's to the registration
process on the condition that registrants comply with the
label changes and data requirements specified in the Decision
Document.
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Since issuance of the Decision Document, the Agency has issued
seven data call-in notices for metiram as follows:
1. January 17, 1983: This notice required the submission of
the metabolism, dermal penetration and mutagenicity data
identified in the 1982 Decision Document.
2. July 25, 1984: This notice advised registrants of the
Agency's concern about the existence of pesticides in
ground water and the designation of a number of chemicals,
including metiram, which may have the potential to con-
taminate ground water. The chemicals were designated
based on such factors as chemical structure, solubility,
and use patterns. The notice required submission of
certain environmental fate and product chemistry data
forithe agricultural uses only.
3. October 19, 1984: This notice required dietary exposure,
product chemistry and toxicological (subchronic feeding and
inhalation) data considered necessary to reassess the
registration status of metiram.
4. March 20, 1985: This notice required registrants of all
pesticide products containing metiram to submit all outstanding
data requirements as outlined under 40 CFR 158 regulations
for disciplines including product chemistry, toxicology,
wildlife and aquatic organisms, and environmental fate.
5. April 30, 1985: This notice required additional data,
not identified in the October 1984 call-in notice, but
considered necessary to the reassessment of the chemicals.
These data were additional toxicological (subchronic feeding
and inhalation - ETU) and residue data for ETU as well as
metiram.
6. March 31, 1987: Residue chemistry data were required in the
October 19, 1984 Data Call In Notice. Because adequate storage
stability data were not submitted to ascertain whether
residues of metiram and/or ETU are stable in or on plant
commodities when stored, firm conclusions on dietary exposure
to metiram or ETU from the use of metiram could not be
drawn based on data available at that time. Therefore,
this DCI required storage stability data and crop residue
data for metiram and ETU.
7. April 1, 1987: This notice required additional data
necessary to support the continued registration of metiram.
These data requirements pertain in general to the compre-
hensive review of the chemical which included the
reassessment of tolerances. This data included environ-
mental fate, product chemistry, residue chemistry, toxicology
and wildlife and aquatic organisms.
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FIGURE 1
CHEMICAL STRUCTURE OF EBDC'S AND ETU
ETHYLENE THIOUREA (ETU)
H
I
CH2 - NN
CH2 - N
I
H
= S
NABAM
AMOBAM
CH2
CH2
- N - C - S -
N - C - S
J If
H S
MANEB
- N,
CH2
I
CH2
H
1
- N
- N
I
H
S
II
- C -
- C -
II
S
S -
S - Mn
X > I
MANCOZEB
CH2-N-C-S- NH4
CH2-N-C-S-NH4
ZINEB
CH2
1
CH2
H
1
- N -
- N -
1
H
S
II
C - S -
C - S -
II
S
Zn
> 1
METIRAM
H S
1 If
CH2 - N - C - S -
1
CH2-N-C-S-Mn
1 II
H S
ZHy
X
H S
1 "
CH2 - N - C - S -
CHo - N - C - S - Zn(NH3) —
1 II
H a
.
H S
I II
CH2-N-C-S-
CH2-N-C-S-
1 H
3 H S
> I
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The data required by the first five call-in notices to support
the continued registration of metiram products have been
received and considered by the Agency in its evaluation of
metiram, as presented in the assessment section of this
Standard. Data submitted in response to the April 1, 1987,
Notice was such that the time frames for submission of
data were too late for the data to be reviewed and consequently
are not included in this Standard. However, all metiram data
submitted are being reviewed and the registrants) will be
informed as to the results of the Agency review when completed.
In June 1987, the Agency initiated another Special Review for
the EBDC'S. The Agency initiated this Special Review of the
EBDC pesticides because of concern about the oncogenic risk
to consumers from dietary exposure to ETU from foods treated
with these pesticides, and the risks of teratogenicity and
adverse thyroid effects to applicators and mixer/loaders
from exposure to ETU. ETU is present as part of the residue
of the EBDC pesticides on or in treated agricultural commodities.
In addition, a portion of the EBDC pesticide residues convert
into ETU in the body after ingestion. At the time of initiating
the Special Review, the Agency estimated that the lifetime
dietary oncogenic risk to consumers from these two sources
of exposure to ETU was 2.2 x 10" . This estimate is based
on exposure to ETU from the residues of only one of the EBDC
pesticides, mancozeb. Consequently, the overall dietary
risk may be higher due to contributions from the other EBDC's.
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III. AGENCY ASSESSMENT
A. SUMMARY
Based on the review of available data, the Agency has reached
the conclusions set forth in this Standard. A summary of
those conclusions follow. A more detailed discussion is
contained in the remainder of this Chapter.
1. A major toxicological concern from exposure to metiram
is the hazard to the human thyroid from presence of
ethylenethiourea (ETU), a contaminant, degradation product,
and metabolite present in metiram and other EBDC products.
Additional chronic studies on metiram are required for
further evaluation.
2. ETU has caused developmentally toxic/teratogenic
effects in rats and hamsters. There are no adequate
teratology studies on metiram. A rat teratology study
on metiram may partially fill the teratology requirement
if additional information on stability and homogeneity
on metiram technical can be provided. No teratogenic
effects associated with metiram administration were
noted in this study. A rabbit teratogenicity study
is required with metiram in order to fully assess its
teratogenicity.
3. ETU has been classified as a Group B2 carcinogen in accordance
with the Agency's Guidelines for Carcinogen Risk Assessment
(September 26, 1986, 51 CFR 33992), based on studies which
show that it induced an increased incidence of thyroid
adenomas and adenocarcinomas in rats and hepatomas in mice.
4. In June 1987, the Agency initiated a second Special
Review for the EBDC's because of concern about the oncogenic
risk to consumers from dietary exposure to ETU from
foods treated with these pesticides, and the risks of
teratogenicity and adverse thyroid effects to applicators
and mixer/loaders from exposure to ETU.
As a result of this review, the Agency has identified missing
data needed to further evaluate the environmental and human
risks associated with the use of metiram. These data must be
submitted in order to maintain registrations of products or
register new products containing metiram. Almost all of these
data have been required in previous Data Call In Notices.
Complete details can be obtained by referring to the tables
in Appendix I.
The Agency has also determined that certain label restrictions
or revisions are necessary in order for metiram products to
remain in compliance with FIFRA, as indicated below. Chapter
1 1
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IV, Section D, Labeling, contains the specific wording for
each of the labeling statements and identifies the products
to which each labeling statement applies.
o
0 Protective clothing requirements
0 Environmental hazard precautions
Reentry intervals
0 Worker safety rules
0 Preharvest interval emphasis
0 Grazing restrictions
The regulatory Position and Rationale section discusses the
Agency's position regarding metiram.
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B. PRELIMINARY RISK ASSESSMENT
Toxicology Studies - Metiram. In its review of metiram, the
Agency has considered the available data as summarized below:
1. Acute Toxicity and Irritation Studies. No data were
available for the evaluation of the acute toxic effects of
Metiram Technical. Data are required to assess the acute
oral, acute dermal, and acute inhalation toxicity, primary
eye and dermal irritation and skin sensitization potential of
metiram.
2. Subchronic Testing
Oral (Rodent, Nonrodent) Studies. Studies submitted in
response to the Data Call In Notice of October 19, 1984, may
satisfy these data requirements if additional information on
the stability and homogeneity of metiram technical is provided.
In a 13-week feeding study, metiram was fed to Sprague-Dawley
rats at levels of 0, 50, 100, 300, or 900 ppm (0 2.5, 5, 15,
45 mg/kg/day). Hind-limb paralysis was observed in the high
dose females but not males. Atrophic lesions of th'igh muscle
were increased in males receiving 900 ppm and in females
receiving 300 or 900 ppm (15, 45 mg/kg/day) after 13 weeks.
Weight gains for these groups were also significantly decreased
during the first 3 weeks of the study. Serum thyroxine
levels were decreased after 11-12 weeks in males and females
receiving 300 or 900 ppm (15, 45 mg/kg/day), and [131I]
uptake by the thyroid (measured at week 13) was decreased
compared to controls in all dosed groups of males and in
females receiving 100, 300, or 900 ppm (5, 15, 45 mg/kg/day).
There was a minimal degree of thyroid follicular hyperplasia
in 2 of the 15 males receiving 900 ppm (45 mg/kg/day).
After withdrawing the test compound for a 6-week period
there was a reversal of all effects noted except skeletal
muscle lesions in high-dose females. The LEL, based on.thyroid
function tests, is 100 ppm (5 mg/kg/day) in females and 50
ppm in males; a NOEL was not achieved for males but is considered
to be 50 ppm (2.5 mg/kg/day) in females.
Information on the purity and stability of the metiram test
substance is needed to complete evaluation of these studies.
In a 26 week feeding study, metiram was orally administered
to Rhesus monkeys at dosage levels of 5, 15, 75 mg/kg/day.
There were decreased serum levels of 3,3', 5,5'-tetraiodothyronine
(T4) (a thyroid hormone) in males and females and increased
thyroid weights in males at all dose levels. Decreased
serum levels of 3,5,3'triiodothyronine (T3) (a thyroid hormone)
in males and females, increased thyroid weights in females,
and follicular epithelial hyperplasia of the thyroid in
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males and females were observed in the 15 and 75 mg/kg/day
groups. T4 serum levels in 75 mg/kg/day animals appeared
reversed after 5 weeks of recovery; however, this effect was
not consistent at 15 weeks. Thyroid hyperplasia showed some
reversibility by week 15 of the recovery period.
When metiram was orally administered to a second set of Rhesus
monkeys (2/sex/dose) for 27 weeks at dosage levels of 5 and
75 mg/kg/day to assess the effect on thyroid function, there
was an initial reduction in iodine uptake in males and females
at 5 and 75 mg/kg/day followed by a significant increase in
iodine uptake in high-dose males and females after 27 weeks
of dosing.
Based on thyroid function studies and increased thyroid
weights,, the LEL is 5 mg/kg/day, the lowest dose tested. This
study did not provide a basis to establish a NOEL for metiram.
The subchronic oral studies may be upgraded with stability
and purity information on the test substance. Since a chronic,
non-rodent study is required, further subchronic studies in
non-rodents will not be necessary.
Dermal Studies - No data were available for the evaluation
of the subchronic dermal effects of metiram. A 21-day dermal
toxicity study is required.
Subchronic Inhalation - Sufficient data are available to
satisfy this data requirement for metiram technical. Metiram
was administered to rats in a 13-week inhalation study at
levels of 0, 2.1, 20 and 101 mg/m^ to groups of 28 males and
28 females. Group mean body weights in high dose males were
significantly lower than controls from weeks 7 through 12
and in high-dose females during weeks 12 and 13. A slight
decrease in body weight was observed in mid-dose males (20 mg/m^)
and females. Thyroxine and TSH were found to be slightly
decreased in high-dose males and females. Blood urea nitrogen
levels were significantly increased in high-dose females
compared to controls, but were apparently within the range
(of age and strain) of historical controls. Results of
urinalysis and pathology at sacrifice showed metiram is
excreted in the _urine and high quantities were found in lung
tissue, increasing with dosage. Several significant
organ weight effects were noted including increased relative
brain/bodyweight ratio, increased lung/trachea ratio in
males and lowered liver weight, and lower relative liver/bodyweight
ratio in high-dose males compared to controls. In females, in
the high-dose group, lung/trachea weight was significantly
greater than controls. In the 13-14 animals sacrificed at
13 weeks a significant number showed pigmentation of the
14
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kidneys in the convoluted tubule epithelium [11/11 males
examined at the high dose vs. 0/11 controls (none were examined
at the mid-dose)]. Lung alveolitis was found in 10/10 mid-
dose and 10/11 high-dose males compared to 0/11 controls.
Females showed an incidence of kidney pigmentation similar
to males, with 10/10 high-dose and 8/10 mid-dose females
compared to 0/10 controls. The NOEL (based on alveolitis
found in mid- and high-dose male and female rats) was
2.1 mg/m3 and the LEL effect level was 20
No further subchronic inhalation studies are required at this time,
3 . Chronic Testing
Chronic Toxicity Studies. Metiram was fed to CD rats at
dietary levels of 0, 5, 20, 80, or 320 ppm (0, .25, 1, 4, 16
mg/kg/day) for two years. The only compound-related effect
observed was an increase in skeletal muscle atrophy in males
and females receiving 320 ppm. There were no effects of
dosing on survival, body weights, or clinical laboratory
findings. Fluctuations of triiodothyronine (T3) or thyroxine
(T4) serum levels, and thyroid function (as assessed by
[131 j] uptake) were observed. However, the data on T3
and T4 serum levels cannot be adequately evaluated since
they were not measured on the same animals throughout the
study. Based on skeletal muscle atrophy, the LEL is considered
to be 320 ppm (16 mg/kg/day) and the NOEL is 80 ppm (4 mg/kg/day)
metiram in the diet. This rat study may be upgraded if
additional information on stability and homogeneity of metiram
technical is provided.
No data are available on the chronic toxicity of metiram to
non-rodents. Chronic studies in both rats and dogs are
required.
Oncogenicity Studies-Rats. Data on the oncogenicity phase of
the 2-year rat feeding study (also described under chronic
toxicity) indicated that under the testing conditions, metiram
was not oncogenic in CD rats. However, it appears that
the maximum tolerated dose was not approached in this study.
At the highest dose tested (320 ppm) (16 mg/kg/day) the only
effect noted was an increased incidence of minimal to moderate
muscle atrophy of the thighs in males and females. D.ose
15
-------
levels were selected on the basis of the 13 week subchronic
feeding study in rats which used doses up to 900 ppm (45 mg/kg/
day). Decreases in serum thyroxine levels in males and
females and decreased [ISlj] uptake by the thyroid at all
doses were several observations noted in the 13 week study.
Based on these and other observations the Agency believes
the choice of 320 ppm (16 mg/kg/day) as the highest dose is
low.
Zymbal gland squamous cell carcinoma was observed in several
treated males (2 in each of the low, medium-low, and medium-high
dose groups; one in the high dose group) and in one female
of the mid-dose group but none in the control groups. However,
because of the lack of historical background incidence of
this tumor in this strain of rat, the significance of this
incidence could not be evaluated. Analyses of test substance
for stability, homogeneity and purity were not reported.
Mice
In a 1979 oncogenicity study, CFLP mice were fed 0, 100, 300,
or 1000 ppm (0, 15, 45, 150 mg/kg/day) of the test material
in the diet. A compound-related oncogenic response was not
apparent. However, this study could not be fully evaluated
because of the following deficiencies:
a. The summary tabulation of histopathology data did not
list the number of tissues examined, only the number of
animals.
b. Examination of a sampling of individual pathology
data records indicated that many essential
tissues may not have been examined histologically.
c. Historical laboratory data for neoplasms in the CFLP
strains of mouse were not provided.
The data as presented are inconclusive. In addition,
the maximum tolerated dose was apparently not reached
in this study since the highest dose level failed to induce
any overt toxic effects in both sexes; the animals could
have tolerated higher dose levels. Analyses of the test
substance for stability and homogeneity were not reported.
If adequate histopathology information and stability information
on the test substance cannot be provided, a repeat study
will be necessary.
These studies may suffice if additional information on the
selection of dose (for mouse and rat studies), on histopathology
(for the mouse study), and on stability, homogeneity and
purity on Metiram Technical (for both mouse and rat studies)
can be provided.
16
-------
Teratogenicity Testing In a 1979 teratogenicity study in
Sprague-Dawley rats, metiram was administered at 0, 40, 80,
and 160 mg/kg/day to 20 female rats per group. Maternal
body weight gains for high dose dams were significantly
reduced on gestation days 10 and 14 when compared with controls.
No teratogenic effects associated with metiram administration
were noted in this study.
Maternal toxicity no observed effects level (NOEL) was 80
mg/kg/day with bodyweight changes in high-dose dams 15 and
16% lower than controls on treatment days 10 and 14. Based
on the above findings, the LEL for maternal toxicity was 160
mg/kg/day. The lowest observed effect level for developmental
toxicity was assessed at 160 mg/kg/day and the NOEL was 80
mg/kg/day based on preimplantation and postimplantation
losses. At the high dose these values were 13.3% and 6.9%,
respectively, with corresponding control values of 5.9%
and 4.0%. No teratogenic effects associated with metiram
administration were noted in this study. This study was
inadequate for complete evaluation, but may be acceptable if
adequate stability and homogeneity on metiram technical are
provided.
A rat and rabbit teratology study are required. The rat
study failed to include information on stability and homogeneity
on metiram technical; if this is provided, the study may not
have to be repeated.
Reproduction Study In a reproduction study with Sprague-Dawley
rats, metiram mixed in the diet at concentrations of 0, 5,
40, and 320 ppm (0, .25, 2, 16 mg/kg/day) produced mild
decreases in parental bodyweights and parental food consumption
at 320 ppm. In addition, the following effects in reproductive
performance and developmental effects were noted: 1) Litter
size for animals dosed with 5, 40, and 320 ppm were reduced
compared with controls for the ?2b anc^ ^3t> (significant
at all dose levels); however these reductions did not occur
in dose-related patterns. 2) The mating performance of
animals dosed at 320 ppm (16 mg/kg/day) was slightly reduced
when compared with controls; the length of gestation at this
dose level was slightly increased when compared with controls.
3) Based on the above findings, the NOEL for parental toxicity
of metiram is assessed at 40 ppm, (2 mg/kg/day) and ttie LEL
is 320 ppm (16 mg/kg/day). A NOEL for developmental toxicity
was not established in this study; effects were seen at all
dosage levels (reduced litter size). Also mating performance
was reduced at the high dose in the F3 generation. Because
of the lack of a NOEL for reproductive effects, the submitted
study does not satisfy the data requirements. A new study
is required.
Mutagenicity Studies - Metiram was tested for its potential
to induce unscheduled DNA synthesis in the primary hepatocyte
in rats. Under the test conditions, "the test material did
17
-------
not induce significant changes in the nuclear labeling of rat
primary hepatocytes in concentrations ranging from 0'.492 to
49.2 ug/ml of the test material and 25.8% to 107.2% cell
survival rate."
In an in vivo bone marrow cytogenetic assay in rats, the acute
(one dose") oF subacute (daily x 5 days) oral exposure to male
rats to 2.4 or 0.2 g/kg, respectively, of metiram technical
did not cause a significant increase in chromosomal aberrations
from bone marrow cells sampled over the entire mitotic cycle.
The following studies were submitted in response to an earlier
Data Call In Notice with the results given and the Agency's
classification of the study:
a) S. Cerevisiae reverse mutation (presumptive positive)
(inconclusive/unacceptable).
b) UDS/rat primary hepatocytes (negative) (acceptable)
c) In vivo bone marrow cytogenetic assay/rat (negative)
(acceptable)
d) Transformation/promotion in C3H 10 T 1/2 cells
(negative/weak positive) (acceptable/inconclusive)
e) Mouse/host-mediated assay (negative) (acceptable)
f) In vitro SCE in CHO cells (positive without S9, and
with mouse S9; negative with rat S9) (acceptable)
g) Point (gene) mutation (HGPRT) in CHO cells (positive
without S9, marginal positive with rat S9) (inconclusive)
A repeat assay (point mutation in CHO cells) is required.
The majority of acceptable mutagenicity studies on metiram
were negative. However, the in vitro sister chromatid
exchange assay in CHO cells was positive and is considered
a sensitive test for chromosomal effects. Metiram is
considered positive for chromosomal damage.
Metabolism Studies - The metabolism and clearance of metiram
were studied in male and female CD rats. The data indicate
that the polymer is hydrolyzed and readily absorbed and
eliminated in the urine and feces. Elimination in the urine
is slightly higher in females than in males. Residues were
highest in the thyroids, kidneys, and gastrointestinal (G.I.)
tract and were higher in the tissues of female rats than
male rats. Some accumulation of residues in the tissues was
seen after repeated dosing of C^-^C] Metiram (seven daily
oral dosages at ,5 mg/kg/day). Analysis of metabolites indicates
that metiram is catabolized to numerous compounds of low
molecular weight.
ETU was reported to be one of the metabolites in the urine
and bile of rats dosed with radiolabeled metiram mixtures.
ETU was reported to comprise roughly 30 percent of the 0-24
hour urinary radioactivity and 4.2 to 18.0 percent of the 0-
12 hour biliary radioactivity.
Percutaneous Absorption - Metiram technical is not significantly
absorbed through the skin. C^C] Metiram was not significantly
absorbed when topically applied to the shaved skin of adult
IS
-------
male CD-I rats. Less than 1 percent of the 240 mg/kg dose
of [14C] metiram was absorbed through'the skin after 8
hours of contact. In contrast, at a dose level of 0.24 mg/kg
a higher percentage of the radioactivity was absorbed (about 5
fold). A dermal absorption factor of 6 percent was employed
in the risk assessment based on the exposure to applicators.
Toxicological Studies - ETU - Since ETU, a contaminant,
degradation product, and metabolite of metiram and other EBDC
products, presents toxicological concerns, available data on ETU
were considered in the overall evaluation of metiram. These
data are summarized as follows:
Subchronic Studies - During a 90-day rat feeding study with
mancozeb, an additional group of animals received 250 ppm
(12.5 mg/kg/day) ETU. Compound related effects in this
group were generally comparable to those observed at 1000
ppm (50 mg/kg/day) mancozeb (depressed body weight and changes
in hormone levels accompanied by diffused hyperplasia of
thyroid follicular epithelium). Residue analysis for ETU in
mancozeb-treated animals revealed that no ETU was present in
the blood.
In a rat study conducted to examine the subchronic effects
of ETU on the thyroid, levels of 50, 100, 500, and 750 ppm
(2.5, 5, 25, 37.5 mg/kg/day) ETU were fed for 30, 60, 90,
and 120 days. A NOEL was not determined in this study due
to effects of ETU seen on thyroid weights at all dosage
levels at 120 days. In a second rat study, levels of 0, 1,
5, 25, 125, and 625 ppm (.05, .25, 1.25, 6.25, 31.25 mg/kg/day)
ETU were fed for 30, 60, and 90 days. Thyroid hyperplasia,
decreased uptake of 125j j-,v ^Ine thyroid, and decreased
serum T3 (triiodothyronine) and T4 (tetraiodothyronine)
were seen. The LEL was 25 ppm (1.25 mg/kg/day) for these
effects with 5 ppm (0.25 mg/kg) considered the NOEL.
In a 90-day mouse study, ETU fed at levels of 0, 1, 10, 100,
and 1000 ppm (0, .15, 1.5, 15, 150 mg/kg/day) resulted in
increased thyroid weights in females and an increased incidence
of follicular cell hyperplasia in both sexes at levels of
100 ppm (15 mg/kg/day) and higher. Liver toxicity was only
observed at the highest level, 1000 ppm (150 mg/kg/day).
In a 21-week study in Rhesus monkeys, at dosage levels of 0,
2, 10, 50, and 250 ppm (0, 0.1, 0.5, 2.5, 12.5 mg/kg/day),
serum thyroid hormone concentrations were measured as well
as iodine uptake in the thyroid. Mild to moderate pituitary
hypertrophy was seen at 50 and 250 ppm, as well as thyroid
follicular lining cell hypertrophy and hyperplasia (mild at
50 ppm; moderate to severe at 250 ppm). Serum levels of T4
were significantly decreased in the 250 ppm group. Free
serum T4 levels were also significantly decreased in both
the 50 and 250 ppm group; iodine uptake was significantly
increased at these levels and thyroid stimulating hormone
(TSH) levels were significantly increased at 250 ppm.
-------
In a 6-month Rhesus monkey study, at dosage levels of 0, 50,
150, and 450 ppm (0, 2.5, 7.5, 22.5 mg/kg/day), pituitary as
well as thyroid hormone levels were measured. A NOEL was
not demonstrated.
On c ogenici ty Studies - Three oncogenicity studies have
been reviewed, as discussed below:
In a mouse study (Innes), two hybrid strains of mice were
used [(C57BL/6 x C3H/Anf)Fi (Strain X) and (C57BL/6 x
AKR)F]_ (Strain Y)]. Eighteen mice per sex per group were
used in the treatment group. Only one dose was tested which
was stated to be the maximum tolerated dose. When the mice
were 7 days old, 215 mg/kg ETU was given by stomach daily.
At 28 days of age, the mice were given diets containing 646
ppm (96.9 mg/kg/day) of ETU. The mice were sacrificed after
a total of 83 weeks of treatment. Histopathology consisted
of examination of all major organs and of all grossly visible
lesions. Thyroid glands were not examined. The incidence
of liver tumors, which were not classified as adenomas or
carcinomas but only as hepatomas, is outlined in the following
table:
Male Female
Control Treated Control Treated
Strain X 3/14 14/16 0/18 18/18
Strain Y 1/18 18/18 0/18 9/16
Totals: Controls - 4/68 Treated - 59/68
In a study with Charles River CD-I rats, 175 or 350 ppm
(8.75, 17.5 mg/kg/day) ETU was administered in the diet for
18 months. At that time, 5 rats/sex were sacrificed and the
remaining rats were placed on control diets until termination
of the study at 24 months. The control group consisted of
32 male and 36 female rats. No thyroid lesions were seen in
the control group. The incidence of thyroid lesions in the
ETU-treated rats is presented below. The number of animals
examined was not given.
JJLP_p_p_m
Lesion Males* F_§J!!§.!§JEL Males* Females
Thyroid carcinoma** 17 8 33
(follicular)
Thyroid solid cell 01 02
ademona
Hyperplastic goiter 17 13 96
Simple goiter 24 42
*A11 five male rats in the high-dose group sacrificed
at 18 months had hyperplastic goiter; 3 had follicular
thyroid cancer.
**Two with lung metastases.
20
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In a "2-year study, Charles River rats were placed on diets
containing 0, 5, 25, 125, 250, or 500 ppm (0, .05, .25, 6.25
12.5, 25 mg/kg/day) ETU. Body weight gain was adversely
affected at the highest dose tested at 18 and 24 months for
both males and females. 131j uptake was statistically
increased in male rats at 18 months in the 25 and 125 ppm
(.25, 6.25 mg/kg/day) groups and decreased at 500 ppm (25
mg/kg/day). At 24 months in the male rats, 131I uptake
was significantly increased in the 5 ppm (.05 mg/kg/day)
group and decreased in the 500 ppm (25 mg/kg/day) group.
Because of large variability in the values obtained, there
were no statistically significant differences in 13^I
uptake in female rats.
Histopathology incidence data were combined for males and
females. An increase in the number of rats with cataracts/
keratitis and with thyroid follicular adenocarcinoma/ carcinoma
was observed in the groups fed 250 and 500 ppm (12.5, 25 mg/kg/day)
ETU; with thyroid adenomas in the 250 ppm (12.5 mg/kg/day)
group; and with thyroid hyperplasia in the 5, 25, 125, and
250 ppm (.05, .25, 6.25 mg/kg/day) groups. The LEL
is 5 ppm (0.25 mg/kg/day) for the effects of ETU on the
thyroid in this study. Relevant data are summarized as
follows:
Tumor Incidence Data for Rats,
Including 18-Month Interim
Sacr_i_fice^_Fed_ETU_in the Diet
Dose Levels in ppm
0 5 25 125' 250 500
Pathological lesions
Cataracts/keratitis 2 10 2 6 12
Thyroid carcinoma/
adenocarcinoma
(follicular) 2 2 1 2 16 62
Thyroid adenomas 2 — 5 1 21 3
Thyroid hyperplasia 4 20 41 44 27 3
Parathyroid hyperplasia 6 11 8 2 3 0
Number of Rats per Group 72 75 73 73 69 70
Statistics were not reported on the histopathological data.
Historical control data were not available. More detailed
information on this study is not available.
Teratology Studies - ETU has been shown to be a teratogen in
studies with rats and hamsters. In rats, it produces a wide
variety of anomalies in the central nervous, urogenital and
skeletal systems as well as other organs at dosages that do
21
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not produce maternal toxicity or fetotoxicity. The NOEL for
these effects is 5 mg/kg. Administration of T3/T4 with
ETU to pregnant rats appears to reduce the incidence of some
of these effects.
Mutagenjxrity Studies - Results of short-term assays indicate
that ETU is weakly genotoxic; ETU has been shown to give
mixed results for gene mutation in both bacterial and mammalian
cell lines, but positive results for DNA repair in human
cells, yeast, and bacteria. Although reportedly positive in
one mammalian cell transformation assay using hamster cells,
an adequate assay in mouse cells was negative.
Metabolism Studies - In a study with Rhesus monkeys, 50
percent of an administered dose of ^-^C-ETH] was excreted
in the urine within 24 hours and 90 percent within 72
hours. Only 0 to 0.68 percent of the label was eliminated
in the feces at 24 hours and no radioactivity was found
at the 48- and 72-hour sampling periods.
In another study with Wistar rats, ^-^C-ETU was predominantly
excreted in the urine. The ratio of urine to fecal excretion
varies with dose, (i.e., for 0.1 ppm ETU the ratio was 55/25,
and at 10 ppm ETU the ratio was 70/10). Minimal radioactivity
was recovered as C02 (£ 0.5%). The level of radioactivity
plateaued in the thyroid gland after 8 days of dosing and
declined rapidly once dosing was terminated.
Structure Activity Information - ETU is structurally related
to thiourea, methimazole, propylthiouracil, and thiouracil,
and thyroid inhibitors. Chronic studies on thiourea in rats
have shown that it induces hepatomas and thyroid enlargement.
Methimazole, propylthiouracil and thiouracil all induce
thyroid tumors in rats. Propylthiouracil also induces thyroid
tumors in hamsters and guinea pigs and pituitary adenomas in
mice. Thiouracil induces hepatomas and thyroid tumors in
mice.
Risk Assessment - The Agency does not have any acceptable
oncogenicity data on metiram. However, based on the data
available on ETU, as discussed in the preceding section, the
Agency has classified ETU, in accordance with the Agency's
Guidelines for Carcinogen Risk Assessment (September 26,
1986, 51 FR 33992), as a Group B2 oncogen, Probable Human
Carcinogen.
The Agency's classification of ETU was made in accordance with
its guidelines for carcinogen risk assessment. These guidelines
categorize the evidence on carcinogenicity of chemicals in terms
of how likely it is that the chemical is a human carcinogen.
Under this scheme, Group B2 categorization is appropriate if
there is "sufficient evidence" of the chemical's carcinogenicity
from animal studies. "Sufficient evidence" is defined as an
22
-------
increased incidence of malignant tumors (or combined malignant
and benign tumors) in multiple species or strains, in multiple
experiments, or' to an unusual degree with regard to incidence,
site or type of tumor, or age at onset.
ETU induced an increased incidence of thyroid adenomas and
adenocarcinomas in two separate studies with rats and hepatomas
in two strains of mice. Furthermore, ETU induced the thyroid
tumors in rats after 1 year or less of treatment and induced both
the thyroid tumors in rats and the hepatomas in mice to an unusual
degree in a single experiment.
The classification as a Group B2 oncogen is also supported by
positive structure-activity data since several other thyroid
inhibitors (i.e., thiouracil and thiourea) have been found to
induce hepatomas and/or thyroid tumors in rodents.
t
EPA acknowledges that the studies considered in arriving at its
classification of ETU were not carried out in accordance with EPA
guidelines for oncogenicity studies. EPA, however, does consider
the studies adequate to conclude that ETU is oncogenic to rats
and mice due to the magnitude of the response seen.- The Agency's
conclusions regarding the classification of ETU will be reconsidered
when results of additional studies on ETU are available.
Worker Expo s ur e and Ri s k s - The Agency is currently assessing
risks associated with systemic effects of metiram and the
teratogenic, thyroid and oncogenic effects attributable to ETU.
Information available to the Agency about use practices indicates
that aerial loading and application are generally performed
by different people. For other application methods (ground
boom, airblast, sprinkler and seed treatment), loading and
application are generally performed by the same person.
Mixer/loaders and applicators are also exposed to ETU when the
EBDC pesticides are used in a tank mix. Available data
indicate that the concentration of ETU as a contaminatit can
vary between products. For calculating direct exposure to
mixers and loaders while preparing and loading metiram spray
mixture, the Agency used 0.1% of the metiram exposure. This
represents the typical level of ETU contamination of EBDC
products for which we have data. The pesticide applicator
is exposed not only to the amount of ETU which contaminates
the technical and tank mix but also to the additional. ETU
formed while spraying. There are no available data for
metiram, therefore, the Agency used the available data for
maneb to calculate direct ETU exposure to applicators.
Metiram
An oral subchronic study of metiram in rats showed thyroid
effects at the lowest dose tested (2.5 mg/kg) in male rats.
No teratogenic effects were seen at the highest dose tested
23
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(160 mg/kg/day) when metiram was tested in the rat. The
Agency calculated a ratio for metiram exposure to the lowest
dose level for the subchronic thyroid effects; however, this
is not a true MOS as no NOEL was found for males in the rat
study. Only for oncogenicity, for which the Agency has no
studies for metiram, was a metabolic conversion to ETU
performed. The Agency also calculated MOSs for teratogenic
and thyroid effects of ETU from direct exposure to ETU as an
impurity and environmental degradate from the use of metiram.
In these calculations, dermal absorption figures of 30% and
6% were used for ETU and metiram, respectively. See Table
2.
ETU - ETU has been shown to be teratogen in studies with -rats
and hamsters. In rats, it produces a wide variety of anomalies
in the* central nervous, urogenital and skeletal systems. The
NOEL for these effects is 5 mg/kg.
In assessing teratogenic margins of safety, the Agency has
assumed 30 percent dermal absorption based on a dermal
absorption study for the' ETU contaminant in the tank mix.
Because metiram did not demonstrate teratogenic effects at
160 mg/kg/day, we did not perform an _in v^vo conversion calculation
The exposures to applicators and the margins of safety for
teratogenic effects of ETU from exposure to metiram and ETU
in the tank mix are shown in Table 3.
ETU has also demonstrated thyroid hyperplasia, decreased
uptake of 125i (iodine) by the thyroid and decreased serum T3
and T4 in a subchronic feeding study in rats. The NOEL for
these effects is 5 ppm (0.25 mg/kg/day). Margins of safety
for thyroid effects were calculated for direct exposure to
ETU and are given in Table 3.
The Agency has also calculated the oncogenic risk to loaders
and applicators from exposure to ETU both from metiram absorbed
and metabolized to ETU and from direct exposure to ETU as a
contaminant in the tank mix. The exposures and risks are given
in Table 3. The range of oncogenic risk is 4 x 10~8 to
3 x 10~5.
Dietary Exposure and Risk - The Agency has assessed 'dietary risks
attributed to exposure to ETU resulting from application of
metiram to crops. Risks were calculated for certain chronic
adverse effects from chronic dietary exposure to ETU and
metiram. In addition, oncogenicity and teratology dietary risks
were calculated for ETU.
Chronic Adverse Effects
Dietary exposure to ETU from use of metiram and potential
risks for adverse effects from this exposure were assessed.
Average field trial residues of ETU, obtained from studies
submitted in support of metiram tolerances, were used for this
24
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dietary exposure analysis. The ETU residues for processed
products were calculated by using the appropriate conversion
factors, calculated from the available data, for each of the
processed commodities since some metiram converts to ETU
during the processing of the raw agricultural commodities.
These residues were then reduced by the percent of crop
treated with metiram obtained from actual usage data
except a percent crop treated value of 10 was used for all
commodities where the estimated percent crop treated was less
than 10. The results of this analysis indicate that the
average consumer in the U.S. population receives a direct
dietary exposure to ETU from metiram use of 0.00008 mg/kg/day.
The PADI for ETU was derived from the 2-year chronic feeding
study in Charles River rats with an LEL of 0.25 mg/kg/day.
An uncertainty factor of 3,000 was applied. This resulted
in a PADI of 0.00008 mg/kg/day. The effect on which the
PADI is based was hyperplasia of the thyroid; a NOEL for
this effect was not established for this study.
The dietary exposure to ETU of 0.00008 mg/kg/day occupies
98 per cent of the PADI.
Secondly, dietary exposure to metiram and potential risks
for adverse effects were assessed. The residues used in the
analysis were the average field trial residues of metiram,
obtained from data submitted in support of established
tolerances, considering the percent of crop treated. Based on
these average residues, the average consumption estimate for
the U.S. population is calculated as 0.0004 mg/kg/day metiram.
The PADI for metiram was derived from a three generation rat
reproduction study with a LEL (NOEL has not been established)
of 0.25 mg/kg/day and a safety factor of 1000 for a PADI of
0.0003 mg/kg/day.
The dietary exposure to metiram of 0.0004 mg/kg/day utilizes
128 percent of the PADI.
Oncogenicity Risks
A risk assessment was conducted to determine potential
oncogenic risks from dietary exposure to ETU from use of
metiram. For this assessment, average residues for both ETU
and metiram from field trials were used. The Agency's
Carcinogen Assessment Group derived risk models based on
various bioassays on ETU. The most sensitive sex/species end
point was found to be male mouse liver tumors in the Innes
study. The potency, or Qi*, was calculated to be 0.14
(mg/kg/day)~1.
Using the Tolerance Assessment System (TAS), the dietary
exposure analysis indicates that the average consumer in the
-------
TABLE 2
NONDIETARY RISK ASSESSMENT FOR METIRAM
mg/kg/day mg/kg/day tng/kg/day METIRAM
METIRAM a/ METIRAM METIRAM TOTAL
DERMAL ABSORBED INHALATION DAILY
EXPOSURE DERMALLY EXPOSURE EXPOSURE
1 mg/kg/day
PPLES:
AERIAL
IRBLAST
ITATOES :
AERIAL
LOADER
APPLICATOR
' LOADER
APPLICATOR
COMBINE
LOADER
APPLICATOR
FLAGGER
tOUNDBOOM LOADER
APPLICATOR
COMBINE
0
0
0
2
3
1
0
0
0
0
0
.2300
.0081
.9400
.2000
.1400
.9000
.0380
.0210
.2200
.2900
.5100
0
0
0
0
0
0
0
0
0
0
0
.0138
.0005
.0564
.1320
.1884
.1140
.0023
.0013
.0132
.0174
.0306
0
0
0
0
0
0
0
0
0
0
0
.0035
.0003
.0140
.0033
.0170
.0290
.0012
.0120
.0034
.0053
.0087
0
0
0
0
0
0
0
0
0
0
0
.0173
.0008
.0704
.1353
.2054
.1430
.0035
.0133
.0166
.0227
.0393
)ME OWNER
ROSES COMBINE
mg/kg/day mg/kg/day mg/kg/day mg/kg/day ETU
b/ METIRAM ETU C/ ETU ETU FROM TOTAL
METABOLIZED DERMAL ABSORBED INHALATION DAILY
TO ETU EXPOSURE DERMALLY EXPOSURE EXPOSURE
mg/kg/day
0.0035
0.0002
0.0141
0.0271
0.0411
0.0002
0.0140
0.0009
\ 0.1300
0.1309
0.0001
0.0042
0.0003
0.0390
0.0393
0.0000
0.0000
0.0001
0.0000
0.0001
0.0035
0.0044
0.0144
0.0661
0.0804
0.0286
0.0007
0.0027
0.0033
0.0045
0.0079
0.0019
0.0023
0.0130
0.0002
0.0170
0.0172
0.0006
0.0007
0.0039
0.0001
0.0051
0.0052
0.0009
0.0000
0.0009
0.0000
0.0000
0.0000
0.0300
0.0014
0.0074
0.0034
0.0096
0.0130
0.0053
0.0003
0.0000
0.0003
0.0001
0.0000
0.0000
0.0000
0.0001
f 6% DERMAL ABSORPTION FOR METIRAM
t 20% METABOLIC CONVERSION OF METIRAM TO ETU
f 30% DERMAL ABSORPTION FOR ETU
ro
ON
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NONDIETARY RISK ASSESSMENT FOR METIRAM
METIRAM ETU ETU ETU TOTAL
TOTAL TOTAL DAYS TOTAL YEARLY
DAILY DAILY EXPOSED YEARLY DIRECT
EXPOSURE EXPOSURE EXPOSURE EXPOSURE
rog/kg/day mg/kg/day rag/kg mg/kg
VPPLES:
AERIAL
URBLAST
DTATOES :
AERIAL
LOADER
APPLICATOR
-' LOADER
APPLICATOR
COMBINE
LOADER
APPLICATOR
FLAGGER
ROUNDBOOM LOADER
APPLICATOR
COMBINE
OMEOWNER
ROSES
/ RISK
COMBINE
0.0173
0.0008
0.0704
0.1353
0.2054
0.1430
0.0035
0.0133
0.0166
0.0227
0.0393
0.0003
- YEARLY EXPOSURE/365
0.0035
0.0044
0.0144
0.0661
0.080.4
0.0300
0.0014
0.0074
0.0034
0.0096
0.0130
0.0001
X 430/70
1
1
7
7
7
4
4
4
7
7
7
0.0035
0.0044
0.1009
0.4626
0.5631
0.1201
0.0055
0.0296
0.0237
0.0675
0.0911
0.0001
0.0042
0.0024
0.2731
0.2755
0.0057
0.0028
0.0190
0.0004
0.0357
0.0361
METIRAM SYSTEMIC
TOTAL THYROID MOS
YEARLY SEASONAL TERATO
EXPOSURE METIR. MOS ETU
mg/kg 2.5 mg/kg 5 rag/kg
10
0.0007
0.0001
0.0173
0.0008
0.4928
0.9471
1.4378
0.5720
0.0139
0.0530
0.1162
0.1589
0.2751
0.0032
13006
286260
457
238
156
393
16164
4242
1936
1416
818
70755
1420
1148
347
76
62
167
3608
675
1479
519
384
68306
SYSTEMIC
THYROID
SEASONAL
ETU MOS
.25 mg/kg
375000
5357
9454
82
82
a/ ONCO
RISK
ETU
1.93E-07
2.39E-07
5.53E-06
2.53E-05
3.09E-05
3961 6.58E-06
8152 3.04E-07
1184 1.62E-06
53571 1.30E-06
630 3.70E-06
623 4.99E-06
234375 4.01E-08
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U.S. population receives a dietary exposure of 0.00008
mg/kg body weight/day ETU from conversion of metiram on
crops. This analysis was based on average field residues
for ETU considering the percent crop treated with metiram.
The potential dietary risk is calculated by multiplying
exposure by the Q]_*:
Dietary Risk = Exposure x Q]_*
= 0.00008 x 0.14
= 1.1 x 10~5
In addition, there is dietary exposure from conversion of
metiram to ETU in vivo after eating food containing metiram
residues. Metabolism studies in rats show that approximately
20 percent of metiram is metabolically converted to ETU. In
order*to determine the dietary exposure to ETU from conversion
of metiram residues in this way, the metiram dietary exposure
of 0.0004 mg/kg/day is multiplied by 20 percent to yield
an exposure of 7.7 x 10~5 mg/kg/day ETU. Multiplying this
by the Q-.* of 0.14 (mg/kg/day)"1 yields a risk of 1.1 x
10-5.
The total potential dietary risk from exposure to ETU from
use of metiram on food crops is obtained by adding 1.1 x 10~5
and 1.1 x 10~5.
Total Dietary Oncogenic Risk = 2.2 x 10~5
Ter_atogenicity Risks
Because ETU has been shown to be a teratogen in studies with
rats and hamsters, an exposure and risk assessment was conducted
for this effect. In rats, ETU produces a wide variety of
anomalies in the central nervous, urogenital, and skeletal
systems as well as other organs at dosages that do not produce
maternal or fetotoxicity. The NOEL for these effects is 5
mg/kg/day.
Metiram and ETU crop residues were derived from studies
submitted by the registrant. The analysis was conducted
assuming that ETU was present uniformly in the food commodities
at the maximum.residue observed in field tests conducted closest
to the maximum application rate, the minimum PHI, and the
typical number of applications. The percent of crop treated
was not considered because this is a single exposure rather than
a lifetime exposure.
The acute dietary exposure for ETU is compared to a NOEL for
teratological effects of 5 mg/kg. The population subgroup
of interest is females of child-bearing age. The Margin of
Safety (MOS) for acute exposure is calculated as the ratio
of the NOEL to the estimated exposure. The estimate
of the average MOS for females of child-bearing age is:
28
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MOS = (5mg/kg) / (0.001141 mg/kg) = 4300
Based on the TAS, only two percent of theTfemales are estimated
to be exposed to ETU levels exceeding 0.007 mg/kg, corresponding
to an MOS of less than 700. The exposure distribution indicates
that no member of the subgroup is expected to have an MOS of
less than 300.
C. OTHER SCIENCE FINDINGS
Environmental Fate. Available data are insufficient to fully
assess the environmental fate of metiram. Presently, only
the hydrolysis, and photodegradation in soil and in water
data requirements on both metiram and ETU are fully satisfied.
The ETU studies were submitted in response to the Mancozeb
Registration Standard and reviewed for metiram. Some
aerobic(and anaerobic soil metabolism, leaching and field
dissipation data are also available on metiram but the data
requirements for registration remain unsatisfied since additional
dissipation and leaching data on ETU are required.
Metiram has a very limited solubility in water. Metiram, in
water solution, degrades primarily to ETU (85%) and other
transient degradates. ETU is also a soil degradate of metiram
and its formation in 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.
Hydrolysis - An acceptable study demonstrated that the hydrolysis
of metiram results in formation of ETU as a major degradate
(over 85% after 40 days at pH 5, 7, and 9). ETU is quite
stable to hydrolysis at pH 5 and 7 and undergoes a slow
decomposition at pH 9 to polar degradates. Ethyleneurea
(EU), hydantoin and uncharacterized polar degradates are
also present in small quantities. An acceptable ETU 'hydrolysis
study indicated that no detectable degradation of ETU occurred
at pH 5, 7, and 9 in 30 days. Therefore, no breakdown of
ETU due to hydrolysis is expected in the environment.
Photodegradation in Soil & Water - An acceptable water photo-
degradation study showed that breakdown of metiram in water
occurred primarily by hydrolysis and not by photodegradation.
ETU was formed as a major degradate at 71% after 5 days at a
somewhat faster rate than observed in hydrolysis studies.
Ethyleneurea (EU) and uncharacterized polar degradates were
also present in small quantities. Photodegradation does not
appear to be a significant mode of degradation in water for
metiram or ETU. In a separate ETU study, no significant
degradation of ETU occurred at pH 7 water solution during
29
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the 30 days study period and thus no breakdown of ETU due to
photodegradation is expected in the environment in absence
the of photosensitizers.
An acceptable metiram photodegradation study on soil showed
that product formation under exposure to xenon lamp radiation
was generally controlled by soil metabolism and not by photo-
degradation. ETU was slightly more significant in irradiated
samples and the level of ETU was maintained fairly consistent
at 3.3% during the exposure period. ETU appeared quite stable
under xenon lamp irradiation. Hydantoin, carbamid and EU
(ethylene urea) that were also formed via soil metabolism,
underwent degradation under sunlight with half-lives of less
than a month. An acceptable ETU study demonstrated that the
degradation pattern and rates of ETU on soil were almost
identical on both exposed and non-exposed ETU fortified soil
samples. Therefore, photodegradation is not expected to
affect the environmental fate of ETU.
Ground water - Leaching and field dissipation data are
insufficient to allow a final ground water assessment to be
conducted. A 30-day aged soil leaching study was conducted,
but it was not determined how much ETU was present in the
aged soil prior to the application of water and whether ETU
was present in the leachate. The soil column was analyzed
and most of the aged residues were present in the top 10 cm
of the soil column. Field dissipation studies on two sites
were conducted to a depth of only 12 inches with an analytical
method of limited sensitivity to 10 ppb level.
Although available aerobic and anaerobic soil metabolism data
and two field dissipation studies appear to indicate that ETU
degrades rapidly in soil, it has been reported that ETU has
been detected in ground water in Collier County, Florida.
Because ETU is a suspected leacher and an oncogen, the Agency
is requiring a small-scale retrospective monitoring study to
analyze specifically for metiram and ETU.
Ecological Effects. Available data are insufficient to
completely evaluate the ecological effects of metiram.
The following conclusions can be made based on available
data:
1. Toxicity to Birds. Based on a mallard duck and a bobwhite
quail study, there is sufficient information available to
characterize metiram on an subacute dietary basis as
slightly toxic to birds. Formulated metiram showed that
LC50 values for mallard duck and bobwhite quail are both
greater than 3712 ppm.
2. Toxicity to Fish, Aquatic Invertebrates, and Estuarine/Marine
Organisms. No data were available in this area at the time of
this review. Studies have recently been submitted and are
under review.
30
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3. Effects on Beneficial Insects. Based on an acute contact
honeybee toxicity study, there is sufficient information
to characterize metiram as practically nontoxic to honeybees.
Metiram has been characterized as slightly toxic to two
species of birds tested and practically nontoxic to honeybees.
It is generally unstable in the moist environment and
biological systems, and degrades rather rapidly to ETU in
water. The maximum Estimated Environmental Concentrations
(EEC's) from runoff of metiram in one acre pond (6-foot
deep) are 9.8 ppb and 42.9 ppb for potato end-use and apple
end-use, respectively. However, there are no other fish and
wildlife toxicity data and chemical fate information available.
Therefore, a risk assessment of metiram for these kinds of effects,
is deferred due to lack of complete fish and wildlife toxicity
data and environmental fate information.
Reentry Consideration. Toxicity and exposure criteria are set
forth in 40 CFR f58. If a chemical meets the specified
criteria, reentry data are required.
Metiram does not meet the acute toxicity criteria, and there
is no epidemiological evidence that residues of this- pesticide
cause adverse effects on persons entering treated sites.
However, ETU has demonstrated evidence of oncogenicity,
mutagenicity, teratogenicity and thyroid effects. Therefore,
the chronic toxicity criteria have been met. Metiram also
meets the exposure criteria in that it is registered for use
on crops which may involve substantial exposure to residues
of the pesticide. Reentry data are required. An interim
24-hour reentry interval requirement is imposed until the
required data are submitted and evaluated and a change in
this reentry interval is announced.
31
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D. TOLERANCE REASSESSMENT
Tolerances, expressed as zinc ethylene bisdithiocarbamate
equivalents, have been established for residues of metiram in
a variety of raw agricultural commodities and meat byproducts
(40 CFR 180.217 and 180.319). EPA has evaluated the residue
and toxicology data supporting these tolerances. The following
were considered during this evaluation:
0 Whether the current tolerances and food additive regulations
are sufficient to cover the actual residues resulting from
use (including FIFRA section 24(c) and intrastate uses).
0 Whether group tolerances can be established in accordance
with 40 CFR 180.34(f).
0 Whether, in the absence of tolerances, restrictions on use,
grazing, or feeding of treated commodities are necessary.
0 Whether the tolerances are expressed accurately and in
current terminology.
The regulatory results of the Agency's review are set out in
Section IV.A., Regulatory Positions and Rationales.
Residue Data. The residue data reviewed in support of these
tolerances include the following:
1. Data on the nature of the residues in both plants and
livestock, including identification of major metabolites
and degradates of metiram. The metabolism is not completely
understood. Metabolites identified thus far include
ethylenethiourea (ETU), ethyleneurea (EU) and hydantoin (HT),
ethylenediamine (EDA), 3-(2-imidazolin-2-yl)-2-
imidazolidinethione, glycine and oxalic acid. Additional
data are required.
2. Analytical methodology for determining the levels of
residues of metiram in plants and animals. Present
colorimetric CS2 evolution methods are adequate for
collection of data pertaining to residues of metiram
in or on plant and animal commodities. However, none
of the colorimetric methods are specific for metiram and
are therefore inadequate for enforcement purposes. Additional
data are required.
3. Storage stability data. Some storage stability data was
submitted in response to the March 31, 1987 Data Call In
Notice. These data have been screened and are being reviewed.
The Agency concludes that it is prudent to require storage
stability data be conducted concurrently with residue
-------
analysis for each laboratory conducting residue studies,
and for each crop for which studies are required in this
Standard. Additional storage stability data are required.
4. Data on the magnitude and levels of residues of metiram
in individual raw agricultural commodities, animal products
and processed food and feed items. Data are inadequate
to support tolerances. Data show that ETU concentrates
on processing. Additional residue date are required.
Toxicology Data. The toxicology data are insufficient to
determine an Acceptable Daily Intake (ADI) or whether the
toxicity observed in the studies is due to metiram or ETU.
There are no acceptable chronic studies on which to calculate
an ADI, therefore, a three generation rat reproduction study
has been used to calculate a Provisional ADI (PADI). Because
a NOEL was not established in this 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
contain residues at the tolerance level, is 0.009 mg/kg/day
or approximately 3000 percent of the PADI. Based on a more
realistic dietary assessment, using anticipated residue
contributions and estimated percent crop treated, the estimated
average consumption for the U.S. population is 0.0004
mg/l
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IV. REGULATORY_POSITION_AND_RAT^ONALE
A• REGULATORY POSITIONS AND RATIONALES
Based on the review and evaluation of all available data on
metiram, the Agency has made the following determinations.
Where it is the Agency position that label revisions are needed
in order for a product to remain in compliance with FIFRA,
specific language will be set forth in Section D of this
Chapter.
1. The Agency has initiated a Special Review of metiram
as part of the EBDC Special Review. EPA is currently
evaluating the potential human health risks resulting
from the food, field and food crop, and terrestrial non-food
u*ses of metiram and the other EBDC pesticides containing
the common contaminant, degradation product, and metabolite,
ETU.
Rationale: The EBDC's were placed in Special Review in
1977 based on the presumption that the EBDC's and ETU
posed potential risks to human health or the environment.
The Special Review was concluded in 1982 and the EBDC's were
returned to the registration process.
In June 1987, the Agency initiated a Special Review of
the EBDC pesticides because of concern about the oncogenic
risk to consumers from dietary exposure to ETU from
foods treated with these pesticides, and the risks of
teratogenicity and adverse thyroid effects to applicators
and mixer/loaders from exposure to ETU. ETU is present
as part of the residue of the EBDC pesticides or their
conversion on or in treated agricultural commodities.
In addition, a portion of the EBDC pesticide residues
converts into ETU in the body after ingestion of
commodities with EBDC residues. The Special Review
issues are discussed in the Background section of this
document.
ETU, a contaminant, degradation product, and metabolite
of all the EBDC's, is mutagenic, oncogenic and teratogenic,
and the Agency has classified it as a Group B2 oncogen
(Probable Human Carcinogen). See the Agency Assessment
section of this Standard for a discussion of the classi-
fication of ETU.
34
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2. At this time the Agency will not restrict the use of
metiram products to certified applicators.
Rationale; Based on available data, metiram products
have not met or exceeded any criteria specified in
40 CFR 152.170 which would indicate a need to restrict
the use of metiram to certified applicators. However,
additional data have recently been received and are being
reviewed. Once the data are reviewed, the Agency will make
a determination regarding restricted use for metiram and
the other EBDC's.
3. The Agency will not consider establishment of any new
food use tolerances for metiram.
Rationale; The current residue chemistry and toxicology
data are not sufficient to assess existing and pending
tolerances. The toxicology data base is insufficient to
determine an ADI and also does not allow a decision as
to whether observed toxicity is due to metiram or ETU.
Using anticipated residues, dietary exposure currently
is 128% of the preliminary ADI. Moreover, the anticipated
dietary exposure to ETU from metiram use alone is 98%
of the preliminary ADI. Although this percentage may be
adjusted downward as additional data become available,
the ETU dietary contribution from other EBDC's has not
been included.
4. The Agency will consider the need for establishment of
tolerances for ETU and any intermediate metabolites
when data are sufficient to permit such decisions.
Rationale; The toxicology data base for metiram is
insufficient to determine whether observed toxicity is
due to metiram, ETU, or additional metabolites.
5. The Agency will not establish any food/feed additive
regulations pursuant to Section 409 of the Federal Food,
Drug and Cosmetic Act (FFDCA).
Rationale; The Delaney Clause in Section 409 of the
FFDCA bars the establishment of food additive regulations
for substances which induce cancer in man or test animals,
with certain1 exceptions. The Agency is currently developing
a position relative to the Delaney Clause and FIFRA.
Once this policy has been established, the Agency will
determine what action is required in relation to pesticides
which have produced positive oncogenic responses in
chronic animal studies.
6. Metiram is currently registered for use on peanut foliage.
The Agency is requiring a tolerance and supporting data
for residues on peanut hulls.
-------
Rationale; A tolerance has not been established for peanut
hulls in which residues of metiram could occur. The
registrant(s) must propose a tolerance and provide
supporting data.
7. Protective clothing labeling for metiram products, as
stipulated as a result of the 1982 Decision Document,
should be updated as noted herein in order to remain in
compliance with FIFRA.
Rationale. A major toxicological concern from exposure
to metiram at this time is the hazard to the human thyroid
from the degradation product, ETU, an acknowledged goitrogen,
teratogen, and oncogen. Additional data are required to
determine whether metiram also poses a teratogenic risk.
The Agency believes that risks of teratogenicity and
thyroid toxicity to commercial applicators can be
reduced by maintaining the requirement that protective
clothing be worn while mixing, loading and applying the
chemical. The Agency believes that the same is true for
other agricultural mixers, loaders, and applicators.
Updated labeling statements are given in Chapter IV. D.
8. In order to remain in compliance with FIFRA, the importance
of observing the preharvest intervals must be highlighted
on labels of residential (homeowner) products. Language
is specified Chapter IV. D.
Rationale. In the 1982 Decision Document, the Agency
determined that, as a risk reduction measure to reduce
human dietary exposure, preharvest intervals must be
highlighted on residential labels so that home garden
users will be encouraged to comply with them. Although
the risks from dietary exposure to metiram cannot be fully
assessed at this time, the Agency believes continuation
of this emphasis as a risk reduction measure is warranted.
Specific language has been chosen to emphasize to users
the importance of adherence to the preharvest intervals.
9. 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 labels of all metiram end-use products registered for
agricultural use, until the required data are submitted
and evaluated and any change in this reentry interval
is announced.
Rationale. Metiram meets both the chronic toxicity and
exposure criteria specified in 40 CFR 158.140 for reentry
data. Until these data are received and evaluated, an
interim 24-hour reentry interval will serve to reduce
exposure of field workers to this chemical.
10. The Agency will evaluate the potential of metiram to
contaminate ground water after it has received and
36
-------
evaluated additional required environmental fate data.
Special ground water monitoring studies are being required.
Rationale. Metiram was identified as a chemical with the
potential to contaminate ground water and a Data Call In
was issued. Results of the studies received were
inconclusive, but, they demonstrate that ETU has the
potential to leach. Additional data are required to
fully assess the potential of metiram and ETU from the
use of metiram to contaminate ground water.
11. The Agency is not specifying endangered species labeling
at this time.
Rationale; A risk assessment of metiram is deferred
until the Agency has reviewed fish and wildlife toxicity
data which have recently been submitted to the Agency.
Once the data are reviewed, the Agency may need to consult
with the U.S. Fish and Wildlife Service. Endangered
species labeling may then be necessary in the future
based on the results of the studies and this consultation.
12. The Agency is requiring analysis of metiram to determine
whether nitrosamines may be formed.
Rationale; There is a possibility for the formation of
nitrosamines during the manufacture of metiram; however, the
Agency does not have adequate data to determine whether
nitrosamines may be formed.
13. The Agency has determined that all data will be immediately
reviewed as they are submitted.
Rationale; Because of the general concerns over ETU and
the EBDC's, the Agency believes it is essential that these
data be reviewed as they are received.
14. While 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 and provide additional
data, as specified in the Data Appendices, in order to
maintain existing registrations.
Rationale; Under FIFRA, the Agency may elect not to
cancel or withhold registration even though data are
missing or are inadequate (see FIFRA section 3(c)(2)(B)
and 3(c)(7)). Issuance of this Standard provides a
mechanism for identifying data needs. These data will
be reviewed and evaluated, after which the Agency will
determine if additional regulatory changes are necessary.
The Agency will not consider registration of any new
uses while data gaps are being filled and data evaluated,
based on its concerns for metiram and ETU as explained
herein.
37
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B. CRITERIA FOR REGISTRATION
To be registered or reregistered under this Standard, products
must contain metiram as the sole active ingredient, bear
specified labeling, and conform to the product composition,
acute toxicity limits, and use pattern requirements listed
in this section.
C. ACCEPTABLE RANGES AND LIMITS
Product Composition Standard - To be registered or reregis-
tered under this Standard, manufacturing-use products (MP's)
must contain metiram as the sole active ingredient. Each
MP formulation proposed for registration must be fully des-
cribed with an appropriate certification of limits, stating
maximum and minimum amounts of the active ingredient and
inert ingredients which are present in products, as well as
impurities found at greater than 0.1% and any N-nitroso
compounds at greater than 1 ppm.
Acute Toxicity Limits - The Agency will consider registration
of technical grade and manufacturing-use products containing
metiram provided that the product labeling bears appropriate
precautionary statements for the acute toxicity category in
which each product is placed.
Use Patterns - To be registered under this Standard,
manufacturing-use products must be labeled for formulation
into other manufacturing-use products or into end-use products
bearing federally registered uses. The use Index (EPA Compendium
of Acceptable Uses) (for availability see page 7) lists all
federally-registered uses of metiram, as well as approved
maximum application rates and frequencies.
D. LABELING
All metiram products must bear appropriate labeling as specified
in 40 CFR 156.10. Appendix II contains additional information
on labeling.
In order to remain in compliance with FIFRA, no pesticide
product containing metiram may be released for shipment by the
registrant after' November 1, 1989, unless the product bears
an amended label which complies with the specifications of
this Standard.
3b
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In order to remain in compliance with FIFRA, no pesticide
product containing metiram may be distributed, sold, offered
for sale, held for sale, shipped, delivered for shipment, or
received and (having been so received) delivered or offered
to be delivered by any person after November 1, 1990, unless
the product bears an amended label which complies with the
specifications of this Standard.
In addition to the above, in order to remain in compliance
with FIFRA, the following information must appear on the
labeling:
1. Ingredient Statement. The ingredient statement for HP's
and EP's must list the active ingredient as:
A mixture of 5.2 parts by weight (83.9%) of
ammoniates of [ethylenebis(dithiocarbamato)]-
zinc with 1 part by weight (16.1%) ethylenebis=
[dithiocarbamic acid] bimolecular and trimolecular
cyclic anhydrosulf ides and disulf ides (%)
Inert Ingredients (%)
2. Use Pattern Statements. All manufacturing-use products
must state that they are intended for formulation into
end-use products only for acceptable use patterns.
However, no use may be included on the label where the
registrant fails to agree to comply with the data requirements
in Table A for that use pattern.
3. Disposal Statements. Because metiram has not been
designated as an acute or toxic hazardous waste under
the Resource Conservation and Recovery Act (RCRA), the
following is the appropriate pesticide disposal statement
for metiram products:
"Wastes resulting from the use of this product
may be disposed of on site or at an approved
waste disposal facility."
The labels of all products must bear the appropriate
container disposal statement (See Appendix II).
4. Precautionary Statements
Manufacturing-Use Products
"This pesticide is toxic to fish. Do not discharge
effluent containing this product into lakes, streams,
ponds, estuaries, oceans, or public water unless this
product is specifically identified and addressed in an
39
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NPDES permit. Do not discharge effluent containing this
product to sewer systems without previously notifying
the sewage treatment plant authority. For guidance, con-
tact your State Water Board or Regional Office of the EPA."
End-Use Products
a. Agricultural Use Products
"This pesticide is toxic to fish. Drift and runoff
from treated areas may be hazardous to aquatic organ-
isms in neighboring areas. Do not apply directly to
water or wetlands (swamps, bogs, marshes, and potholes).
Do not contaminate water when disposing of equipment
washwaters."
All Home Use Products
"PROTECTIVE MEASURES: Always spray with your back to
the wind. Wear long-sleeve shirt, long pants, and
rubber gloves. Wash gloves thoroughly with soap and
water before removing. Change your clothes immediately
after using this product and launder separately from
other laundry items before reuse. Shower immediately
after use."
Home Use Products with Food Uses
"Preharvest intervals on this label are specified so
that pesticide residues will be at an acceptable
level when the crop is harvested."
All Agricultural Products
"After (sprays have dried or dusts have settled as
applicable) do not enter or allow entry into treated
areas or areas where there is a danger of drift
until the 24-hour reentry interval has expired unless
wearing the personal protective equipment listed on
the label."
"Keep all unprotected persons, children, livestock, and
pets away from treated area or where there is danger of
drift."
"Do not rub eyes or mouth with hands. See First Aid
(Practical Treatment Section)."
40
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" PERS_°_NAL_PROTECT I VE_EQU IPMENT
HANDLERS (MIXERS, LOADERS, AND APPLICATORS) AND
EARLY REENTRY WORKERS MUST WEAR THE FOLLOWING PROTECTIVE
CLOTHING AND EQUIPMENT: a long-sleeve shirt and long
pants or a coverall; chemical resistant gloves,
shoes, socks, and goggles or a face shield. During
mixing and loading, a chemical resistant apron
must also be worn.
During application from a tractor with a completely
enclosed cab with positive pressure filtration, or
aerially with an enclosed cockpit, a long-sleeve
shirt and long pants may be worn in place of the
above protective clothing. Chemical resistant gloves
1 must be available in the cab or cockpit and worn
while exiting.
IMPORTANT! Before removing gloves, wash them with
soap and water. Always wash hands, face, and arms
with soap and water before eating, smoking or drinking.
Always wash hands and arms with soap and water before
using the toilet.
After work take off all clothes and shoes. Shower
using soap and water. Wear only clean clothes. Do
not use contaminated clothing. Wash protective
clothing and protective equipment with soap and water
after each use. Personal clothing worn during use
must be laundered separately from household articles.
Clothing and protective equipment drenched with
metiram must be destroyed according to state and
local regulations.
DRENCHED CLOTHING CANNOT BE ADEQUATELY DECONTAMINATED.
During aerial application, human flaggers are prohibited
unless in totally enclosed vehicles."
Grazing Statements - As appropriate, the following grazing
statements must appear on EP labels containing metiram:
0 For apples, pecans:
"Do not graze livestock on treated areas"
0 For corn (sweet):
"Do not feed forage to livestock"
41
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0 For cotton:
"Do not graze treated fields or feed gin trash to dairy
or meat animals"
0 For peanuts:
"Do not feed treated forage to dairy or meat animals"
0 For sugar beets:
"Do not feed treated tops to dairy or meat animals"
0 For potato (seed pieces):
"Do not use treated seed pieces for food or feed purposes"
i
0 For asparagus
"Do not harvest during season of application"
42
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V. PRODUCTS SUBJECT TO THIS STANDARD
All products containing one or more of the pesticides
identified in Section II.A. are subject to certain requirements
for data submittal or changes in composition, labeling or
packaging of the product. The applicable requirements depend
on whether the product is a manufacturing or end use product
and whether the pesticide is the sole active ingredient or
one of multiple active ingredients.
Products are subject to this Registration Standard as
follows:
A. Manufacturing use products containing this pesticide as
the sole active ingredient are subject to:
1. The restrictions (if any) upon use, composition, or
packaging listed in Section IV, if they pertain to the
manufacturing use product.
2. The data requirements listed in Tables A and B2
3. The labeling requirements specified for manufacturing
use products in Section IV.
4. Administrative requirements (application forms, Confiden-
tial statement of Formula, data compensation provisions)
associated with reregistration.
2 Data requirements are listed in the three Tables in
Appendix I of this Registration Standard. The Guide to
Tables in that Appendix explains how to read the Tables.
Table A lists generic data requirements applicable to all
products containing the pesticide subject to this Registra-
tion Standard. Table B lists product-specific data applicable
to manufacturing use products. The data in Tables A and B
need not be submitted by an end use producer who is eligible
for the generic data exemption for that active ingredient.
Table C lists product-specific data applicable to end use
products. The Agency has decided that, in most cases, it
will not require the submittal of product-specific data for
end use products at this time. Therefore most Registration
Standards do not contain a Table C.
43
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B. Manufacturing use products containing this pesticide
as one of multiple active ingredients are subject to:
1. The data requirements listed in Table A.
2. The labeling requirements specified for manufacturing
use products in Section IV.
C. End use products containing this pesticide as the
sole active ingredient are subject to:
1. The restrictions (if any) upon use, composition, or
packaging listed in Section IV if they pertain to the
end use product.
(2. If eligible for the generic data exemption3, the
data requirements listed in Table C.
3. If not eligible for the generic data exemption, the
data requirements listed in Table A and the data require-
ments listed in Table C.
4. The labeling requirements specified for end use
products in Section IV.
D. End use products containing this pesticide as one of
multiple active ingredients are subject to:
1. If not eligible for the generic data exemption,
the data requirements listed in Tables A and C.
3 If you purchase from another producer and use as the
source of your active ingredient only EPA-registered products,
you are eligible for the generic data exemption for generic
data concerning that active ingredient (Table A) and product-
specific data for the registered manufacturing use product
you purchase (Table B).
Two circumstances nullify this exemption:
1) If you change sources of active ingredient to an
unregistered product, formulate your own active ingredient,
or acquire your active ingredient from a firm with ownership
in common with yours, you individually lose the exemption
and become subject to the data requirements in Table A.
2) If no producer subject to the generic data requirements
in Table A agrees to submit the required data, all end use
producers lose the exemption, and become subject to the data
requirements in Table A.
44
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2. If eligible for the generic data exemption, the
data requirements listed in Table C.
3. The labeling requirements specified
products in Section IV.
for end use
VI. REQUIREMENT FOR SUBMISSION OF GENERIC DATA
This portion of the Registration standard is a notice
issued under the authority of FIFRA sec. 3(c)(2)(B). It
refers to the data listed in Table A, which are required to
be submitted by registrants to maintain in effect the regis-
tration of products containing this active ingredient.4
A. What are generic data?
Generic data pertain to the properties or effects of a
particular active ingredient. Such data are relevant to an
evaluation of all products containing that active ingredient
regardless of whether the product contains other ingredients
(unless the product bears labeling that would make the data
requirement inapplicable).
Generic data may also be data on a "typical formulation"
of a product. "Typical formulation" testing is often required
for ecological effects studies and applies to all products
having that formulation type. These are classed as generic
data/ and are contained in Table A.
B. Who must submit generic data?
All current registrants are responsible for submitting
generic data in response to a data request under FIFRA sec.
3(c)(2)(B) (DCI Notice). EPA has decided, however, not to
require a registrant who qualifies for the formulator's
exemption (FIFRA sec. 3(c)(2)(D) and § 152.85) to submit
generic data in response to a DCI notice if the registrant
who supplies the active ingredient in his product is complying
with the data request.
If you are granted a generic data exemption, you rely on
the efforts of other persons to provide the Agency with the
required data. If the registrants who have committed to
generate and submit the required data fail to take appropriate
steps to meet the requirements or are no longer in compliance
with this data requirements notice, the Agency will consider
4 Registrations granted after issuance of this Standard will
be conditioned upon submittal or citation of the data listed
in this Registration Standard.
45
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that both they and you are not in compliance and will normally
initiate proceedings to suspend the registrations of both
your product(s) and their product(s) unless you commit to submit
and submit the required data in the specified timeframe. In
such cases, the Agency generally will not grant a time extension
for submitting the data.
If you are not now eligible for a generic data exemption,
you may qualify for one if you change your source of supply
to a registered source that does not share ownership in
common with your firm, if you choose to change sources of
supply, the Confidential Statement of Formula must identify
the new source(s) and you must submit a Generic Data Exemption
Statement.
t
If you apply for a new registration for products containing
this active ingredient after the issuance of this Registration
Standard, you will be required to submit or cite generic data
relevant to the uses of your product if, at the time the
application is submitted, the data have been submitted to the
Agency by current registrants. If the required data have not
yet been submitted, any new registration will be conditioned
upon the new registrant's submittal or citation of the
required data not later than the date upon which current
registrants of similar products are required to provide such
data. See FIFRA sec. 3(c)(7)(A). If you thereafter fail to
comply with the condition of that registration to provide
data, the registration may be cancelled (FIFRA sec. 6(e)).
C. What generic data must be submitted?
You may determine which generic data you must submit by
consulting Table A. That table lists the generic data needed
to evaluate current uses of all products containing this
active ingredient, the uses for which such data are required,
and the dates by which the data must be submitted to the
Agency.
D. How to comply with PCI requirements.
within 90, days of your receipt of this Registration
Standard, you must submit to EPA a completed copy of the form
entitled "FIFRA Section 3(c)(2)(B) Summary Sheet" (EPA Form
8580-1, enclosed) for each of your products. On that form
you must state which of the following six methods you will
use to comply with the DCI requirements:
1. You will submit the data yourself.
2. YOU have entered into an agreement with one or more
registrants to jointly develop (or share in the cost of
developing) the data, but will not be submitting the data
yourself. If you use this method, you must state who will
46
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submit the data on which you will rely. You must also provide
EPA with documentary evidence that an agreement has been
formed which allows you to rely upon the data to be submitted.
Such evidence may be: (1) your letter offering to join in
an agreement and the other registrant's acceptance of your
offer/ (2) a written statement by the parties that an agreement
exists, or (3) a written statement by the person who will be
submitting the data that you may rely upon its submittal.
The Agency will also require adequate assurance that the
person whom you state will provide the data is taking appropriate
steps to secure it. The agreement to produce the data need
not specify all of the terms of the final arrangement between
the parties or a mechanism to resolve the terms.
If you and other registrants together are generating or
submitting requested data as a task force or consortium, a
representative of the group should request a Joint Data
Submitter Number, as part of your 90-day response. The
request must include the following information:
a. A list of the members of the consortium;
b. The name and address of the designated representative
of the consortium, with whom EPA will correspond
concerning the data;
c. Identity of the Registration Standard containing
the data requirement;
d. A list of the products affected (from all members
of the consortium); and
e. Identification of the specific data that the con-
sortium will be generating or submitting.
The Agency will assign a number to the consortium, which
should be used on all data submittals by the consortium.
3. You have attempted to enter into an agreement to
jointly develop data, but no other registrant has accepted
your offer. You request that EPA not suspend your registration
for non-compliance with the PCI. EPA has determined that,
as a general policy/ it will not suspend the registration of
a product when the registrant has in good faith sought and
continues to seek to enter into a data development/cost
sharing program, but the other registrants developing the
data have refused to accept its offer. [If your offer is
accepted, you may qualify for option 2 above by entering
into an agreement to supply the data.]
In order to qualify for this method, you must:
1. File with EPA a completed "Certification of Attempt
to Enter into an Agreement with other Registrants for Develop-
ment of Data" (EPA Form 8580-6, enclosed).
47
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2. Provide us with a copy of your offer to the other
registrant and proof of the other registrant's receipt of your
offer (such as a certified mail receipt). Your offer must,
at a minimum, contain the following language or its equivalent:
[Your company name] offers to share in the burden of
producing the data required pursuant to FIFRA sec.
3(c)(2)(B) in the [name of active ingredient] Registration
Standard upon terms to be agreed or failing agreement •
to be bound by binding arbitration as provided by FIFRA
section 3(c)(2)(B)(iii).
The remainder of your offer may not in any way attempt to
limit this commitment. If the other registrant to whom your
offer; is made does not accept your offer, and if the other
registrant informs us on a DCI Summary sheet that he will
develop and submit the data required under the DCI, then you
may qualify for this option. In order for you to avoid
suspension under this method, you may not later withdraw or
limit your offer to share in the burden of developing the
data.
In addition, the other registrant must fulfill its
commitment to develop and submit the data as required by this
Notice in a timely manner. If the other registrant fails to
develop the data or for some other reason would be subject to
suspension, your registration as well as that of the other
registrant will normally be subject to initiation of suspension
proceedings, unless you commit to submit and submit the required
data in the specified timeframe. In such cases, the Agency
generally will not grant a time extension for submitting the data.
4. You request a waiver of the data requirement. If
you believe that a data requirement does not (or should not)
apply to your product or its uses, you must provide EPA with
a statement of the reasons why you believe this is so. Your
statement must address the specific composition or use factors
that lead you to believe that a requirement does not apply.
Since the Agency has carefully considered the composition and
uses of pesticide products in determining that a data require-
ment applies, EPA does not anticipate that many waivers will
be granted. A request for waiver does not extend the time-
frames for developing required data, and if your waiver
request is denied, your registration may be suspended if you
fail to submit the data. The Agency will respond in writing
to your request for a waiver.
5. YOU request that EPA amend your registration bv deleting
the uses for which the data are needed. You are not required
to submit data for uses which are no longer on your label.
-------
6. You request voluntary cancellation of the registration
of your product(s) for which the data are needed.
E. Regiscrant Requests Regarding Data Requirements and Agency
Responses
All requests for modification of data requirements
(inapplicability, waiver)/ approval of protocols or protocol
changes, or time extensions must be submitted in writing.
The original requirement remains in effect unless the Agency
has notified you in writing that it has agreed to a change in
the requirement. While being considered by the Agency, such
requests for changes in the requirements do not alter the
original requirements or extend the time allowed for meeting
the requirement.
F. Test Protocols and standards
All studies required under this Notice must be conducted
in accordance with test standards outlined in the Pesticide
Assessment Guidelines, unless other protocol or standards are
approved for use by the Agency in writing. All testing must
be conducted in accordance with applicable Good Laboratory
Practices regulations in 40 CFR Part 160.
The Pesticide Assessment Guidelines, which are referenced
in the Data Tables, are available from the National Technical
Information Service (NTIS), Attn: Order Desk, 5285 Port Royal
Road, Springfield, VA 22161 (tel: 703-487-4650).
Protocols approved by the Organization for Economic
Cooperation and Development (OECD) are also acceptable if
the OECD-recommended test standards conform to those specified
in the Pesticide Data Requirements regulation (Part 158.70).
please note, however, that certain OECD standards (such as
test duration, selection of test species, and degradate
identification which are environmental fate requirements) are
less restrictive than those in the EPA Assessment Guidelines
listed above. When using the OECD protocols, they should be
be modified as appropriate so that the data generated by the
study will satisfy the requirements of Part 158. Normally,
the Agency will not extend deadlines for complying with data
requirements when the studies were not conducted in accord
with acceptable standards. The OECD protocols are available
from OECD, 1750 Pennsylvania Avenue, N.W., Washington, D.C.
20006.
49
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G. Procedures for requesting a change in test protocol.
If you will generate the required data and plan to use
test procedures which deviate from EPA's Pesticide Assessment
Guidelines or the Reports of Expert Groups to the Chemicals
Group, Organization for Economic Cooperation and Development
(OECD) Chemicals Testing Programme, you must submit for EPA
approval the protocols you propose to use.
You should submit your protocols before beginning testing,
because the Agency will not ordinarily accept as sufficient
studies using unapproved protocols. A request for protocol
approval will not extend the timeframe for submittal of the
data, nor will extensions generally be given to conduct
studies due to submittal of inappropriate protocols. The
Agency will respond in writing to your request for protocol
approval or change.
H. Procedures for requesting extensions of time.
If you think that you will need more time to generate
the data than is allowed by EPA's schedule, you may submit a
request for an extension of time.
EPA will view failure to request an extension before
the data submittal response deadline as a waiver of any
future claim that there was insufficient time to submit the
data. While EPA considers your request, you must strive to
meet the deadline for submitting the data.
The extension request should state the reasons why you
believe that an extension is necessary and the steps you
have taken to meet the testing deadline. Time extensions
normally will not be granted due to problems with laboratory
capacity or adequacy of funding, since the Agency believes
that with proper planning these can be overcome. The Agency
will respond in writing to any requests for extension of time.
I. Data Format and Reporting Requirements
All data submitted in response to this Notice must comply
with EPA requirements regarding the reporting of data,
including the manner of reporting, the completeness of results,
and the adequacy of any required supporting (or raw) data,
including, but not limited to, requirements referenced or
included in this Notice or contained in PR Notice 86-5 (issued
July 29, 1986). All studies must be submitted in the form of
a final report; a preliminary report will not be considered
to fulfill the submittal requirement.
50
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j. Existing stocks provision upon suspension or cancellation.
The Agency has determined that if a registration is
suspended for failure to respond to a DCI request under
FIFRA sec. 3(c)(2)(B), an existing stocks provision for the
registrant is not consistent with the Act. Accordingly, the
Agency does not anticipate granting permission to sell or
distribute existing stocks of suspended product except in
rare circumstances. If you believe that your product will be
suspended or cancelled and that an existing stocks provision
should be granted, you have the burden of clearly demonstrating
to EPA that granting such permission would be consistent with
the Act. The following information must be included in any
request for an existing stocks provision:
1. Explanation of why an existing stocks provision is
necessary, including a statement of the quantity of
existing stocks and your estimate of the time required
for their sale or distribution; and
2. Demonstration that such a provision would be consis-
tent with the provisions of FIFRA.
VII. REQUIREMENT FOR SUBMISSION OF PRODUCT-SPECIFIC DATA
Under its DCI authority, EPA has determined that certain
product-specific data are required to maintain your registrations
in effect. Product-specific data are derived from testing
using a specific formulated product, and, unlike generic
data, generally support only the registration of that product.
All such data must be submitted by the dates specified in
this Registration Standard.
If you have a manufacturing use product, these data are
listed in Table B. If you have an end use product, the data
are listed in Table C. As noted earlier, the Agency has
decided that it will not routinely require product-specific
data for end use products at this time. Therefore, Table C
may not be contained in this Registration Standard; if there
is no Table C, you are not required to submit the data at
this time.
In order to comply with the product specific data require-
ments, you must follow the same procedures as for generic data.
See Section VI.D through J. You should note, however, that
product chemistry data are required for every product, and the
only acceptable responses are options VI.D.I. (submit data)
or VI.D.6.(cancellation of registration).
Failure to comply with the product-specific data require-
ments for your products will result in suspension of the
product's registration.
r, 1
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VIII. REQUIREMENT FOR SUBMITTAL OF REVISED LABELING
FIFRA requires each product to be labeled with accurate,
complete and sufficient instructions and precautions, reflecting
the Agency's assessment of the data supporting the product
and its uses. General labeling requirements are set out in
40 CFR 156.10 (see Appendix II - LABELING and SUMMARY). In
addition, labeling language specific to products containing
this pesticide is specified in Section IV.D of this Registra-
tion Standard. Responses to this Registration Standard must
include draft labeling for Agency review.
Labeling must be either typewritten text on 8-1/2 x 11
inch paper or a mockup of the labeling suitable for storage
in 8-1/2 x 11 files. Draft labeling must indicate the intended
colors of the final label, clear indication of the front
panel of the label, and the intended type sizes of the text.
t
If you fail to submit revised labeling as required,
which complies with 40 CFR 156.10 and the specific instructions
in Section IV.D., EPA may seek to cancel the registration of
your product under FIFRA sec. 6.
IX. INSTRUCTIONS FOR SUBMITTAL
All submittals in response to this Registration Standard
must be sent to the following address:
Office of Pesticide Programs
OPP Mailroom (TS-767C)
Environmental Protection Agency
401 M St., SW
Washington, D.C. 20460
Attn: Metiram Registration Standard
All submittals in response to this Registration Standard
are non-fee items, including 90-day responses, protocols and
waiver requests, data, and revised labeling. Submittals must
be clearly identified as being in response to the Registration
Standard. Under no circumstances may Registration Standard
responses be combined with other types of filings for which
fees are required.
A. Manufacturing Use Products (MUPs) containing the subject
pesticide as sole active ingredient.
1. Within 90 days from receipt of this document, you
must submit for each product subject to this Registration
Standard:
52
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a. Generic Data Exemption Statement (EPA Form 8580-3),
if applicable, or the "FIFRA Section 3(c)(2)(B) Summary
Sheet" (EPA Form 8580-1), with appropriate attachments.
b. Confidential Statement of Formula (EPA Form 8570-4).
c. Evidence of compliance with data compensation
requirements of FIFRA sec. 3(c)(l)(D). Refer to 40 CFR
152.80-152.99.
2. Within 9 months from receipt of this document you
must submit:
a. Application for Pesticide Registration (EPA
F(orm 8570-1).
b. Two copies of any required product-specific data
(See Table B).
c. Three copies of draft labeling, including the
container label and any associated supplemental labeling.
d. Product Specific Data Report (EPA Form 8580-4).
3. Within the times set forth in Table A, you must
submit all generic data, unless you are eligible for the
generic data exemption. If for any reason any test is delayed
or aborted so that the schedule cannot be met, immediately
notify the Agency of the problem, the reasons for the problem,
and your proposed course of action.
B. Manufacturing Use Products containing the subject pesticide
in combination with other active ingredients.
1. Within 90 days from receipt of this document, you
must submit:
a. Generic Data Exemption Statement (EPA Form 8580-3),
if applicable, or the FIFRA sec. 3(c)(2)(B) Summary
Sheet, with appropriate attachments (EPA Form 8580-1).
b. Confidential Statement of Formula (EPA Form 8570-4)
2. Within 9 months of receipt of this document, you must
submit:
Three copies of draft labeling, including the container
label and any associated supplemental labeling.
3. Within the time frames set forth in Table A, you must
submit all generic data, unless you are eligible for the
generic data exemption. If for any reason any test is delayed
or aborted so that the schedule cannot be met, immediately
53
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notify the Agency of the problem, the reasons for the problem,
and your proposed course of action.
C- End Use Products containing the subject pesticide as sole
active ingredient.
1- Within 90 days from receipt of this document, you
must submit:
a. Generic data exemption Statement (EPA Form 8580-3),
if applicable, or the FIFRA Section 3(c)(2)(B) Summary
Sheet, with appropriate attachments (EPA Form 8580-1).
b. Confidential Statement of Formula (EPA Form 8570-4).
\
2. Within 9 months from receipt of this document you
must submit:
a. Two copies of any product-specific data, if required
by Table C.
b. Product Specific Data Report (EPA Form 8580-4),
if Table C lists required product-specific data.
c. Three copies of draft labeling, including the
container label and any associated supplemental labeling.
3. Within the times set forth in Table A, you must
submit all generic data, unless you are eligible for the
generic data exemption. If for any reason any test is delayed
or aborted so that the schedule cannot be met, immediately
notify the Agency of the problem, the reasons for the problem,
and your proposed course of action.
D. End use Products containing the subject active ingredient
as one of multiple active ingredients
1. within 90 days from receipt of this document, you
must submit:
a. Generic data exemption Statement (EPA Form 8580-3),
if applicable, or the FIFRA Section 3(c)(2)(B) Summary
Sheet, with appropriate attachments (EPA Form 8580-1).
b. Confidential Statement of Formula (EPA Form 8570-4).
2. Within 9 months from the receipt of this document, you
must submit:
Three copies of draft labeling, including the container
label and any associated supplemental labeling.
54
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3. within the times set forth in Table A, you must
submit all generic data, unless you are eligible for the
generic data exemption. If for any reason any test is delayed
or aborted so that the schedule cannot be met, immediately
notify the Agency of the problem, the reasons for the problem,
and your proposed course of action.
E. Intrastate Products
Applications for full Federal registration of intrastate
products were required to be submitted no later than July 31,
1988. Unless an application for registration was submitted
by that date, no product may be released for shipment by the
producer after July 31, 1988.
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APPENDIX I
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TGUIDE-1
GUIDE TO TABLES
a
Tables A and B contain listings of data requirements
for the pesticides covered by this Registration Standard.
Table A contains generic data requirements that apply to
the pesticide in all products, including data requirements
for which a "typical formulation" is the test substance.
Table B contains product-specific data requirements that
apply only to a manufacturing use product.
The data tables are generally organized according to the
following format:
\. Data Requirement (Column 1). The data requirements are
listed in the order in which they appear in 40 CFR Part 158.
The reference numbers accompanying each test refer to the
test protocols set out in the Pesticide Assessment Guidelines,
which are available from the National Technical Information •
Service, 5285 Port Royal Road, Springfield, VA 22161.
2. Teat Substance (Column 2). This column lists the composition
of the test substance required to be used for the test, as
follows:
TGAI = Technical grade of the active ingredient
PAI = Pure active ingredient
PAIRA 3 Pure active ingredient, radio labeled
TEP = Typical end use formulation
MP = Manufacturing use product
EP = End use product
Any other test substances, such as metabolites, 'will be
specifically named in Column 2 or in footnotes to the table.
3. Use pattern (Column 3). This column indicates the use
patterns to which the data requirement applies. Us« patterns
are the same as those given in 40 CFR Part 158. The following
letter designations are used for the given use patterns:
A » Terrestrial, food
B » Terrestrial, non-food
C * Aquatic, food
D * Aquatic, non-food.
E » Greenhouse, food
F » Greenhouse, non-food v ^
G » Forestry
H » Domestic outdoor
I » Indoor
Any other designations will be defined in a footnote to the table
57
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.TGUIDE-2
4. Does EPA have data? (Column 4). This column indicates one
of three answers:
YES - EPA has data in its files that satisfy this data
requirement. These data may be cited by other registrants
in accordance with data compensation requirements of
Part 152, Subpart E.
PARTIALLY - EPA has some data in its files, but such data
do not fully satisfy the data requirement. In some cases,
the Agency may possess data on one of two required species,
or may possess data on one test substance but not all.
The term may also indicate that the data available to
EPA are incomplete. In this case, when the data are
clarified, or additional details of the testing submitted
by the original data submitter, the data may be determined
to be acceptable. If this is the case, a footnote to
the table will usually say so.
NO - EPA either possesses no data which are sufficient
to fulfill the data requirement, or the data which EPA
does possess are flawed scientifically in a manner that
cannot be remedied by clarification or additional inforr
mation.
5. Bibliographic citation (Column 5). If the Agency has
acceptable data in its files, this column lists the identifying
number of each study. This normally is the Master Record
Identification (MRID) number, but may be a GS number if no
MRID number has been assigned. Refer to the Bibliography
Appendices for.a complete citation of the study.
6. Must additional data be submitted? (Column 6). This
column indicates whether the data must be submitted to the
Agency. If column 3 indicates that the Agency already has
data, this column will usually indicate NO. If. column 3
indicates that the Agency has only partial -data or no data,
this column will usually indicate YES. In some cases, even
though the Agency does not have the data, EPA will not require
its submission because of the unique characteristics of the
chemical; because data on another chemical can be used to
fulfill the data requirement; or because the data requirement
has been waived or reserved. Any such unusual situations
will be explained in a footnote to the table.
7. Timeframe for submission (Column 7). If column 5 requires
that data be submitted, this column indicates when the data
are to be submitted, based on the issuance date of the Regis-
tration Standard. The timeframes are those established either
as a result of a previous Data Call-in letter, >or.standardized
timeframes established by PR Notice 85-5 (August 22, 1985).
8. Footnotes (at the end of each table). Self-explanatory.
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TABLE A
GENERIC DATA REQUIREMENTS FOR TECHNICAL GADE OF THE ACTIVE INGREDIENT METIRAM
Data Requirement
Part 158
Subpart C - Product Chemistry
Product Identity and Composition;
61-2 Description of Beginning Mater- TGAI
ials and Manufacturing
Process
61-3 - Discussion of Formation of TGAI
Impurities
Analysis and Certification of
Product Ingredients
62-1 - Preliminary Analysis of Product
Samples TGAI
Physical and Chemical Characterises
Must Additional Time Frame
Does EPA Bibliographic Data be for4
Conposition1 Have Data? Citation be Submitted? Submission
Yes
Yes
Partially
40507102
40507102
40507102
No
NO
2/
Yes
63-2
63-3
63-4
63-5
63-6
- Color
- Physical
- Odor
- Melting
- Boiling
State
Point
Point
TGAI
TGAI
TGAI
TGAI
TGAI
Yes
Yes
Yes
Yes
N/A
00149526
00149526
00149526
00149526
N/A
No
No
No
NO
No"
I/
4/88"
5/6/
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TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Data Requirement
Does EPA Bibliographic
Compositionl Have Data? Citation
Must Additional Time Frame
Data be for4
be Submitted? Submission
Part 158
Subpart C - Product Chemistry (Continued)
Physical and Chemical Characteristics
(Continued)
63-7
63-8
63-9
63-10
63-11
63-12
63-13
Other
64-1
- Density, Bulk Density, or
Specific Gravity
- Solubility
- Vapor Pressure
- Dissociation Constant
- Octanol/Water Partition
Coefficient
- pH
- Stability
Requirements:
- Submittal of samples
TGAI Yes 00149526
TGAI or PAI Yes 40507102
40507101
TGAI or PAI Yes 00149526
TGAI or PAI Yes 40507102
PAI Yes 00157997
TGAI Yes 00149526
TGAI Yes 00149526
N/A N/A
No
No
No
No
No
No
No
No
I/ TGAI = technical grade of the active ingredient. PAI = purified active ingredient
2/ Five or more representative samples of the unregistered 89% T must be analyzed for the amount of active
~ ingredient using a method capable of differentiating metiram from interfering CS2-liberating impurities.
If the CSo-liberation and metiram specific methods yield different results, the CS2~liberating impurities must
be quantified. Also, complete validation data (accuracy and precision) must be submitted for each analytical
method used in generating previously submitted preliminary analysis data for impurities in the 89% technical.
-------
V Data are not required because the technical product is a solid at room temperature.
4/ These data have previously been requested in the Comprehensive Data Call In Notice issued April 1987. The time
frame for submission of data is the same as required in the April 1987 Data Call In Notice.
5/ Data recently submitted and are being reviewed.
6/ All nitrosamines must be identified and quantified in six samples; two samples of each must be analyzed shortly
after production, 3 months after production and 6 months after production. A method sensitive to 1 ppm of
N-nitroso contaminants must be used.
O\
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Test Does EPA
Data Requirement Substance1 Have Data?
S158.240 Residue Chemistry
171-3 - Directions for Use —
171-4 - Nature of Residue
(Metabolism)
- Plants PAIRA Partially
- Livestock PAIRA and Partially
Plant metabolites
171-4 - Residue Analytical TGAI and Partially
°N Method Metabolites
ro
Bibliographic Must Additional
Citation2 Data be
Submitted?
00088894
00160790
00088894
00160534
00063821
00098677
00098689
00157033
00160784
00160786
147
Yes
V
00160789 Yes
V
00157034 Yes
00161338
6/7/
00098644 Yes
00098685
00157032
00160639
00160785
00161939
Time Frame
for
Submissions
10/88
10/88
15 Months
8/9/
171-4 - Storage Stability
TEP or PAI, &
Metabolites
No
Yes
10/88
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TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Data Requirement
Test
Substance^
Does EPA Bibliographic Must Additional Time Frame
Have Data? Citation2 Data be for 3
Submitted? Submission
S158.240 Residue Chemistry (continued)
171-4 - Magnitude of the Residue-
Residue Studies for Each
Food Use 10/
- Crop Group #1 - Root and Tuber Veqetables
o Crop 1 - Potatoes
— Crop field trials TEP
— Processed Food/Feed EP
No
No
Yes
Yes
IV
5
127
10/88
4/89
0 Crop 2 - Sugar Beet Roots
— Crop field trials TEP
— Process Food/Feed EP
Crop Group #2 - Leafy Veqetables
0 Crop 1 - Celery
— Crop field Trials TEP
No
No
No
Yes
W
Yes
16/
Yes
10/88
4/89
10/88
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TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Data Requirement
Test
. Substance*
Does EPA
Have Data?
Bibliographic Must Additional Time Frame
Citation2 Data be . for-*
Submitted? Submission
S158.240 Residue Chemistry (continued)
171-4 - Magnitude of the Residue-
Residue Studies for Each
Food Use
- Crop Group #3 - Fruiting Vegetables
o Crop 1 - Tomatoes
— Crop field trials TEP
— Processed Food/Feed EP
- Crop Group #4 - Cucurbits Vegetables
o Crop 1 - Cucumbers
— Crop field trials TEP
o Crop 2 - Melons
— Crop field trials TEP
- Crop Group #5 - Pome Fruits
o Crop 1 - Apples
— Crop field trials TEP
— Processed Food/Feed EP
ON
NO
NO
NO
No
No
NO
17/
Yes
Yes
10/88
4/89
19/
Yes
Yes
207
Yes
Yes
217 22_7
237
10/88
10/88
10/88
4/89
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TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Data Requirement
Test
Substance*
Does EPA Bibliographic Must Additional Time Frame
Have Data? Citation2 Data be for3
Submitted? Submission
S158.240 Residue Chemistry (continued)
171-4 - Magnitude of the Residue-
Residue Studies for Each
Food Use
- Crop Group #6 - Tree Nuts Group
o Crop 1 - Pecans
— Crop field trials TEP No
- Crop Group #7 - Cereal Grains
o Crop 1 - Corn, fresh
— Crop field trials TEP No
- Crop Group #8 - Miscellaneous Commodities
o Crop 1 - Asparagus
— Crop field trials - TEP No
o Crop 2 - Peanuts
— Crop field trials TEP No
' — Processed Food/Feed EP No
C\
cn
24/
Yes
25/
Yes
267
Yes
27_/28/29/
Yes
30/
Yes
10/88
10/88
10/88
10/88
4/89
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TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Test Does EPA Bibliographic Must Additional Time Frame
Data Requirement Substance1 Have Data? Citation2 Data be for3
Submitted? Submission
S158.240 Residue Chemistry (continued)
171-4 - Magnitude of the Residue-
Residue Studies for Each
Food Use
o Crop 3 - Tobacco
31/32/
— Crop field trials TEP No Yes 10/88
IV
— Processed Food/Feed EP No Yes 4/89
34/
171-4 - Magnitude of the Residue TGAI or Plant No Reserved
in Meat/Milk/Poultry/Eggs Metabolites
I/ Test Substance: TGAI = Technical grade of the active ingredient; PAIRA = Pure active ingredient,
radiolabeled; TEP = Typical end-use product; PAI = Pure active ingredient.
2/ The references cited here include only those MRIDs that contain data considered partially useful for
fulfillment of data requirements for plant and animal metabolism and residue analytical methods.
3/ Data must be submitted according to due dates estabished in the previous Data Call In Notices. When
^ numbers of months are provided, these are new data requirements which must be fulfilled in the number
crs of months specified from the registrant's receipt of this document.
4/ Data must be submitted depicting the uptake, distribution, and metabolism of [14C]metiram in root and tuber
~ and pome fruit crops following a foliar application. Sampling intervals through at least 21 days must be
included. The identities and quantities of residues in or on mature plant parts must be determined in order
to elucidate the terminal residues. Residue identities must be confirmed by a method such as GC, HPLC, and/or
mass spectrometry. Data reflecting solvent extraction efficiency of metiram residues must be represented.
Representative samples from these tests must also be analyzed by enforcement methods to ascertain that these
methods are capable of determining all metabolites of concern.
5/ Metabolism studies utilizing ruminants and poultry in which animals must be dosed for a minimum of three days
~ with [l^cjmetiram at a level sufficient to make residue identification and quantification possible must be
submitted. Milk and eggs must be collected twice a day during the dosing period. Animals must be sacrificed
24 hours after the final dose. The distribution and characterization of residues must be determined in
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
S158.240 Residue Chemistry (continued)
milk, eggs, liver, kidney, muscle, and fat. Data reflecting solvent extraction^ efficiency of metiram residues
must also be represented. Note: Representative samples from the above-described tests must also be analyzed
by current enforcement methods to ascertain the validity of these methods.
6/ A confirmatory enforcement method must be developed and validated that is capable of differentiating
between EBDC fungicides as well as other contaminants that degrade to CS2. Also, residues of
ethylenethiourea (ETU), metiram per se and any other residues of concern discovered in the required plant
metabolism studies in or on crop samples must be subjected to analysis by multiresidue method protocols I -
IV, available from NTIS under order No. PB203734/AS. If it is determined that tolerances must be
established for residues of metiram in animal commodities, these data will also be required for
representative animal commodities.
7/ All residue data required in this Standard must be accompanied by a complete description of all analytical
methods used in data collection along with complete method validation data (accuracy, precision, sensitivity)
for each residue in/on each commodity.
8/ The Agency has considered possible validation of earlier submitted data, but has concluded that
validation of existing crop residue, processing, and animal commodity samples would not be acceptable due to the
highly variable and in many instances unknown conditions (e.g., ambient and freezer temperatures, sample
handling, preparation and extraction parameters prior to analyses) which may have existed at the
laboratories generating the residue data which were evaluated. In view of the lack of information on the
storage conditions in the earlier studies and the importance of storage stability studies which accurately
reflect storage conditions of the samples of the treated crop, processed food, and animal products, the
Agency has concluded that frozen storage stability data on metiram and ETU must be generated
concurrently with the required crop residue, processing, and animal commodity studies on these chemicals.
j Thus, the Agency considers all previously submitted field residue data, processing studies, and animal feeding
studies as invalid. Footnotes 11-33 specifically detail all field residue and processing data
for metiram. Data requirements for feeding studies will be determined on receipt of the required animal metabolism
data.
9/ To support crop residue data, storage stability studies must be conducted on both weathered samples (metiram) and
fortified frozen samples (metiram, metabolites and ETU) of one representative crop from each crop grouping (40 CFR
180.34) on which registered uses of metiram exist. Analyses of each crop must be conducted over a time period that
includes the time interval that the raw agricultural commodity is held in frozen storage prior to the crop residue
analysis. To support residue data on processed commodities, fortified storage stability data are required for all
processing studies submitted to the Agency. Analyses must be conducted over a time period that includes the frozen
storage of the raw agricultural commodity prior to processing and each processed commodity prior to the.residue
analyses. Protocols for these studies must be submitted to and approved by the Agency prior to initiating the
studies.
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
S158.240 Residue Chemistry (continued)
(a) Storage stability data using weathered samples. Data are required on the-parent compound, metiram, in which
crop samples field treated with a typical end use product are frozen immediately upon harvesting. The integrity
of the samples must be maintained by freezing. The samples must be analyzed for metiram on the day they arrive
at the analytical laboratory, and then stored frozen and analyzed periodically for metiram during the time
intervals specified in the Agency approved protocol.
(b) Storage stability data using fortified samples. Data are required on metiram, ETU, and metabolites in
which a group of untreated samples of raw agricultural commodities and processed crops are fortified (spiked)
with only metiram (pure active ingredient), another group of samples is fortified with only ETU, and other groups
are fortified individually with each additional metabolite. Immediately after fortification, the samples fortified
with metiram must be analyzed for metiram and ETU; samples fortified with ETU must be analyzed for only ETU;
and samples fortified with other metabolites must be analyzed for only the metabolite with which the sample was
fortified. Sample integrity must be maintained by freezing, and analyses for metiram, ETU, and metabolites
must be conducted periodically during the time intervals specified in the Agency approved protocol.
(c) Storage stability data for livestock/poultry feeding studies. If cattle and poultry feeding studies are
required (see footnote 34), fortified storage stability studies will be required on all animal commodities
(i.e., tissues, milk and eggs) for which residue data are submitted to the Agency. Analyses must be conducted
over a time period that includes the time interval that each commodity is held in frozen storage prior to
residue analyses.
x>
1Q/ For this Registration Standard, to ensure proper sequencing, the Registrant should complete and submit all plant
metabolism data to the Agency for review prior to initiation of residue field trials and processing studies.
ll/ Data must be submitted depicting residues of metiram, ETU, and other residues of concern in or on potatoes
harvested immediately after the last of several foliar applications made at 5-day intervals with a WP formulation
at 1.6 lb ai/A. Tests must be conducted in ID(24%), WA(16%) or OR(6%), ME(6%), ND(6%), WI(6%), and 00(5%) which
together produced 69% of U.S.-grown potatoes in 1984 (preliminary figures, Agricultural Statistics, USDA, 1985).
The Registrant must propose a maximum number of applications per season or a maximum seasonal application rate
consistent with the data submitted.
12/ Data depicting metiram, ETU, and other residues of concern in chips, granules, and wet and dried potato peel
processed from potatoes bearing measurable weathered residues must be submitted. If residue concentration
occurs, appropriate food/feed additive tolerances must be proposed.
13/ Data depicting metiram, ETU, and other residues of concern in or on sugar beets following multiple foliar
applications (using ground and aerial equipment) of a WP formulation at 2.4 lb ai/A, in 5rlQ gaX/^WUSt -,
be submitted. Applications must begin at the time of normal disease onset an3 continue at 7-W internals.
must be conducted in CA(23%), ID(15%), MI(10%), and MN(20%) or ND(10%) to adequately represent ca. 80%
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
S158.240 Residue Chemistry (continued)
14/ The registrant must propose a maximum number of seasonal applications or a maximum seasonal rate and a PHI
Required tests must reflect this maximum rate and proposed PHI.
15/ Data depicting metiram, ETU, and other residues of concern in dehydrated pulp, molasses, and refined sugar
processed from sugar beets bearing measurable weathered residues must be submitted. If concentration of
residues occurs, the registrant must propose appropriate food/feed additive tolerances.
16/ Data reflecting metiram, ETU, and other residues of concern in or on unstripped, untrimmed and unwashed celery
harvested 14 days following the last of multiple foliar applications, at 3-day intervals, of the 80% WP formulation
must be submitted. Applications must begin when plants are set in the field. Separate tests must be performed
using ground and aerial equipment. The registrant must propose a maximum number of applications per season
or a maximum seasonal use rate; test data must reflect this proposed maximum rate. Tests must be conducted in
CA which produces 69% of the total U.S. celery crop (Agricultural Statistics, 1985, p. 154).
IT/ Data depicting metiram, ETU, and other residues of concern in or on tomatoes harvested five days after the
last of multiple foliar applications, at 7-day intervals, of the 80% WP formulation at 2.4 Ib ai/A must be
submitted. Separate tests must be performed using ground and aerial equipment. Applications must begin 10
days after field-seeded tomatoes emerge or soon after transplanting. The registrant must propose a maximum
number of applications per season or a maximum seasonal use rate; required studies must reflect the proposed
maximum rate. Tests must be conducted in CA(27%) and FL(50%), which collectively produce 77% of the U.S.
tomatoes grown for fresh market (Agricultural Statistics, 1985, p. 172).
v°18/ Data depicting metiram, ETU, and other residues of concern in wet and dry pomace, tomato juice, puree, and
catsup processed from tomatoes bearing measurable, weathered residues must be submitted. Should residues
concentrate in any of these processed commodities, appropriate food/feed additive tolerances must be
proposed.
19/ Data depicting metiram, ETU, and other residues of concern in or on cucumbers harvested 5 days following
the last of multiple foliar applications of the 80% WP formulation at 1.6 Ib ai/A must be submitted.
Treatments must be applied using ground and aerial equipment. The registrant must propose a maximum
seasonal use rate or a maximum number of applications per season; test data must reflect the proposed maximum
rate. Tests must be conducted in CA(8%), FL(4%), MI(18%), NC(14%), TX(7%), and WI(10%) which collectively
produced 61% of the total U.S. cucumbers (for pickles) in 1984 (Agricultural Statistics, 1985, p. 157).
20/ Data depicting residues of metiram, ETU, and other residues of concern in or on cantaloupes harvested 5
days following the last of multiple foliar applications of the 80% WP formulation at 1.6 Ib ai/A must be
submitted. Applications must be made using ground and aerial equipment..!!]! separate tests ^0Tha_.tegi.stacant
must propose a maximum seasonal use rate or a maximum number oF1 applications £et beas^fty test QatSywafet
reflect the proposed maximum rate. Tests must be conducted in CA(52%) and TX(21%) which accounted for 73% of
the 1982 U.S. cantaloupe acreage (1982 Census of Agriculture, Vol. 1, Part 51, p. 339).
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
§158.240 Residue Chemistry (continued)
21/ Data must be submitted depicting residues of concern in/on apples harvested 15 "days after the last of several foliar
applications made at intervals to be specified by the Registrant using a WP formulation as follows: (i)' by ground
equipment, at 1.6 Ib ai/100 gal to runoff [up to 12.8 Ib ai/A - maximum rate currently specified on label] until
petal fall followed by cover sprays at 1.2 Ib ai/100 gal to runoff [up to 9.6 Ib ai/A - maximum cover spray rate];
and (ii) by aerial equipment, at 6.4 Ib ai/A through the first cover spray followed by 4.8 Ib ai/A at the second
and later cover sprays. Information regarding tree size and spacing and the number of gal/A applied must be
provided for each test. Tests must be conducted in IL, PA, and VA, major apple production states where the
15-day PHI is permitted (Agricultural Statistics, USDA, 1985). [In more major production states such as WA, NY,
MI and CA, the PHI is 30 days.
22/ The registrant must propose label revisions that limit the number of applications per season (or set a
maximum seasonal application rate) and specify a minimum interval between applications which must be reflected by
the submitted data.
23/ Data must be submitted depicting residues of metiram, ETU, and other residues of concern in wet and dry pomace and
juice processed from apples bearing measurable weathered residues. If residues concentrate in juice, an appropriate
food additive tolerance must be proposed. Also, an appropriate feed additive tolerance must be proposed for residues
in dry pomace.
24/ Data depicting metiram, ETU, and other residues of concern in or on pecans harvested at maturity following
multiple foliar applications of the 80% WP formulation must be submitted. The last application must occur at
shuck split. Separate tests must be conducted using ground equipment (at 1.6 Ib ai/100 gal), and aerial
equipment or mist blowers (at 6.4 Ib ai/A). The registrant must propose a maximum number of applications
per season or a maximum seasonal use rate. Required tests must reflect the proposed maximum rate. Tests
must be conducted in AZ(13%), GA(47%), and TX(14%), which produce 74% of the total U.S. pecan crop (1982
Census of Agriculture Vol. 1, Part 51, p. 368).
25/ Data must be submitted depicting residues in or on sweet corn (kernels plus cob with husks removed) harvested 1
day after the last of several foliar applications made at intervals to be specified by the Registrant using the 80%
WP formulation at 3.2 Ib ai/200 gal/A. The Registrant must propose label restrictions specifying the minimum
interval between applications and the maximum permissible number of applications or Ib ai/A/season. The submitted
data must reflect these proposed restrictions. Tests must be conducted in FL, the only state in which metiram
use on sweet corn is permitted.
26/ Data depicting metiram, ETU, and other residues of concern in or on asparagus harvested from plants
treated with multiple postharvest foliar applications of the 80% WP formulation at 2.4 Ib ai/A using both
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
S158.240 Residue Chemistry (continued)
ground and aerial equipment in separate tests must be submitted. The registrant must propose a maximum
seasonal rate or number of applications per season which must be reflected by the submitted data. Also, the
registrant must propose a label restriction against harvesting during the season of application. Tests must
be conducted in CA(36%), MI{20%), and WA(31%), which collectively account for Ca. 90% of U.S. commercial
asparagus production (1982 Census of Agriculture, Vol. 1, Part 51, p. 335).
27/ Data depicting metiram, its metabolite ETU, and any additional residues of concern in or on nuts and hulls
from peanuts treated (using both ground and aerial equipment) with multiple foliar applications of the 80% WP
at 1.6 Ib ai/A and the 3.5, 5, or 7% D at 1.5 Ib ai/A repeated at 10-day intervals must be submitted. Tests
must be conducted in AL(15%), GA(49%), and NC(10%) to adequately represent Ca. 70% of U.S. peanut production
(Agricultural Statistics, 1985, p. 121).
28/ The registrant must propose a PHI and a maximum number of applications per season or a maximum seasonal
rate which must be reflected in the required data.
29/ Since peanut hulls are a raw agricultural commodity, the registrant must propose a tolerance for
residues in or on peanut hulls.
30/ The registrant must submit data depicting concentration of metiram, ETU, and other residues of concern
during the processing of meal, crude oil, refined oil and soapstock from treated peanuts. If concentration
occurs in any of these products during processing, appropriate food/feed additive tolerances must be proposed.
However, final disposition of these food/feed additive regulations is dependent upon the Agency's position
~^J regarding Delaney Clause issues.
31/ Data must be submitted depicting metiram, ETU, and other residues of concern in or on green, freshly
harvested tobacco receiving the following full-season treatment schedule: multiple foliar plant bed treatment
of the 80% WP formulation at 1.6 Ib ai/100 gal (3-6 gal/100 sq yd) and the 3.5% D formulation at 0.14 Ib
ai/100 sq yd, respectively. The registrant must propose a maximum seasonal application rate or a maximum
number of applications per season. Required studies must reflect these rates.
32/ Data depicting metiram, ETU, and other residues of concern in or on green, freshly harvested tobacco
receiving multiple foliar applications of the 80% WP formulation in the plant bed, and in the field, at 2.4
Ib ai/A must be submitted. Tests must be conducted in GA, IN, KY, OH, and SC, states in which this use
is permitted under SLN registration
33/ If residues in freshly harvested green tobacco equal or exceed 0.1 ppm, data depicting residues in or on
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
S158.240 Residue Chemistry (continued)
dried or cured tobacco will be required. If residues in or on dried or cured tobacco equal or exceed 0.1
ppm, pyrolysis products derived from the active ingredient must be characterized and the level of residue in
smoke must be quantified. ([l^ClMetiram roust be used for identification of pyrolysis products.
34/ Presently, the nature of the residue of metiram in animals is not adequately understood. On receipt of the
data required for animal metabolism, the need for, and nature of tolerances for residues of metiram in meat, milk,
poultry and eggs will be assessed and, if necessary, feeding studies will be required. Also see footnot^ 8.
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Data Requirement
S158.290 Environmental Fate
DEGRADATION STUDIES-LAB:
161-1 - Hydrolysis
Ph ot odeqr adat i on
161-2 - In water
161-3 - On soil
161-4 - In Air
^METABOLISM STUDIES-LAB:
162-1 - Aerobic Soil
162-2 - Anaerobic Soil
162-3 - Anaerobic Aquatic
162-4 - Aerobic Aquatic
Composition1
PAIRA
ETU
PAIRA
ETU
PAIRA
ETU
PAIRA
PAIRA
ETU
PAIRA
ETU
PAIRA
PAIRA
Use
Patterns2
A,B
A,B
A,B
A,B,
A
A
A
A,B
A,B
A
A
Does EPA Have Data
to Satisfy This Bibliographic
Requirement? (Yes, Citation
No or Partially?)
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
No
Yes
No
-
00155189
00161937
40466103
00155190
00161938
40466102
00157031
40466101
00155162
00155288
00155162
00155288
Must Additional Time Frame
Data be for 3
Submitted? Submission
No
No
No
No
No
NO
4/
NO
NO
Yes 7/89
No
Yes 7/89
y
NO
No"
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TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Data Requirement Composition1 Use
Patterns^
Does EPA Have Data
to Satisfy This Bibliographic Must Additional
Requirement? (Yes, Citation Data be
No or Partially?) Submitted?
Time Frame
for3
Submission
§158.290 Environmental Fate (continued)
MOBILITY STUDIES:
163-1 - Leaching and
Adsorption/Desorption
163-2 - Volatility (Lab)
163-3 - Volatility (Field)
DEGRADATION STUDIES-FIELD:
164-1 - Soil
164-2 - Aquatic (Sediment)
164-3 - Forestry
164-5 - Soil, Long-term
ACCUMULATION STUDIES:
PAIRA A,B
ETU A,B
ETU A
TEP A
TEP A,B
ETU A,B
TEP
TEP
TEP A,B
ETU A,B
6/
Partially 00155162 Yes
00155288
No Yes~
Z/
No Yes
No Reserved""
Partially 00161935 Yes
No Yes
5/
No
5/
No
9/
No Yes9_/
No Yes
r 1
ll/
4/88
4/88~
12 Months
,
7/89
7/89
50 Months
50 Months
165-1 - Rotational Crops PAIRA
(Confined)
165-2 - Rotational Crops TEP
(Field)
A
A
No
No
Yes
7/90
Reserved
10/
165-3 - Irrigated Crops
TEP
No
-------
UAM'A KCUUlKUJXltJNrrb £UK MtM/lKAM
Does EPA Have Data
Data Requirement Composition 1 Use to Satisfy This Bibliographic Must Additional Time Frame
Patterns2 Requirement? (Yes, Citation Data be for3
_ No or Partially?) _ Submitted? _ Submission
§158.290 Environmental Fate (continued)
ACCUMULATION STUDIES (continued)
i/ 127
165-4 - In Fish PAIRA A,B No Yes 4/88
ETU A,B Mb Yes 12 Months
v
165-5 - In Aquatic Nontarget TEP - No
Organisms
Special Studies
Small Scale Retrospective Metiram A,B No Yesl3/ Protocols
Groundwater Monitoring Study ETU A,B No Yes due 120 days
Report due
36 months
after Agency
acceptance
of protocol.
Progress
reports :
every 6
"^ _ months _
I/ Composition: TGAI = Technical Grade of the Active Ingredient, PAIRA = Pure Active Ingredient,
Radiolabeled, TEP = Typical End-Use Product.
2/ Use Patterns are coded as follows: A = Terrestrial, Food Crop; B = Terrestrial, Non-Food
_3/ This data has previously been requested in the Comprehensive Data Call In Notice issued April 1987.
The time frame for submission of data is the same as required in the April 1987 Data Call In Notice.
Where number of months are provided, these are new data requirements which must be fulfilled in the
number of months specified from the registrant's receipt of this document.
4/ Metiram has low volatility. Volatility data on ETU is not available. ETU may volatilize
but is unlikely to degrade in air since it does not degrade under sunlight in water and on soil.
-------
5/ Metiram does not have aquatic or forestry use and is not applied to crops grown/harvested
~~ under flooded conditions.
6/ Data required on both metiram and ETU. Emphasis must be placed on ETU.
7/ Studies needed for ETO.
8/ Reserved pending results of laboratory volatiltiy data and review of toxicological and
reentry issues.
9/ Prospective monitoring studies and field leaching studies addressing ETO and metiram are optional as replacement
~~ for the conventional long-term field dissipation study. This study would trace the movement of ETO through the
soil profile in soil pore water in the vadose zone and in shallow groundwater. Interim results of this study
must be submitted for assessment 6 months after the studies are initiated. Whether the registrant elects to
submit the conventional long-term field dissipation study or the prospective study, an adequate study must be
submitted to the Agency within 50 months from receipt of this Registration Standard.
10/ Reserved pending results of confined rotational crop study.
ll/ Data has recently been submitted and is being reviewed.
12/ A waiver request is currently under review for this requirement. '
13/ A small-scale retrospective ground-water monitoring study is required. Semi-annual progress reports are due six
months after receipt of this Registration Standard. During the three year period, allowed for conducting and
submission of this study, it is expected that 1 year will be needed to set-up the study, and the remaining 2
years will be necessary to conduct and complete the study including preparation and submission of the final
report.
-------
p. 24
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Does EPA Have Data
Data Requirement Composition 1 Use to Satisfy This Bibliographic Must Additional Time Frame
Patterns^ Requirement? (Yes, Citation Data be for
- ' No or Partially?) Submitted? Submission
S158.440 Spray Drift
201-1 - Droplet Size Spectrum A No Yes 6 Months
202-1 - Drift Field Evaluation A No Yes 6 Months
I/ Composition: TGAI = Technical Grade of the Active Ingredient, PAIRA = Pure Active INgredient, Radiolabeled, TEP =
Typical End-Use Product...
2_/ Use Patterns are coded as follows: A = Terrestrial, Food Crop
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Data Requirement
§158.340 Toxicology
ACUTE TESTING:
81-1 - Acute Oral - Rat
81-2 - Acute Dermal
81-3 - Acute Inhalation
Composition-'-
TGAI
TGAI
TGAI
Use
Patterns^
All
All
All
Does EPA Have Data
to Satisfy This
Requirement? (Yes,
No or Partially?)
No
No
No
Bibliographic
Citation
Mast Additional
Data be
Submitted?
Yes
Yes
Yes
Time Frame
for 3
Submission
14/
1/88
14/
1/88
14/
1/88
- Rat
81-4 - Eye Irritation TGAI
- Rabbit
81-5 - Dermal Irritation TGAI
- Rabbit
81-6 - Dermal Sensitization TGAI
- Guinea Pig
81-7 - Delayed
TGAI
All
All
All
All
No
No
No
No
Yes
Yes
Yes
4/
No
l/88~
14/
l/88~
14/
1/88
14/
Neurotoxicity - Hen
Or.'
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Data
§158
Requirement Composition-^
Use
Patterns^
Does EPA Have Data
to Satisfy This
Requirement? (Yes,
No or Partially?)
Must Additional
Bibliographic Data be
Citation Submitted?
Time Frame
for3
Submission
.340 Toxicology - Continued
SUBCHRONIC TESTING:
82-1
82-2
82-3
82-4
82-5
- 90-Day Feeding:
- Rodent, and
- Non-rodent (Dog)
- 21-Day Dermal
- Rabbit
- 90-Day Dermal
- Rabbit
- 90-Day Inhalation:
- Rat
- 90-Day Neurotoxicity
-
TGAI
TGAI
TGAI
TGAI
TGAI
TGAI
All
All
All
All
All
Partially
Partially
No
No
Yes
No
5/
000126738 Yes
40290601
000031591 No~
7/
Yes
O /
O/
Reserved
00164083 No
40044701
9/
No
14/
7/88~
14/
4/88
CHRONIC TESTING:
83-1
-J
- Chronic Toxicity:
- Rodent
-Stability of test
substance
- Nonrodent
TGAI
-
ETU
TGAI
ETU
All
All
All
All
Partially
No
No
No
10/
00098449 Yes
Yes
ll/
Yes
Yes
6/90
4 months
6/90
6/90
6/90
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Data Requirement
Composition-'-
Use
Patterns2
Does EPA Have Data
to Satisfy This
Requirement? (Yes,
No or Partially?)
Bibliographic
Citation
Must Additional
Data be
Submitted?
Time Frame
for3
Submission
§158.340 Toxicology - Continued
83-2 - Oncogenicity:
- Rat
- Mouse
- Histopath &
Stability info.
83-3 - Teratogenicity:
- Rat
- Rabbit
83-4 - Reproduction
CD
O
MUTAGENICITY TESTING
84-2 - Gene Mutation
TGAI
TGAI
TGAI
TGAI
TGAI
ETU
TGAI
84-2 - Chromosomal Aberration TGAI
84-4 - Other Mechanisms of
Mutagenicity
SPECIAL TESTING
TGAI
All
All
All
All
All
All
All
All
All
Partially
Partially
Partially
No
No
No
Partially
Yes
Yes
00098449
00030245
00030565
00148682
00148681
00163786
00148680
00148679
00149528
10/
Yes
12/
Yes
5/
Yes
Yes
Yes
Yes
137
Yes
No
No
6/90
6/90
4 months
, M/
7/88
14/
7/88
7/90
7/90
9 Months
1
85-1 - General Metabolism PAI or PAIRA
85-2 - Domestic Animal Choice
Safety
All
Yes
No
00155160
No
No
-------
TABLE A
GENERIC DATA REQUIREMENTS EDR METIRAM
Does EPA Have Data
to Satisfy This Must Additional Time Frame
Use Requirement? (Yes, Bibliographic Data be for^
Data Requirement Composition^- Patterns^ No or Partially?) Citation. Submitted? Submission
§158.340 Toxicology - Continued
85-2 - Dermal (Percutaneous) TGAI All Yes 00155161 No
Absorption - Rat ETU
I/ Composition: TCAI = Technical Grade Active Ingredient; PAI = Pure Active Ingredient; PAIRA = Pure Active
Ingredient, Radiolabelled; Choice = Choice of several test substances determined on a case-by-case basis.
2/ The use patterns are coded as follows: A = Terrestrial, Food Crop; B = Terrestrial, Non-Food; C = Aquatic,
Food Crop; D = Aquatic, Non-Food; E = Greenhouse, Non-Food; G = Forestry; H = Domestic Outdoor;
I = Indoor; IP = Industrial Preservative.
3/ This data has previously been requested in the Comprehensive Data Call In Notice issued April 1987. The
time frame for submission of data is the same as required in the April 1987 Notice. When number of months
are provided, these are new data requirements which must be fulfilled in the number of months specified
CO from the registrnts receipt of this document.
4/ The chemical does not belong to the organophosphate pesticides, nor is it considered to be a cholinesterase
inhibitor.
5_/ The available study may be upgraded to acceptable if the registrant adequately addresses the problem of
stability of compound as administered. Otherwise, the study may need to be repeated.
6/ Since a chronic non-rodent study is required, further subchronic studies in non-rodents will not be required.
7_/ 21-day dermal study is required before a decision can be made for the need for a longer term dermal study.
8/ Contingent upon the results of the worker exposure analysis arcl review of the 21-day dermal toxicity (82-2).
9_/ A subchronic neurotoxicity study is not required since the acute neurotoxicity study was not required and
neurotoxicity was not observed in other species.
-------
§158.340 Toxicology (Continued)
1Q/ The rat study apparently did not demonstrate a maximum tolerated dose. Stability information on compound as
administered will be necessary and if you elect to submit this information it must, be submitted within 4 months
of receipt of this document. A repeat study may be necessary if dose justification and stability information
cannot be provided. An adequate oncogenicity study must be submitted to the Agency by June 1990.
ll/ Special neurological observations must be added to this study. The registrant must submit a protocol within 120
days from receipt of this Registration Standard, to the Agency for consideration prior to commencing the study.
[Ref: DeLahunta, A. (1983) Small animal neurologic examination and index of diseases of the nervous system. In
Veterinary Neuroanatomy and Clinical Neurology, pp. 365-387. W.B. Sauders, Philadelphia.]
12/ The mouse study apparently did not demonstrate a maximum tolerated dose. Histopathology and stability
information on compound as administered will be necessary. This information must be submitted to the
Agency within 120 days from receipt of this document if you elect to upgrade the previous study.
A repeat study may be necessary if dose justification, stability information and full histopathology information
cannot be provided. An adequate oncogenicity study must be submitted to the Agency by June 1990.
13/ Marginal positive (inconclusive) results must be confirmed or refuted in a repeat assay (point mutation
in CHO cells).
14/ Studies have recently been submitted and are currently being reviewed.
CD
ro
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Use
Data Requirement Composition1 Pattern2
S158.390 Reentry Protection
132-1 - Foliar Dissipation TEP A,B
132-1 - Soil Dissipation TEP A
133-3 - Dermal Exposure TEP A,B
133-4 - Inhalation Exposure TEP A,B
CO
Osl
Does EPA Have Data
To Satisfy This
Requirement? (Yes, Bibliographic
No or Partially) Citation
No
No
No
No
Must Additional Data
Be Submitted Under
FIFRA §3(c)(2)(B)?
Time Frames for Data
Submission^
4/
Yes 7/89
Yes 7/89
6/
NO
i/
No
I/ TEP = Typical end-use product
2/ The use patterns are coded as follows: A=Terrestrial Food Crop; B=Terrestrial Non-Food Crop
3/ This data has previously been requested in the Comprehensive Data Call In Notice issued April 1987. The
time frame for submission of data is the same as required in the April 1987 Notice.
4/ For each end-use, the registrant is required to propose an acceptable reentry interval based either upon data:
(a) on dissipation of residues (decline curve), on human exposure to those residues, and on toxicity of the residues;
or (b) on determination of that time beyond which there are no detectable dislodgeable or inhalable residues remaining
in the worker environment.
5/ Soil dissipation data are required only for uses where workers will be exposed directly to substantial quantities of
soil during their work, e.g. for use on potatoes or peanuts if hand harvesting will be performed.
6/ Human-exposure monitoring data may be submitted, if the registrant wishes to use the "allowable exposure method" of
determining reentry intervals. The data submitted are limited to foliar and soil dissipation studies, human
exposure (and reentry intervals) would be estimated from dislodgeable residues as explained in Subdivision K of the
Guidelines. If exposure studies are submitted, both dermal exposure and inhalation exposure must be submitted.
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Data
§158.
Requirement Conposition1
490 Wildlife and Aquatic
Organisms
Use2
Patterns
Does EPA Have Data
to Satisfy This
Requirement? (Yes, Bibliographic
No or Partially?) Citation
Must Additional
Data be
Submitted?
AVIAN AND MAMMALIAN TESTING
71-1
71-2
71-3
71-4
71-5
CO
- Avian Oral LD5Q
- Avian Dietary LC5Q
- Wild Mammal Toxicity
- Avian Reproduction
- Simulated and Actual
Field Testing
- Mammals, and Birds
TGAI
TGAI
TGAI
TGAI
TEP
A,H
A,H
A,H
A,H
A,H
No
Yes 108004,108005
No
No
Yes
No
No
No
No
AQUATIC ORGANISM TESTING
72-1
72-2
- Freshwater Fish LC5Q
- Acute LCsn
TGAI
TGAI
A,H
A,H
No
No
Yes
Yes
Time Frame
Submission
4/
1/88
i/
7/88
i/
7/88
Freshwater
Invertebrates
72-3 - Acute LCso Estuarine TGAI
and Marine Organisms
No
No
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Does EPA Have Data
to Satisfy This Must Additional Time Frame
Use Requirement? (Yes, Bibliographic Data be for 3
Data Recfliirement Composition^ Patterns2 No or Partially?) Citation Submitted? Submission
S158.490 Wildlife and Aquatic Qr-ganisms - Continued
72-4 - Fish Early Life Stage and
Invertebrate Life-
Cycle TGAI A No No
72-5 - Fish Life-Cycle TGAI A No No
72-6 - Aquatic Organism TGAI A No No
Accumulation (Fish)
72-7 - Simulated or Actual TEP A No No
Field Testing
Aquatic Organisms
CO
(Ji
I/ Composition: TGAI = Technical grade of the active ingredient.
2/ A = Terrestrial, Food Crop, H = Domestic Outdoor.
3/ This data has previously been required in the Comprehensive Data Call In Notice of April 1987. The
~ time frame for submission of data is the same as required in the April 1987 Notice.
4/ Studies have recently been submitted and are currently under review.
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Data Requirement
Composition1
Does EPA Have Data
to Satisfy This
Use2 Requirement? (Yes,
Patterns No or Partially?)
Must Additional Time Frame
Bibliographic Data be for
Citation Submitted? Submission
S158.550 Nontarqet Insect
NONTARGET INSECT TESTING -
POLLINATORS;
141-1 - Honey bee acute
contact LD50
141-2 - Honey bee - toxicity
of residues on
foliage
141-3 - Honey bee subacute
feeding study
141-4 - Field testing for
pollinators
NONTARGET INSECT TESTING -
AQUATIC INSECTS;
142-1 - Acute toxicity to
aquatic insects
142-2 - Aquatic insect
life cycle study
142-3 - Simulated or actual
field testing for
aquatic insects
TGAI
TEP
[Reserved]
TEP
4/
[Reserved]
i/
[Reserved]
6/
[Reserved]
6/
Yes
No
00132710
No
3/
No
5/
NO
NO
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Data Requirement
Composition-1
Does EPA Have Data
to Satisfy This
Use2 Requirement? (Yes,
Patterns No or Partially?)
Must Additional Time Frame
Bibliographic Data be for
Citation Submitted? Submission
S158.550 Nontarqet Insect
NONTARGET INSECT TESTING -
POLLINATORS:
141-1 - Honey bee acute
contact LD5Q TGAI
141-2 - Honey bee - toxicity
of residues on
foliage TEP
141-3 - Honey bee subacute
feeding study [Reserved]
141-4 - Field testing for
pollinators TEP
CO
--MONTARGET INSECT TESTING -
AQUATIC INSECTS:
142-1 - Acute toxicity to [Reserved]
aquatic insects
142-2 - Aquatic insect
life cycle study [Reserved]
142-3 - Simulated or actual
field testing for
aquatic insects [Reserved]
I/
i/
6/
6/
Yes
No
00132710
No
3/
NO
NO
NO
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR METIRAM
Data Requirement
Composition].
Does EPA Have Data
to Satisfy This
Use2 Requirement? (Yes,
Patterns No or Partially?)
Bibliographic
Citation
Must Additional
Data be
Submitted?
Time Frame
for
Submission
S158.550 Ncntarget Insect
143-1 - NONTARGET INSECT TESTING -
thru PREDATORS AND PARASITES 6/
143-3 [Reserved]
I/ Composition: TGAI = Technical grade of the active ingredient; TEP = Typical end-use product.
2/ Use Patterns are coded as follows: A=Terrestrial, Food Crop
3/ As data from acute contact test indicate low toxicity, data on residual toxicity are not required.
4/ Requirement reserved pending development of test methodology.
V Requirement applied on a case-by-case basis. Data reviewed to date do not indicate the need for a field study;
if a need arises, registrants will be informed.
6/ Reserved pending Agency decision as to whether the data requirement should be established.
CO
CC
-------
TABLE B
PRODUCT SPECIFIC DATA REQUIREMENTS FOR MANUFACTURING-USE PRODUCTS; METIRAM
Data Requirement
Must Additional Time Frame
I/ Does EPA Bibliographic Data be for
Composition Have Data? Citation be Submitted? Submission
Part 158
Subpart C - Product Chemistry.
Product Identity and Composition:
61-1 - Product Identity and Disclosure
of Ingredients
61-2 - Description of Beginning
Materials and Manufacturing
Process
61-3 - Discussion of Formation of
Impurities
Analysis and Certification of
MP
MP
MP
Yes
Yes
Yes
40507102
40507102
CO
No
No
No
Product Ingredients
62-1 - Preliminary Analysis of Product
Samples
62-2 - Certification of Ingredient
Limits
62-3 - Analytical Methods to Verify
Certified Limits
Physical and Chemical Characteristics
63-2 - Color
63-3 - Physical State
MP
MP
MP
MP
MP
Partially 40507102
Partially
Partially 40507102
Yes 00149526
Yes 00149526
2/11/
Yes 12 Months
v
Yes 12 Months
4/
Yes 12 Months
No
NO
-------
TABLE B
PRODUCT SPECIFIC DATA REQUIREMENTS FOR MANUFACTURING-USE PRODUCTS; METIRAM
Data Requirement
Part 158
Subpart C - Product Chemistry (Continued)
Physical and Chemical Characteristics
(Continued)
63-4 - Odor
63-7 - Density, Bulk Density, or
Specific Gravity
63-12 - pH
63-14 - Oxidizing or Reducing Action
63-15 - Flammability
> 63-16 - Explodability
63-17 - Storage Stability
63-18 - Viscosity
63-19 - Miscibility
63-20 - Corrosion Charasteristics
Other Requirements:
64-1 - Submittal of samples
!/
Composition
MP
MP
MP
MP
MP
MP
MP
MP
MP
MP
N/A
Does EPA
Have Data?
Yes
Yes
Yes
No
No
No
No
N/A
N/A
No
N/A
Bibliographic
Citation
00149526
00149526
40507102
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
Must Additional
Data be
be Submitted?
No
No
No
5/6/
Yes
5/7/
Yes
5/8/
Yes
Yes"
9/
No
NO
Yes"
NO
Time Frame
for
Submission
6 Months
6 Months
6 Months
15 Months
15 Months
-------
TABLE B
PRODUCT SPECIFIC DATA REQUIREMENTS FOR MANUFACTURING-USE PRODUCTS; METIRAM
Part 158
Subpart C - Product Chemistry (Continued)
I/ Composition: MP = Manufacturing-Use Product.
2/ Five or more representative samples of the 80% FIs (EPA Reg. Nos. 279-2514 and 7969-71)'must be analyzed
for the amount of active ingredient and each impurity for which certified limits are required. The
active ingredient in these samples must be analyzed for metiram per se using a method capable of differentiating
metiram from interfering CS2-liberating impurities. If the CS2-liberation and metiram specific methods yield
different results, the CS2~liberating impurities must be quantified. Complete validation data (accuracy
and precision) must be submitted for each analytical method used.
3/ Upper and lower limits for the active ingredient based on the analyses of metiram per se using a method
capable of differentiating metiram from interfering CS2~liberating impurities for the 80% FIs (EPA Reg.
Nos. 279-2514 and 7969-71) must be submitted. Also, upper limits for each impurity associated with the
active ingredient present at X).l% (w/w) and each "toxicologically significant" impurity associated with
the active ingredient present at <0.1% (w/w) must provided and certified. Limits for impurities not
associated with the active ingredient need be provided only if the are considered to be of toxicological
^-j concern, regardless of the concentration at which they are present. An explanation of how each
_ certified limit was established must be provided (e.g., sample analysis using validated analytical
procedures, quantitative estimate based on amounts of ingredients used, ets.).
4/ Analytical methods must be provided for the 80% FIs to determine the active ingredient and each
impurity for which a certified-limit is required. The analytical method for the active ingredient must
be able to differentiate metiram per §j? from interfering CS2-liberating impurities. For CS2-
liberating impurities, HPLC methodology may be most appropriate for achieving the required specificity.
All methods must be accompanied by validation studies indicating accuracy and precision. These methods
must be suitable for enforcement of certified limits.
5/ As required in 40 CFR 158.120 and more fully described in the Pesticide Assessment Guidelines, Subdivision
D, data on oxidizing or reducing action, flammability, explodability, storage stability, and corrosion
characteristics must be submitted for the 80% FIs (EPA Reg. Nos. 279-2514 and 7969-71).
-------
6/ Data required if the product contains an oxidizing or reducing agent.
7/ Data required if the product contains combustible liquids.
§/ Data required if the product is potentially explosive.
9/ No data are required because the 80% FI is not a liquid at room temperature.
1Q/ Data are not required because the 80% FI is not a liquid at room temperature nor is it to be
diluted with petroleum solvents.
ll/ All nitrosamines must be identified and quantified in six samples; two samples of each must
be analyzed shortly after production, 3 months after production and 6 months after production.
A method sensitive to 1 ppm of N-nitroso contaminants must be used.
ro
-------
APPENDIX II
-------
n
SUMMARY-1
LABEL CONTENTS
40 CPR 156.10 requires that certain specific labeling
statements appear at certain locations on the label. This
is referred to as format labeling. Specific label items listed
below are keyed to the table at the end of this Appendix.
Item 1. PRODUCT NAME - The name, brand or trademark is
required to be located on the front panel, preferably centered
in the upper part of the panel. The name of a product will
not be accepted if it is false or misleading.
Item 2. COMPANY NAME AND ADDRESS - The name and address
of the registrant or distributor is required on the label.
The name and address should preferably be located at the
bottom of the front panel or at the end of the label text.
Item 3. NET CONTENTS - A net contents statement is
required on all labels or on the container of the pesticide.
The preferred location is the bottom of the front panel
immediately above the company name and address, or at the end
of the label text. The net contents must be expressed in the
largest suitable unit, e.g./ "1 pound 10 ounces" rather than
26 ounces." In addition to English units, net contents may
be expressed in metric units. [40 CFR 156.10(d)]
Item 4. EPA REGISTRATION NUMBER - The registration
number assigned to the pesticide product must appear on the
label, preceded by the phrase "EPA Registration No.," or "EPA
Reg. No." The registration number must be set in type of a
size and style similar to other print on that part of the
"label on which it appears and must run parallel to it. The
registration number and the required identifying phrase must
not appear in such a manner as to suggest or imply recommendation
or endorsement of the product by the Agency.
[40 CFR 156.10(e)]
Item 5. EPA ESTABLISHMENT NUMBER - The EPA establishment
number, preceded by the phrase "EPA Est." is the final estab-
lishment at which the product was produced, and may appear
in any suitable location on the label or immediate container.
It must also appear on the- wrapper or outside container of
the package'if the EPA establishment number on the immediate
container cannot be clearly read through such wrapper or container.
[40 CFR 156.10U)]
Item 6A. INGREDIENTS STATEMENT - An ingredients statement
is required on the front panel. The ingredients statement must
contain the name and percentage by weight of each active ingredient
and the total percentage by weight of all inert ingredients.
The preferred location is immediately below the product name.
The ingredients statement must run parallel with, and be clearly
distinguished from, other text on the panel. It must not be
placed in the body of other text. [40 CFR 156.10(g)]
94
-------
SUMMARY-2
Item 6B. POUNDS PER GALLON STATEMENT - For liquid agricul-
tural formulations, the pounds per gallon of active ingredient
must be indicated on the label.
Item 7. FRONT LABEL PRECAUTIONARY STATEMENTS - Front panel
precautionary statements must be grouped together, preferably
within a block outline. The table below shows the minimum type
size requirements for various size labels.
Size of Label Signal Word "Keep Out of Reach
on Front Panel Minimum Type Size of- Children"
in Square Inches All Capitals Minimum Type Size
5 and under 6 point „ 6 point
above 5 to 10 10 point 6 point
above 10 to 15 12 point 8 point
above 15 to 30 14 point 10 point
i over 30 18 point 12 point
Item 7A. CHILD HAZARD WARNING STATEMENT - The Statement
"Keep Out of Reach of Children" must be located on the front
panel above the signal word except where contact with children
during distribution or use is unlikely. [40 CFR 156.10(h ) (1) (ii ) 1
Item 7B. SIGNAL WORD - The signal word (DANGER, WARNING,
or CAUTION) is required on the front panel immediately below
the child hazard warning statement. [40 CFR 156.10(h) (1)(i ) ]
Item 7C. SKULL & CROSSBONES AND WORD "POISON" - On products
assigned a toxicity Category I on the basis of oral, dermal,
or inhalation toxicity, the word "Poison" shall appear on the
label in red on a background of distinctly contrasting color and
the skull, and crossbones shall appear in immediate proximity to
the word POISON. [40 CFR 156.10(h)(1)(i)]
Item 70. STATEMENT OF PRACTICAL TREATMENT - A Statement
of practical treatment (first aid or other) shall appear on
the label of pesticide products in toxicity Categories I,
II, and III. [40 CFR 156.10(h)(1) (iii ) ]
Item 7E. REFERRAL STATEMENT - The statement "See Side
(or Back) Panel for Additipnal Precautionary Statements" is
required on the front panel for all products, unless all
required precautionary statements appear on the front panel.
[40 CFR 156.10(h)(l)(iii)J
Item 8. SIDE/BACK PANEL PRECAUTIONARY LABELING - The
precautionary statements listed below must appear together
on the label under the heading "PRECAUTIONARY STATEMENTS."
The preferred location is at the top of the side or back
panel preceding the directions for use, and it is preferred
that these statements be surrounded by a block outline. Each
of the three hazard warning statements must be headed by the
appropriate hazard title. [40 CFR 156.10(h)(2)].
-95
-------
SUMMARY-3
Item 8A. HAZARD TO HUMANS AND DOMESTIC ANIMALS - Where a
hazard exists to humans or domestic animals, precautionary
statements are required indicating the particular hazard, the
route(s) of exposure and the precautions to be taken to avoid
accident, injury or damage. [40 CFR 156.10(h)(2 ) (i ) ]
Item 8B. ENVIRONMENTAL HAZARD - Where a hazard exists to
non-target organisms excluding humans and domestic animals,
precautionary statements are required stating the nature of
the hazard and the appropriate precautions to avoid potential
accident, injury, or damage. [40 CFR 156.10(h) (2) tii ) ]
Item 8C. PHYSICAL OR CHEMICAL HAZARD - FLAMMABILITY
Precautionary statements relating to flammability of a product
are required to appear on the label if it meets the criteria
in the PHYS/CHEM Labeling Appendix. The requirement is
based on the results of the flashpoint determinations and.
flame extension tests required to be submitted for all products.
These statements are to be located in the side/back panel
precautionary statements section, preceded by the heading
"Physical/Chemical Hazards." Note that no signal word is
used in conjunction with the flammability statements.
Item 9A. RESTRICTED USE CLASSIFICATION - FIFRA sec. 3(d)
requires that all pesticide formulations/uses be classified
for either general or restricted use. Products classified
for restricted use may be limited to use by certified applicators
or persons under their direct supervision (or may be subject
to other restrictions that may be imposed by regulation).
In the Registration Standard, the Agency has (1) indicated
certain formulations/uses are to be restricted (Section IV
indicates why the product has been classified for restricted
use); or (2) reserved any classification decision until
appropriate data are submitted.
The Regulatory Position and Rationale states whether
products containing this active ingredient are classified
for restricted use. If they are restricted the draft label(s)
submitted to the Agency as part of your application must
reflect this determination (see below).
If you do not believe' that your product should be classified
for restricted use, you must submit any information and
rationale with your application for reregistration. During
the Agency's review of your application, your proposed classi-
fication determination will be evaluated in accordance with
the provisions of 40 CFR Part 152, Subpart I. You will be
notified of the Agency's classification decision.
96
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SUMMARY-1
Classification Labeling Requirements
If your product has been classified for restricted use,
the following label requirements apply:
1. All uses restricted.
a. The statement "Restricted Use Pesticide" must
appear at the top of the front panel of the label. The
statement must be set in type of the same minimum size
as required for human hazard signal word (see table in
CPR
b. Directly below this statement on the front panel,
a summary statement of the terms of .restriction must
appear (including the reasons for restriction if specified
in Section I). If use Is restricted to certified applicators,
t the following statement is required: "For retail sale
to and use only by Certified Applicators or persons
under their direct supervision and only for those uses
covered by the Certified Applicator's Certification."
2. Some but not all uses restricted. If the Regulatory
Position and Rationale atates that some uses are classified
for restricted use, and some are unclassified, several courses
of action are available:
a. You may label the product for Restricted use.
If you do so, you may include on the label uses that
are unrestricted, . but you may not distinguish them
on the label as being unrestricted.
b. You may delete all restricted uses from your
label and submit draft labeling bearing only unrestricted
uses.
c. You oay "split" your registration, I.e., register
two separate products with Identical formulations, oce
bearing only unrestricted uses, and the other bearing
restricted uses. To do so, submit two applications for
rereglstration, each containing all forms and necessary
labels. Both applications should be submitted simul-
taneously. Note that the products will be assigned
separate registration numbers.
Itea 9B. MISUSE STATEMENT - All products must bear the
misuse statement, "It is a violation of Federal law to use
this product in a manner inconsistent with ita labeling."
This statement appears at the beginning of the directions
for use, directly beneath the heading of that section.
97
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SUMMARY-5
Item 10A. REENTRY STATE_MENT - If a reentry interval
has been established by the Agency, it must be included on
the label. Additional worker protection statements may be
required in accordance with PR Notice 83-2, March 29, 1983.
Item 10B. STORAGE AND DISPOSAL BLOCK - All labels are
required to bear storage and disposal statements. These
statements are developed for specific containers, sizes, and
chemical content. These instructions must be grouped and
appear under the heading "Storage and Disposal" in the directions
for use. This heading must be set in the same type' sizes as
required for the child hazard warning. Refer to Appendix II,
STOR, PEST/DIS, and CONT/DIS to determine the storage and
disposal instructions appropriate for your products.
Item IOC. DIRECTIONS FOR USE - Directions for use must
be stated in terms which can be easily read and understood by
the average person likely to use or to supervise the use of
the pesticide. When followed, directions must be adequate to
protect the public from fraud and from personal injury and to
prevent unreasonable adverse effects on the environment.
[40 CFR 156.10]
COLLATERAL LABELING
Bulletins, leaflets, circulars, brochures, data sheets,
flyers, or other written or graphic printed matter which is
referred to on the label or which is to accompany the product
are termed collateral labeling. Such labeling may not bear
claims or representations that differ in substance from those
accepted in connection with registration of the product. It
should be made part of the response to this notice and submitted
for review.
98
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SUMMARY-6
LABELING REQUIREMENTS OF THE FIFRA, AS AMENDED
ITEM
1
2
3
4
5
6A
•>
' 6B
7
7A
- — —
7B
LABEL ELEMENT
Product name
Company name
and address
Net contents
EPA Reg. No.
EPA Est. NO.
Ingredients
statement
Pounds/gallon
statement
Front panel
precautionary
o t- A t~ ^*n**nt* Q
Keep Out of Reach
of Children
(Child hazard
warning)
Signal word
— — — • • — —
APPLICABILITY
OF REQUIREMENT
All products
All products
All products
All products
All products
All products
Liquid products
where dosage
given as Ihs.
ai/unit area
All products
All products
All products
PLACEMENT
REQUIRED
Front panel
None
None
None
None
Front panel
Front panel
Front panel
Front panel
Front panel
ON LABEL
PREFERRED
Center front
panel
Bottom front
panel or end
of label text
Bottom front
panel or end
of label text
Front panel
Front panel,
immediately
before or
following
Reg. No.
Immediately
following
product name
Directly below
the main
ingredients
statement
Above signal
word
Immediately
below child
hazard
warning
COMMENTS
If registrant is not the producer, must
be qualified by "Packed for . . .,"
"Distributed by. . . £" etc.
May be in metric units in addition to
U.S. units
Must be in similar type size and run
parallel to other type.
May appear on the container instead of
the label.
Text must run parallel with other text
on the panel.
All front panel precautionary statements
must be grouped together, preferably
blocked.
Note type size requirements.
Note type size requirements.
-------
SUMMARY-7
ITEM
i/"
fC
7D
7E
8
8A
8B
LABEL ELEMENT
Skull & cross-
bones and word
POISON (in red) .
Statement of
Practical
Treatment or
First Aid
Referral
statement
Side/back panel
precautionary
statements
Hazards to
humans and
domestic
animals
Envi ronmental
hazards
APPLICABILITY
OF REQUIREMENT
All products
which are Cat-
egory I based
on oral, der-
mal, or inhala-
tion toxicity
All products
in Categories
I, II, and in
All products
where pre-
cautionary
labeling
appears on
other than
front panel.
All products
All products
in Categories
I, II, and III
All products
PLACEMENT ON LABEL
REQUIRED
Front panel
Category I:
Front panel
unless refer-
ral statement
is used.
Others:
Grouped with
side panel
precautionary
statements.
Front panel
None
None
None
PREFERRED
Both in close
proximity to
signal word
Front panel
for all.
Top or side
of back panel
preceding
directions
for use
Same as above
Same as above
COMMENTS
<.*
Must be grouped under the headings in
8A, 8B, and 8C;^ preferably blocked.
Must be preceded by appropriate signal
word.
Environmental hazards include bee
caution where applicable.
O
O
-------
SUMMARY-8
ITEM
8C
9A
9B
10A
10B
IOC
LABEL ELEMENT
Physical or
chemical
hazards
Restricted
block
Misuse
statement
Reentry
statement
Storage and
disposal block
Directions
for use
APPLICABILITY
OF REQUIREMENT
All pressurized
products, others
with flash
points under
150°P
All restricted
products
All products
PR Notice 83-2
or as determined
by the Agency
All products
All products
PLACEMENT ON LABEL
REQUIRED
None
Top center
of front
panel
Immediately
following
heading of
direct ibns
for use
In the
directions
for use
In the
directions
for use
None
PREFERRED
Same as above
Preferably
blocked
Immediately
after misuse
statement
Immediately
before
specific
directions
for use or
at the end of
directions
for use
None
COMMENTS
Refer to Appendix II guide
PHYS/CHEM
Includes a statement of the terms of
restriction. The words "RESTRICTED USE
PESTICIDE" must be same type size as
siqnal word.
Required statement is:
"It is a violation of Federal law
to use this product in a manner
inconsistent with its labeling."
Must be set apart and clearly distin-
guishable from from other directions
for use.
Refer to Appendix II guides STOR,
CONT/DIS, and PEST/DIS for further
information and required statements.
May be in metric as well as U.S. units
o
-------
PHYS/CHEM-1
PHYSICAL/CHEMICAL HAZARDS "
Criteria
I. pressurized Containers
A.
Flashpoint at or below
20°F;' or if there is a
flashback at any valve
opening.
B,
Flashpoint above 20°F
and not over 80°F;' or
if the flame extension
is more than 18 inches
long at a distance of
6 inches from the
valve opening.
All Other Pressurized
Containers
II. Non-Pressurized Containers
A. Flashpoint at or below
20°F.
B. Flashpoint above 20°F
and not over 80°F.
C. Flashpoint over 80°F
and not over 150 °F-.
D. Flashpoint above
1508F.
Required Label Statement
Extremely flammable.
Contents under pressure.
Keep away from fire, sparks,
and heated su.rfaces. Do not
puncture or incinerate
container. Exposure to
temperatures above 130°F
may cause bursting.
Flammable. Contents under
pressure. Keep away from
heat, sparks, and flame. Do
not puncture or incinerate
container. Exposure to
temperatures above 130°F
may cause bursting.
Contents under pressure.
Do not use or store near
heat or open flame. Do not
puncture or incinerate
container. Exposure to
temperatures above 130°F
may cause bursting.
Extremely flammable. Keep
away from fire, sparks, and
heated surfaces.
Flammable. Keep away from
heat and open flame.
Do not use or store near
heat and open flame.
None required.
102
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STOR-1
STORAGE INSTRUCTIONS FOR PESTICIDES
Heading:
All products are required to bear specific label instructions
about storage and disposal. Storage and disposal instructions
must be grouped together in the directions for use portion of
the label under the heading STORAGE AND DISPOSAL. Products
intended solely for domestic use need not include the heading
"STORAGE AND DISPOSAL."
Storage Instructions;
All product labels are required to have appropriate storage
instructions. Specific storage instructions are not prescribed.
Each registrant must develop his own storage instructions,
considering, when applicable/ the following factors:
1. Conditions of storage that might alter the composition or
usefulness of the pesticide. Examples could be temperature
extremes, excessive moisture or humidity, heat, sunlight,
friction, or contaminating substances or media.
2. Physical requirements of storage which might adversely
affect the container of the product and its ability to
continue to function properly. Requirements might include
positioning of the container in storage, storage or damage
due to stacking, penetration of moisture, and ability to
withstand shock or friction.
3. Specifications for handling the pesticide container,
including movement of container within the storage area,
proper opening and closing procedures (particularly for
opened containers), and measures to minimize exposure
while opening or closing container.
4. Instructions on what to do if the container is damaged in
any way, or if the pesticide is leaking or has been
spilled, and precautions to minimize exposure if damage occurs.
5. General precautions concerning locked storage, storage in
original container only, and separation of pesticides
during storage to prevent cross-contamination of other
pesticides, fertilizer, food, and feed.
6. General storage instructions for household products should
emphasize storage in original container and placement in
locked storage areas.
103
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CONT/DIS-1
CONTAINER DISPOSAL INSTRUCTIONS
The label of each product must bear container disposal
instructions appropriate to the type of container.
1. Domestic use products must bear one of the following
container disposal statements:
Container Type
Statement
Non-aerosol products
(bottles, cans, jars)
Non-aerosol products
(baqs)
Aerosol products
Do not reuse container (bottle, can, jar).
Rinse thoroughly before discardinq in trash
Do not reuse bag. Discard -bag in trash.
Replace cap and discard containers in
trash. Do not incinerate or puncture.
2. All other products must bear container disposal instruction
based on container type, listed below:
Container Type
Statement
Metal
containers
(non-aerosol)
Plastic containers
Glass containers
Fiber drums
with liners
Paper and
plastic bags
Compressed gas
cylinders
Triple rinse (or equivalent). Then offer
for recycling or reconditioning, or punctur
and dispose of in a sanitary landfill, or b
other procedures approved by state and loca
authorities.
Triple rinse (or equivalent). Then offer
for recycling or reconditioning, or punctur
and dispose of in a sanitary landfill, or
incineration, or, if allowed by state and
local authorities, by burning. If burned,
stay out of smoke.
Triple rinse (or equivalent). Then dispose
of in a sanitary landfill or by other
approved state and local procedures.
Completely empty liner by shaking and
tapping sides and bottom to loosen clinging
particles. Empty residue into application
equipment. Then dispose of liner in a
sanitary landfill or by incineration if
allowed by state and local authorities.
If drum is contaminated and cannot be
reused^-, dispose of in the same manner.
Completely empty bag into application
equipment. Then dispose 'of empty bag in
a sanitary landfill or by incineration,
or, if allowed by State and local
authorities, by burning. If burned, stay
out of smoke.
Return empty cylinder for reuse (or
similar wording)
Manufacturer may replace this phrase with one indicating
whether and how fiber drum may be reused.
-------
PEST/DIS-1
PESTICIDE DISPOSAL INSTRUCTIONS
The label of all products, except those intended solely for domestic
use, must bear explicit instructions about pesticide disposal. The
statements listed below contain the exact wording that must appear on
the label of these products:
1. The labels of all products, except domestic use, must contain the
statement, "Do not contaminate water, food, or -feed by storage or disposal."
2. Except those products intended solely for domestic use, the labels
of all products that contain active ingredients that are Acute Hazardous
Wastes or are assigned to Toxicity Category I on the basis of oral or
dermal toxicity, or Toxicity Category I or II on the basis of acute
inhalation toxicity must bear the following pesticide disposal statement:
"Pesticide wastes are acutely hazardous. Improper disposal of
excess pesticide, spray mixture, or rinsate is a violation of Federal
\ Law. If these wastes cannot be disposed of by use according to
label instructions, contact your State Pesticide or Environmental
Control Agency, or the Hazardous Waste representative at the nearest
EPA Regional Office for guidance."
3. The labels of all products, except those intended for domestic use,
containing active or inert ingredients that are Toxic Hazardous Wastes
or meet any of the criteria in 40 CFR 261, Subpart C for a hazardous
waste must bear the following pesticide disposal statement:
"Pesticide wastes are toxic. Improper disposal of excess pesticide,
spray mixture, or rinsate is a violation of Federal Law. If these
wastes cannot be disposed of by use according to label instructions,
contact your State Pesticide or Environmental Control Agency, or the
Hazardous waste representative at the nearest EPA Regional Office
for guidance."
4. Labels for all other products, except those intended for domestic
use, must bear the following pesticide disposal statement:
"Wastes resulting from the use of this product may be disposed of on
site or at an approved waste disposal facility."
5. Products intended for domestic use only must bear the following
disposal statement: "Securely wrap original container in several layers
of newspaper and discard in trash."
105
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Chapter 1—Environmental Protection Agency
§156.10 Labeling Requirements
previously cited as §162.10
(a) General—(1) Contents of the label. Every pesticide
product shall bear a label containing the information specified by
the Act and t;he regulations in this Part. The contents of a
label must show clearly and prominently the following:
(i) The name, brand, or trademark under which the product is
sold as prescribed in paragraph (b) of this section;
(ii) The name and address of the producer, registrant, or
person for whom produced as prescribed in paragraph (c) o£ this
section;
(i'ii) The net contents as prescribed in paragraph (d) of this
section;
(iv) The product registration number as prescribed in paragraph
(e) of this section;
(v) The producing establishment number as prescribed in para-
graph (f) of this section;
(vi) An ingredient statement as prescribed in paragraph (g) of
this section;
(vii) Warning or precautionary statements as prescribed in
paragraph (h) of this section;
(viii) The directions for use as prescribed in paragraph (i)
of this section; and
(ix) The use classification(s) as prescribed in paragraph (j)
of this section.
(2) Prominence and legibility. (i) All words, statements,
graphic representations, designs or other information required on
the labeling by the Act or the regulations in this part must be
clearly legible to a person with normal vision, and must be placed
with such conspicuousness (as compared with other words, state-
ments, designs, or graphic matter on the labeling) arid expressed
in such terms as to render it likely to be read and understood
by the ordinary individual under customary conditions of purchase
and use.
(in All required label text mos«-?
(A) Be set in 6-point or larger type;
(B) Appear on a clear contrasting background; and
(C) Not be-obscured or crowded.
(3) Language to be used. All required label or labeling text
shall appear in the English language. However, the Agency may
require or the applicant may propose additional text in other
languages as is considered necessary to protect the public. When
additional text in another language is necessary, all labeling
requirements will be applied equally to both the English and
other-language versions of the labeling.
(4) Placement of Label—(i) General. The label shall appear
on or be securely attached to the immediate container of the
106
-------
pesticide product. For purposes of this Section, and the mis-
branding provisions of the Act, "securely attached" shall mean
that a label can reasonably be expected to remain affixed during
the foreseeable conditions and period of use. If the immediate
container is enclosed within a wrapper or outside container
through which the label cannot be clearly read, the label must
also be securely attached to such outside wrapper or container,
if it is a part of the package as customarily distributed or
sold.
(ii) Tank cars and other bulk containers—(A) Transportation.
While a pesticide product is in transit, the appropriate
provisions of 49 CFR Parts 170-189, concerning the transportation
of hazardous materials, and specifically those provisions con-
cerning the labeling, marking and placarding of hazardous materials
and the vehicles carrying them, define the basic Federal require-
ments. In addition, when any registered pesticide product is
transported in a tank car, tank truck or other mobile or portable
bulk container, a copy of the accepted label must be attached to
the shipping papers, and left with the consignee at the time of
delivery.
(B) Storage. When pesticide products are stored in bulk
containers, whether mobile or stationary, which remain in the
custody of the user, a copy of the label of labeling, including
all appropriate directions for use, shall be securely attached to
the container in the immediate vicinity of the discharge control
valve.
(5) False or misleading statements. Pursuant to section
2(q)(l)(A) of the Act, a pesticide or a device declared subject
to the Act pursuant to $ 162.15, is misbranded if its labeling is
false or misleading in any particular including both pesticidal
and non-pesticidal claims. Examples of statements or representations
in the labeling which constitute misbranding include:
(i) A false or misleading statement concerning the composition
of the product;
(ii) A false or misleading statement concerning the effectiveness
of the product as a pesticide or device;
(iii) A false or misleading statement about the value of the
pro^uc*- f^" purposes other than as a pesticide or device;
(iv) A false or misleading comparison with other pesticides or
devices;
(v) Any statement directly or indirectly implying that the
pesticide or device is recommended or endorsed by any agency of
the Federal Government;
(vi) The .name of a pesticide which contains two or more
principal active ingredients if the name suggests one or more but
not all such principal active ingredients even though the names
of the other ingredients are stated elsewhere in the labeling;
(vii) A true statement used in such a way as to give a false
or misleading impression to the purchaser;
(viii) Label disclaimers which negate or detract from labeling
statements required under the Act and these regulations;
107
-------
(ix) Claims as to the safety of the pesticide or its ingredients
including statements such as "safe," "nonpoisonous," "noninjurious,'
"harmless" or "nontoxic to humans and pets" with or without such
a qualifying phrase as "when used as directed"; and
(x) Non-numerical and/or comparative statements on the safety
of the product, including but not limited to:
(A) ''Contains all natural ingredients";
(B) "Among the least toxic chemicals known"
(C) "Pollution approved"
(6) Final printed labeling. (i) Except as provided in
paragraph (a)(6)(ii) of this section, final printed labeling must
be submitted and accepted prior to registration. However, final
printed labeling need not be submitted until draft label texts
have been provisionally accepted by the Agency.
(ii) Clearly legible reproductions or photo reductions will be
accepted for unusual labels such as those silk-screened directly
on^o glass or metal containers or large bag or drum labels. Such
reproductions must be of microfilm reproduction quality.
(b) Name, brand, or trademark. (1) The name, brand, or
trademark under which the pesticide product is sold shall appear
on the front panel of the label.
(2) No name, brand, or trademark may appear on the label which:
(i) Is false or misleading, or
(ii) Has not been approved by the Administrator through
registration or supplemental registration as an additional name
pursuant to $ 162.6(b)(4).
(c) Name and address of producer, registrant, or person for
whom produced. An unqualified name and address given on the
label shall be considered as the name and address of the producer.
If the registrant's name appears on the label and the registrant
is not the producer, or if the name of the person for whom the
pesticide was produced appears on the label, it must be qualified
by appropriate wording such as "Packed for ***," "Distributed by
***," or "Sold by ***" to show that the name is not that of the
producer.
(d) Net weight or measure of contents. (1) The net weight or
measure of content shall be exclusive of wrappers or other
materials and shall be the average content unless explicitly
stated as a minimum quantity.
(2) If the pesticide is a liquid, the net content statement
shall be in terms of liquid measure at 68°F (20°C) and shall be
expressed in conventional American units of fluid ounces, pints,
quarts, and gallons.
(3) If the pesticide is solid or semisolid, viscous or
pressurized, or is a mixture of liquid and solid, the net content
statement shall be in terras of weight expressed as avoirdupois
pounds and ounces.
(4) In all cases, net content shall be stated in terms of the
largest suitable units, i.e., "1 pound 10 ounces" rather than
"26 ounces."
108
-------
(5) In addition to the required units specified, net content
may be expressed in metric units.
(6) Variation above minimum content or around an average is
permissible only to the extent that it represents deviation
unavoidable in good manufacturing practice. Variation below a
stated minimum is not permitted. In no case shall the average
content of the packages in a shipment fall below the stated
average content.
(e) Product registration number. The registration number
assigned to the pesticide product at the time of registration
shall appear on the label, preceded by the phrase "EPA Registration
No.," or the phrase "EPA Reg. No." The registration number shall
be set in type of a size and style similar to other print on that
part of the label on which it appears and shall run parallel to
it.\ The registration number and the required identifying phrase
shall not appear in such a manner as to suggest or imply
recommendation or endorsement of the product by the Agency.
(£) Producing establishments registration number. The producing
establishment registration number preceded by the phrase "EPA
Est.", of the final establishment at which the product was produced
may appear in any suitable location on the label or immediate
container. It must appear on the wrapper or outside container ofr
the package if the EPA establishment registration number on the
immediate container cannot be clearly read through such wrapper
or container.
(g) Ingredient statement—(1) General. The label of each
pesticide product must bear a statement which contains the name
and percentage by weight of each active ingredient, the tocal *
percentage by weight of all inert ingredients; and if the pesticide
contains arsenic in any form, a statement of the percentages of
total and water-soluble arsenic calculated as elemental arsenic.
The active ingredients must be designated by the term "active
ingredients" and the inert ingredients by the term * inert
ingredients," or the singular forms of these terms when appropriate.
Both terms shall be in the same type size, be aligned to the same
margin and be equally prominent. The statement "Inert Ingredients,
none" is not required for pesticides which contain 100 percent
active ingredients. (tnio«s« «-.he ingredient statement is a complete
analysis of the pesticide, the term "analysis" shall not be used
as a heading for the ingredient statement.
(2) Position of ingredient statement. (i) The ingredient
statement is normally required on the front panel of the label.
If there is an outside container or wrapper through which the
ingredient statement cannot be clearly read, the ingredient
statement must also appear on such outside container or wrapper.
If the size or form of the package makes it impracticable to place
the ingredient statement on the front panel of the label, permission
may be granted for the ingredient statement to appear elsewhere.
(ii) The text of the ingredient statement must run parallel
with other text on the panel on which it appears, and must be
clearly distinguishable from and must not be placed in the body
of other text.
109
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(3) Names to be used in ingredient statement. The name used
for each ingredient shall be the accepted common name, if there
is one, followed by the chemical name. The common name may be
used alone only if it is well known. If no common name has been
established, the chemical name alone shall be used. In no case
will the use of a trademark or proprietary name be permitted unless
such name has been accepted as a common name by the Administrator
under the authority of Section 25(c)(6).
(4) Statements of percentages. The percentages of ingredients
shall be stated in terms of weight-to-weight. The sum of per-
centages of the active and the inert ingredients shall be 100.
Percentages shall not be expressed by a range of values such as
"22-25%." If the uses of the pesticide product are expressed as
weight of active ingredient per unit area, a statement of the
weight of active ingredient per unit volume of the pesticide
formulation shall also appear in the ingredient statement.
(5) Accuracy of stated percentages. The percentages given
shall be as precise as possible reflecting good manufacturing
practice. If there may be unavoidable variation "between manu-
facturing batches, the value stated for each active ingredient
shall be the lowest percentage which may be present.
(6) Deterioration. Pesticides which change in chemical
composition significantly must meet the following labeling re-
quirements :
(i) In cases where it is determined that a pesticide formulation
changes chemical composition significantly, the product must bear
the following statement in a prominent position on the label: "Not
for sale or use after [date]."
(ii) The product must meet all label claims up to the expiration
time indicated on the label.
(7) Inert ingredients. The Administrator may require the name
of any inert ingredient(s) to be listed in the ingredient statement
if he determines that such ingredient(s) may pose a'hazard to man
or the environment.
(h) Warnings and precautionary statements. Required warnings
and precautionary statements concerning the general areas of
toxicological hazard including hazard to children, environmental
hazard, and physical cr chcxis-1 hazard fall into two groups; those
required on the front panel of the labeling and those which may
appear elsewhere. Specific requirements concerning content,
placement, type size, and prominence are given below.
(1) Required front panel statements. With the exception of the
child hazard warning statement, the text required on the front
panel of the label is determined by the Toxicity Category of the
pesticide. The category is assigned on the basis of the highest
hazard shown by any of the indicators in the table below:
no
-------
1
| Hazard Indicators
I
I
I Oral LO
I 5°
1
I
I Inhafatlon LC
I 50
I
j Dermal LD
50
Eye effects
Skin effacts
1
Up to and
Includ Ing
50 mg/kg
Up to and
Inctud Ing
.2 mg/l Iter
Up to and
Including
200 ng/kg
Corrosive;
cornea! opacity
not reversible
• Ithln 7 days
Corrosive
Toxicity <
1 1
F-om 50 thru
500 mg/kg
From .2 thru
2 mg/l Iter
From 200
thru 2000
Cornea! opacity
reversible
• Ithln 7 days;
Irritation
persisting for
7 days
Seve-e Irritation
at 72 hours
rategor IBS
II 1
F-am 500 thru
5000 mg/Kg
F-om 2 thru
20 mg/flter
From 2,000 thru
20,000
No cornea 1 -opacity;
Irritation
reversible
• Ithln 7 days
Moderate Irritation
at 72 hog-s
IV
Greater than
5000 mg/Vg
Greater than
20 ng/llter
Greater than
20,000
No Irritation
•
Mild or 5! 'ght
Irritation at
72 hours
(i) Human hazard signal word.--(A) Toxicity Category I. All
pesticide products meeting the criteria of Toxicity Category I
shall bear on the front panel the signal word "Danger." In
addition if the product was assigned, to Toxicity Category I on
the basis of its oral/ ir.halati.cr. or dermal toxicity (as distinct
from skin and eye local effects) the
in red on a background of distinctly
skull and crossbones shall appear in
word "poison."
dermal toxicity (as
word "Poison" shall appear
contrasting color and the
immediate proximity to the
(B) Toxicity Category II.
criteria of Toxicity Category
the signal word "Warning."
(C) Toxicity Category III.
criteria of Toxicity Category
the signal word "Caution."
(D) Toxicity Category IV.
criteria of Toxicity Category
the signal word "Caution."
All pesticide
II shall bear
products meeting the
on the front panel*
All pesticide products meeting the
III shall bear on the front panel
All pesticide products meeting the
IV shall bear on the front panel
1 11
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(E) Use of signal words. Use of any signal word(s) associated
with a higher Toxicity Category is not permitted except when the
Agency determines that such labeling is necessary to prevent
unreasonable adverse effects on man or the environment. In no
case shall more than one human hazard signal word appear on the
front panel of a label.
(ii) Child hazard warning. Every pesticide product label shall
bear on the front panel the statement "keep out of reach of
children." Only in cases where the likelihood of contact with
children during distribution, marketing, storage or use is
demonstrated by the applicant to be extremely remote, or if the
nature of the pesticide is such that it is approved for use on
infants or small children, may the Administrator waive this
requirement.
(iii) Statement of practical treatment—(A) Toxicity
Category I. A statement of practical treatment (first aid or
other) shall appear on the front panel of the label of all
pesticides falling into Toxicity Category I on the basis of oral,
inhalation or dermal toxicity. The -Agency may, however, permit
reasonable variations in the placement of the statement of
practical treatment is some reference such as "See statement of
practical treatment on back panel" appears on the front panel
near the word "Poison" and the skull and crossbones.
(B) Other toxicity categories. The statement of practical
not required on the front panel except as described
(h)(1)(iii)(A) of this section. The applicant may,
however, include such a front panel statement at his option.
Statements of practical treatment are, however, required elsewhere
on the label .in accord with paragraph (h)(2) of this section if
they do not appear on the front panel.
(iv) Placement and prominence. All the required front panel
warning statements shall be grouped together on the label, and
shall appear with sufficient prominence relative to other front
panel text and graphic material to make them unlikely to be over-
looked under customary conditions of purchase and use. The
following table shows the minimum type size requirements for the
front panel warning statements on various sizes of labels:
treatment is
in paragraph
Size of label front panel
in square inches
Poin
Required
signal word,
all capitals
6
10
12
14
18
ts
"Keep out
of reach of
Children"
6
6
8
10
12
112
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(2) Other required warnings and precautionary statements. The
warnings and precautionary statements as required below shall appear
together on the label under the general heading "Precautionary
Statements" and under appropriate subheadings of "Hazard to Humans
and Domestic Animals," "Environmental Hazard" and "Physical or
Chemical Hazard."
(i) Hazard to humans and domestic animals. (A) Where a hazard
exists to humans or domestic animals, precautionary statements
are required indicating the particular hazard, the route(s) of
exposure and the precautions to be taken to avoid accident, injury
or damage. The precautionary paragraph shall be immediately
preceded by the appropriate hazard signal word.
(B) The following table depicts typical precautionary statements.
These statements must be modified or expanded to reflect specific
hazards.
ToxicIT> I
Precautionary statements by toxic I ty category
category | Oral, Inhalation, or dermal toxlclty
Skin and eye local effects
II I
IV
Fatal (poisonous) If stationed (Inhaled or
absorbed through skin). Do not breathe
vapor Idustl or spray mist). Do not get
In eyes, on skin, or on clothing (Front
panel statement of practical t-eatment
Hay be fatal If swallowed (Inhaled or
aOso-bed through the skin). Do not breathe
vapo-s (dust or spray nlstl. Do not get In
eyes, on skin, or on clothing. (Appropriate
first aid statements required. I.
Harmful If swallowed (Inhaled or absorbed
through the skin). Avoid breathing vapors
(dust or spray •jl«t|. Avoid contact with
sk'n (eyes or clothing). (Appropriate
first «fd statement required.).
(No precautionary statements required.).
Corrosive, causes eye and skin damage lor
skin Irritation). Do not gat In eyes, on
skin, or on clothing. Wear goggles or face
shield and rubber gloves when handling.
Harmful or fatal If swallowed.
(Appropriate first aid statement required.!
Causes eye land skin) Irritation. Do not
get In eyes, on skin, or on clothing.
Harmful If swallowed. (Appropriate first
aid statement required.!.
Avoid contact with sk"ln, eyes or clothing.
In case of contact Immediately flush
eyes or skin with plenty of water. Get
•ted 1 cat attention If Irritation persists.
(No precautionary statements required.).
(ii) Environmental hazards. Where a hazard exists to non-
target organisms excluding humans and domestic animals, precautionary
statements are required stating the nature of the hazard and the
appropriate precautions to avoid potential accident, injury or
1 -7
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damage. Examples of the hazard statements and the circumstances
under which they are required follow:
(A) If a pesticide intended for outdoor use contains an activi
ingredient with a mammalian acute oral LD5Q of 100 or less, the
statement "This Pesticide is Toxic to Wildlife" is required.
(B) If a pesticide intended for outdoor use contains an activi
ingredient with a fish acute LC5Q of 1 ppm or less, the statemen
"This Pesticide is Toxic to Fish" is required.
(C) If a pesticide intended for outdoor use contains an activ
ingredient with an avian acute oral LD^Q of 100 mg/kg or less, o
a subacute dietary LC$Q of 500 ppm or less, the statement "This
Pesticide is Toxic to Wildlife" is required.
(D) If either accident history or field studies demonstrate
that use of the pesticide may result in fatality to birds, fish
or mammals, the statement "This pesticide is extremely toxic to
wildlife (fish)" is required.
(E) For uses involving foliar application to agricultural
crops, forests, or shade trees, or for mosquito abatement
treatments, pesticides toxic to pollinating insects must bear
appropriate label cautions.
(F) For all outdoor uses other than aquatic applications the
label must bear the caution "Keep out of lakes, ponds or streams
Do not contaminate water by cleaning of equipment or disposal of
wastes."
(iii) Physical or chemical hazards. Warning statements on th
flammability or explosive characteristics of the pesticide are
required as follows:
Flash point
Required text
(A) PRESSURIZED CONTAINERS
Flasn point at or belo* 20*F; If there Is a
flashback at any valve opening.
Flash point above 20'f and not over 80*F or If
tha flam* extension Is mar* than 18 In. long
at a distance of 6 In. fro» the flame.
AI I other pressurized containers
Extremely flammable. Cgntents under pressure.
Keep a«ay from Tire, sparks, and heated
surfaces. Do not puncture or Incinerate
container. Exposure to temperatures above
IJO'F r-y c--^» H..-.»ing.
Flammable. Contents under pressure. Keep away
from heat, sparks, and open flame. Oo not
puncture or Incinerate container. Exposure to
temperatures above 130*F may cause bursting.
Contents under pressure. Oo not use or store
near heat or open flame. Oo not puncture or
Incinerate container. Exposure to tempera-
tures above 130'F may cause bursting.
(B) NOWPRESSURIZED CONTAINERS
At or belov 20*F | Extremely flammable. Keep a«ay from fire,
| sparks, and heated surfaces.
Above 20*F and not over 80*F | Flammable. Keep away from heat and open Mame.
Above 80*F and not over I50*F I Do not use or store near heat or open flame.
1 14
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(i) Directions for Use—(1) General requirements—(i) Adequacy
and clarity of directions. Directions for use must be stated in
terms which can be easily read and understood by the average
person likely to use or to supervise the use of the pesticide.
When followed, directions must be adequate to protect the public
from fraud and from personal injury and to prevent unreasonable
adverse effects on the environment.
(ii) Placement of directions for use. Directions may appear
on any portion of the label provided that they are conspicuous
enough to be easily read by the user of the pesticide product.
Directions for use may appear on printed or graphic matter which
accompanies the pesticide provided that:
(A) If required by the Agency, such printed or graphic matter
is securely attached to each package of the pesticide, or placed
within the outside wrapper or bag;
(B) The label bears a reference to the directions for use in
accompanying leaflets or circulars, such as "See directions in
the enclosed circular." and
(C) The Administrator determines that it is not necessary for
such directions to appear on the label.
(i i i) Exceptions to requirement for direction-for use—(A)
Detailed directions for use may be omitted from labeling of
pesticides which are intended for use only by manufacturers of
products other than pesticide products in their regular manu-
facturing processes, provided that:
(^_) The label clearly shows that the product is intended for
use only in manufacturing processes and specifies the type(s) of
products involved.
(2) Adequate information such as technical data sheets or
bulletins, is available to the trade specifying the type of
product involved and its proper use in manufacturing processes;
(_3) The product will not come into the hands of the general
public except after incorporation into finished products; and
M) The Administrator determines that such directions are not
necessary to prevent unreasonable adverse effects on man or the
environment.
(B) Detailed directions for use may be omitted from the labeling
of pesticide products for which sale is limited to ohysicians,
veterinarians, or druggists, provided that:
(^) The label clearly states-that the product is for use only
by physicians or veterinarians;
(2) The Administrator determines that such directions are not
necessary to prevent unreasonable adverse effects on man or the
environment; and
(.3) The product is also a drug and regulated under the provisions
of the Federal Food, Drug and Cosmetic Act.
(C) Detailed directions for use may be omitted from the labeling
of pesticide products which are intended for use only by formulators
in preparing pesticides for sale to the public, provided that:
(I) There is information readily available to the formulators
on the composition, toxicity, methods of use, applicable restrictions
or limitations, and effectiveness of the product for pesticide
purposes ;
1 15
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(2) The label clearly states that the product is intended for
use only in manufacturing, formulating, mixing, or repacking for
use as a pesticide and specifies the type(s) of pesticide products
invoIved;
(j[) The product as finally manufactured, formulated, mixed, or
repackaged is registered; and
(£} The Administrator determines that such directions are not
necessary to prevent unreasonable adverse effects on man or the
env ironment.
(2) Contents of Directions for Use. The directions for use
shall include the following, under the headings "Directions for
Use" :
(i) The statement of use classification as prescribed in
162.10(j) immediately under the heading "Directions for Use."
(jii) Immediately below the statement of use classification,
the statement "It is a violation of Federal law to use this
product in a manner inconsistent with its labeling."
(iii) The site(s) of application, as for example the crops,
animals, areas, or objects to be treated.
(iv) The target pest(s) associated with each site.
(v) The dosage rate associated with each site and pest.
(vi) The method of application, including instructions for
dilution, if required, and type(s) of application apparatus or
equipment requried.
(vii) The frequency and timing of applications necessary to
obtain effective results without causing unreasonable adverse
effects on the environment.
(viii) Specific limitations on reentry to areas where the
pesticide has been applied, meeting the requirements concerning
reentry provided by 40 CFR Part 170.
(ix) Specific directions concerning the storage and disposal
of the pesticide and its container, meeting the requirements of
40 CFR Part 165. These instructions shall be grouped and appear
under the heading "Storage and Disposal." This heading must be
set in type of the same minimum sizes as required for the child
hazard warning (See Table in 5 162.10(h)(1)(iv).)
(x) Any limitations or restrictions on use required to prevent
unreasonable adverse effects/ such as:
(A) Required intervals between application and harvest of food
or feed crops.
(B) Rotational crop restrictions.
(C) Warnings as required against use on certain crops, animals,
objects, or in or adjacent to certain areas.
(0) (Reserved]
(E) For restricted use pesticides, a statement that the
pesticide may be applied under the direct supervision of a
certified applicator who is not physically present at the site of
application but nonetheless available to the person applying the
pesticide, unless the Agency has determined that the pesticide
may only be applied under the direct supervision of a certified
applicator who is physically present.
116
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(F) Other pertinent information which the Administrator
determines to be necessary for the protection of man and the
envi ronment.
(j) Statement of Use Classification. By October 22, 1976, all
pesticide products must bear on their labels a statement of use
classification as described in paragraphs (j)( 1) and (2) of this
section. Any pesticide product for which some uses are classified
for general use and others for restricted use shall be separately
labeled according to the labeling standards set forth in this
subsection, and shall be marketed as separate products with
different registration numbers, one bearing directions only for
general use(s) and the other bearing directions for restricted
use(s) except that, if a product has both restricted use(s) and
general use(s), both of these uses may appear on a product labeled
for* restricted use. Such products shall be subject to the
provisions of $ 162.10(j)(2).
(1) General Use Classification. Pesticide products bearing
directions for use(s) classified general shall be labeled with
the exact words "General Classification" immediately below the
heading "Directions for Use." And reference to the general
classification that suggests or implies that the general utility.
of the pesticide extends beyond those purposes and uses contained
in the Directions for Use will be considered a false or misleading
statement under the statutory definitions of misbranding.
(2) Restricted Use Classification. Pesticide products bearing
direction for use(s) classif iedrestricted shall bear statements
of restricted use classification on the front panel as described
below:
(i) Fjront panel statement of restricted use classification.
(A) At the top of the front panel of the label/ set in type of
the same minimum sizes as required for human hazard signal words
(see table in S 162.10(h)(1)(iv)), and appearing with sufficient
prominence relative to other text and graphic material on the
front panel to make it unlikely to be overlooked under customary
conditions of purchase and use, the statement "Restricted Use
Pesticide" shall appear.
(B) Directly below this statement on the front panel, a summary
statement of the terras of restriction imposed as a precondition
to registration shall appear. If use is restricted to certified
applicators, the following statement is required: "For retail
sale to and use only by Certified Applicators or persons under
their direct supervision and only for those uses covered by the
Certified Applicator's certification." If, however, other
regulatory restrictions are imposed, the Administrator will define
the appropriate wording for the terms of restriction by regulation.
(k) Advertising. (Reserved]
(40 FR 28268, July 3, 1975; 40 FR 32329, Aug. I, 1975; 40 FR
38571, Aug. 21, 1975, as amended at 43 FR 5786, Feb. 9, 1978]
17
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APPENDIX III
-------
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BIBGUIDE-1
GUIDE TO USE Of THIS BIBLIOGRAPHY
1. CONTENT OP BIBLIOGRAPHY. This bibliography contains
citations of all studies considered relevant by EPA in
arriving at the positions and conclusions stated elsewhere
in the Standard. Primary sources for studies in this
bibliography have been the body of data submitted to EPA
and its predecessor agencies in support of past regulatory
decisions. Selections from other sources including the
published literature, in those instances where they have
been considered/ will be included.
2. UNITS OF ENTRY. The unit of entry in this bibliography
is called a "study." In the case of published materials,
this corresponds closely to an article. In the case of
unpublished materials submitted to the Agency, the Agency
has sought to identify documents at a level parallel to
the published article from within the typically larger
' volumes in which they were submitted. The resulting
"studies" generally have a distinct title (or at least a
single subject), can stand alone for purposes of review,
and can be described with a conventional bibliographic
citation. The Agency has attempted also to unite basic
documents and commentaries upon them, treating them as a
single study.
3. IDENTIFICATION OF ENTRIES. The entries in this bibliography
are sorted numerically by "Master Record Identifier," or
MRID, number. This number is unique to the citation, and
should be used at any time specific reference is required.
It is not related to the six-digit "Accession Number"
which has been used to identify volumes of submitted
studies;' see paragraph 4(d)(4) below for a further explana-
tion. In a few cases, entries added to the bibliography
late in the review may be preceded by a nine-character
temporary identifier. These entries are listed after
all MRID entries. This temporary identifier number is
also to be used whenever specific reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier
(MRID), each entry consists o£ a citation containing
standard elements followed, in the case of material
submitted to EPA, by a.description of the earliest known
submission. Bibliographic conventions used reflect the
standards of the American National Standards institute
(ANSI)/ expanded to provide for certain special needs.
19
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BIBGUIDE-2
a. Author. Whenever the Agency could confidently identify
one, the Agency has chosen to show a personal author.
When no individual was identified, the Agency has
shown an identifiable laboratory or testing facility
as author. As a last resort, the Agency has shown
the first submitter as author.
b. Document Date. When the date appears as four digits
with no question marks, the Agency took it directly
from the document. When a four-digit date is followed
by a question mark, the bibliographer deduced the
date from evidence in the document. When the date
appears as (19??), the Agency was unable to determine
( or estimate the date of the document.
c. Title. In some cases, it has been necessary for
Agency bibliographers to create or enhance a document
title. Any such editorial insertions are contained
between square brackets.
d. Trailing Parentheses. For studies submitted to the
Agency in the past, the trailing parentheses include
(in addition to any self-explanatory text) the fol-
lowing elements describing the earliest known submission:
(1) Submission Date. The date of the earliest known
submission appears immediately following the word
"received."
(2) Administrative Number. The next element,
immediately following the word "under," is the
registration number, experimental use jpermit
number, petition number, or other -administrative
number associated with the earliest known submission.
(3) Submitter. The third element is the submitter,
following the phrase "submitted by." When
authorship is defaulted to the submitter, this
element is omitted.
(4) Volume Identification (Accession Numbers). The
final element in the trailing parentheses
identifies the EPA accession number of the volume
in which the original submission of the study
appears. The six-digit accession number follows
the symbol "CDL," standing for "Company Data
Library." This accession number is in turn
followed by an alphabetic suffix which shows the
relative position of the study within the volume.
For example, within accession number 123456, the
first study would be 123456-A; the second, 123456-
B; the 26th, 123456-Z; and the 27th, 123456-AA.
12r>
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metiram Standard
MRID CITATION
00030245 Hunter, B.; Barnard, A.V.; Prentice, D.E.; et al. (1979) Metiram
Tumorigenicity to Mice in Long Term Dietary Administration.
Final rept. (Unpublished study received Apr 10, 1980 under 279-
2514; prepared by Huntingdon Research Centre, submitted by FMC
Corp., Philadelphia, Pa.; CDL-.242192-A, 242193)
00030565 Palmer, A.K.; Simons, R. (1979) Effect of Metiram Technical on
Pregnancy of the Rat: BSF 302/79616. (Unpublished study includ-
t ing submitter summary, received Apr 10, 1980 under 279-2514;
prepared by Huntingdon Research Centre, submitted by FMC Corp.,
Philadelphia, Pa.; CDL:242188-A)
00031591 Sortwell, R.J.; Allen, D.G.; Heywood, R.; et al. (1979) Metiram:
(Containing 2.2% Ethylenethiourea) Oral Toxicity Study in Rhesus
Monkeys: BSF 267/78263. Final Report. (Unpublished study in-
cluding submitter summary, received Apr 10, 1980 under 279-2514;
prepared by Huntingdon Research Centre, submitted by FMC Corp.,
Philadelphia, Pa.; CDL-.242190-A)
00063821 Shuttleworth, J.M. (1974) Letter sent to Route List dated Nov 14,
1974: Determination of polyram residues on apples resulting from
a polyram—benlate program: M-3589. (Unpublished study received
Feb 6, 1975 under 279-2032; submitted by'FMC Corp., Philadel-
phia, Pa.; CDL:227773-A)
00088894 Lyman, W.R. (1977) The Fate of Ethylenebisdithiocarbamate Fungi-
cides in the Environment. (Unpublished study received Dec 9,
1981 under 707-78; submitted by Rohm & Haas Co., Philadelphia,
Pa.; CDL:070520-A)
00098449 Hunter, B.; Barnard, A.V.; Street, A.E.; et al. (1981) Metiram Tox-
icity and Tumorigenicity in Prolonged Dietary Administration to
the Rat: BSF 199/80391; WNT No. 77/951. Final rept. (Unpub-
lished study received Apr 8, 1982 under 279-2032; prepared by
Huntingdon Research Centre, England, submitted by FMC Corp.,
Philadelphia, Pa.; CDL-.247211-A; 247209; 247210; 247212; 247213)
00098644 Cullen, T.E. (1964) Spectrophotometric determination of dithio-
carbamate residues on food crops. Analytical Chemistry 36(1):
221-224. (Also in unpublished submission received Nov 16, 1965
under unknown admin, no.; submitted by FMC Corp., Philadelphia,
Pa.; CDL:120299-A)
121
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metiram Standard
MRID CITATION
00098677 FMC Corporation (1973) Polyram 80 Wettable Powder: Residues. (Un-
published study received Feb 20, 1974 under 279-2032; CDL:
023021-B)
00098685 Munger, D.M.; Berger, E.; Stanovick, R.P. (1967) Determination of
Polyram Residues in or on Cows Milk and Tissues: M-2128. (Un-
published study received on unknown date under 7F0550; submitted
by Niagara Chemical, Div. of FMC Corp., Los Fresnos, Tex.;
CDL:092839-A)
00098689 pevine, J.M. (1970) Polyram Metabolite Method Development: Con-
tract No. L1045-06. Final rept. (Unpublished study received
on unknown date under 1F1088; prepared by Syracuse Univ. Re-
search Corp., submitted by Niagara Chemical, Div. of FMC Corp.,
Los Fresnos, Tex.; CDL:098619-B)
00108004 Fink, R. (1974) Final Report: Eight-day Dietary LC:50—Bobwhite
Quail: Project No. 104-105. (Unpublished study received Apr 2,
1974 under 279-2032; prepared by Truslow Farms, Inc., submitted
by FMC Corp., Philadelphia, Pa.; CDL:132451-A)
00108005 Fink, R. (1974) Final Report: Eight-day Dietary LC:50—Mallard
Ducks: Project No. 104-106. (Unpublished study received Apr 2,
1974 under 279-2032; prepared by Truslow Farms, Inc., submitted
by FMC Corp., Philadelphia, Pa.; CDL:132451-B)
00126738 Hunter, B.; Barnard, A.; Heywood, R.; et al. (1977) Metiram:
Toxicity to Rats in Dietary Administration for 13 Weeks Followed
by a 6 Week Withdrawal Period: BSF/197/77612. Final rept.
(Unpublished study received Mar 24, 1983 under 279-2023; pre-
pared by Huntingdon Research Centre, Eng., submitted by FMC
Corp., Philadelphia, PA; CDL:249885-A)
00132710 Atkins, E.; Anderson, L.; Kellum, D.; et al. (1977) Protecting Hon-
ey Bees from Pesticides. Riverside, CA: Univ. of California.
(Leaflet 2883; also in unpublished submission received Nov 2,
1983 under 239-2507; submitted by Chevron Chemical Co., Rich-
mond, CA'; CDL:251760-B)
122
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metiram Standard
MRID CITATION
00148679 Tu, A. (1985) Evaluation of Metiram in the C3H-10T 1/2 Cell System
for Transformation and Promotion Activities: Final Report: ADL
Reference 54045 (1-5527). Unpublished study prepared by Arthur
D. Little, Inc. 23 p.
00143680 Jagannath, D. (1985) Mouse Host-mediated Assay of Metiram Tech K38/
33A: Final Report: LBI Project No. 20988. Unpublished study
prepared by Litton Bionetics, Inc. 15 p.
00148681 ivett, J. (1985) Mutagenicity Evaluation of Metiram Technical K38/
33A in an in vitro Sister Chromatid Exchange Assay in Chinese
* Hamster Ovary (CHO) Cells: Final Report: LBI Project No. 20990.
Unpublished study prepared by Litton Bionetics, Inc. 28 p.
00148682 Jaeckh, R. (1985) Report on a Point Mutation Test Carried Out on
CHO Cells (HGPRT Locus) with the Test Substance Metiram (Techn.
Purity). Unpublished study prepared by BASF AG. 20 p.
00149526 BASF (1985) Product Chemistry Data for Metiram. Unpublished
compilation prepared by FMC Corporation. 48 p.
00149528 Cifone, M. (1984) Evaluation of Metiram Tech. in the Rat Primary
Hepatccyte Unscheduled DNA Synthesis Assay: Final Report: Pro-
ject No. 20991. Unpublished study prepared by Litton Bionetics,
Inc. 14 p.
00155160 Hawkins, D.; Elsom, L.; Midgley, I.; et al. (1985) The Biokinetics
and Metabolism of Carbon-14-Metiram in the Rat: HRC Report
No. BSF 410/85720. Unpublished study prepared by Huntingdon
Research Centre Ltd. 184 p.
00155161 Hawkins, D.; Elsom, L.; Girkin, R.; et al. (1984) Dermal Absorption
of Metiram in Rats: HRC Report No. BSF 411/84694. Unpublished
study prepared by Huntingdon Research Centre pic. 75 p.
00155162 Keller, E.; Huber, R. (1985) Summary of Metiram Soil Metabolism
Studies. Unpublished study. 8 p.
00155189 Klein, W. (1985) Report on: Hydrolysis of the EBDC Fungicide
Metiram. Unpublished study prepared by Fraunhofer Institut fur
Umweltchemie und Oekotoxikologie. 97 p.
123
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metiram Standard
MRI.D CITATION
00155190 Klein, W. (1985) Report on: Water Photolysis of the EBDC Fungicide
Metiram. Unpublished study prepared by Fraunhofer Institut fur
Umweltchemie und Oekotoxikologie. 97 p.
00155288 Keller, E.; Huber, R. (1985) The Fate of Metiram in Soil: Rep.
No. 2208. Unpublished compilation prepared by BASF AG. 29 p.
00157031 Klein, W. (1986) Report on Soil Photolysis of the EBDC Fungicide
Metiram-complex. Unpublished study prepared by Fraunhofer In-
stitut fuer Umweltchemie und Oekotoxikologie. 93 p.
00157032*Novak, R. (1986) Determination of Residues of Polyram and Ethylene-
thiourea in Apples: NPC Project No. 86-2001: FMC-01-85. Unpub-
lished study prepared by NPC, Inc. and Enviro-Bio-Tech, Ltd.
27 p.
00157033 Novak, R. (1986) Determination of Residues of Polyram and Ethylene-
thiourea in Potatoes: NPC Project No. 86-2001: FMC-02-85. Un-
published study prepared by NPC, Inc. and Enviro-Bio-Tech, Ltd.
20 p.
00157034 Holloway, C.; Kargarotos, B.; Kurth, B.; et al. (1986) The Bioki-
netics and Metabolism of Metiram Complex in Lactating Goats:
NATEC Projects NA 85 9658, NA 85 9668, NA 85 9676 and NA 85
9678. Unpublished study prepared by NATEC Institute. 131 p.
00157997 BASF Wyandotte Chemical Corp. (1985?) Product Chemistry Data:
Metiram. Unpublished compilation. 73 p.
00160534 Cameron, D.; Gummer, J.; Gillard, D. (1986) Residues of Metiram in
Milk and Tissues of Dairy Cows: Rept. No. BSF/443/86353. Un-
published study prepared by Huntingdon Research Centre. 51 p.
00160639 Cameron, D.; Gummer, J. (1986) Residues of ETU (Ethylene Thiourea)
in Milk and Tissues of Dairy Cows following Oral Administration
of Metiram: HRC Report No. BSF/443/86353/b. Unpublished study
prepared by Huntingdon Research Centre. 34- p.
00160784 Novak, R. (1986) Determination of Residues of Polyram and Ethylene-
thiourea in Apples and Process Fractions: Project No.: G237.111:
PC-0050. Unpublished compilation prepared by Enviro-Bio-Tech,
Ltd. 30 p.
124
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metiram Standard
CITATION
00160785 Novak, R. (1986) Determination of Residues of Polyram and Ethyl-
enethiourea in Potato Process Samples: Project No. G237.111:
NPC Project No.: 86-2001. Unpublished study prepared by FMC
Corp. 30 p.
00160786 Roberts, R.; Cameron, D.; Gummer, J. (1986) Residues of Metiram
in Milk and Tissues of Dairy Cows: HRC Study No.: BSF/443/86353.
Unpublished study prepared by Huntingdon Research Centre. 40 p.
00160789 Bieber, W.; Kroehn, R. (1986) Study on the Metabolism of the
Metiram Complex (Ethylene-:Carbon-14-labelled:) in Apples:
1 Proj.: NA 85 9620/11. Unpublished study prepared by BASF, AG.
68 p.
00160790 Bieber, W.; Kroehn, R. (1986) Study on the Metabolism of the
Metiram Complex (Ethylene-Carbon-14-labelled) in Potatoes:
Proj.: NA 85 9620/1. Unpublished study prepared by BASF, AG.
67 p.
00161338 Holloway, C.; Kargarotos, B.; Baustian, M.; et al. (1986) The Bio-
kinetics and Metabolism of Metiram Complex in Laying Hens: Part
I: Biokinetics: [Part II: Metabolism]. Unpublished compilation
prepared by Institut fur Naturwissenschaftlichtechnische Dienste
GmbH. 157 p.
00161935 Novak, R. A. (1986) Polyram Soil Dissipation: Determination of
POLYRAM and Ethylenethiourea Residues
00161937 Regenstein (1986) Hydrolysis of the EBDC Fungicide Metiram - Com-
plex: Addendum. Unpublished study prepared by BASF Aktienge-
sellschaft. 4 p.
00161938 Regenstein (1986) Water Photolysis of the EBDC Fungicide Metiram -
Complex: Addendum. Unpublished study prepared by BASF Aktien-
gesellschaft. 5 p.
00161939 Roberts, N.; Fairley, C.; Gummer, J.: et al. (1986) The Determina-
tion of -Residues of Metiram in the Eggs and Tissues of the
Laying Hen following Oral Gavage of Metiram: BSF 449BR/86777b.
Unpublished study prepared by Huntingdon Research Centre Ltd.
133 p.
125
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Metiram Standard
MRID CITATION
00163786 Ivett, J. (1986) Mutagenicity Evaluation of Metiram Technical K38/
33A in the Rat Bone Marrow: Cytogenetic Assay: Amended Final
Rept.: LBI Proj. No. 22202. Unpublished study prepared by Lit-
ton Bionetics, Inc. 29 p.
00164083 Ulrich, C. (1986) Thirteen Week Subchronic Inhalation Toxicity
Study on Metiram in Rats - Final Report: Study No. 312-015. Un-
published study prepared by International Research and Develop-
ment Corporation. 371 p.
40044701 Ulrich, C. (1986) Thirteen Week Subchronic Inhalation Toxicity
* Study on Metrim in Rats - Final Report: Laboratory Project ID:
312-015: BASF Doc. No. 86/0407. Unpublished study prepared by
International Research and Development Corp. 385 p.
40290601 Offer, J.; Gopinath, C. (1987) Metiram: Toxicity to Rats in Dietary
Administration for 13 Weeks Followed by a 6-week Withdrawal Per-
iod: HRC Report No. BSF 197/8713, Addendum to BSF 197/77612.
Unpublished study prepared by Huntingdon Research Centre, Ltd.
11 p.
40466101 Carpenter, M. (1987) Determination of the Photolysis Rate of Ethy-
lenethiourea (ETU) on the Surface of Soil: ABC Final Report No.
36289. Unpublished study prepared by Analytical Bio-Chemistry
Labs., Inc. 504 p.
40466102 Carpenter, M.; Fennessey, M. (1987) Determination of the Photolysis
Rate of [Carbon 14]-Ethylenethiourea in pH 7 Aqueous Solution:
ABC Re-amended Final Report No. 36288. Unpublished study pre-
pared by Analytical Bio-Chemistry Labs., Inc. 658 p.
40466103 Carpenter, M. (1987) Hydrolysis as a Function of pH AT 25 [degree]
C OF [Carbon 14]-Ethylenethiourea: ABC Final Report No. 36287.
Unpublished study prepared by Analytical Bio-Chemistry Labs.,
Inc. 543 p.
40507101 Schneider/ A.; Redeker, J. (1988) Solubility of Metiram in Ethanol
and DMSO: Reg. Document No. BASF 88/5006. Unpublished study
prepared by BASF Aktiengesellschaft. 7 p.
40507102 Ohnsorge (1988) Amendment on Product Chemistry Submission Based on
Discission [sic] with EPA on September 11, 1987: Reg. Document
No. 88/5007. Unpublished study prepared by BASF Aktiengesell-
schaft. 11 p.
126
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APPENDIX IV
-------
Form Approved. OMB No. 2070-0057. Approval expires 11-30-89.
J
FIFHA SECTION 3(C)(2)(B) SUMMARY SHEET
EPA REGISTRATION NO.
PRODUCT NAME
APPLICANT'S NAME
DATE GUIDANCE DOCUMENT ISSUED
With respect to the requirement to submit "generic" data imposed by the FIFRA section 3(C)(2)(B) notice contained in the referenced
Guidance Document, I am responding in the following manner:
Q 1. 1 will submit data in a timely manner to satisfy the following requirements. If the test procedures I will use deviate from (or are not
specified in) the Registration Guidelines or the Protocols contained in the Reports of Expert Groups to the Chemicals Group. OECO
Chemicals Testing Programme, I enclose the protocols that 1 will use:
[HI 2. I have entered into an agreement with one or more other registrants under FIFRA section 3(C)(2)(B)tii) to satisfy the following data
requirements. The tests, and any required protocols, will be submitted to EPA by:
NAME OP OTHER REGISTRANT
LJ3. I enclose a completed "Certification of Attempt to Enter Into an Agreement with Other Registrants for Development of Data" with
respect to the following data requirements:
LJ 4. I request that you amend my registration by deleting the following uses (this option is not available to applicants for new products):
LJ 5. I request voluntary cancellation of the registration of this product. (This option is nor availa&le to applicants for new products.)
REGISTRANTS AUTHORIZED REPRESENTATIVE
SIGNATURE
i «-,,-.
EPA Form 8580-1 (10-82) ' £ ^
DATE
-------
OMB Approval No. 2070-0057
Expiration Date 11/30/89
GENERIC DATA EXEMPTION STATEMENT
EPA Product Registration Number:
Registrant's Name and Address:
As an authorized representative of the registrant of the product identified above, I
certify that:
(1) I have read and am familiar with the terms of the Notice from EPA dated
, concerning a requirement for submission of "generic" data on the active
Ingredient named under FIFRA Section 3(c)(2)(B).
(2) My firm requests that EPA not suspend the registration of our product, despite
our lack of intent to submit the generic data in question, on the grounds that the product
contains the active ingredient solely as the result of the incorporation into the product
of another product which contains that active ingredient, which is registered under FIFRA
Section 3, and which is purchased by us from another producer.
(3) An accurate Confidential Statement of Formula (CSF) for the above-identified
product is attached to this statement. That formula statement indicates, by company name,
registration number, and product name, the source of the subject active ingredient in my
firm's product, or
The CSF dated on file with EPA is complete, current and accurate and
contains the Information requested on the current CSF Form 8570-4. The registered
source(s) of the above named active ingredient in my product(s) is/are
and their registration number(s) is/are .
My firm will apply for an amendment to the registration prior to'changing the source
of the active ingredient in our product.
(4) I understand, and agree on behalf of my firm, that if at any time any portion of
this Statement is no longer true, or if my firm fails to comply with the undertakings made
in this Statement, my firm's product's registration may be suspended under FIFRA Section
3(cJ(2)(B).
(5) I further understand that if my firm is granted a generic data exemption for the
product, my firm relies on the efforts of other persons to provide the Agency with the
required generic data. If the registrant(s) who have committed to generate and submit the
required data fail to take appropriate steps to meet requirements or are no longer in
compliance with this Notice's data requirements, the Agency will consider that both they
and my firm are not in compliance and will normally initiate proceedings to suspend the
registrations of my firm's product(s) and their product(s), unless my firm commits to
submit and submits the required data in the specified time frame. I understand that, in
such cases, the Agency generally will not grant a time extension for submitting the data.
Registrant's authorized representative:
(Signature
Dated:
(Typed)
EPA Form 8570-27 ' j p o
-------
OMB Approval No.
2070-0057
Expires 11/30/89
PRODUCT SPECIFIC DATA REPORT
EPA Reg. No.
Date
Guidance Document for
"Registration
Guideline No.
Sec. 1WJ.12U
PRODUCT
CHEMISTRY
fal-1
61-2
61-3
62-1
62-2
62-3
63-2
63-3
63-4
63-b
63-6
63-/
63-8
63-9
63-10
63-11
63-12
1 Name of Test
Identity of
ingredients
Statement of
composition
Discussion of
formation of
ingredients
Preliminary
analysis
Certification of
1 i mi ts
Analytical methods
for enforcement
limits
Color
Physical state
Odor
Melting point
Boi ling point
Density, bulk-
density, or
specific gravity
Solubility
Vapor pressure
Dissociation
constant
Octanol /water
partition
coefficient
PH
Test not
required
for my
product
listed
above
(check
below)
I am complying with
data requirements by
Citing MR ID i
Number or
EPA Accession
Number
Submit-
ting
Data
(At-
tached)
(For EPA Use Only)
Accession Numbers
Assigned
.-
i i
EPA Form 8580-4
130
-------
OMB Approval No.
2070-0057
Expires 11/30/89
EPA Reg. Ho.
PRODUCT SPECIFIC DATA REPORT (cont'd)
Date
Guidance Document for
Registration
Guideline No.
Sec. lbb.120
PRODUCT
CHEMISTRY
(cont'd)
63-13
63-13
fal^lb
63-16
63-17
63-18
53^19
63-20
63-21
58.135 '
TOXICOLOGY
81-1 '
BT^2 '
81-3 '
bl-4
81-5 r
81-6 r
81-7 r
Name of Test
Stability
Oxidizing/reducing
reaction
Flammabi li ty
1 Explodabi nty
Storage stabi 11 ty
Viscosity
Miscibi lity
Corrosion
characteristics
Dielectric break-
down voltage
Acute oraj
toxicity, rat
Acute dermal
toxicity, rabbit
Acute inhalation,
toxicity, rat
Primary eye
irritation, rabbit
Primary dermal
Irritation
Dermal sensitiza-
tlon,
Acute Delayed
neurotoxicity, hen
Test not
required
for my
product
listed
above
(check
be! ow }
I am complying with
data requirements by
Citing MRID
Number or
EPA Accession
Number
Submit-
ting
Data
(At-
tached)
_ i
(For EPA Use Only)
Accession Numbers
Assigned
-•
r
i . — - — —
'•-
EPA Forra 8580-4 (cont'd)
131
-------
Foim Atxxowd. OMB No. »7O-0057. Expire* 11
CERTIFICATION OF ATTEMPT TO ENTER
INTO AN AGREEMENT WITH OTHER REGISTRANTS
(To qualify, certify ALL four items) FOR DE VE LOPMENT OF DATA
I. I am duly authorized to represent the following firm(s) who are subject to the require-
ments of a Notice under FIFRA Section 3(c)(2)(B) contained in a Guidance Document
to submit data concerning the active ingredient:
NAME OF FIRM
.
GUIDANCE DOCUMENT DATE
ACTIVE INGREDIENT
EPA COMPANY NUMBER
(This firm or group of firms is referred to below as "my firm".)
2. My firm is willing to develop and submit the data as required by that Notice, if necessary. However, my firm would prefer to
into an agreement with one or more other registrants to develop jointly, or to share in the cost of developing, the following req
hems or data:
3. My firm has offered in writing to enter into such an agreement. Copies of the offers are attached. That offer was irrevocable and included an offer
bound by an arbitration decision under FIFRA Section 3(c)(2)(BHiii) if final agreement on all terms could not be reached otherwise. This offer was
to the following firm(s) on the following dated):
NAME OF FIRM
DATE OF OFFER
However, none of those firm(s) accepted my offer.
4. TWy firm requests that EPA not suspend the registration(s) of my firm's product(s), if any of the firms named in paragraph (3) z
have agreed to submit the data listed in paragraph (2) above in accordance with the Notice. I understand EPA will promptly in
me whether my firm must submit data to avoid suspension of its registration(s) under FIFRA Section 3(c)(2)(B). (This state
does not apply to applicants for new products.) I give EPA permission to disclose this statement upon request.
TYPED NAME
SIGNATURE
DATE
EPA Form 858O-6 (10-82)
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