SEPA
United
Envkw
N«lc**« tntf Toxfe
WMhingtonOC JMtt
Octcter 1988
540/RS-89-006
Guidance for the
Reregistration of
Pesticide Products
Containing M&NEB
as the Active Ingredient
540/RS-89-006
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OMB Control No. 2070-0057
Expires 11/89
GUIDANCE FOR THE
REREGISTRATION OF PESTICIDE PRODUCTS
CONTAINING
MANEB
AS THE ACTIVE INGREDIENT
CASE NUMBER 0642
CAS (DOCKET) NUMBER 12427-38-2
EPA CHEMICAL CODE: 014505
OCTOBER 1988
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
WASHINGTON, D.C. 20460
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TABLE OF CONTENTS
Glossary of Terms and Abbreviations
I. Introduction 1
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 40
A. Regulatory Positions
B. Criteria for Registration
C' Acceptable Ranges and Limits
D. Required Labeling
V. Products Subject to this Standard 50
VI. Requirement for Submission of Generic Data 52
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. Registrants Requests Regarding Data Requirements
and Agency Response
F. Test Protocol 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 Stocks Provisions upon Suspension or
Cancellation
VII. Requirement for Submission of Product-Specific Data 58
VIII. Requirement for Submission of Revised Labeling ... 59
IX. Instructions for Submission 59
A. Manufacturing use products (sole active)
B. Manufacturing use products (multiple active)
C. End-Use Products (sole active)
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 .64
Guide to Tables
Table A
Table B
II. LABELING APPENDICES 120
Summary 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 145
Guide to Bibliography
Bibliography
IV. FORMS APPENDICES 155
EPA Form 8580-1 FIFRA §3(c)(2)(B) Summary Sheet
EPA Form 8580-3 Generic Data Exemption Statement
EPA Form 8580-4 Product Specific Data Report
EPA Form 8580-6 Certification of Attempt to Enter Into an
Agreement with Other Registrants for Development
of Data
ii
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GLOSSARY OF TERMS AND ABBREVIATIONS
The following terms are used throughout this Registration
Standard and axe 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)
Core Classification: A general guide to the acceptability of data
for the purpose of supporting registration
(invalid, supplementary, minimum, or guideline)
EEC: (Estimated Environmental Concentration) Estimated pesticide
concentration in the environment (terrestrial or aquatic
ecosystem).
EP: End-use Product
EPA: The Environmental Protection Agency, also "the Agency"
FIFRA: The Federal Insecticide, Fungicide, and Rodenticide Act
HOT: Highest dose tested
Invalid: Studies which are deficient in some vital parameter
or those studies which have been judged not to be
scientifically sound or those studies whose
reliability is seriously questioned.
LC5O: (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).
* • •
111
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(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).
MOSs Margin of Safety - The calculation of a margin of safety
involves division of an appropriate NOEL by a worker's
estimated exposure. The result is a unitless figure
which gives an indication of how close a worker's internal
dose is in relation to the NOEL for laboratory animals.
MPIs Maximum Permissible Intake
MRID: Master Record Identification (number)—EPA's system of
tracking studies used in support of registrations
MPs Manufacturing-use product
NPDES: National Pollutant Discharge Elimination System
NOEL: No Observed Effect Level:—the maximum dose used in a
test which produces no observed adverse effects.
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) An estimate of
dietary exposure obtained by multiplying residue tolerance
levels for a given pesticide by the average daily per
capita food consumption figure, then adding the exposure
figures for each crop. TMRC is usually expressed in
terms of mg ai/day, assuming a 60 kg person.
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 the 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
reassess 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 are available upon request*,
focus 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.
scientific reviews and use index are available from the
National Technical information Service, 5285 Port Royal
Road, Springfield, Va. 22161 or from 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. 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 issuance of a Notice of Intent to Suspend.
Failure to comply with the other requirements in this Standard
may result in 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 believes 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
become aware of such information. Registrants must notify
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the Agency of any information, including interim or preliminary
result* 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 FIPRA.
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II. CHEMICAL(S) COVERED BY THIS STANDARD
A. Description of chemical(s)
The following chemical(•) are covered by this Registration
Standards
Common names Maneb
Chemical namei Manganese ethylene bisdithiocarbamate
CAS Numbers 12427-38-2
OPP (Shaughnessy) Numbersi 014505
Empirical Formulas (C4HgMnN284)x
Trade namesi Dithane* M-22, Manzate*, Manex*
Description of physical characteristics of chemical
Colon Yellow
Physical States Powder
Odors Faint
B. Use Profile
Type of Pesticides Fungicide
Pests Controlled (in general)i Foliar fungal diseases of
selected fruit, nut, vegetable, grain, field and
ornamental (including turf) crops.
Registered Usess Terrestrial food crop use on fruit (apple,
apricot, banana, caprifig, cranberry, fig (Kadota), grapes,
nectarine, papaya, peach, pineapple (progagation stock)),
nuts (almonds and peanuts), vegetables (asparagus
(including plant stock), beans (including dried-type,
succulent, lima beans, blackeyed peas and cowpeas),
broccoli, Brussels sprouts, cauliflower, cabbage,
carrots, celery, Chinese cabbage, collards,
corn (field, pop, sweet), cucumber, eggplant, endive,
kale, kohlrabi, lettuce, melons (cantaloupe, casaba
melons, crenshaw melons, honeydew melons, muskmelons,
Persian melons, and watermelons), onion, peppers,
potatoes (including seed pieces), pumpkins, spinach,
squash (summer and winter), sugar beets, tomato,
turnips, and agricultural seed treatment (barley,
beans, peas, corn, cotton, flax, oats, peanuts, rice,
rye, safflower, sorghum, soybeans, sugar beets, sunflower,
wheat); Terrestrial nonfood crop use on tobacco and
ornamental flowering plants, shrubs, shade trees, and
grasses (seed crop) and turf; Greenhouse food crop
use(on rhubarb and tomato; Greenhouse nonfood crop
use on Epcot display crops.
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Predominant Use(s): The major use sites are potatoes,
tomatoes, apples and sweet corn.
Mode of Activity: Inhibition of certain fungal enzyme systems
Formulation Types Registered: Technical (85%, 86%, 90%) and
Formulation Intermediate (80%) maneb
End-Use Products - dusts,
granulars, wettable powders,
wettable powder/dusts
flowable concentrates,
and ready-to-use formulations
Method(s) of Application: The major volume of use for
maneb is for foliar application to vegetable crops and
apples. Spray application of maneb to foliage of all
crops for which it is registered may be accomplished
by aerial equipment as well as by ground equipment.
For ground equipment, maneb suspensions typically are
made from a wettable or flowable powder that would
be applied by means of air blast sprayers or by means
of tractor mounted boom sprayers. For application of
dust formulations, maneb would be applied by means of
truck or tractor drawn duster or aerial equipment.
For foliar treatment of tobacco or vegetable seed
beds, application of sprays or dusts might be by means
of hand-held compressed air sprayers or dusting equipment.
Potato and tomato foliage may be treated by means of
solid set, wheel move, or center pivot sprinkler irrigation
equipment.
Application Rates: Terrestrial food crop: 0.01 - 8.4 Ib ai/A
Terrestrial nonfood crop: 0.8 - 3.2 Ib ai/A
Greenhouse food crop: 1.1 - 2.4 Ib ai/100 gal
Greenhouse nonfood crop: 0.8 - 2.4 Ib ai/100 gal
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C. Background
Maneb 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 maneb and the other EBDC's (amobam, metiram, nabam, mancozeb,
and zineb) and their metabolite, ethylenethiourea (ETU), are
depicted in Table 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 biological 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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TABLE 1
CHEMICAL STRUCTURE OF EBDC'S AND ETU
ETHYLfNE THIOUREA (ETU)
H
CH2 - Nv
I
H
NABAM
•A W
I Jl
CH2-N-C-S-Na
aJ2-N-C-S-Na
I II
H S
AMDBAM
H S
I II
CH2-N-C-S-NH4
CH2-N-C-S-NH4
I II
H S
MANEB
^•••^••V ^•^••^K^M^H
H S
I II
CH2-N-C-S-
CHo-N-C-S-Mn
I If
x > 1
ZINEB
0*2
1
CH2
H S
/ II
- N - C -
- N - C -
I I
S -
S -
Zn
X > 1
MANOOZEB
m^m^m^f^ —^-^—»
H S
I I/
CH2-N-C-S-
Ofo-N-C-S-Mn
METIRAM
H
1
C«2 - N
CH2-N
H
S
II
- C - S -
- C - S - Zn(NH3>—
S
7
GH2 - N -
CH2-N-
3 H
S
11
C - S -
C - S -
I
X > 1
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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 i_n 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
8
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Document.
Since issuance of the Decision Document, the Agency has issued
eight data call-in notices for maneb 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 maneb, 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
for the agricultural uses ohly.
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 maneb.
4. March 20, 1985: This notice required registrants of
pesticide products containing maneb 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
maneb.
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 maneb and/or ETU are stable in or on
plant commodities when stored, firm conclusions on dietary
exposure to maneb or ETU from the use of maneb could not
be drawn based on data available at that time. Therefore,
this DCI required storage stability data and crop residue
data for maneb and ETU.
7. April 1, 1987s This notice required additional data
necessary to support the continued registration of maneb.
These data requirements pertain in general to the compre-
hensive review of the chemical which included the re-
assessment of tolerances. These data included environmental
fate, product chemistry, residue chemistry, toxicology.
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and wildlife and aquatic organisms studies.
8. April 25, 1988s The Notice required a small-scale
retrospective ground water monitoring study. Results of
previous studies indicated that maneb/ETU and/or its
degradate(s) have the potential to leach into ground
water. The Agency decided that additional data were
needed to define further the extent of the ground water
problem.
The data required by the first five call-in notices to support
the continued registration of maneb products have been
received and considered by the Agency in its evaluation of
maneb, as presented in the assessment section of this
Standard. Data submitted in response to the March 31, 1987,
April 1, 1987 and April 25, 1988 Data Call In Notices were
not due in time to be reviewed and included in this Standard.
However, all maneb data submitted are being reviewed and the
registrant(s) 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 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 10~5. 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 follows. A more detailed discussion is
contained in the remainder of this Chapter.
1. A major toxicological concern from exposure to maneb
is the hazard to the human thyroid from ethylenethiourea
(ETU), a contaminant, degradation product, and metabolite
present in maneb and other EBDC products. Additional
chronic studies on maneb are required for further evaluation.
2. ETU has caused developmentally toxic/teratogenic
effects in rats and hamsters. There are no adequate
teratology studies on maneb. Teratology studies
with maneb are required before its teratogenicity can
be fully assessed.
3. ETU has been classified as a Group B2 oncogen 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 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 maneb. These data must be
submitted in order to maintain registrations of products or
register new products containing maneb. Almost all of these
data have been required in previous Data Call-in Notices.
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 maneb products to
remain in compliance with FIFRA, as indicated below. Chapter
IV, Section D, Labeling, contains the specific wording for
each of the labeling statements and identifies the products
to which each labeling statement applies.
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o Protective clothing requirements
o Environmental hazard precautions
o Reentry interval
o Worker safety rules
o Preharvest interval emphasis
o Grazing Restrictions
The Regulatory Position and Rationale section discusses the
Agency's position regarding maneb.
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III. AGENCY ASSESSMENT
B. PRELIMINARY RISK ASSESSMENT
Toxicology Studies - Maneb. In its review of maneb, the
Agency has considered the available data as summarized below:
1. Acute Toxicity and Irritation Studies. The acute studies
are adequate to fulfill the data requirements. Maneb
(80%) does not appear to be acutely toxic (Toxicity Category
III or IV, except for eye irritation, Toxicity Category II).
An acute oral study on "Technical Maneb" (% not given) showed
it to be of lesser toxicity than the 80% compound.
2. Subchronic Testing
Oral (Rodent, Nonrodent) Studies. The nonrodent study submitted
in response to the Data Call In Notice of October 19, 1984,
is acceptable. Although there is no adequate rodent feeding study,
this will not be required if additional information is submitted
on the 31-month rat feeding study.
Monkeys were fed 0, 100, 300 or 3000 ppm (0, 5, 15, 150 mg/kg/day)
of technical maneb for 6 months. There was no mortality at
any dose level; the NOEL was 100 ppm (5 mg/kg/day), and the
LEL (increase in thyroid weight in males) was 300 ppra (15 mg/kg/day).
Effects at 3000 ppm (150 mg/kg/day) were an increase in mean
thyroid weight associated with an enlargement of this organ,
along with significantly reduced !31j absorption in the
thyroid, and lower mean percentage of protein-bound 131I at
26 weeks. Males at 3000 ppm (150 mg/kg/day) showed reduced
weight gains and somewhat lower food consumption relative to
their controls. This study satisfies the data requirement
for a 90-day nonrodent feeding study.
In an unpublished study conducted on a "Manzate" formulation of
manganese ethylenebisdithiocarbamate, groups of weanling
rats are reported as having been fed 0, 100, 1,000 or 10,000
ppm (0, 5, 50, 500 mg/kg/day) "active ingredient" for 97
days. At 10,000 ppm (500 mg/kg/day) there was considerable
reduction in mean body weight, and there was only 40% survival
to termination in male rats. An autopsy revealed "general
emaciation of the organs, exophthalmos, and extensive hyperplasia
of the thyroid." There was no mortality at 1,000 ppm (50 mg/kg/day);
male rats at this level showed no effects, but 80% of females
had some degree of thyroid hyperplasia. No effects were
observed at 100 ppm (5 mg/kg/day). Because of a number of
deficiencies (including, but not limited to, an insufficient
number of animals/group and lack of analytical data for
13
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ma neb and/or ETU) this particular study has been classified
as supplementary data. The requirement for a subchronic
rodent feeding study has not been satisfied. However, since
a chronic rodent study is required, further subchronic studies
in rodents will not be necessary.
Dermal Studies - No data were available for the evaluation
of the subchronic dermal effects. Based on the use patterns,
a 21-day dermal toxicity study is required.
Subchronic Inhalation - A 90-day subchronic inhalation study
on technical maneb was conducted on groups of Sprague-Dawley
derived rats. The animals were exposed 6 hours/day, 5 days
a week for 13 consecutive weeks to gravimetrically determined
concentrations of 0, 10, 32 or 98 mg/m3 of technical maneb.
There were statistically significant reduced mean body
weights at 13 weeks in females which had been exposed to 32
and 98 mg/m3. Males exposed to 98 mg/m3 consistently had
lower mean body weights than their controls through week 13,
but this was statistically significant only at 1, 2 and 3 weeks.
Chorioretinal hypoplasia occurred (at low incidence) only in
rats exposed to 32 and 98 mg/n3, while ophthalmological
keratitis was present (at an incidence of 5%) only in rats
exposed to 98 mg/m3.
No dose-related effects were observed in the histopathologic
examination conducted on rats sacrificed at 13 weeks.
The major value of this study is that it provides some ETU
thyroid residue data at the highest exposure level.
Paradoxically, it was the high-dose males which showed the
higher levels of ETU residue associated with the thyroid
(23.6 meg/ml versus 8.4 meg/ml for females), while females showed
possible (but not statistically significant) decreases in two
thyroid hormones Tj (triiodothyronine) and T4 (tetraiodothyronine)
This study is currently classified as supplementary, partly
because the toxic effects observed at the highest concentration
(98 mg/sP) of maneb tested were such that the question exists
as to whether this is a maximally tolerated dose or is
sufficiently close to it. There was some mortality in a
preliminary 5-day study at 290 mg/m*, but that level is more
than twice 98 mg/m-*, highest concentration in the 90-day study.
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An additional concern is that no residue data for ETU and/or
maneb were obtained for lung tissue. Also, manganese by
inhalation is a potential hazard, as humans exposed to
manganese salts or ores by this route may develop symptoms
similar to those of Parkinsonism. For this reason, some
analytical determination of manganese in the lung tissue of
exposed rats is appropriate. However, these analyses could
be done on rats exposed for considerably less than 90 days.
Histopathology data from rats sacrificed after a 13-week
recovery period and analytical data for lung tissue are
required to upgrade the existing study.
3. Chronic Testing
Chronic Toxicity Studies* In a two year study, CFW albino
rats received 0, 25, 250 or 2500 ppm (0, 1.25, 12.5 and 125
mg/kg/day) of the active ingredient in their diet. An
additional group was fed 1250 ppm (62.5 mg/kg/day) for a
period of 97 days, and some of the rats were then sacrified.
At 97 days, the mean thyroid weight for 1250 ppm (62.5 mg/kg/day)
rats was significantly elevated, along with a reduction in
growth rate as compared to controls.
In rats sacrificed at one year, the goitrogenic effect was
evident as a significant increase in the weight of the thyroid
in rats fed 2500 ppm (125 mg/kg/day) maneb, with females at
250 ppm showing a smaller increase in thyroid weight. Rats
fed lower levels were unaffected.
Twenty-one of forty rats receiving 2500 ppm (125 mg/kg/day)
maneb for one to two years developed nodular goiter, and
four of these twenty-one also had well-developed thyroid
adenomas. No nodular goiters were observed in rats receiving
0, 25, or 250 ppm (0, 1.25, 12.5 mg/kg/day) maneb for 1-2
years, although there were three occurrences of small thyroid
adenomas.
The NOEL in this study was 250 ppm (12.5 mg/kg/day). The
classification of this study is supplementary, because of
an insufficient number of animals at each dosage level (after
the one-year sacrifice there were 20 rats/sex/group) and
lack of individual necropsy data.
In a second rat feeding study, groups of 90 male and 90 female
Spr ague-Daw ley rats were fed technical maneb at concentrations
of 0, 30, 100, 300 and 1000 ppm (0, 1.5, 5, 15, 50 mg/kg/day)
for 31 months. There were interim sacrifices at 3, 6 and 12
months.
In a sampling of rats, there were statistically significant
increases in the half-life for 131I retention at 1000 ppm
15
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(50 ing/kg/day). Additionally, there were elevated 131I
retention times at 12 and 24 months in 1000 ppm (50 mg/kg/day)
females, and in 1000 ppm (50 mg/kg/day) males at 24 months.
There were indications of effects (decrease in mean body
weight, increase in mean absolute thyroid weight, an increased
incidence of bladder epithelial dysplasia in males only) in
rats at 1000 ppm (50 mg/kg/day). However, this 31-month rat
feeding study is classified as supplementary, with the possibility
that it can be upgraded with additional data and some clarifi-
cations concerning the analysis of the diet fed to the rats.
In a one-year dog feeding study, doses of 0, 2, 20, 75 and
200 mg/kg/day of technical maneb were administered by capsule
to groups of 2 male dogs. Muscular weakness of the hind
legs occurred in all dogs at the two highest dose levels;
the report notes that this was possibly induced by the manganese
in the formulation.
The study stated that "Microscopic examination of the brain,
spinal cord and peripheral nerves disclosed pathologic
lesions of a degenerative nature in both control and test
animals."
Muscle sections from dogs at 200 mg/kg/day and from one dog
of the 75 mg/kg/day group showed striking degeneration or myopathy.
Dogs at 200 mg/kg/day showed a weight loss, and one of these
animals, with severe signs of toxicity, was sacrificed after
57 doses of the' test material and a 15-day recovery period.
Clinical signs in both dogs at 200 mg/kg/day included loss of
appetite, yellowish-orange feces, unkempt appearance, salivation,
involuntary and excessive urination, muco-purulent nasal
discharge, vomiting, fetid breath, signs of abdominal discomfort,
cold extremities, tremors and posterior weakness progressing
to flaccid paralysis of the hindquarters.
Despite a statement in the text of the report that there were
no goitrogenic effects at any level, it is noteworthy that
both dogs at 75 mg/kg/day were reported as having a heavier than
usual thyroid, and in the dog at 200 mg/kg, which was treated
with 202 doses before sacrifice, there were thyroid findings
suggestive of hyperplasia.
This study indicates that maneb may cause neurologic toxicity
at levels for which thyroid effects may not occur. This
neurologic toxicity is not to be confused with the delayed
neurotoxic effect of some organophosphates.
This study is classified as supplementary (reasons include but
are not limited to, the low number of dogs per dosage group (2),
16
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use of only males and animals older than 9 months at initiation
of the study). The classification of this study cannot be upgraded.
A one-year feeding study on a nonrodent (preferably the dog)
is required. Additional information on the analysis of the diet
fed to the rats is required for the rodent 31-month study
before it is upgraded.
Oncogenicity Studies - There are no currently acceptable
oncogenicity studies on maneb. The supplementary classification
of the 31-month rat feeding study, may with additional data
and clarifications as stated above, be upgraded. There were
indications of thyroid oncogenicity in rats fed 0.25% Maneb
for 1-2 years. A metabolite of maneb, ETU has been demonstrated
to have oncogenic effects on the thyroid.
There are two published mouse oncogenicity studies on Maneb.
Innes et al. (1969) reported negative results from FI C57BL/6
x C3H/Anf and C57BL/6 x AKR mice, which received the test
material from 7 days of age (doses: 46.4 mg/kg/day through
day 28; then 158 ppm (23.7 mg/kg/day) in the diet) to about
18 months. Balin (1970) reported a significantly increased
incidence of lung adenomas in mice receiving 500 mg/kg/week
of maneb. Neither of these studies is acceptable by the
review criteria currently used by the Agency.
Rat and mouse oncogenicity studies are required.
Teratogenicity Testing - There are no acceptable teratogenicity
studies for maneb. Because of anticipated human exposure to
maneb, studies on two mammalian species (preferably rat and
rabbit) are required to support all registered uses.
Reproduction Study - There is no accceptable reproduction
study on maneb.
In an unpublished three-generation rat (Sprague-Dawley strain)
study, the animals were fed dietary levels of 0, 30, 100 or
500 ppm (0, 1.5, 5, 25 mg/kg/day). In another unpublished
three-generation rat (Chr-CD Strain) study, dietary levels of
0, 125 and 250 ppm (0, 6.25, 12.5 mg/kg/day) were given.
There was no evidence of toxicity or reproductive and/or
teratogenic effects in either study. Since no effects of any
kind were reported, it appears that for both studies the
test material was not administered at either a maximally
tolerated dose or sufficiently close to it.
An acceptable two-generation reproduction study is required
to support the continued registration of maneb for use on
food crops.
17
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Mutaqenicitv Studies - In response to the January 17, 1983,
Data Call In Notice, several mutagenicity studies were submitted.
Gene Mutation - Five tester strains of Salmonella typhimurium
were used to test 0, 3, 10, 15, 30, 50, and 100 ug/plate of "•
technical maneb. The results were negative for base pair
substitutions and frame-shift mutations, with and without
metabolic activation. The ability of maneb to induce forward
mutations at the HGPRT locus in Chinese Hamster Ovary (CHO)
cells was evaluated in two different studies in the presence
and absence of a metabolic activation system. In the first
study, maneb did not exhibit mutagenic activity. In the
second study, maneb was found not to induce an increase in
mutation frequency with and without S-9 activation.
In a host-mediated assay in mice, maneb did not demonstrate a
mutagenic response when tested using Salmonella typhimurium
strain TA1530 as the indicator strain and B6C3F1 mice as the
host.
Structural Chromosomal Aberration - Maneb was found to be
negative for induction of Sister Chromatid Exchange in CHO
cells in the absence of a metabolic activation system and
positive with activation.
Other Mutagenic Mechanisms - Technical maneb was tested for
induction of unscheduled DNA synthesis (UDS) using rat
hepatocytes in vitro. Although maneb did not appear to induce
unscheduled DNA* synthesis under the conditions of the assay,
sufficient evidence of the validity of the experiment was not
provided in that individual data were not submitted. Once
these are provided, the study may be upgraded to acceptable status,
The January 17, 1983, Data Call In Notice required a mammalian
cell transformation assay on maneb (with and without metabolic
activation) in a cell system capable of detecting initiation,
as well as enhancement, of transformation. In one of the studies
submitted, maneb, at five concentrations ranging from 0.05 to
0.20 ug/ml, did not induce transformation in C3H-10T 1/2 cells
in the absence of metabolic activation. In another study,
under the conditions of the cell transformation assay, maneb
showed no indication of any promotion activity as a result of
sequential exposure of C3H-10T 1/2 cells to MNNG and technical
maneb.
Two of the mutagenicity studies require additional data in
order to upgrade their status to acceptable. Clarification
of the percent of active ingredient is required for the
CHO/HGPRT forward mutation assay and individual data are
required for a final evaluation of the unscheduled DNA
synthesis assay in rat hepatocytes.
18
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Metabolism Studies - In an adequate study, the metabolism of
maneb was studied in three groups of rats. The data indicate
that in all three groups more than 70% of the 14C was
excreted in the urine and feces, and 20 to 30% of the 14C
in urine was ETU in the first 12 hours after dosage. ETU
was 40 to 50% of the 14C present in fecal samples in the
period from 12 to 24 hours after dosage from rats dosed at
2235 ing/kg, but it was only 3.7 to 12% of the 14C in feces
from rats which received 25 mg/kg doses of 14C-labeled
maneb. The thyroid was a target organ; 0.3% of the total
dose was present per gram of this organ at day 5 in females
receiving a single 25 mg/kg dose. Females at 2235 mg/kg, on
day 7, had mean ug maneb equivalents per gram organ weight
of 218, 235 and 363 for thyroid, kidneys and liver, respectively,
An additional single-dose metabolism study was submitted
which supports the results from the previous study; (i.e. the
liver, kidneys, and thyroid contained the highest levels of
Maneb; the major metabolite was ETU; and total excretion was
greater than 70%).
No additional metabolism data are required.
Dermal Absorption - In an unpublished study, mixtures of *4C-
labeled and unlabeled maneb were applied at dosage levels of
0.195, 1.92, 19 or 133 mg total maneb to approximately 4.9 cm^
of rat skin for a period of 10 hours. The study demonstrates
that the amount of maneb bound to the skin following dermal
exposure is concentration and/or dose dependent. At the
lowest dose level of 0.195 mg/rat approximately 30% of the
radioactivity (approximately 0.06 mg maneb) was bound to the
rat skin; at the highest dose level of 133 mg/rat approximately
O.7%, or 0.9 mg maneb, was bound to the skin.
The amount of 14C activity excreted in the urine during
the period from 4 to 10 hours following application of the
test material is about 1% of the amount bound to the skin at
each dose level. This represents the lower limit of absorption.
Since 14C activities were only measured for urine, blood and
feces (not for carcasses), the study does not adequately
define the upper limit for absorption.
While the study is acceptable as core minimum data, additional
work is necessary to determine what levels of 14C activity
are associated with the carcass in order to obtain a more
precise measurement of the amount of maneb absorbed.
Additionally studies are also required to determine whether
(and if so, at what rate) the maneb bound to the skin is
absorbed after 10 hours.
19
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Toxicological Studies - ETU - Since ETU, a contaminant,
degradation product, and metabolite of maneb and other EBDC
products, presents toxicological concerns, available data on ETU
were considered in the overall evaluation of maneb. These
data are summarized as followsi
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
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 study, rats were fed levels
of 0, 1, 5, 25, 125, and 625 ppm (0, .05, .25, 1.25, 6.25
31.25 mg/kg/day) ETU for 30, 60, and 90 days. Thyroid hyper-
plasia, decreased uptake of 125i by the thyroid, and
decreased serum Tj (triiodothyronine) and T4 (tetraiodothyronine)
were seen. The LEL was 25 ppm 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 (15 mg/kg/day).
In a 21-week study in Rhesus monkeys, at dosage levels of 0,
2, 10, 50, and 250 ppm (0, .10, 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 (2.5, 12.5 mg/kg/day)
as well as thyroid follicular lining cell hypertrophy
and hyperplasia (mild at 50 ppm (2.5 mg/kg/day); moderate to
severe at 250 ppm) (12.5 mg/kg/day). Serum levels of TA
were significantly decreased in the 250 ppm (12.5 mg/kg/day)
group. Free serum TA levels were also significantly decreased
in both the 50 and 250 ppm (2.5, 12.5 mg/kg/day) group;
iodine uptake was significantly increased at these levels
and thyroid stimulating hormone (TSH) levels were significantly
increased at 250 ppm (12.5 mg/kg/day).
20
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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.
Oncogenicity Studies - Three oncogenicity studies have been
reviewed, as discussed below:
In a mouse study (Innes), two hybrid strains of mice were
used C(C57BL/6 x C3H/Anf)Fi (Strain X) and (C57BL/6 x
AKR)FI (Strain Y)3* 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.
350 ppm 175 ppm
Lesion Males* Females 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.
21
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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, 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
nales and females. 131I uptake was statistically increased
in male rats at 18 months in the 25 and 125 ppm (.25, 12.5
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 (0.05 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 131-1 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
followss
Tumor Incidence Data for Rats,
Including 18-Month Interim
Sacrifice, Fed ETU in the Diet
Dose Levels in ppm
5 25 125 250 500
Pathological lesions
Cataract s/kerat it is
Thyroid carcinoma/
adenocarcinoma
(follicular)
Thyroid adenomas
Thyroid hyperplasia
Parathyroid hyperplasia
2
2
2
4
6
1
2
—
20
11
0
1
5
41
8
2
2
1
44
2
6
16
21
27
3
12
62
3
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
22
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not produce maternal toxicity or fetotoxicity. The NOEL for
these effects is 5 mg/kg. Administration of T*/T4 with
ETU to pregnant rats appears to reduce the incidence of some
of these effects.
Mutagenicity 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-ETU 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, l^C-ETU wag 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 CO2 (± 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,
all 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 maneb. 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
23
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Guidelines for Carcinogen Risk Assessment (September 26,
1986, 51 FR 33992), as a Group B2 oncogen, Probable Human
Carcinogen.
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 categori-
zation is appropriate if there is "sufficient evidence" of
the chemical's carcinogenicity from animal studies. "Sufficient
evidence" is defined as an 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 thyroid
tumors in rats after 1 year or less of treatment and induced both
thyroid tumors in rats and hepatomas in mice to a high
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.
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 Exposure and Risks - The Agency is currently assessing risks
associated with systemic effects of maneb and the teratogenic,
thyroid and oncogenic effects attributed 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 in the
tank mix. Available data indicate that the concentration of
ETU as a contaminant can vary between products. For calculating
direct exposure to mixers and loaders while preparing and
loading maneb spray mixture, the Agency used 0.1% of the
maneb 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 amounts of
ETU which contaminates the technical and tank mix but also the
24
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additional ETU formed while spraying. Available data indicate
that ETU residues increase in the spraying equipment to 6% of
the amount of maneb products.
An oral subchronic study of maneb in monkeys showed thyroid
effects at 15 ing/kg, with a NOEL of 5 mg/kg/day. No developmental
studies were available.
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. The
NOEL for these effects is 5 mg/kg/day.
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 and
added a 20 percent conversion factor for metabolic conversion
of maneb to ETU. A 30 percent dermal absorption figure was
used for maneb in the absence of adequate data. The exposures
to applicators and the margins of safety for teratogenic
effects of ETU from exposure to maneb and ETU in the tank mix
are shown in Table 2.
ETU has also demonstrated thyroid hyperplasia, decreased
uptake of 125i (iodine) by the thyroid and decrease serum
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 maneb 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 3 x 10"' to
4 x 10~4
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TABLE 2
NONDIETARf RISK ASSESSMENT FOR HANBB
•g/kg/day ag/kg/day mg/kg/day MANBB
HANBB a/ HANBB HANBB TOTAL
DERMAL ABSORBED INHALATION DAILY
EXPOSURE pBRMALLY EXPOSURE EXPOSURE
APPLES 1
AERIAL LOADER
APPLICATOR
AIRBLAST LOADER
APPLICATOR
COMBINE
ONIONS 1
AERIAL LOADER
APPLICATOR
FLAGGBR
GROUNDBOOH LOADER
APPLICATOR
COMBINE
POTATOES 1
AERIAL LOADER
APPLICATOR
PLAGGBR
GROUNDBOOH LOADER
APPLICATOR
COMBINE
CHEMGATION COMBINE
SEED TREAT PILL/CUT
PLANT
•g/kg/day
0.2300
0.0061
0.9400
2.2000
3.1400
0.5000
0.0140
0.0780
0.2100
0.4700
0.6800
1.9000
0.0380
0.0210
0.2200
0.2900
0.5100
1.6000
0.0840
0.0300
0.0690
0.0024
0.2820
0.6600
0.9420
0.1500
0.0042
0.0234
0.0630
0.1410
0.2040
0.5700
0.0114
0.0063
0.0660
0.0870
0.1530
0.4800
0.0252
0.0090
0.0035
0.0003
0.0140
0.0033
0.0170
0.0077
0.0004
0.0044
0.0032
0.0086
0.0118
0.0290
0.0012
0.0120
0.0034
0.0053
0.0087
0.0250
0.0058
0.0030
0.0725
0.0027
0.2960
0.6633
0.9590
0.1577
0.0046
0.0278
0.0662
0.1496
0.2158
0.5990
0.0126
0.0183
0.0694
0.0923
0.1617
0.5050
0.0310
0.0120
•gAg/day BgAg/day MgAg/day «gAg/day BTU
b/ HANEB BTU C/ BTU BTU PROM TOTAL
NBTABOLI2BD DERMAL ABSORBED INHALATION DAILY
TO BTU EXPOSURE DBRMALLY EXPOSURE EXPOSURE
•g/kg/day
0.0145
0.0005
0.0592
0.1327
0.1918
0.0315
0.0009
0.0056
0.0132
0.0299
0.0432
0.1198
0.0025
0.0037
0.0139
0.0185
0.0323
0.1010
0.0062
0.0024
0.0002
0.0005
0.0009
0.1300
0.1309
0.0005
0.0008
0.0002
0.0002
0.0280
0.0282
0.0019
0.0023
0.0130
0.0002
0.0170
0.0172
0.0016
0.0001
0.0000
0.0001
0.0002
0.0003
0.0390
0.0393
0.0002
0.0003
0.0000
0.0001
0.0084
0.0085
0.0006
0.0007
0.0039
0.0001
0.0051
0.0052
0.0005
0.0000
0.0000
0.0000
0.0000
0.0000
0.0002
0.0002
0.0000
0.0000
0.0000
0.0000
0.0005
0.0005
0.0000
0.0001
0.0007
0.0000
0.0003
0.0003
0.0000
0.0000
0.0000
0.0146
0.0007
0.0595
0.1719
0.2313
0.0317
0.0012
0.0056
0.0133
0.0388
0.0521
0.1204
0.0033
0.0083
0.0139
0.0239
0.0378
0.1015
0.0062
0.0024
•/ 301 BTU DERMAL ABSORPTION
b/ 30% DERMAL ABSORPTION OP MANBB
C/ 20% METABOLIC CONVERSION OP MANEB TO BTU
-------
NOND1ETARY RISK ASSESSMENT FOR MANEB
Mg/kg/day Mg/kg/day mg/kg/day MANEB
MANEB a/ MANEB MANEB TOTAL
DERMAL ABSORBED INHALATION DAILY
EXPOSURE DBRMALLY EXPOSURE EXPOSURE
Mg/kg/day
1.2000
1 0.0300
0.1700
0.2000
R 0.4000
0.6000
0.2000
ft 0.3000
0.5000
0.2400
R 0.5700
0.8100
0.0190
R 2.9000
2.9200
0.0890
0.0620
4.9000
0.7700
0.3600
0.0090
0.0510
0.0600
0.1200
0.1800
0.0600
0.0900
0.1500
0.0720
0.1710
0.2430
0.0057
0.8700
0.8760
0.0267
0.0186
1.4700
0.2310
0.0019
0.0010
0.0095
0.0031
0.0073
0.0104
0.0030
0.0056
0.0086
0.0037
0.0009
0.0046
0.0003
0.0023
0.0026
0.0000
0.0000
0.0000
0.0000
0.3619
0.0100
0.0605
0.0631
0.1273
0.1904
0.0630
0.0956
0.1586
0.0757
0.1719
0.2476
0.0060
0.8723
0.8786
0.0267
0.0186
1.4700
0.2310
tONATOBSi
AERIAL LOADER
APPLICATOR
PLAGGBR
GROUNDBOOM LOADER
APPLICATOR
COMBINE
SWEET CORNI
GROUNDBOOM LOADER
APPLICATOR
COMBINE
GRAPESI
GROUNDBOOM LOADER
APPLICATOR
COMBINE
COMMERCIAL
ORNAMENTALS!
LOADER
APPLICATOR
COMBINE
HOMEOWNER
VEGETABLE COMBINE
ORNAMENTAL COMBINE
TURP COMBINE
PRUIT TREE COMBINE
a/ 30% DERMAL ABSORPTION OP MANBB
b/ 20% METABOLIC CONVERSION OP NANBB TO BTU
C/ 30% ETU DERMAL ABSORPTION
Mg/kg/day Mg/kg/day mg/kg/day Mg/kg/day ETU
b/ MANBB ETU C/ ETU BTU PROM TOTAL
METABOLIZED DERMAL ABSORBED DIRECT DAILY
TO ETU EXPOSURE DBRMALLY INHAL* BXP EXPOSURE
Mg/kg/day
0.0724
0.0020
0.0121
0.0126
0.0255
0.0381
0.0126
0.0191
0.0317
0.0151
0.0344
0.0495
0.0012
0.1745
0.1757
0.0053
0.0037
0.2940
0.0462
0.0012
0.0018
0.0100
0.0002
0.0240
0.0242
0.0002
0.0180
0.0180
0.0002
0.0340
0.0342
0.0000
0.1700
0.1700
0.0053
0.0037
0.2900
0.0460
0.0004
0.0005
0.0030
0.0001
0.0072
0.0073
0.0001
0.0054
0.0054
0.0001
0.0102
0.0103
0.0000
0.0510
0.0510
0.0016
0.0011
0.0870
0.0138
0.0000
0.0001
0.0006
0.0000
0.0004
0.0004
0.0000
0.0003
0.0003
0.0000
0.0001
0.0001
0.0000
0.0001
0.0001
0.0000
0.0000
0.0000
0.0000
0.0728
0.0026
0.0157
0.0127
0.0331
0.0458
0.0127
0.0249
0.0375
0.0152
0.0446
0.0598
0.0012
0.2256
0.2269
0.0069
0.0048
0.3810
0.0600
fVJ
-------
IKBLt *
NONDIETARY RISK ASSESSMENT FOR MANEB
APPLES i
AERIAL
AXRBLA8T
ONIONS 1
AERIAL
MANEB BTU
TOTAL TOTAL DAYS
DAILY DAILY EXPOSED
EXPOSURE EXPOSURE
•gAg/day ngAg/day
LOADER
APPLICATOR
LOADER
APPLICATOR
COMBINE
LOADER
APPLICATOR
PLAGGBR
GROUNDBOOM LOADER
APPLICATOR
COMBINE
0.0725
0.0027
0.2960
0.6633
0.9590
0.1577
0.0046
0.0278
0.0662
0.1496
0.2158
0.0146
0.0007
0.0595
0.1719
0.2313
0.0317
0.0012
0.0056
0.0133
0.0388
0.0521
1
1
7
7
7
6
6
6
6
6
6
BTU MANEB BTU TOTAL THYROID THYROID
TOTAL TOTAL DIRECT SEASONAL MOS SEASONAL
YEARLY YEARLY YEARLY SYSTEMIC TBRATO SYSTEMIC
EXPOSURE EXPOSURE EXPOSURE MANEB MOS BTU BTU MOS
•gAg «gAg »gAg 5 «gAg S «gAg .25 »g/kg
0.0146
0.0007
0.4164*
1.2030
1.6190
0.1901
0.0072
0.0336
0.0798
0.2330
0.3128
0.0725
0.0027
2.0720
4.6431
6.7130
0.9462
0.0276
0.1668
0.3972
0.8976
1.2948
0.0001
0.0002
0.0020
0.2744
0.2764
0.0009
0.0017
0.0003
0.0004
0.0535
0.0539
6207
164835
217
97
67
476
16304
2698
1133
501
348
343
7184
84
29
22
158
4174
892
376
129
96
326087
150000
11398
82
81
25000
13489
78125
59524
420
418
•/ ONCO
RISK
BTU
7.98E-07
3. 8 IB-OB
2.28B-05
6.S9B-05
8.87B-05
1.04B-05
3.94E-07
1.84B-06
4.37B-06
1.28B-05
1.7 IB-OS
POTATOESI
AERIAL LOADER
APPLICATOR
PLAGGBR
GROUNDBOOM LOADER
APPLICATOR
COMBINE
CHEMGATION COMBINE
SEED TREAT PILL/CUT
PLANT
0.5990
0.0126
0.0183
0.0694
0.0923
0.1617
0.5050
0.0310
0.0120
0.1204
0.0033
0.0083
0.0139
0.0239
0.0378
0.1015
0.0062
0.0024
4
4
4
7
7
7
2
5
5
0.4815
0.0131
0.0331
0.0976
0.1672
0.2647
0.2030
0.0312
0.0120
2.3960
0.0504
0.0732
0.4858
0.6461
1.1319
1.0100
0.1550
0.0600
0.0023
0.0030
0.0185
0.0005
0.0379
0.0384
0.0010
0.0002
NBGL.
188
8929
6148
926
696
398
446
2903
7500
42
1524
604
9868
7401
1218
359 48701
209 593
132 587
49 23438
803 150000
2083 »»100
2.64B-05
7.19B-07
1.81E-06
S.35B-06
9.16B-06
1.4SB-OS
1.1IB-OS
1.716-06
6.58B-07
a/ RISK • YEARLY EXPOSURE/365 X 40/70 X 0.14/ngAg/day
GO
-------
NONDIBTARY RISK ASSESSMENT MR MANBB
MANEB ETU ETU
TOTAL TOTAL DAYS TOTAL
DAILY DAILY EXPOSED YEARLY
EXPOSURE EXPOSURE EXPOSURE
•g/kg/day ng/kg/day ng/kg
0.3619
1 0.0100
0.0605
0.0631
I 0.1273
0.1904
0.0630
1 0.0956
0.1586
0.0757
* 0.1719
0.2476
0.0060
R 0.8723
0.8786
0.0267
0.0186
1.4700
0.2310
0.0728
0.0026
0.0157
0.0127
0.0331
0.0458
0.0127
0.0249
0.0375
0.0152
0.0446
0.0598
0.0012
0.2256
0.2269
0.0069
0.0048
0.3810
0.0600
3
3
3
7
7
7
4
4
4
15
15
15
30
30
30
6
5
2
6
0.2183
0.0078
0.0470
0.0888
0.2317
0.3205
0.0506
0.0994
0.1498
0.2282
0.6694
0.8975
0.0370
6.7680
6.8058
0.0416
0.0242
0.7620
0.3600
MANEB BTU TOTAL THYROID THYROID
TOTAL DIRECT SEASONAL MOS SEASONAL
YEARLY YEARLY SYSTEMIC TBRATO SYSTEMIC
EXPOSURE EXPOSURE MANEB MOS ETU ETU MOS
•g/kg «gAg 5 ng/kg 5 «gAg »25 agAg
1.0857
0.0300
0.1815
0.4417
0.8911
1.3328
0.2520
0.3824
0.6344
1.1355
2.5779
3.7140
0.1797
26.1690
26.3580
0.1602
0.0930
2.9400
1.3860
0.0011
0.0018
0.0107
0.0004
0.0535
0.0539
0.0002
0.0229
0.0230
0.0011
0.1538
0.1547
0.0010
1.5342
1.5342
0.0095
0.0056
0.1740
0.0828
414
15000
2479
1019
505
338
1786
1177
709
396
175
121
2504
17
17
2809
4839
153
325
69
1925
319
394
151
109
395
201
133
329
112
84
4056
22
22
3145
4505
57
362
19789
12563
2101
53571
421
417
93750
981
980
20833
146
145
87656
59
59
2358
4054
129
272
•/ ONCO
RISK
ETU
1.20E-05
4.27E-07
2.58E-06
4.86E-06
1.27B-05
1.76B-05
2.77B-06
5.45E-06
B.21B-06
1.2 SB-OS
3.67B-05
4.92B-05
2.03E-06
3.71B-04
3.73B-04
2.28B-06
1.32B-06
4.18E-05
1.97E-05
TOMATOESI
AERIAL LOADER
APPLICATOR
FLAGGER
GROUNDBOOM LOADER
APPLICATOR
COMBINE
SWEET CORN!
GROUNDBOOM LOADER
APPLICATOR
COMBINE
GRAPESI
GROUNDBOOM LOADER
APPLICATOR
COMBINE
COMMERCIAL
ORNAMENTALS!
LOADER
APPLICATOR
COMBINE
HOMEOWNER
VEGETABLE COMBINE
ORNAMENTAL COMBINE
TURF COMBINE
PROIT TREE COMBINE
a/ RISK • YEARLY EXPOSURE/365 X 40/70 X 0.14/ngAg/day
-------
NONDXBTARY RISK ASSESSMENT FOR HANEB
MANEB
TOTAL
DAILY
EXPOSURE
ftgAo/day
ETU
TOTAL
DAILY
EXPOSURE
•g/kg/day
THYROID
DAILY
SYSTEMIC
MANEB M08
5 «gAg
THYROID
SEASONAL
SYSTEMIC
MANEB M08
3 «g/kg
MOS
TERATO
BTU
5 agAg
THYROID
DAILY
SYSTEMIC
BTU MOS
.25 Mg/kg
THYROID
SEASONAL
SYSTEMIC
BTU MOS
.25 mq/kq
•/ ONCO
RISK
BTU
GRAPESI
OROUND600M LOADER 0.0757 0.0152 66 396 329 16
APPLICATOR 0.1719 0.0446 29 175 112 6
COMBINE 0.2476 0.0598 20 12V 84 4
COMMERCIAL
ORNAMENTALSi
LOADER 0.0060 0.0012 835 2504 4056 203
APPLICATOR 0.8723 0.2256 6 17 22 1
COMBINE 0.8786 0.2269 6 17 22 1
•/ RISK - YEARLY BXPOSURE/365 X 40/70 X 0.14/ngAg/day
20833 1.25B-05
146 3.67B-05
145 4.92E-05
87656 2.03B-06
59 3.71E-04
59 3.73B-04
-------
Dietary Exposure and Risk. The Agency has assessed dietary
risks attributed to exposure to ETU resulting from application
of maneb to crops. Risk assessments were calculated for certain
chronic adverse effects from chronic dietary exposure to ETU
and maneb. In addition, oncogenicity and teratology dietary
risk assessments were calculated for ETU.
Chronic Effects
First, dietary exposure to ETU from use of maneb and potential
risks for adverse effects from this exposure were assessed.
Average field trial residues of ETU, obtained from studies
submitted in support of maneb tolerances, were used for this
dietary exposure analysis. 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 maneb converts to ETU during
the processing of the raw agricultural commodities. These
residues were then reduced by the percent of crop treated
with maneb obtained from actual use data, except a percent crop
treated value of 10 was used for all commodities for which
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 maneb use of 0.0005 mg/kg/day.
The PAD I 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 because a NOEL
was not reached and the reproduction study is lacking and
the follicular cell hyperplasia was observed in a significant
number of animals at the LEL of 5 ppm. This resulted in a PAD I
of 0.00008 mg/kg/day. The effect on which the PAD I is based
was hyperplasia of the thyroid; a NOEL for this effect was
not established for this study.
The dietary exposure to ETU of 0.0005 mg/kg/day occupies
580 percent of the PADI.
Secondly, dietary exposure to maneb and potential risks for
adverse effects were assessed. The residues used in the
analysis were the average field trial residues of maneb
obtained from data submitted in support of established
tolerances, reduced by the percent of crop treated. Based
on these average residues, the average consumption estimate
for the U.S. population is calculated as 0.0036 mg/kg/day
maneb.
A PADI of 0.005 mg/kg/day for maneb was derived from a six
month monkey study with a NOEL of 5.0 mg/kg/day and a safety
factor of 1000 was used to account for the lack of an adequate
data base on chronic toxicity. The effect noted was an
increase in the mean thyroid weight.
The dietary exposure to maneb of 0.0036 mg/kg/day occupies
70 percent of the PADI.
31
-------
Oncogen!c Risks
Thirdly, a risk assessment was conducted to determine potential
oncogenic risks from dietary exposure to ETU from use of
•aneb. For this assessment, average residues for both
ETU and maneb 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
U.S. population receives a dietary exposure of 0.0005
mg/kg/day ETU from conversion of maneb on crops. This analysis
was based on average field residues for ETU considering the
percent of crop treated with maneb. The potential dietary
risk is calculated by multiplying exposure by the QI*:
Dietary Risk = Exposure x Qj*
= 0.0005 x 0.14
= 6.5 x 10~5
In addition, there is dietary exposure from conversion of
maneb to ETU in vivo after eating food containing maneb
residues. Metabolism studies in rats show that approximately
20 percent'of maneb is metabolically converted to ETU. In
order to determine the dietary exposure to ETU from conversion
of maneb residues in this way, the maneb dietary exposure of
mg/kg/day.
The total potential dietary risk from exposure to ETU from
use of maneb on food crops is obtained by adding .65 x 10"4
and 1.0 x 10"4.
Total Dietary Oncogenic Risk - 1.7 x 10~4
Teratogenic Risks
Lastly, 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.
32
-------
Maneb 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 residues 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 is not appropriate because this is a single exposure.
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 MOS for the average females
is:
MOS = (5 mg/kg) / (0.0064 mg/kg)
« 770
Based on the TAS, ninety-eight percent of the females are
estimated to have an MOS of at least 100, corresponding to
an exposure of 0.05 mg/kg or less. The exposure distribution
indicates that no member of the subgroup is expected to have
an MOS of less than 70.
-------
C. OTHER SCIENCE FINDINGS
Environmental Fate Available data are insufficient to fully
assess the environmental fate of maneb. Available data
indicate that maneb degrades to ETU and other transient
degradates in water and soil. ETU is stable in water at pH 5 to 9
and under sunlight and the degradation of ETU in soil is not
enhanced by sunlight radiation. ETU is the degradate of
major environmental concern. Preliminary data from the Metiram
and Mancozeb Registration Standards indicate that soil
metabolism is the major route of degradation of ETU. Both
maneb and ETU degrade in soil under aerobic conditions and
slowly under anaerobic conditions. Acceptable anaerobic
aquatic soil data on maneb and ETU indicate that maneb degrades
very rapidly under anaerobic aquatic soil conditions but ETU
is relatively stable under these conditions, having a degradation
half life of 146 days.
Hydrolysis - Three studies were reviewed and considered to
be unacceptable for maneb. There is acceptable ETU hydrolysis
data which 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 Water - One study was reviewed and consid-
ered unacceptable for maneb. An acceptable ETU study indicated
that no significant degradation of ETU occurred in a pH 7 water
solution during the 30 day study period and thus no breakdown
of ETU due to photodegradation is expected in the environment
in absence of photosensitizers.
Photodegradation on Soil - One study was reviewed for maneb
and considered unacceptable. An adequate ETU study exists
that concluded that ethyleneurea (EU)f carbamid and hydantoin
degradation is facilitated by sunlight. On the other hand,
ETU is formed at somewhat larger amounts on exposed soil but
does not undergo photodegradation and dissipates only via
aerobic soil degradation.
Anaerobic Aquatic Metabolism - Maneb degraded completely
within an hour under anaerobic aquatic conditions to three
major degradates: EBIS (ethylenebis(isothiocyanate)sulfide),
ETU, EU and one major unidentified degradate. Levels of EU
remained fairly constant from day 0 to day 275 at below
19.2%. EBIS degraded rapidly to ETU from 35% at day 0 to 4%
after 3 days. ETU degraded very slowly from a maximum concen-
tration of 38.6% on day 3 with an estimated half-life of 149
days. Thus, ETU is considered to be reasonably stable under
aquatic anaerobic conditions and is of environnmental concern.
The mean material balance (the amount of applied material
34
-------
recovered) was above 95% throughout the study period.
Ground water. Leaching and field dissipation data are insuf-
ficient to allow a final ground water assessment to be made,
but available data indicate that maneb and ETU have moderate
mobility in soils. Unidentified maneb residues were found
in all soil leachate.
Degradation of ETU in soil under anaerobic aquatic conditions
was reported and supplemental data also show moderate mobility
of ETU and maneb in soils. 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
also requires for its ground water assessment a small-scale
retrospective ground water monitoring study to analyze
specifically for maneb and ETU.
Ecological Effects. Available data are insufficient to
completely evaluate the ecological effects of maneb. Data,
as set forth in Table A, are either required or reserved
pending further evaluation. The following conclusions can be
made based on available data:
1. Toxicity to Birds. Based on subacute dietary studies, maneb
can be characterized as practically nontoxic to birds (LCso >
9000 ppm).
2. Toxicity to Fish, Aquatic Invertebrates, and Estuarine/Marine
Organisms.There is sufficient information to characterize
the toxicity of an 80% product to warmwater fish as highly
toxic. No studies were submitted for the acute aquatic
invertebrate, fish and estuarine/marine organisms on the
technical.
3. Risks to Nontarget Organisms (Including Endangered
Species).The Agency has assessed the risks, based on
the available data, from the aquatic, terrestrial and seed
treatment uses of maneb. Based on these assessments,
there does not appear to be a concern for acute effects
to birds for any use of maneb. Additional data are
required to complete a chronic risk assessment for these
organisms as well effects on aquatic organisms.
a. Terrestrial Organisms. Maneb's highest registered use
rate is for turf (17.0 Ibs. ai/A). A single application
of maneb at 17.0 Ib ai/A would result in an initial
maximum residue level on short grass of 4080 ppm.
This level is below the no effect level for both
waterfowl and upland game species; therefore, there is
no concern for acute exposure to endangered or non-
35
-------
endangered species. Since maneb can be applied at
3-5 day intervals, there is a potential for
chronic exposure. An avian reproduction study is
required to complete the hazard assessment to birds.
Regarding risk to avian species from the cranberry
use, the 6.0 Ib ai/A rate may, immediately after
application, result in maximum estimated residues as
followss short grass-1440 ppm; forage and small
insects-340 ppm; and berries-42 ppm. These residues
are below the no effect level for the mallard duck and
bobwhite quail. Therefore, neither endangered or
non-endangered birds would be at risk from an acute
exposure to maneb.
There are no avian acute oral studies on technical or
single active products containing maneb. A hazard
assessment of birds consuming treated seeds is not
possible at this time. However, given the practically
non-toxic nature of maneb there would not appear to
be a concern for endangered or non-endangered birds.
b. Aquatic Organisms. Maneb is registered for use on
cranberries at 3.0 to 6.0 Ibs ai/A by both ground and
air equipment. Cranberry bogs are likely to contain
drainage canals and/or small streams leading into
open water, such as ponds or embayments. Careless
aer.ial application could result in direct contamination
of a 6 foot deep water body at 0.183 to 0.336 ppm.
However, a more likely scenario would be a 300 meter
stream drainage canal receiving input via direct
application and runoff from the surrounding 10 acres.
In turn, the stream/drainage canal empties into the 1
acre, 6 foot pond. In addition, the pond may receive
5% of a single acre application rate via drift. The
resulting maneb concentrations would be .074 to .148
ppm for 3.0 to 6.0 Ibs, respectively.
Aquatic toxicity data on an 80% WP for rainbow trout
(0.20 ppm) and bluegill sunfish (0.27 ppm) were
recently received by the Agency (Aug. 1988). Based
on a preliminary screen of these data and the previously
mentioned exposure estimates for cranberries, rates
of 5.0 Ib ai and above may present a significant
risk to fish. In these instances, the estimated
environmental concentration (EEC) of 0.10 ppm and
above exceeds one half the rainbow trout LCso
(0.20 ppm /2 » 0.10 ppm). Furthermore, even the
lower rate of 3.0 Ibs. ai would potentially exceed
restricted use criteria. Although the endangered
species trigger to fish (1/20 LCso * 0.01 ppm) is
also exceeded, there are no endangered fish associated
with cranberry bogs.
36
-------
Fish and aquatic invertebrates may be exposed to
maneb used on golf courses when rainfall occurs soon
after treatment, Assuming maneb to be sufficiently
soluble for 5% runoff to occur, the residues in a 1
acre, 6 foot deep pond would be .119 ppm. This level
exceeded the following criteriat 1) endangered fish
(1/20 LCso * B.01 ppm), 2) restricted use (1/10 LCso -
0.02 ppm). In keeping with the January 17, 1986,
Biological Opinion on Diazinon, this could effect
the Mohave Tui Chub on the China Lake Naval Weapons
golf course. Therefore, the Agency will be consulting
with the U.S. Fish and Wildlife Service.
Preliminary acute risk assessments have been conducted
also for the major use patterns such as apples (6.8
Ibs. ai/A), potatoes (1.6 Ibs. ai/A) and sweet corn
(2.25 Ibs ai/A). Using models for runoff and assuming
a 5 percent drift, residue levels in 6-foot ponds
for the following crops would be corn (70 ppb), potato
(48.8 ppb) and apples (145.18 ppb). Based upon
these exposure estimates and the rainbow trout LCso
for the 80% WP (0.20 ppm), these uses exceed the
restricted use criteria of 1/10 the LCso to fish.
However, these estimates are based on studies that
have not been fully reviewed by the Agency. A final
determination regarding restricted use will be made
once the recently submitted fish toxicity studies
are fully reviewed.
Reentry Consideration. Toxicity and exposure criteria are set
forth in 40 CFR 158. If a chemical meets the specified criteria,
reentry data are required.
Maneb 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. Maneb meets the exposure
criteria in that it is registered for use on crops which may
involve substantial exposure to residues of the pesticides.
Reentry data are required. Until the required data are
submitted and evaluated and any change in this reentry interval
is announced, in order to remain in compliance with FIFRA,
an interim 24-hour reentry interval requirement for agricultural
uses of maneb must be placed on the labels of all maneb
end-use products.
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D. TOLERANCE REASSESSMENT
V
Tolerances, expressed as zinc ethylene bisdithiocarbamate,
have been established for residues of maneb in a variety of
raw agricultural commodities (40 CFR 180.110). EPA has
evaluated the residue and toxicology data supporting tolerances.
The following were considered during this evaluations
• Whether the current tolerances are sufficient to cover the
actual residues resulting from use (including FIFRA section
24(c) and intrastate uses).
* Whether group tolerances can be established in accordance
with 40 CFR 180.34(f).
* Whether* in the absence of tolerances, restrictions on use,
grazing, or feeding of treated commodities are necessary.
* 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
animals, including identification of major metabolites and
degradates of maneb. The metabolism is not completely
understood.. Metabolites identified thus far include
ethylenethiourea (ETU), ethylenediamine (EDA), ethyleneurea
(EU), hydantoin (HT), ethylenethiuram monosulfide (DIDT,
EBIS) and 3-(2-imidazolin-2-yl)-2-imidazolidinethione
(JB, Jaffe's base).
2. Analytical methodology for determining the levels of
residues of maneb in plants and animals. Present colorimetric
CS2 evolution methods are adequate for collection of data
pertaining to residues of maneb in or on plant and animal
commodities. However, none of the colorimetric methods
are specific for maneb and are therefore, inadequate for
enforcement purposes.
3. Storage stability data. There is not sufficient information
concerning the stability of maneb. Some storage stability
data was submitted in response to the March 31, 1987 Notice.
Storage stability data are being required.
4. Data on the magnitude of residues of maneb in individual
raw agricultural commodities, animal products and processed
food and feed items. Data are inadequate to support
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tolerances. Data show that ETU concentrates on processing.
Toxicology Data. The toxicology data for maneb are insufficient
to determine an Acceptable Daily Intake (ADI) or whether the
toxicity observed in the studies is due to maneb or ETU.
There are no acceptable chronic studies on which to calculate
an ADI, therefore, a subchronic study has been used to
calculate a Provisional ADI (PADI). Because a subchronic
study was used, an uncertainty factor of 1000 (rather than
100 used in chronic studies) was employed. The PADI for
maneb is 0.005 mg/kg/day based on the six month monkey feeding
study with a NOEL of 5 mg/kg/day.
The theoretical maximum residue contribution (TMRC), based on
the assumption that 100 percent of each crop is treated and
contains residues at the tolerance level, is 0.030 mg/kg/day
or approximately 600 percent of the PADI. Based on a more
realistic dietary assessment, using anticipated field residues
and estimate of percent crop treated, the estimated average
consumption for the U.S. population is 0.0036 mg/kg/day or
70 percent of the PADI.
Tolerances Issued. Currently, tolerances for maneb are
expressed as zinc ethylene bisdithiocarbamate equivalents, as
are the tolerances for other pesticides of the dithiocarbamate
class. These tolerances are set forth in 40 CFR 180.110.
There are several Canadian tolerances established for residues
of EBDC's, including maneb, as well as several Codex Alimentarius
tolerances. Several Mexican tolerances are established for
residues of maneb.
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IV. REGULATORY POSITION AND RATIONALE
A. REGULATORY POSITIONS AND RATIONALES
Based on the review and evaluation of all available data on
maneb, 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 F1FRA,
specific language will be set forth in Section D of this
Chapter.
1. EPA is currently evaluating the potential human health
risks resulting from the food, and field crop, and
terrestrial non-food uses of maneb and the other EBDC
pesticides containing the common contaminant, degradation
product, and metabolite, ETU, in the EBDC Special Review.
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 onco-
genic risk from dietary exposure to ETU from foods
treated with these pesticides, and the risks of terato-
genicity 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 to 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.
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2. At this time, the Agency is not specif ing restricted use
classification for maneb-formulated products.
Rationale. Based on recently submitted fish studies, a
preliminary screen indicated that restricted use criteria
may be met. The Agency is currently reviewing the data
and will make a final determination concerning the need
for restricted use classification for maneb as well as
the other EBDC's.
3. The Agency will not consider establishment of any new food
use tolerances for maneb at this time.
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 maneb or ETU. No
new food uses will be considered until these issues are
resolved.
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.
Rationales The toxicology data base for maneb is
insufficient to determine whether observed toxicity is
due to maneb, 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) and is deferring action on
previously established food/feed additive regulations.
Rationales 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 certain 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. Maneb is currently registered for use on almond hulls,
asparagus (post harvest treatment only), corn forage and
sugar beet roots. The Agency is requiring the establishment
of tolerances and submission of supporting data for the
above uses.
Rationales Tolerances have not been established for almond
hulls, asparagus, corn forage and sugar beet roots in
which residues of maneb could occur. The registrant(s)
must propose a tolerance and provide supporting data.
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7. The Agency has determined that all data will be immediately
reviewed as they are submitted.
Rational eg Because of the concerns over ETU and the
EBDC's, the Agency believes it is essential that all
data be reviewed as they are received.
8. It is the Agency's position that, 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
herein.
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 maneb 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 developed to emphasize to users
the importance of adherence to the preharvest intervals.
9 . The Agency is requiring reentry data for maneb. In
order to remain in compliance with FIFRA, an interim
24-hour reentry interval requirement must be placed on
;- the labels
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soybeans, sunflower and wheat. The Agency is requiring
tolerances and supporting data for these treatments.
Tolerances will be required at the maximum residue level,
or, if residues are nondetectable, at the limit of
detection.
Rationale; In the past, seed and planting stock treatments
were considered to be nonfood uses. The Agency now
requires tolerances to ensure that unacceptable residues
do not occur in the commodities grown from treated seed
or stock. For those crops for which seed or planting
stock treatment is the only registered use and which
have no tolerances for maneb, tolerances must be established
to either reflect the maximum expected residue, or if no
measurable residues are detected, the limit of detection
of the analytical method.
12. In order to remain in compliance with FIFRA, it is the
Agency's position that maneb products should continue to
contain precautionary labeling pertaining to fish.
Rationale; In the Decision Document to the Special Review
concluded in 1982, the Agency concluded that the acute
toxicity to aquatic organisms was not unreasonable as
long as an appropriate warning was added to the label.
Mo data have been submitted which modify the Agency's
1982 Position. In recently received acute studies that
have not been fully reviewed, acute fish toxicity data
indicate that the 1>C$Q for both rainbow trout and
bluegill was determined to be below 1 ppm for the 80 WP
formulation of maneb, a level for which precautionary
labeling is appropriate.
13. The Agency is not specifying endangered species labeling
at this time.
Rationale; Based on Jeopardy Opinion on Diazinon, the
Mohave Tui Chub could be at risk from an acute exposure
to maneb resulting from some of its registered uses. The
Agency is consulting with the U.S. Fish and Wildlife
Service. Endangered species labeling may be necessary
in the future based on the results of this consultation.
14. The Agency is requiring analysis of maneb to determine
whether nitrosamines may be formed.
Rational^; There is a possibility for the formation of
nitrosamines during the manufacture of maneb; however,
the Agency does not have adequate data to determine
whether nitrosamines actually are formed.
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15. Protective clothing labeling for maneb 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 roaneb 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 maneb 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.
16. While data gaps are being filled, currently registered
manufacturing-use products (HP's) and end-use products
(EP's) containing maneb as the sole active ingredient may
be sold, distributed, formulated, and used, subject
to the terms and conditions specified in this Standard.
However, significant 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 maneb and ETU as explained
herein.
B. CRITERIA FOR REGISTRATION
To be registered or reregistered under this Standard,
products must contain maneb as the sole active ingredient,
bear specified labeling, and conform to th« 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 (HP's)
must contain maneb as the sole active ingredient. Each
MP formulation proposed for registration must "be fully de-
scribed with an appropriate certification of limits, stating
maximum and minimum amounts of the active ingredient and
44
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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 ppnu
Acute Toxicity Limits - The Agency will consider registration
of technical grade and manufacturing-use products containing
maneb 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 Standrd, 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 roaneb, as well as approved
maximum rates and frequencies.
D. LABELING
All maneb products must bear appropriate labeling as specified
in 40 CFR 156.10. Appendix II contains information on label
specifications.
In order to remain ia compliance with FIFRA, no pesticide
product containing maneb 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.
In order to remain in compliance with FIFRA, no pesticide
product containing maneb 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 MP's
and EP's must list the active ingredient as:
Maneb (manganese ethylenebisdithiocarbamate) (%)
(equivalent to manganese metallic %)
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.
45
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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 maneb 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 maneb 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 III).
3. 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
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
Outdoor Use (other than cranberries and seed treatment):
"This pesticide is toxic to fish. Drift and runoff from
treated areas may be hazardous to aquatic organisms in
neighboring areas. Do not apply directly to water or
wetlands (swamps, bogs, marshes, and potholes). Do not
contaminate water when disposing of equipment wash waters."
Seed Treatment Products*
"This pesticide is toxic to fish. Cover or incorporate
spilled treated seed. Do not contaminate water when
disposing of equipment wash waters."
Cranberry Use Productas
"This pesticide is toxic to fish. Drift and runoff from
treated areas may be hazardous to aquatic organisms in
neighboring areas. Do not contaminate water when disposing
of equipment wash waters."
All Home Use Products:
46
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"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 thi« product end 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/dusts have settled/vapors
have dispersed, 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)."
PERSONAL PROTECTIVE EQUIPMENT
"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
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.
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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
maneb 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 should appear on EP labels containing maneb:
For Almonds:
"If applied after petal fall, do not feed hulls to dairy
animals or animals being finished for slaughter"
For Apples:
"Do not graze livestock in treated areas"
For Beans:
"Do not feed treated forage or hay to livestock"
For Corn (field, pop, sweet):
"Do not feed treated forage to livestock"
For Peanuts:
"Do not feed treated peanut hay to livestock"
For Potato (seed pieces), Agricultural Seed Treatment:
"Do not use treated seed pieces for food, feed or oil purposes'
For Sugar Beets:
"Do not feed treated tops to livestock"
For Ornamental Grasses (seed crop):
"Do not feed treated grass to livestock"
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For Ornamental Turft
"Do not graze treated areas. Do not feed clippings to livestock.*
As appropriate, the following precautionary statements should
appear on EP labels containing maneb:
For Celery, Collards, Kale, Mustard Greens, Turnipss
"Remove residues by stripping, trimming, and/or washing"
For Endive, Lettuce:
"Remove resiudes from head lettuce by striping and trimming
and from leaf lettuce and endive by washing or other
effective means"
For Peach:
"If applied within 14 days of harvest, remove residue by brushing1
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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.
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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 fsxr 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, ©ramposition, or
packaging listed in Section IV if they pen-tain to the
end use. product.
2. If eligible for the generic data exerqption3, the
data requirements listed in Table C.
3. If not eligible for the generic data exemption, the
data requirements listed in Table A and ttihe data require-
ments listed in Table C.
4. The labeling requirements specified fox end use
products in Section IV.
D. End use products containing this pesticifle as one of
multiple active ingredients are subject to:
1. If not eligible for the generic data exemption,
the data requirements listed in Tables £ anvd C.
3 If you purchase from another producer and use as the
source of your active ingredient only EPA-regis±«ered products,
you are eligible for the generic data exemptioni for generic
data concerning that active ingredient (Table &9 -and product-
specific data for the registered manufacturing uise product
you purchase (Table B).
Two circumstances nullify this exemptions
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.
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2. If eligible for the generic data exemption, the
data requirements listed in Table C.
3. The labeling requirements specified for end use
products in Section IV.
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 S 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
gene.rate 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
* Registrations granted after issuance of this Standard will
be conditioned upon submittal or citation of the data listed
in this Registration Standard.
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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.
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
53.
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submit the data on which you will rely. You roust 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 Data11 (EPA Form 8580-6, enclosed).
-------
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)(iif).
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 otfcer 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 by 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.
55
-------
6. You request voluntary cancellation of the registration
of your product(s) for which the data are needed.
E. Registrant Requests Regarding Data Requirements and Agency
Responses
^•^^^•^^^v^^^^^^^w •
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 Pestifcide 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.
56
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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.
57
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J. Existing stocks provision upon suspension or cancellation.
- i
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.
58
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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.
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: Maneb 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:
-------
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
Form 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
60
-------
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.
61
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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.
62
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APPENDIX I
-------
TGUIDE-1
GUIDE TO TABLES
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 formats
1. Data Requirement (Column 1). The data requirements are
' 11 sled 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:
TGAX * Technical grade of the active ingredient
PAI » Pure active ingredient
PAIRA * 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 requiresent applies. Use patterns
are the saae as those given in 40 CFR Part 158. The following
letter designations are used for the given use pattern!s
A
B
C
0
E
V
G
U
X
Terrestrial* food
Terrestrial, non-food
Aquatic* food
Aquatic, non-food.
Greenhouse, food
Greenhouse, non-food
Forestry
Domestic outdoor
• *
Indoor
Any other designations will be defined in a footnote to the table
64
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TGUIDE-2
4. Poet EPA have data? (Column 4). This column indie*tes one
of three answersi ""
YES - EPA has data in its files that satisfy this data
requirement. These data nay 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
MRIO 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 MO. 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 th« data
are to be submitted, based on the issuance date of the Regis-
tration Standard. The timeframes arc 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 th« «nd ot each table). Self-explanatory.
65
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TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
Test
Substance^
Use
Patterns
Does EPA
Have Data?
Bibliographic
Citation
Must Additional
Data be
Submitted?
Time Frame
for2
Submission
Part 158
Subpart C - Product Chemistry
Product Identity
61-2 - Description of Beginning
Materials and Manufacturing
Process
61-3 - Discussion of Formation of
Impurities
Analysis and Certification of
Product ingredients
62-1 - Preliminary Analysis
Physical and Chemical
Characteristics
63-2 - Color
Cs
o\ 63-3 - Physical State
63-4 - Odor
63-5 - Melting Point
63-6 - Boiling Point
TGAI
TGAI
All
All
TGAI
All
Partially 00161800
Partially 00161800 00151415
Partially 00161800 00151415
Yes
Yes
Yes
§/
TGAI
TGAI
TGAI
TGAI
TGAI
All
All
All
Partially
Partially
Partially
N/A
N/A
00151415
00151415
00151415
N/A
N/A
Yes
Yes
§/
Yes
y
NO
NO
10/87
10/87
12/
4/88
12/13/
10/87
10/87
12/
10/87
12/
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TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
Test Use
Substance1 Patterns
Does EPA Bibliographic Must Additional
Have Data? Citation Data be
Submitted?
Time Frame
Submission
Part 158
Subpart C - Product Chemistry (Continued)
Physical and Chemical Characteristics
(Continued)
63-7
63-8
63-9
63-10
- Density, Bulk Density, or
Specific Gravity
- Solubility
- Vapor Pressure
- Dissociation constant
TGAI
TGAI or PAI
TGAI or PAI
TGAI or PAI
All
All
All
All
NO
NO
No
NO
N/A
Yoder letter, 1985
N/A
N/A
V
Yes
*/
Yes
V
Yes
y
Yes
9/
y
y
6 9/ lO/
63-11
63-12
0 63-13
Other
64- 1
- Octanol/water partition
coefficient
- pH
- Stability
Requirements:
- Submittal of samples
PAI
TGAI
TGAI
N/A
All
All
All
N/A
NO
NO
NO
N/A
N/A
N/A
N/A
N/A
Yes
6/
Yes
Yes
NO
w
12/
10/87
12/
10/87
12/
10/87
12/
10/87
12/
10/87
12/
10/87
10/87
I/ TGAI « Technical grade of the active ingredient, registered or unregistered. PAI - Purified active ingredient
y 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.
-------
Part 158
Subpart C - Product Chemistry {Continued)
3/ For each technical product complete information must be provided regarding the nature of the process (batch or
continuous), the relative amounts of beginning materials and the order in which they are added, the chemical
equations for each intended reaction, equipment used to produce each intermediate and the final product, reaction
conditions, the duration of each step of the process, purification procedures, and quality control measures. In
addition, the name and address of the manufacturer, producer, or supplier of each beginning material used in the
manufacture of each product must be provided, along with information regarding the properties of those materials.
4/ A detailed discussion must be submitted for each technical product of all impurities that are or may be present
at >. 0.1%, based on knowledge of the beginning materials, chemical reactions (intended and side) in the
manufacturing process, and any contamination during and after production.
5/ For all technical products, five or more representative samples 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 maneb per se using a method capable of differentiating maneb from interfering CS^-liberating
impurities. If the (^-liberation and maneb-specific methods yield different results, the ^-liberating
impurities must be quantified. Complete validation data (accuracy and precision) must be submitted for each
analytical method used.
§/ As required in 40 CFR 158.120 and more fully described in the Pesticide Assessment Guidelines, Subdivision D,
data on color, physical state, and odor must be submitted for the 90% T Drexel and Aceto (EPA Reg. Nos 19713-64
and 2749-18), and the 86% T Drexel (EPA Reg. No. 19713-185). Specific gravity* solubility, vapor pressure,
dissociation constant, partition coefficient, pH, and stability must be submitted for each technical.
7/ Data needed if the technical chemical is a solid at roan temperature.
§/ Data needed if the technical product is a liquid at room temperature.
$/ Data submitted by the Maneb Task Force concerning an 88% T has been identified as a Rohm and Haas manufacturing-
use product. EPA Reg. No. 707-103. The only requirements in common for any active ingredient, and that may be
O\ shared, are the analytical method for the active ingredient, solubility of the pure active ingredient (PAI), vapor
oo pressure for the PAI, dissociation constant fof the PAI, octanol/water partition coefficient for the PAI and the
submittal of samples of the PAI. Therefore, product chemistry data submitted by the Maneb Task Force may not be
shared unless it can be shown that the chemical composition of this T is the same as the other technical products
for which data is wished to be shared.
Data required if the technical product is organic and nonpolar.
Data required if the test substance is dispersible in water.
12/ Data has been submitted by the Maneb Task Force and is currently being reviewed.
13/ 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.
lO/
n
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C\
TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
Test Use
Substance* Patterns
Does EPA Bibliographic
Have Data? Citation
Must Additional
Data be
Submitted?
Time Frame
for2
Submission
S158.240 - Residue Chemistry
171-2 - Chemical Identity
171-3 - Directions for Use
171-4 - Nature of Residue
(Metabolism)
- Plants
PAIRA
- Livestock
171-4 - Residue Analytical
Method
171-4 - Storage Stability
171-4
PAIRA & Plant
Metabolites
TGAI &
Metabolites
TEP & metabolites
- Magnitude of the Residue-
Residue Studies for Each
Food Use
- Crop Group II - Root & Tuber Vegetables
o Crop 1 Carrots
— Crop field trials TEP
Partially
00088826 00088894
00088923 00088931
00159847 00159848
00159849 00159850
Partially 00159851 00159852
Partially
00002931 00040149
00041799 00041800
00090132 00090152
00090174 00097198
00098644
No
No
Yes
Yes
6
Yes"
6/77
Yes
S/io/ii/
6 Months
10/88
10/88
7/88
115/
9/88
nsy
Yes
12/13/14/
10/88
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TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
Test Use Does EPA Bibliographic
Substance1 Patterns Have Data? Citation
Must Additional
Data be
Submitted?
Time Pra
foc2
Subnissi
S158.240 - Residue Chemistry - Continued
171-4 - Magnitude of the Residue -
Residue Studies
o Crop 2 - Potatoes
— Crop Field Trials TEP
— Processed Pood/Peed EP
- Crop Group 3 - Sugar Beet Roots
— Crop Pield Trials TEP
— Processed Pood/Peed EP
- Crop Group 4 - Turnip Roots
— Crop Pield Trials TEP
- Crop Group 12 - Leaves of Root & Tuber
Vegetables
o Crop 1 Sugar Beet Top
-- Crop field trials TEP
o Crop 2 Turnip Tops
— Crop field trials TEP
NO
NO
NO
NO
NO
NO
NO
Yes
Yes
Yes
18/20/2i/
Yes
No
19/
10/88
4/89
10/88
4/89
Yes
23/24/25/26/
10/88
No
27/
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TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
Test Use Does EPA Bibliographic
Substance1 Patterns Have Data? Citation
Must Additional Time Fra
Data be for2
Submitted? Submissi
5158.240 - Residue Chemistry - Continued
- Crop Group 13 - Bulb Vegetables
o Crop 1 Onions
— Crop field trials TEP
- Crop Group 14 -Leafy Vegetables
o Crop 1 Celery
— Crop field trials TEP
o Crop 2 Endive
— Crop field trials TEP
o Crop 3 Lettuce
— Crop field trials TEP
I
o Crop 4 Rubarb
— Crop field trials TEP
o Crop 5 Spinach
— Crop field trials TEP
- Crop Group 15 - Brassica Leafy Vegetables
o Crop 1 Broccoli
— Crop field trials TEP
No
No
No
No
No
No
No
28/29/30/31/
Yes 10/88
32/33/34/3I/
~
10/88
38/
No
Yes
39/40/41/42/43 10/88
Yes
44/
45/46/47/4J/
Yes
10/88
10/88
49/50/
Yes
10/88
-------
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
Test
Substance1
Use Does EPA Bibliographic
Patterns Have Data? Citation
Must Additional
Data be
Submitted?
Time Frame
for2
Submission
ro
o Crop 9 Mustard Greens
— Crop field trials
TEP
TEP
S158.240 - Residue Chemistry - Continued
o Crop 2 Brussels sprouts
— Crop field trials TEP
o Crop 3 Cabbage
— Crop field trials
o Crop 4 Cauliflower
— Crop field trials
o Crop 5 Chinese Cabbage
— Crop field trials TEP
o Crop 6 Collards .
— Crop field trials
o Crop 7 Kale
— Crop field trials
o Crop 8 Kohlrabi
— Crop field trials
TEP
TEP
TEP
NO
NO
NO
NO
NO
NO
NO
Yes
Yes
Yes
52/53/S4/
Yes
56/
5Z/
No
Yes
No
eg/
TEP
NO
NO
61/
10/88
10/88
10/88
10/88
10/88
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
Test
Substance*
Use
Patterns
Does EPA
Have Data?
Bibliographic
Citation
Must Additional
Data be
Submitted?
Time Frame
for2
Submission
S158.240 - Residue Chemistry - Continued
- Crop Group 16 - Legume Vegetables
(Succulent or dried)
o Crop 1 Beans (Succulent and dry)
— Crop field trials TEP
— Processed Food/Feed EP
- Crop Group 17 - Fruiting Vegetables
o Crop 1 Eggplant
— Crop field trials TEP
o Crop 2 Peppers
— Crop field trials TEP
o Crop 3 Tomatoes
— Crop field trials TEP
— Processed Food/Feed EP
- Crop Group 18 - Cucurbit Vegetables
o Crop 1 cucumbers
— Crop field trials TEP
o Crop 2 Melons
— Crop field trials TEP
No
No
No
No
No
No
Yes
62/63/64/6§/
Yes
66/
10/88
4/89
No
Yes
68/69/
Yes
70/71/72/
Yes
7J/
10/88
10/88
4/89
Yes
74/7§/7§/
Yes
77/78/79/80/
10/88
10/88
-------
Data Requirement
Test Use Does EPA Bibliographic
Substance1 Patterns Have Data? Citation
Must Additional
Data be
Submitted?
Time Frame
for*
Submission
5158.240 - Residue Chemistry - Continued
o Crop 3 Pumpkins
— Crop field trials TCP
o Crop 4 Squash
— Crop field trials TCP
- Crop Group 19 - Pome Fruit
o Crop 1 Apples
— Crop field trials TEP
— Processed Food/Feed EP
- Crop Group 110 - Stone Fruit
o Crop 1 Apricots
— Crop field trials TEP
o Crop 2 Nectarines
— Crop field trials TEP
o Crop 3 Peaches
— Crop field trials TEP
No
No
No
No
NO
NO
NO
NO
81/
NO
82/
Yes
83/
Yes
84/
Yes
8J5/86/
No
87/
Yes
88/89/90/
10/88
4/89
10/88
10/88
-------
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
Test
Substance1
Use Does EPA Bibliographic
Patterns Have Data? Citation
Must Additional
Data be
Submitted?
Time Frame
for2
Submission
LH
S158.240 - Residue Chemistry - Continued
- Crop Group 111 - Small Fruits & Berries
o Crop 1 Cranberries
— Crop field trials TEP
o Crop 2 Grapes
— Crop field trials TEP
— Processed Food/Feed EP
- Crop Group 112 - Tree Nuts
o Crop 1 Almonds
— Crop field trials TEP
- Crop Group 113 - Cereal Grains
o Crop 1 Corn, Sweet
— Crop field trials TEP
— Processed Food/Feed EP
- Crop Group 114 - Forage, Fodder & Straw
of Cereal Grains
o Crop 1 Corn forage, fodder & Silage
— Crop field trials TEP
No
NO
NO
NO
NO
NO
NO
Yes
91/92/93/
Yes
94/
Yes
9§/
10/88
10/88
4/89
Yes
96/9T/98/
10/88
99/101/
Yes
Yes
100/
10/88
4/89
Yes
102/103/
10/88
-------
GENERIC DATA REQUIREMENTS FOR MANEB
ON
Test Use
Data Requirement Substance1 Patterns
5158.240 - Residue Chemistry - Continued
- Croo Group 115 - Miscellaneous Commodities
o Crop 1 Asparagus
— Crop field trials TEP
o Crop 2 Bananas
— Crop field trials TEP
o Crop 3 Pigs
— crop field trials TEP
— Processed Pood/Peed EP
o Crop 4 Papayas
— Crop field trials TEP
o Crop 5 Seed, Seed Piece,
planting stock, &
propagation stock
— Crop field trials TEP
o Crop 6 Tobacco
— crop field trials TEP
— Processed Pood/Peed EP
Does EPA Bibliographic
Have Data? Citation
NO
No
NO
NO
NO
NO
NO
NO
Must Additional
Data be
Submitted?
104/105/
Yes
106/
Yes
107/108/
Yes
109/
Yes
HO/
Yes
m/
Yes
112/
Yes
Yes
Time Prams
for*
Submission
10/88
10/88
10/88
4/89
10/88
10/88
10/88
4/89
171-4 - Magnitude of the Residue TGAI or Plant
in Meat/Milk/Poultry/Eggs Metabolites
Reserved
10/114/
-------
FOOTNOTES!
I/ Test Substance: TGAI - Technical grade of the active ingredient; PAIRA - Pure active ingredient, radiolabeledi
TEP » Typical end-use product; EP - End-use product; PAI « Pure active ingredient.
2/ 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. When number of
months are provided, these are new data requirements which must be fulfilled in the number of months specified
from the registrants receipt of this document.
3/ Refer to the Product Chemistry Data Requirement tables.
4/ The uptake, distribution, and metabolism of [Hcjmaneb in root and tuber vegetables, pome fruit, fruiting
vegetables, and cereal grain crops following a foliar application mast be included. 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 maneb residues
must also be represented. For the purpose of 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.
5/ 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.
6/ Metabolism studies utilizing ruminants and poultry. Animals must be dosed for a minimum of three days with
[14C]maneb at a level sufficient to make residue identification and quantification possible. Milk and eggs
must be collected twice daily during the dosing period. Animals must be sacrificed within 24 hours of the
final dose. The distribution and characterization of residues must be determined in milk, eggs, liver, kidney,
muscle, and fat. Data reflecting solvent extraction efficiency of maneb residues must also be represented.
7/ Representative samples from the above-described tests must also be analyzed by current enforcement methods
to ascertain the validity of these methods.
8/ 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. Residues of ethylenethiourea (ETO)
and maneb per se in/on crop samples must be subjected to analysis by the multiresidue methods published in PAM
vol. I. Protocols for methods I, II, III, and IV are available from NTIS. if tolerances are established for
residues in livestock products, then these products must also be subject to multiresidue methodologies.
-------
9/ To support crop residue data, storage stability studies must be conducted on both weathered samples Imaneb) and
fortified frozen sanples (tnaneb, metabolites and ETU) of one representative crop from each crop grouping (40 CFR
180.34) on which registered uses of maneb exist. Analyses of each crop mast 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
analysis. Protocols for these studies must be submitted to and approved by the Agency prior to initiating the
studies.
(a) Storage stability data using weathered samples* Data are required on the parent compound, maneb, in which
crop sanples 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 maneb on the day they arrive
at the analytical laboratory, and then stored frozen and analyzed periodically for maneb during the time
intervals specified in the Agency approved protocol.
(b) Storage, stability data using £ortif ied samples. Data are required on maneb, ETU, and metabolites in
which a group of untreated samples of raw agricultural commodities and processed crops are fortified (spiked) with
only maneb (pur* 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 maneb must be analyzed for maneb and ETU; samples fortified with ETU must be analyzed for only ETUr
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 maneb, ETU, and metabolites
must be conducted periodically during the time intervals specified in the Agency approved protocol.
10/ Storage stability data for livestock/poultry feeding studies. If cattle and poultry feeding studies are
required (see footnote 114), 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.
oc-
-------
U/ 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 residue laboratories
generating the residue data which were evaluated. The available storage stability data demonstrate that
maneb and ETU are not stable under the storage conditions associated with many of the existing residue studies*
The Agency has concluded that new frozen storage stability data on Maneb and ETU must be generated (refer to
footnote 9) concurrently with the required crop residue, processing, and animal commodity studies on these
chemicals*
12/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on carrots following multiple
foliar applications of a WP or PIC formulation at 2.4 Ib ai/A and, in a separate test, a D formulation at 2.7
Ib ai/A. Aerial and ground equipment must be represented in separate tests. The first application must be
made when the plants are 6 weeks old and be repeated at 7-day intervals until the day of harvest. The registrant
must propose a maximum seasonal application rate or maximum number of applications per season. Required data
must reflect the proposed maximum rate. Tests must be conducted in CA(66%), Ml(10%) and TX(12%) which collectively
account for 88% of U.S. carrot production (Agricultural Statistics, 1985, p. 151).
13/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on carrots harvested on the
day of the last of several foliar applications of an 80% WP at 2.96 Ib ai/A (aerial and ground equipment must
be represented in separate tests). Tests must be conducted in CA. Alternatively, the registrant may elect to
cancel this state use permitted under EPA Reg. No. 5967-5138.
14/ The available data for the 80% WP indicate that tolerance-exceeding residues will occur following use at the
registered rate. Upon generation of the data requested above, the registrant may propose a higher tolerance or
amend the labels (propose a PHI, maximum seasonal application rate, and/or decrease the single application
rate). If the label is amended, data must support these amendments.
15/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on potatoes following multiple
foliar applications (using ground and aerial equipment in separate tests) of: (i) a D formulation at 3.3 Ib
ai/A; (ii) a PIC or WP forrrulaticn at 3.2 Ib ai/A; and (iii) a WP/D formulation at 3.3 Ib ai/A. The registrant
must propose a maximum seasonal application rate or maximum number of applications p season. Required studies
must reflect this propose maximum rate. Required studies must be conducted in CA(6%), ID(25%), ME(7%), ND(6%),
and WA(16%), which collectively produce 60% of U.S. potatoes (Agricultural Statistics, 1984, p. 165).
16/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on potatoes harvested 0-days
following the last of several foliar applications of a 80% WP at 4 Ib ai/A (aerial and ground equipment must be
represented in separate tests). Tests must be conducted in CA. Alternatively, the registrant may elect to
cancel the state use permitted under EPA Reg. No. 5967-5138.
-------
IT/ Data must be submitted depicting maneb, ETU, and other residues of concern in potato chips, granules* wet peel,
and dry peel processed from potatoes bearing measurable weathered residues* If residues concentrate during
processing appropriate food/ feed additive tolerances must be proposed*
18/ Data must be submitted depicting maneb. ETU, and other residues of concern in or on sugar beet roots following
five applications of, in separate tests, a WP, WP/D, or FlC formulation at 2.6 Ib ai/A and in a separate test
a D formulation at 1.2 Ib ai/A; use of aerial and ground equipment mist be represented. The first application
should begin at the normal time of disease development and be repeated at 7- to 10-day intervals until 10
days prior to harvest. Studies must be conducted CA(19%), ID(17%), MN(23%), and ND(11%), which collectively
account for 70% of U.S. sugar beet production Agricultural Statistics, 1984, p.76).
19/ Data must be submitted depicting maneb, ETU, and other residues of concern in dehydrated pulp, molasses, and
refined sugar processed from sugar beets bearing measurable, weathered residues. If concentration of residues
occurs during processing, the registrant must propose appropriate food/feed additive tolerances.
20/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on sugar beets harvested on
the day of the last of several foliar applications of the 5.6% D at 1.56 Ib ai/A (aerial and ground equipment
must be represented in separate tests). Tests must be conducted in CA. Alternatively, the registrant may
elect to cancel the state use permitted under EPA Reg. No. 11169-50024.
21/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on sugar beets harvested 10
days following the last of several foliar applications of the 6% D at 2.58 Ib ai/A (aerial and ground equipment
must be represented in separate tests). Tests must be conducted in CA. Alternatively, the registant may
elect to cancel the state use permitted under EPA Reg. No. 7001-7772.
22/ NO data were submitted pertaining to maneb residues in or on turnip roots. However, no residue data are required
The data requested for sugar beet roots will be translated to turnips since the registered uses on sugar beets
are similar to those for turnips.
23/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on sugar beet tops harvested
14 days following the last of five foliar applications (using ground and aerial equipment in separate tests)
of a WP, WP/D or PIC formulation at 2.6 Ib ai/A (in separate tests). Studies must be conducted in CA(19%),
ID(17%), MN(23%), and ND(11%), which collectively account for 70% of U.S. sugar beet production (Agricultural
Statistics, 1984, p. 76).
-------
24/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on sugar beet tops harvested
on the day of the last of several foliar applications of the 5.6% D formulation at 1.56 Ib ai/A (aerial and
ground equipment must be represented in separate tests). Tests must be conducted in CA. Alternatively, the
registrant may elect to cancel the state use permitted under EPA Reg. No. 11169-50024.
25/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on sugar beet tops harvested
10 days following the last of several foliar application of the 6% D formulation at 2.58 Ib ai/A. Applications
with aerial and ground equipment must be represented in separate tests. Tests must be conducted in CA. Alternatively
the registrant may elect to cancel the state use permitted under EPA Reg. No. 7001-7772.
26/ The registrants must also propose label restrictions for the 5.6% D (EPA Reg. No. 11169-50024) and 6% D formula-
tion (EPA Reg. No. 7001-7772) limiting the maximum number of applications and maximum seasonal use rate and
specifying a minimum interval between applicaitons, and specifying a minimum PHI for the 5.6% D.
27/ No data were submitted pertaining to maneb residues in or on turnip tops. However, no residue data are required.
The data required for sugar beet tops will be translated to turnip tops since the registered uses on sugar beets
are similar to those for turnips. In addition, the registrant must propose a maximum seasonal application rate
or maximum number of applications per season consistent with the submitted residue data.
28/ Data must be submitted depicting maneb residues of concern in or on green and dry bulb onions harvested on the
day after the final application of the following full season treatment schedule: a soil application with the
seed, of the 4 Ib/ gal PIC formulation at 2.4 Ib ai/A, followed by multiple foliar applications of a registered
D formulation at 3 Ib ai/A and, in a separate test, a WP or FLC at 3.0 Ib. ai/A. Foliar applications must be
made using both ground and aerial equipment, in separate tests. The registrant must propose a maximum seasonal
application rate or maximum number of applications per season. Required studies must reflect the proposed
maximum rate. Tests on green onions must be conducted in AZ(15%) CA(36%), and TX(23%) which collectively account
for 74% of U.S. green onion acreage; tests with bulb onions must be conducted in CA(23%), 00(8%), HI(7%), NY(11%),
and TX(20%), which collectively account for 69% of U.S. bulb onion acreage (1982 Census of Agriculture, Vol. 1,
Part 51, pp. 346-347).
29/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on onions harvested on the day
of the last of several foliar applications of a 80% WP at 2.96 Ib ai/A (aerial and ground equipment must be
represented in separate tests). Tests must be conducted in CA. Alternatively, the registrant may elect to
cancel the state use permitted under EPA. Reg. No. 5967-5138.
30/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on onions harvested 4-days
following the last of several foliar applications of the 80% WP at 2 Ib ai/100 gal (aerial and ground equipment
must be represented in separate tests). Tests must be conducted in PL. Alternatively, the registrant may
elect to cancel the state use permitted under EPA Reg. No. 9782-3633.
-------
31/ Available data indicate that tolerance-exceeding residues may occur following foliar applications of the WP.
Upon receipt of the requested data, a proposal for a tolerance increase or label modification my be necessary.
32/ Data must be submitted depicting maneb, ETU, and other residues of concern in or en celery 14 days following
the last of multiple foliar applications of a WP or pic formulation at 2.4 Ib ai/A, and, in a separate test; a
D formulation at 2.7 Ib ai/A. Separate studies must be made using aerial and ground equipment. Tests must be
conducted in CA(68%), PL(22%) and MI(7%) to provided adequate geographic representation (Agricultural statistics*
1984, p. 156). The registrant must propose a maximum seasonal application rate or maximum number of applications
per season. Requirement studies must reflect this maximum rate*
33/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on celery harvested 14-days
following the last of several foliar applications of the 80% WP at 3.2 Ib ai/A (aerial and ground equipment
must be represented in separate tests). Tests must be conducted in CA. Alternatively! the registrant may
elect to cancel the state use permitted under EPA Reg. No. 5967-5138.
34/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on celery harvested on the day
of the last of several foliar applications of a 42.5% PIC at 2.7 Ib ai/A (aerial and ground equipment must be
represented in separate tests). Tests must be conducted in PL. Alternatively, the registrant may elect to
cancel the state use permitted under EPA Reg. No. 9859-9146.
35/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on celery harvested 0-days
following the last of several foliar applications of the 3.2% D at 1.6 Ib ai/A (aerial and ground equipment
must be represented in separate tests). Tests must be conducted in PL. Alternatively, the registrant may
elect to cancel the state use permitted under EPA Reg. No. 9782-3634.
367 Data must be submitted depicting maneb, ETU, and other residues of concern in or on celery harvested 0-days
following the last of several foliar applications of the 5.6% D at 2.8 Ib ai/A (aerial and ground equipment
must be represented in separate tests. Tests must be conducted in CA. Alternatively, the registrant may elect
to cancel the state use permitted under EPA Reg. No. 1202-5059.
37/ Note that tolerance-exceeding residues occur following foliar treatments with the 80% WP. Upon generation of
all requested data, the registrant may either propose a higher tolerance or propose label revisions to reduce
residues to subtolerance levels, provided that data support such revisions.
-------
38/ No data were submitted pertaining to maneb residues of concern in or on endive. However, no data are required.
The revested data for lettuce will be translated to endive since the registered uses are identical for
the two crops.
39/ Data must be submitted depicting maneb residues of concern in or on lettuce 10 days following multiple foliar
applications (in separate tests) of a WP or PIC formulation at 2.4 Ib ai/A and a D formulation at 3.2 Ib ai/A.
Studies must reflect ground and aerial applications (in separate tests) and must be conducted in CA which
accounts for 69% of U.S. lettuce production (Agricultural Statistics, 1984, p. 160). The registrant must
propose a maximum seasonal application rate or maximum number of applications per season; this proposed maximum
rate must be reflected in the studies submitted.
40/ Data must be submitted from a test conducted in CO depicting maneb, ETU, and other residues of concern in or on
lettuce harvested 7 days following the last of multiple foliar applications of the 5% D MAI formulation at 1.25
Ib ai/A. Alternatively, the registrant may elect to cancel the state use permitted by EPA Reg. No. 960-3828.
41/ Data must be submitted from a test conducted in CA depicting maneb, CTU, and other residues of concern in or on
lettuce harvested on the day of the last of a series of foliar applications of a D formulation at 3.08 Ib ai/A.
Alternatively, the registrant may elect to cancel the state use permitted by EPA Reg. Nos. 1202-5059 and 6023-3042.
42/ Data must be submitted from a test conducted in PL depicting maneb, ETU, and other residues of concern in or on
lettuce harvested on the day of the last in a series of foliar applications of the 7% D MAI formulation at 2.1
Ib ai/A. Alternatively, the registrant may elect to cancel the state use permitted by EPA Reg. No. 14775-8738.
43/ Data must be submitted depicting residues of concern in or on lettuce harvested on the day of the last of several
foliar applicatio of the 4.8% D formulation at 2.4 Ib ai/A (aerial and ground equipment must be represented in
separate tests). Tests must be conducted in CA. Alternatively, the registrant may elect to cancel the state
use permitted by EPA Reg. No. 6023-3042.
CD
44/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on greenhouse-grown rhubarb
following the last of four foliar applications (made at 7-day intervals) of the 80% WP or an PIC formulation at
1.6 Ib ai/100 gal. The PHI must reflect that proposed by the registrant. Studies must be conducted in HI.
45/ Data must be submitted depicting maneb residues of concern, including ETU, in or on spinach 10 days following
the last of multiple foliar applications of a WP or PIC formulation at 2.4 Ib ai/A, and, in a separate test, a
D formulation at 2.7 Ib ai/A. Both aerial and ground equipment must be employed (in separate tests) and required
studies must be conducted in CA(24%), 00(5%), NJ(6%), TN(4%), and TX(25%) which collectively account for 64% of
U.S. spinach acreage (1982 Census of Agriculture, Vol. 1 Part 51, p. 352).
46/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on spinach harvested 7 days
following the last of several foliar applications of the 5.6% D formulation at 2.5 Ib ai/>>. (aerial and ground
equipment must be represented in separate tests). Tests must-be conducted in CA. Alternatively, the registrant
may elect to cancel the state use permitted under EPA Reg. No. 1202-5059.
-------
47/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on spinach harvested 7 days
following the last of several foliar applications of the 4.8% D formulation at 2.4 Ib ai/A (aerial and ground
equipment must be used in separate tests). Tests must be conducted in CA. Alternatively, the registrant may
elect to cancel the state use permitted under EPA Reg. No. 6023-3042.
48/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on spinach harvested 7 days
following the last of several foliar applications of the 6% D formulation at 2.7 Ib ai/A (aerial and ground
equipment must be used in separate tests). Tests must be conducted in CA. Alternatively, the registrant may
elect to cancel the state use permitted under EPA Reg. No. 7001-7772.
49/ Data must be submitted depicting maneb residues of concern, including ETU, in or on broccoli resulting from the
following fullseascn application schedule: multiple soil applications to the plant bed of a WP formulation at
1.4 Ib ai/100 gal followed by multiple foliar applications (by aerial and ground equipment in separate tests)
of a WP, WP/D, or PIC formulation applied as spray at 3.2 Ib ai/A and a D or WP/D formulation as a dust at 3.3
Ib ai/A (each formulation in a separate test). These tests must be conducted in CA(82%) to provide adequate
geographic representation (acreage percentage is from 1982 Census, of Agriculture* Vol. 1, Part 51, pp. 337-338).
SO/ The registrant must propose a maximum seasonal application rate or a maximum number of applications per season.
Required studies must reflect residues resulting from such usage.
51/ No data were submitted pertaining to residues of maneb in or on Brussels sprouts. However, no data are required;
broccoli data may be translated to Brussels sprouts since the registered uses on the two crops are similar. >.;
The registrant must propose a maximum seasonal application rate or maximum number of applications per season.
Translated data must reflect this maximum rate. It should be noted that translated data may not be used to
support a crop group tolerance.
52/ Data must be submitted depicting maneb residues of concern, including ETU, in or en cabbage following multiple
foliar applications of a WP, WP/D, or F1C formulation at 1.8 Ib applied as a spray and, in separate tests, a D
or WP/D formulation as a dust at 2.6 Ib ai/A. Ground and aerial applications must be represented in separate
tests. Studies must be conducted in CA(8%), PL(16%), MI(3%), NJ(3%), NY(15%), NC(5%), OH(3%), TX(16%), and
WI(1%) which together account for 70% of U.S. cabbage acreage (1982 Census of Agriculture, Vol. I,
Part 51, pp. 338 and 339).
-------
53/ The registrant must propose a maximum seasonal application rate or maximum number of applications per season.
Required studies must reflect residues resulting from application at the maximum rate.
54/ Data must be submitted depicting maneb ETU, and other residues of concern in or on cabbage harvested 7 days
following the last of several foliar applications of a 42.5% PIC at 2.7 Ib ai/A (aerial and ground equipment
must be represented in separate tests). Tests must be conducted in PL. Alternatively, the registrant may
elect to cancel this state use permitted under EPA Reg. No. 9859-9146.
»
55/ No data were submitted pertaining to residues of maneb in of on cauliflower. However, no data are required;
broccoli data may be translated to cauliflower since registered uses on the two crops are similar, the following
information is required: The registrant must propose a maximum seasonal application rate or maximum dumber of
applications per season. Translated data must reflect this maximum rate.
56/ Data must be submitted from tests conducted in CA depicting maneb, ETU, and other residues of concern irt or
on Chinese cabbage following multiple foliar applications (u*ing ground equipment) of the 80% WP formulation
at 1*2 Ib ai/A. Samples must be collected 7 days following the last treatment.
57/ No data were submitted in support of the tolerance for maneb residues in or on collards. However, no data are
required. The required data for spinach will be translated to collards since the use directions are similar
(see section on spinach for details of data requirements)*
58X Data must be submitted depicting maneb, ETU, and other residues of concern in or on kale following multiple
foliar applications (using ground and aerial equipment in separate tests) of a D formulation and, in a separate
test, a WP formulation at 2.4 Ib ai/A. Tests must be conducted in CA(13%), PL(10%), MD(6%), NJ(5%), PA(6%),
TX(13%), and VA(13%) which collectively account for 66% of U.S. kale acreage (1982 Census of Agriculture,
Vol. 1, Part 51, p. 345) in order to provide adequate geographic representation.
59/ The registrant must propose a maximum seasonal application rate or a maximum number of applications per season.
Required studies must reflect this maximum rate.
60/ NO data were submitted pertaining to residues of maneb in or on kohlrabi. However, no data are required; broc-
coli data may be translated to kohlrabi since registered uses on the two crops are similar. The following
information is required: The registrant must propose a maximum seasonal application rate or maximum number of
applications per season. Translated data must reflect this maximum rate.
-------
61/ No data were submitted in support of the tolerance for maneb residues in or on mustard greens. However* no data
are required. The required data foe spinach will be translated to mustard greens since the use directions are
similar (see section on spinach for details of data requirements).
62/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on dried beans harvested on
the last day of multiple foliar applications (at-4 day intervals) of a WP, WP/D, or F1C formulation and in
separate tests a D or WP/D formulation (applied as a dust) at 2.8 Ib ai/A. These tests must be performed using
aerial and high and low volume ground equipment. Dried bean tests must be conducted in MI (29%), CA(15%),
NE(14%), 00(11%) and ND(11%), which represent ca. 80% of 1983 U.S. dried bean production (data from Agricultural
Statistics, 1984, p. 256).
63/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on succulent beans harvested 4
days after the last of several foliar applications (by aerial and ground equipment) of the 80% WP formulation
at 2.8 Ib ai/A* Snap bean tests should be conducted in the states of WI(36%), OR(21%), NY(15%), and MI(7%)
which collectively represent CA 80% of 1983 U.S. snap bean production (data from Agricultural Statistics, 1984,
p. 151). Lima bean tests must be conducted in CA(58%), WI(9%), and DE(7%), which represent 7.4% of 1977 U.S.
lima bean production (G.W. ware and J.P. McCollum, 1980, Producing Vegetable Crops, Interstate Printers &
Publishers, Inc., Danville IL, 508 pp.).
647 Data must be submitted depicting maneb, ETU, and other residues of concern in or on beans harvested 3 days
following the last of three foliar applications of the 6% D formulation at 1.8 Ib ai/A (aerial and ground equipment
must be represented in separate tests). Tests must be conducted in OR. Alternatively, the registrant may
elect to cancel this state use permitted under EPA Reg. No. 1871-8934.
65/ The registrant(s) must propose a maximum number of applications per season or maximum seasonal use rate for
beans (succulent and dry); requested data must reflect the proposed maximum rate.
CO 66/ Residues must be determined in cannery waste (of dried and succulent beans) obtained from beans bearing measur-
able weathered residues; if residues concentrate in cannery waste, an appropriate feed additive tolerance must
be proposed.
67/ No data were submitted pertaining to residues of maneb in or on eggplant. However, no data are required since
studies requested for tomatoes may be translated to eggplant because registered uses on the two crops are
similar.
68/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on peppers following multiple
foliar applications of a WP or an PIC fonulation at 3 Ib ai/A using aerial and ground equipment and, in separate
tests, a D formulation at 3 Ib ai/A using aerial and ground equipment. The registrant must propose a PHI and a
maximum seasonal application rate or a maximum number of applications per season. Required studies must reflect
these proposed uses. Studies must be conducted in CA(18%), PL(23%), NC(10%), and TX(16%) (acreages follow
-------
state abbreviations parenthetically) which collectively account for 67% of U.S. pepper acreage (1982 Census of
Agriculture, Vol. 1, Part 51, p. 350) in order to provide adequate geographic representation.
69/ Available data indicate that tolerance-exceeding residues will occur following application of the WP at the
maximum registered rate. Upon generation of the requested data, the registrant must propose a tolerance increase
or modify the labels to result in subtolerance residues. Label revisions must be supported by residue data.
TO/ Data must be submitted depicting maneb residues of concern, including ETU, in or on tomatoes 5 days following
multiple foliar applications (using ground and aerial equipment in separate tests) of a WP or PIC at 3.3 Ib
ai/A and a 0 formulation at 3.4 Ib ai/A. Tests must be conducted in PL, CA, HI, and TX which produce 50%,
29%, 1%, and 1%, respectively (totaling 81%), of U.S. tomatoes (production percentages are from Aqricultrual
Statistics, 1984, p. 173) in order to provide adequate geographic representation. The registrant must propose
a maximum number of application per season or a maximum seasonal application rate. Submitted studies must
reflect the proposed use.
71/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on tomatoes harvested 5 days
following the last of several foliar applications of the 80% WP formulation at 4 Ib ai/A (aerial and ground
equipment must be represented in separate tests). Tests must be conducted in CA. Alternatively, the registrant
may elect to cancel the state use permitted under EPA Reg. No. 5967-5138.
72/ Data must be submitted from tests conducted in PL depicting maneb, ETU, and other residues of concern in or
on tomatoes harvested 3 days following the last of multiple foliar applications of a D formulation at 2.4 Ib
ai/A, and in separate tests, a WP formulation at 2 Ib ai/100 gal (tomatoes harvested on the day of the final
application). Alternatively, the registrant may elect to cancel the state use permitted under EPA Reg. Nos.
9169-5295, 9169-5292, and 7478-8009. The application rate(s) associated with EPA Reg. Nos. 7478-8035 and
9782-3634 must be specified. Data must be submitted from a study conducted in CA depicting maneb, ETU, and
other residues of concern in or on tomatoes harvested on the day of the last of multiple foliar applications
of a D formulation at 2.5 Ib ai/A. Alternatively, the registrant may elect to cancel the state use permitted
under EPA Reg. Nos. 1202-5059 and 6023-3042.
73/ A tomato processing study must be conducted and submitted whereby residues of maneb, ETU and other residues
of concern are determined in wet pomace, dry pomace, puree, catsup, and juice processed from tomatoes bearing
detectable field-weathered residues.
-------
74/ Data must be depicting maneb, ETU, and other residues of concern in or on cucumbers harvested 5 days following
the last of nultiple foliar applications (using ground and aerial equipment in separate tests) of a 0 formulation
at 3 ai/A and a WP (or PIC) formulation at 3 Ib ai/A*. Tests must be conducted in CM6%), PL(12%), MI (15%)r
NC(14%), SC(5%), TX(11%), and VA(5%) which collectively account for 68% of U.S. cucumber acreage (1982 Census
of Agriculture, Vol. 1, Part 51, p. 342-343). The registrant must propose a maximum seasonal application rate
or a maximum number of applications per season. Required studies must reflect this proposed maximum rate.
75/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on cucumbers harvested on the
day of the last of the several foliar applications of the 4.8% D fomulation at 2.4 Ib ai/A (aerial and ground
equipment must be represented in separate tests). Tests must be conducted in CA. Alternatively, the registrant
may elect to cancel the state use permitted under EPA1 Reg. No. 6023-3042.
76/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on cucumbers harvested on the
day of the last of the several foliar applications of the 42.5% PIC formulation at 2.7 Ib ai/A (aerial and
ground equipment must be represented in separate tests). Tests must be conducted in PL. Alternatively, the
registrant may elect to cancel the state use permitted under EPA Reg. No. 9859-9146.
77/ Data must be submitted depicting maneb, ETUf and other residues of concern in or on cantaloupes, honeydew
melon, or watermelon harvested 5 days following the last of multiple foliar applications (using ground and
aerial equipment in separate tests) of a D formulation and a WP formulation at 2.4 Ib ai/A. The registrant
must propose a PHI and a maximum seasonal application rate or maximum number of applications per season. Required
studies must reflect these proposals. Tests must be conducted in CA, GA, PL, and TX, which collectively account
for 76% of U.S. cantaloupe acreage, 81% of U.S. honeydew melon acreage, and 63% of U.S. watermelon acreage
(1982 Census of Agriculture, Vol. 1, Part 51, pp. 339, 345, 356, 357, respectively).
78/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on melons harvested on the day
of the last of several foliar applications of the 4.8% D formulation at 2.4 Ib ai/A (aerial and ground equipment
must be used in separate tests). Tests must be conducted in CA. Alternatively, the registrant may elect to
cancel the state use permitted under EPA Reg. No. 6023-3042.
797 Data must be submitted depicting maneb, ETU, and other residues of concern in or on watermelons harvested 5
days following the last of several foliar applications of the 80% WP formulation at 5 Ib ai/A (aerial and ground
equipment must be represented in separate tests). Tests must be conducted in PL.. Alternatively, the registrant
may elect to cancel the state use permitted under EPA Reg. No. 9782-3633.
807 Data must be submitted depicting maneb, ETU, and other residues of concern in or on watermelons harvested on
the day of the last of several foliar applications of the 42.5% PIC formulation at 2.7 Ib ai/A (aerial and
ground equipment must be represented in separate tests). Tests must be conducted in PL. Alternatively, the
registrant may elect to cancel the state use permitted under EPA Reg.No. 9859-9146.
-------
81/ The data submitted were inadequate to support the established tolerance for maneb residues in or on pumpkins.
However, no additonal data are required. The data requested fee melons may be translated to pumpkins since the
registered uses on the two crops are similar (refer to the melons section for details of data requirements).
82/ The data submitted are inadequate to support the established tolerance for maneb residues in or on squash.
However, no additonal data are required since requested residue data for cucumbers may be translat-ed to summer
squash, and data requested for melons may be translated to winter squash.
83/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on apples 15 days following
the last of multiple foliar aerial and ground applications of a WP or FlC formulation at 8.4 Ib ai/A in AR,
DE, IL, IN, KS, KY, MD, NO, NJ, OH, PA, SC, TN, VA, and WV, and 30 days following the last of these applications
in all other states. The registrant must propose a maximum seasonal application rate or a maximum number of
applications per season. Required studies must reflect this proposed maximum rate. Tests must be conducted in
CA(6%), MI(9%), NY(12%), VA(6%), and WA(36%), which collective produce 69% of U.S. apples (Agricultural Statistics,
1985, p. 186) in order to provide adequate geographic representation.
84/ To determine if concentration of residues or conversion of maneb to ETU occurs in dry pomace and juice during
processing, the registrant must conduct and submit appropriate processing studies. Pood/feed additive tolerances
may need to be proposed pending receipt of adequate storage stability data and field residue data determining
the residues in the raw agricultural commodity.
85/ Data must be submitted depicting residues of maneb, its metabolite ETU, and other residues of concern in or on
apjicots harvested 14 days following multiple foliar applications of a WP formulation at 8 Ib ai/A; and (in a
separate test) a D formulation at 8.4 Ib ai/A. Studies must be done using ground and aerial equipment in separate
tests. CA, which produces 97% of U.S. apricots, must be the test state (Agricultural Statistics, 1985, p.
191).
86/ The registrant must propose a maximum seasonal application rate or a maximum number of applications per season.
Required studies must reflect this proposed maximum rate.
87/ NO acceptable data were submitted in support of the established tolerance for residues of maneb in or on
nectarines. However, no data are required; the requested data for peaches may be translated to nectarines since
the registered uses of maneb on nectarines are identical to those on peaches.
88/ Data must be submitted depicting residues of maneb, its metabolite ETU, and other residues of concern in or on
peaches 2 days following the last of multiple foliar applications of (in separate tests) a WP (or a PIC) formulation
at 8.0 Ib ai/A, and a D formulation at 5.6 Ib ai/A. Separate tests must reflect use of ground and aerial equipment.
Tests must be conducted in CA(56%) and SC(18%), which together produce 74% of U.S. peaches, in order to provide
adequate geographic representation (production figures are from Agricultural Statistics, 1985, p. 21). The
registrant must propose a maximum seasonal application rate or a maximum number of applications per season.
-------
Required studies must reflect this proposed maximum rate.
89/ Data must be submitted from tests conducted in CA depicting maneb, ETU, and other residues of concern in or
on peaches harvested 14 days following the last of a series of foliar applications of the 80% WP formulation
at 10 Ib ai/A. Alternatively, the registrant may elect to cancel this state use permitted under EPA Req. No.
5967-5138. ^
90/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on peaches harvested 2 days
following the last of several foliar applications of a 6% D formulation at 6 Ib ai/A (aerial and ground equipment
must be represented in separate tests). Tests must be conducted in CA. Alternatively, the registrant may
elect to cancel this state use permitted under EPA Reg. No. 7001-7772.
- ,*
91/ Residue data must be submitted depicting maneb, ETU,' and other residues of concern in or on cranberries harvested
30 days after the last of multiple foliar applications, in separate tests, of a registered WP (or PIC) and a
D formulation at 6 Ib ai/A. Applications must be initiated at midbloom, and repeated at 10-day intervals, up
to 4 weeks after midbloom. These tests must be conducted in WI(42%) and MA(41%), which collectively represent
ca. 83% of the U.S. cranberry production (1982 Census of Agriculture, Vol. 1, Part 51, p. 321).
92/ Residue data must be submitted for maneb, ETU, and other residues of concern in or on cranberries harvested
30 days after application of a PIC (or WP) at 5.6 Ib ai/A with treatment initiated after midbloom, and repeated
between July 10 and 20, August 1 and 10, and August 10 and 25. Do not apply later than 4 weeks after midbloom.
These tests must be conducted in OR and WA. Each of the above mentioned tests must be conducted using separate
aerial and ground (high and low volume) equipment.
93/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on cranberries harvested 4
^O weeks following the last of several foliar applications of the 5.6% D formulation at 4.7 Ib ai/A (aerial and
° ground equipment must be represented in separate tests). Tests must be conducted in CA. Alternately, the
intrastate label EPA Reg. No. 1202-5059 may be cancelled.
94/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on grapes harvested 7 days
after the last of multiple foliar applications (in separate tests) of a registered WP, WP/D, or Pic at 4.0 Ib
ai/A and a D formulation at 1.5 Ib ai/A, respectively. Each of these tests must be preceded by three applications
of an PIC or WP formulation at 4.0 Ib ai/A to be applied just before bloom, just after bloom, and 10 days
after bloom. The requested tests must be conducted utilizing separate aerial and high- and low-volume ground
equipment. Tests must be performed in CA, which represents Ca. 90% of the U.S. grape production (Agricultural
Statistics, 1985, p. 207).
957 since concentration of maneb and/or conversion of maneb to ETU may occur in dry pomace, raisins, raisin waste,
and grape juice, the registrant must conduct appropriate processing studies. If residues concentrate, approp-
-------
riate food/feed additive tolerances must be proposed.
967 Data oust be submitted depicting naneb, ETO and any other residues of concern in or on almond nuts and hulls
following multiple foliar applications of HP, WP/D, or PIC fonulation at 6.4 Ib ai/A. Studies must use ground
and aerial equipment in separate tests. These tests Mist be conducted in CA, which produces 99% of O.S. almonds
(1982 census of Agriculture Vol. 1, Part 51, p. 367).
97/ Since almond hulls are a raw agricultural commodity, and feeding restrictions are considered impractical, the
registrant must propose a tolerance for maneb residues in or on almond hulls.
98/ The registrant most propose a Maxima seasonal application rate or a maxima number of applications per season.
Required studies Hist reflect the proposed maxima rate.
99/ Data must be submitted depicting residues of maneb, its Metabolite ETO, and other residues of concern in or on
sweet com (kernels plus cob with husks removed) folio-ring multiple folior applications of a D formulation and
a WP or F1C formulation at 2.3 Ib ai/A. Separate testa must reflect use of ground and aerial equipment. The
registrant must propose a maximum seasonal application rate or a maximum number of applications per season.
Required studies oust reflect this proposed rate. Test* most be conducted in FL(8%), IL(6%), N?(8%), HN(11%),
WA(8%), and WI(19%) which collectively produce 60% of O.S. sweot com (Agricultural Statistics, 1985* p. 156).
100/ Data must be submitted depicting residues of maneb, its metabolite ETO and other residues of concern in cannery
waste processed from sweet ccm bearing measurable weathered residues. If residues concentrate during processing,
the registrant must propose aft appropriate" feed additive tolerance.
IQly Data must be submitted depicting maneb, ETO, and other residues of concern in or on sweet corn harvested on the
day of the last of several foliar applications of the 80% WP formulation at 2.5 Ib ai/A (aerial and ground
equipment must be represented in separate tests). Tests must be conducted in PL. Alternatively, the registrant
may elect to cancel this state use permitted under EPA Reg. No. 9782-93633.
1Q2/ Data mst be submitted depicting maneb, ETO, and other residues of concern in or on forage of sweet corn harvested
on the day of the last of several foliar applications of the 80% WP formulation at 2.5 Ib ai/A (aerial and
ground equipment must be represented in separate tests). Tests must be conducted in PL. Alternatively, the
registrant may elect to cancel this state use permitted under EPA Reg. No. 9782-93633.
103/ Data must be submitted depicting residues of maneb, its metabolite ETO, and other residues of concern in or on
sweet corn forage following miltiple foliar applications of a D formulation at 2.4 Ib ai/A. Separate tests
must reflect use of ground and aerial equipment. The registrant must propose a maxima seasonal application
rate or a maximum number of applications per season. Required studies must reflect this proposed rate.
Tests must be conducted in FL(8%), NT(8%), m(U%), NM8%), and WI(19%) which collectively produce 54% of O.S.
sweet corn (Agricultural Statistics, 1965, p. 156).
-------
104/ Data must be submitted depicting Baneb, ETO and other residues of concern in or on asparagus harvested from
plants treated with multiple post-harvest foliar applications of a HP, H?/D, or PIC fonulation at 2.4 Ib
ai/A. The registrant Bust propose a tolerance for residues of maneb in or on asparagus and a ***!•• seasonal
application rate. Required residue data must reflect this proposed maximum rate. Tests must be conducted in
CA(36%), HI(20*), and MA(31%) which collectively account for 87% of O.S. asparagus acreage (1982 Census of
Agriculture, Vol. 1, Part 51, p. 335).
IPS/ Data must be submitted depicting maneb, ETO, and other residues of concern in or on asparagus harvested on
the day of the last of several foliar applications of the 5.6% D at 2.35 Ib ai/A (aerial and ground equipment
Bust be represented in separate tests). Tests Bust be conducted in CA. Alternatively, the registrant Bay
elect to cancel this state use permitted under EPA Reg. No. 1202-5059.
106/ Data aust be submitted depicting Baneb, ETO, and other residues of concern in or on banana fruit (whole) and
banana pulp following Multiple foliar applications of the 80% HP formulation or the 4 Ib PIC formulation at 4
Ib ai/A. Ose of ground and aerial equipment must be represented in separate tests. Tests must be conducted
in HI which produces 82% of O.S. bananas (1982 Census of Agriculture, Vol. 1, Part 51, p. 360). The registrant
Bust propose a mfnrlmimi number of applications per season or'maxiBuiTseasonal application rate. Required
studies must reflect the proposed maximum rate. If maneb products are used on bananas in countries exporting
fruit to the O.S., then copies of product labels and supporting residue data Bust be submitted.
107/ Data must be submitted depicting Baneb, BTO, and other residues of concern in or on figs harvested 10 days
after a single application of a NP (or PIC) formulation at a spray concentration of 0.5-0.6 Ib ai/100 gal.
Tests must be conducted in CA, which accounts for about 99% of O.S. fig acreage (1982 Census of Agriculture.
Vol. 1, Part 51, p. 361).
vb 108/ Data must be submitted depicting Baneb, BTO, and other residues of concern in or on figs harvested 10-days
rro following a single foliar application of the 80% HP formulation at 2.4 Ib ai/A (aerial and ground equipment
Bust be represented in separate tests). Tests Bust be conducted in CA. Alternatively, the registrant Bay
elect to cancel this state use permitted under EPA Reg. No. 5967-50136.
109/ Data Bust be submitted depicting residues in dried figs processed from figs bearing measurable, weathered
residues. If residues concentrate in this processed commodity, an appropriate food additive tolerance Bust
be proposed.
IIP/ Data wast be submitted depicting maneb, ETO, and other residues of concern in or on papayas resulting from
Bultiple foliar applications of the 4 Ib/gal FlC formulation at 2.4 Ib ai/A. Ose of ground and aerial equipment
must be reflected in separate tests. The registrant must propose a maximum seasonal use rate or maximum
number of applications per season, as well as a PHI. Required tests Bust reflect these proposals. Studies
must be conducted in HI which accounts for 99% of O.S. papaya acreage (1982 Census of Agriculture, Vol. 1,
Part 51, p. 363).
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Ill/ Data must be submitted depicting maneb, ETU, and other residues of concern in or on barley, corn (other than
sweet corn), cotton flax, oats, peanuts, pineapple, rice, rye, sorghum, soybeans, sunflower, and wheat resulting
from seed treated with maneb according to the label directions of the product at the maximum permissible use
rate (in some cases, the maximum rate is present on a multiple active ingredient formulation label). Samples
of all raw agricultural commodities for each crop must be collected at the shortest interval after planting
in which they could be used for food or feed purposes. Tolerances must be proposed that reflect either the
maximum expected residue levels or, if no measurable residues are detected, the limit of detection of the
analytical method. All required processing studies must utilize raw agricultural commodities bearing measurable,
weathered residues* Given the long PHI for asparagus crowns or caprifigs, no residue data are required for
these racs.
112/ Data must be submitted depicting maneb, ETO, and other residues of concern in or on green, freshly harvested
tobacco receiving the following full-season treatment schedule: (i) multiple foliar plant bed treatments of
a WP or PIC formulation at 3.2 Ib ai/100 gal (5 gal/100 sq yards) and in a separate test, a D formulation at
0.14 Ib ai/100 sq. yards followed by (ii) multiple foliar applications (to plants set in field) by air and,
in separate tests, by ground equipment of a WP, WP/D or F1C formulation at 3.2 Ib ai/A and, in a separate
test, a D fornulation at 2.1 Ib ai/A. The registrant must propose a maximum seasonal application rate or a
maximum number of applications per season. Required studies must reflect these rates.
1137 If residues in freshly harvested green tobacco exceed 0.1 ppm, data depicting residues in or on dried or cured
tobacco will be required. If residues in or on dried or cured tobacco exceed 0.1 ppm, pyrolysis products derived
from the active ingredient must be characterized and the level of residue in smoke must be quantified. . ([i4Cj-
maneb must be used for identification of pyrolysis products.
114/ Presently, the nature of the residue in animals is not adequately understood. On receipt of the data concerning
nature of the residue in animals, the need for tolerances tor residues in animal products will be reassessed
with consideration for any additional metabolites of toxicological concern.
115/ Data have been submitted by the Maneb Task Force and are currently under review.
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TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
S158.290 - Environmental
DEGRADATION STUDIES-LAB:
161-1 - Hydrolysis
Photodegradation
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 Aouatic
Test
Substance1
Fate
TGAI or PAIRA
ETU
TGAI or PAIRA
ETU
TGAI or PAIRA
ETU
TGAI OC PAIRA
TGAI or PAIRA
ETU
TGAI OC PAIRA
ETU
: TGAI or PAIRA
Use2
Patterns
A,B
A,B
A,B
A,B
A
A
A
A,B
A,B
A
A
Does EPA Bibliographic
Have Data? Citation
No
Yes 40466103
NO
Yes 40466102
No
Yes 40466101
No
NO
NO
Yes 00163335
NO
Yes 00163335
Must Additional
Data be
Submitted?
Yes
No
Yes
No
Yes
No
JP
Reserved
Yes
Yes
§/
NO
Yes
§/
NO
Time Frame
for3
Submission
1/88
1/88
1/88
6/89
6/89
6/89
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TAH.E A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
§158.290 - Environmental Fate -
162-4 - Aerobic Aquatic
MOBILITY STUDIES s
163-1 - Leaching and
Adsorption/Desorption
163-2 - Volatility (Lab)
163-3 - Volatility (Held)
DISSIPATION STUDIES-FIELD:
164-1 - Soil
n 164-2 - Aquatic (Sediment)
164-3 - Forestry
164-5 - Soil. Long-term
ACCUMULATION STUDIES*
Test
Substance1
Continued
TGAI or PAIRA
ETU
TGAI or PAIRA
ETU
EHJ
TEP
TEP
ETU
TEP
ETU
'I'HP
TEP
ETU
Use2
Patterns
A
A
A,B
A,B
A
A
A,B
A,B
A
A
-
A,B
A,B
Does EPA Bibliographic
Have Data? Citation
No
No
No
No
No
No
No
No
No
No
No
No
No
Must Additional
Data be
Submitted?
^
Yes
Yes
Yes
Yes
S/
Reserved
Yes
Yes
Yes|/
Yes
NO
2/
Yes9/
Yes
•* /
Time Frame
for3
Submission
6/89
27 Months
/ ^/
4/88
4/88
12 Months
6/89
6/89
7/89
27 Months
50 Months
50 Months
165-1 - Rotational Crops
(Confined)
PAIRA
No
Yes
7/90
-------
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
Test US62 Does EPA Bibliographic
Substance1 Patterns Have Data? Citation
Must Additional
Data be
Submitted?
Time Frame
for*
Submission
S158.290 - Environmental Fate - Continued
TEP
165-2 - Rotational Crops
(Field)
165-3 - irrigated Crops
165-4 - In Fish
165-5 - In Aquatic Non-Target
Organisms
Special Studies
Small Scale Retrospective Ground- Maneb
Water Monitoring Study ETU
TEP
TGAI or PAIRA
ETU
TEP
A,B
A,B
A,B
A,B
NO
NO
NO
NO
NO
NO
Reserved
10/
§/
Yes
j
Yes"
Yes
No
12/
Yesl2/
Yes
7/90
4/88
12 Months
3 Years from
Agency's
acceptance of
protocol which is
due Sept. 1988.
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;
37 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. When 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/ Maneb has low volatility. Volatility data on ETU is not available. ETU may volatalize but
-------
§158.290 - Enviroranental Fate - Continued
is unlikely to degrade in air since it does not degrade under sunlight in water and on soil.
5/ The anaerobic aquatic data will satisfy this requirement.
6/ Maneb has a registered cranberry use.
7/ Data required on both maneb and ETC. Emphasis nust be placed on ETO.
B/ Reserved pending results of laboratory volatility data and review of toxicological and reentry issues.
9/ Prospective monitoring studies and field leaching studies addressing ETU and maneb is optional as replacement
for the conventional long-term field dissipation study. This study would trace the movement of ETU through the
soil profile in soil pore water in the vadose zone and in shallow groundwater. Interim results of this study nust
be submitted for assessment 6 months after the studies are initiated. Whether the registrant select to generate
the conventional long-term field study or the prospective study, an adequate study must be submitted to the Agency
within 50 months from registrant's receipt of this Registration standard.
10/ Reserved pending results of confined rotational crop study.
\\J Data have recently been submitted and are under review.
12/ A small-scale retrospective ground-water monitoring study on maneb/EFU was required in the April 25, 1988 Data
Call In Notice. Progress reports are due semi-annually, the first one is due November, 1988.
13/ Registrant has requested a waiver of this data requirement which is currently under review by the Agency.
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Date
S158
Requirement
.340 - Toxicology
Test1
Substance
Use2
Patterns
Does EPA
Have Data?
Bibliographic
Citation
Must Additional
Data be
Submitted
Time Frame
for*
Submission
ACUTE TESTING:
81-1
81-2
81-3
81-4
81-5
vO 81-6
CD
81-7
- Acute Oral Toxicity - Rat
- Acute Dermal Toxicity
- Rabbit
- Acute Inhalation Toxicity
- Rat
- Eye Irritation - Rabbit
- Dermal Irritation - Rabbit
- Dermal Sensitization -
Guinea pig
- Acute Delayed
Neurotoxicity - Hen
TGAI
TGAI
TGAI
TGAI
TGAI
TGAI
TGAI
A,B,H
A,B,H
A,B,H
A,B,H
A,B,H
A,B,H
A,B,H
Yes
Yes
Yes
Yes
Yes
Yes
No
00129749
00128936
00129750
00128937
00128938
00141264
No
No
No
No
No
No
47
Jr
NO
SUBCHRONIC TESTING:
82-1
82-2
82-3
82-4
- 90-Day Feeding:
- Rodent , and
- Non-rodent (Dog)
- 21-Day Dermal - Rabbit
- 90-Day Dermal - Rabbit
- 90-Day Inhalation Rat
TGAI
TGAI
TGAI
TGAI
TGAI
A
A
A,B,H
A,B,H
No
Yes
No
No
Partially
00129980
00162084
y
No
NO
Yes
6/
N°l/
Yes^
9/88
12/88
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
Test Use2 Does EPA Bibliographic
Substance1 Patterns Have Data? Citation
Must Additional Time Frame
Data be for^
Submitted? Submission
5158*340 - Toxicology - Continued
82-5 - 90-Day Neurotoxicity:
- Dog
CHRONIC TESTING!
83-1 - Chronic Toxicity -
2 species:
- Rodent, and
- Non-rodent (Dog)
83-2 - Oncogenicity -
2 species:
- Rat (preferred), and
- Mouse (preferred)
83-3 - Teratogenicity -
2 species:
- Rat
- Rabbit
83-4 - Reproduction - Rat
2-generation
TGAI
A,B,H
No
NO
TGAI
ETU
TGAI
ETU
TGAI
TGAI
TGAI
TGAI
TGAI
ETU
A
A
A
A
A
A
ArB,H
A,B,H
A
A
Partially 00129979
NO
No
No
Partially 00129979
NO
No
NO
NO
No
Yes-
Yes
Q/
21
Yes
Yes
§/
Yes
»
Yes
Yes
Yes
*-•
Yes
Yes
11/90
5/90
11/90
5/90
11/90
11/90
12/88
12/88
12/90
12/90
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
Test Use2 Does EPA Bibliographic
Substance^ Patterns Have Data? Citation
Must Additional
Data be
Submitted?
Time Frame
foc3
Submission
O
o
5158.340 - Toxicology - Continued
MUTAGENICITY TESTING
84-2 - Gene Nutation (Ames Test) TGAI
TGAI
84-2 - Structural Chromosomal
Aberration
TGAI
84-4 - Other Genotoxic Effects
SPECIAL,TESTING
85-1 - General Metabolism PAI or PAIRA
85-2 - Domestic Animal Safety Choice
85-3 - Dermal Absorption PAIRA
A,B,H
ArB,H
Partially
Yes
40091303
00149570
40091301
A,B,H
A,B,H
A,B,H
Partially 40163901
Yes
No
Partially
00153352
00153475
Yes
No
Yes
No
NO
Yes
10/
6/88
9/88
3/88
I/ composition: PAI - Pure active ingredient; PAIRA - Pure active ingredient, radiolabelied; Choice - Choice of
several test substance determined on a case-by-case basis.
y The use patterns are coded are follows: A - Terrestrial, Pood Crop! B - Terrestrial, Non-Food; H • Domestic Outdoor
3/ 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.
4/ This test is required only for compounds which are organophosphate inhibitors of cholinesterase, or related to such
inhibitors or metabolites of such inhibitors. Maneb is not an organophosphate, therefore, a study in not required.
5/ This requirement is conditionally waived based on the submission of an acceptable chronic feeding study in the rat.
6/ This study is not required under the existing use patterns. A 21-day dermal study is being required.
-------
7/ Additional information consisting of histopathology data from rats sacrificed after a 13-week recovery period, as
well aa analytical data (manganese in lung tissue and residues of BUI and/or Maneb in lung tissue) is required.
*
§/ The 31-month rat feeding study (MRID 129979), with additional information, may satisfy this data requirement.
If you elect to submit the additional information, it must be submitted to the Agency within 120 days from your
receipt of this document. If this information is submitted and determined to be inadequate or if you do not submit
information within that time period, an acceptable study must be submitted to the Agency by 11/90.
9/ Special neurologic observations must be added to this study. The registrant must submit a protocol to the
Agency for consideration prior to commencing the study. [Rcf.t 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. Saunders, Philadelphia.
10/ Clarification of the percentage of active ingredient in the test substance is required.
ll/ The submission of individual data is required to upgrade this study.
12/ Additional data; i.e., submission of the analyses of samples collected during the study (14C-activities in
the carcasses) are necessary in order to obtain a more precise measurement of the amount of Maneb absorbed.
Additional work may be required, depending on the evaluation of the above-requested analyses, to determine
Whether, (and if so, at what rate) the Maneb bound to the skin is absorbed after 10 hours, and whether
accumulation occurs.
—-13/ The Agency has received and is currently reviewing additional information.
O
~~V14/ Registrant has requested a time extension until October 1988.
-------
TAEBJE A
GENERIC DATA REQUIREMENTS RDR MftNEB
Data Requirement
Test1 Use2 Does EPA Bibliographic
Substance Pattern Have Data? Citation
Most Additional Tine Frame
Data be for3
Submitted? Submission
Si58.:
132-1
132-1
133-3
133-4
yy\) — Reentry protection
- Foliar Dissipation
- Soil Dissipation
- Dermal Exposure
- Inhalation Exposure
TEP
'I'HP
TEP
TEP
A,B
A
A,B
A,B
No
No
No
No
-------
S/ Soil Dissipation data are required only for uses where workers will be exposed directly to substantial
quantities of soil during their workr 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 method11 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.
o
Us!
-------
DATA REQUIREMENTS FOR MANEB
Data
§158,
Requirement
,490 - Wildlife and
Test^ Use^ Does EPA
Substance Pattern Have Data?
Bibliographic Must Additional
Citation Data be
Submitted?3
Time Frame
for4
Submission
Aquatic Organisms
AVIAN AND MAMMALIAN TESTING
71-1
71-2
71-3
71-4
71-5
- Acute Avian Oral Toxicity
- Avian Subacute Dietary
Toxicity
- Upland Game Bird, and
- Waterfowl
- Wild Mammal Toxicity
- Avian Reproduction
- Upland Game Bird, and
- Waterfowl
- Simulated Field Testing
TGAI
TGAI
ETO
TGAI
TGAl
ETU
TEP
3/
A,B,H,[E,Fr
3/5/
A,B,H,[E,F]
A,B,H
A,B
A,B
A,B
A,B
No
€/
Partial
No
No
No
No
NO
Yes
u
00104264 00098651 Yes
^ * t
B/9/
Reserved
No
A *^ t
lo/
Yes
Reserve^
i iii/
Reserved
18/
6/88
i§/
6/88
3/89
- Mammals, and
- Birdd
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
S 158. 490 - Wildlife and
Aquatic Organisms - continued
AQUATIC ORGANISM TESTING
72-1 - Freshwater Fish Toxicity
72-2 - Acute Toxicity to
Freshwater Invertebrates
Test1 Use
Substance Pattern?
3/5
TGAI A,B,H,[E,F]
TEP (80%WP A
4 Ib FC)
ETU A,B
I/
TGAI A,B,H[E,F]
TEP (80%WP A
Does EPA Bibliographic
Have Data? Citation
j/
NO
12/
Partially 97240
No
NO
NO
Must Additional
Data be
Submitted?3
Yes
W
Yes
2/15/
Reserved
Yes
13/
Yes
Time Frame
for*
Submissio
18/
6/88
18/
6/88
!§/
6/88
9 Months
4 Ib FC)
ETU
NO
Reser
2A6/
ved
«.n 72-3 -
Acute Toxicity to
Estuarine and Marine
Organisms
- Fish
- Shrimp
TGAI
TEP (80%WP
4 Ib FC)
ETU
TGAI
TEP (80%WP
A
A
A
A
A
NO
NO
NO
NO
NO
Yes
Yes
Reserved
Yes
Yes
9/88
12 Month)
9/88
12 Month!
4 Ib FC)
ETU
No
Reserved
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data
S158
Requirement
*
.490 - Wildlife and
Test1 Use
Substance Pattern2
Does EPA Bibliographic
Have Data? Citation
Must Additional
Data be
Submitted??
Time Frame
for
Submission4
Aquatic Organisms - Continued
72-4
72-5
72-6
72-7
- Oyster
- Fish Early Life Stage,
and invertebrate Life-
Cycle - Fish
- Invertebrate
(Freshwater &
Estuarine)
- Fish - Life-Cycle
Estuarine
Freshwater
- Aquatic Organism
Accumulation (Fish)
- Sinulted or Actual
TGAI A
TEP (80%WP A
4 lb FC)
ETU A
TGAI A,B
ETU A,B
TGAI A,B
*
ETU A,B
TGAI A
TGAI A
TGAI A
TEP A,B
No
No
No '
No
No
No
NO
NO
NO
NO
NO
Yes
Yes
O /IE/
_J2ri§r
Reserved
W
Yes
W
Reserved
W
Reserved
W
Reserved
IT/
Reserved
IT/
Reserved
Yes
* £ M
15/
Reserved
9/88
12 Months
12/88
19/
6/88
Field Testing -
Aquatic Organism
-------
TABLE A
DATA REQUIREMENTS FOR MANEB
§158.490 - Wildlife and Aquatic Organisms - Continued
I/ TSAI « Technical Grade Active Ingredient, TEP « Typical End-Use Product.
2/ A - Terrestrial, Food Crop? B « Terrestrial, Nonfood; C « Aquatic, Food Crop? D - Aquatic, Non-Pood? E - Green-
house, Pood Crop* F • Greenhoue, Nonfood? G - Forestry? H - Domestic Outdoor? I » Indoor.
3/ Required to support the manufacturing use product for reformulation into these end-use products.
4/ These data requirements that have specific dates under time frames have been previously requested in the
Comprehensive Data Call In Notice issued April 1987. The time frame for submission of these data is the
same as required in the April 1987 Data Call In Notice. When number of months are provided, these are new
data requirements Which must be fulfilled in the number of months specified from the registrants's receipt
of this document.
5/ Only one species is required.
6/ A waterfowl study has been provided but does not fulfill the requirements.
7/ Provision of dose mortality data will fulfill requirement.
8/ Pending the results of photolysis and hydrolysis studies, there may be requirements for waterfowl and uplant
game bird studies.
ETU is the primary degradate of maneb. The material is water soluable and is persistent in water beyond 4 days.
10/ All outdoor uses permit multiple applications before or during breeding season for birds.
ll/ Pending results of avain reproduction studies on technical rtaneb and environmental fate data such as hydrolysis
and photolysis the study could be required to support such uses as apples, corn and cranberries.
12/ Only the requirement for the warmwater fish on an 80WP has been fulfilled.
13/ Required to support cranberry use.
14/ The bluegill LC50 for the 80WP is 1.0 ppn and the estimated environmental concentrations for such sites as
apples, cranberries, potatoes, corn, and turf exceen 0.01 x a fish LC50.
15/ Reserved pending results of environmental fate data such as hydrolysis, photolysis and aquatic field
dissipation and studies on technical maneb.
-------
Footnotes continued,
16/ Reserved pending results of environmental fate data such as hydrolysis and photolysis and the acute aquatic
invertebrate study*
IT/ May be required to support the cranberry use pending the results of partial chronic studies on technical mneb.
18/ Studies have recently been submitted and are being reviewed.
19/ The Agency is currently reviewing a waiver request for this study*
OD
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement Test1 Use2 Does EPA Bibliographic Must Additional Time Frame
Substance Pattern Have Data? Citation Data be for3
Submitted? Submission
S158.540 - Plant Protection
121-1 - TARGET AREA EP A No
PHYTOTOXICITY
NONTARGET AREA PHYTOTOXICITY
TIER I
122-1 - Seed Germination/ TGAI A No
Seedling Emergence
122-1 - Vegetative Vigor . TGAI A No
122-2 - Aquatic Plant Growth TGAI A No
TIER II
123-1 - Seed Germination/ TGAI A No
Seedling Emergence
123-1 - Vegetative Vigor TGAI A No
123-2 - Aquatic Plant Growth TGAI A No
TIER III
124-1 - Terrestrial Field TEP A No
124-2 - Aquatic Field TEP A No
No
§/
NO
5/
NO
Yes 1/88
§/
NO
§/
NO
Reserved
§/
No
y
Reserved
-------
§158.540 - Plant Protection - Continued
I/ TOM • Technical grade of the active ingredient; TEP • typical end-use product,
2/ The use patterns are coded as followss A • Terrestrial* food crop (cranberries)*
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*
4/ Whether data are required is determined on a case-by-case basis, where phytotoxicity issues way be involved.
5/ Use in aquatic sites does not require submission of terrestrial phytotoxicity data.
6/ Reserved pending results of Tier I.
If Reserved pending results of Tier II.
§/ Basic Producer proposed to delete cranberries from their label and this data requirement would not apply to
them. However, unless the formulators have removed the cranberry use from their labels, this data requirement
applies.
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
Test Use Does EPA Bibliographic
Substance1- Pattern2 Have Data? Citation
Must Additional
Data be
Submitted?
Time Frame
for
Submission
§158.590 - Nonjbarqet Jtnsect
NONTARGET INSECT TESTING -
POLLINATORS:
141-1 - Honey bee acute
contact toxicity TGAI A,B Yes
141-2 - Honey bee - toxicity TEP A,B No
of residues on
foliage
141-4 - Honey bee subacute (Reserved)
feeding study
141-5 - Field testing for TEP A,B No
pollinators
_*
•"NONTARGET INSECT TESTING -
""AQUATIC INSECTS;
142-1 - Acute toxicity to (Reserved)
aquatic insects
142-1 - Aquatic insect (Reserved)
life-cycle study
142-3 - Simulated or actual (Reserved)
field testing for
aquatic insects
143-1 - NONTARGET .INSECT (Reserved)
thru TESTING - PREDATORS
143-3 AND PARASITES
00036935
NO
3
NO
NO
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR MANEB
Data Requirement
Test Use Does EPA Bibliographic
Substance1 Pattern2 Have Data? Citation
Must Additional
Data be
Submitted?
Time Frame
foe
Submission
5158.590 - Nontarqet Insect
NONTARGET INSECT JESTING -
POLLINATORS;
141-1 - Honey bee acute
contact toxicity
141-2 - Honey bee - toxicity
of residues on
foliage
141-4 - Honey bee subacute
feeding study
141-5 - Field testing for
pollinators
NONTARGET INSECT TESTING -
— 'AQUATIC INSECTS;
Acute toxicity to
aquatic insects
Aquatic insect
life-cycle study
Simulated or actual
field testing for
aquatic insects
NONTARGET INSECT
TESTING - PREDATORS
AND PARASITES
142-1
142-3
143-1
thru
143-3
TGAI
TEP
A,B
A,B
Yes
NO
(Reserved)
TEP
(Reserved)"
i
«
(Reserved)'
*
(Reserved)"
i
V
(Reserved)"
00036935
No
3
No"
A,B
No
NO
-------
5158.590^- Nonbagget Insect - Continued
I/ Composition: TGAI * Technical grade of the active ingredienti TEP • Typical end-use product*
2/ The use patterns are coded as follows: A • Terrestrial, Pood Crop; B * Terrestrial, Nonfood.
3/ AS data from the acute contact study show low toxicity to honey bees, no further testing is required.
4/ Reserved pending development of test methodology.
5/ Reserved pending Agency decision as to whether the data requirement should be established.
Us!
-------
TABLE B
PRODUCT SPECIFIC DATA REQUIREMENTS FOR MANUFACTURING-USE PRODUCTS CONTAINING MANEB
Data Requirement Test Use Does EPA
Substance1 Pattern Have Data?
Part 158
Subpart C - Product Chemistry
Product Identity;
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 Product
Ingredients
—62-1 - Preliminary Analysis
— *
J^.
62-2 - Certification of Limits
62-3 - Analytical Methods to Verify
Certified Limit
Physical and Chemical Characteristics
63-2 - Color
63-3 - Physical State
63-4 - Odor
MP
MP
MP
MP
MP
MP
MP
MP
MP
All
All
All
All
All
All
All
All
All
Yes
Partially
Partially
Partially
Partially
Partially
Partially
Partially
partially
Bibliographic
Citation
desk reference
40553401
00164487
40553401
00148115
00164487
40553402
00148115
40553401
00164487
00096454
40553403
40553403
40553403
00148115
00096454
00164487
40553402
00164487
00148115
00096318
Must Additional Time Frame
Data be for2
Submitted? Submission
No
y
Yes
I/
Yes
§/
Yes
§/
Yes
y
Yes
§/
Yes
YeV
Sr
Yes
6 Months
6 Months
W
12 Months
12 Months
12 Months
6 Months
6 Months
6 Months
-------
TABLE B
PRODUCT SPECIFIC DATA REQUIREMENTS FOR MANUFACTURING-USE PRODUCTS CONTAINING MANEB
Data Requirement Test Use Does EPA
Substance1 Pattern Have Data?
Part 158
Subpart C - Product Chemistry
Product identity:
61-1 - Product Identity and MP
Disclosure of
Ingredients
61-2 - Description of Beginning MP
Materials and
Manufacturing Process
61-3 - Discussion of Formation MP
of Impurities
Analysis and Certification of Product
Ingredients
^62-1 - Preliminary Analysis HP
62-2 - Certification of Limits MP
62-3 - Analytical Methods to Verify MP
Certified Limit
Physical and Chemical Characteristics
63-2 - Color MP
63-3 - Physical State MP
63-4 - Odor MP
All
All
All
All
All
All
All
All
All
Yes
Partially
Partially
Partially
Partially
Partially
Partially
Partially
partially
Bibliographic Must Additional Time Frame
Citation Data be for2
Submitted? Submission
desk reference No
40553401
00164487
40553401
00148115
00164487
40553402
00148115
40553401
00164487
00096454
40553403
40553403
40553403
3/
00148115 Yes
00096454
00164487 Yes
5/
40553402 Yes
§/
00164487 Yes
y
00148115 Yes
00096318
Yes
8/
Yes2'
yes
6 Months
6 Months
W
12 Months
1 12 Months
12 Months
6 Months
6 Months
6 Months
-------
TABLE B
PRODUCT SPECIFIC DATA REQUIREMENTS FOR MANUFACTURING-USE PRODUCTS CONTAINING MANEB
Data Requirement Test Use Does EPA
Substance1 Pattern Have Data?
Bibliographic
Citation
Must Additional Time Frame
Data be for*
Submitted? Submission
Part 158
Suboart C - Product Chemistry (Continued)
Physical and Chemical Characteristics
(Continued)
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 Characteristics
Other Requirements:
64- 1 - Submittal of samples
MP
MP
MP
MP
MP
*
MP
MP
MP
MP
N/A
All
All
All
All
All
All
All
N/A
NO
Partially
Partially
Partially
NO
Partially
N/A
N/A
Partially
N/A
N/A
40553403
40553403
40553403
N/A
00164057 00164487
N/A
N/A
40553403
N/A
Yes
Yes
U/
Yes
12/
Yes
Yes
I/
Yes
_ - *
w
NO
NO
y
Yes
No
6 Months
6 Months
6 Months
6 Months
6 Months
15 Months
15 Months
2/ Data must be submitted within the time frame indicated from receipt of this package.
-------
Part 158
Subpart C.- Product Chemistry (Continued)
3/ For all formulation intermediates with the exception of the Pennwalt 86% PI (EPA Reg. No. 4581-355), complete
information must be provided regarding the nature of the process (batch or continuous), the relative amounts of
beginning materials and the order in which they are added, the chemical equations for each intended reaction,
equipment used to produce each intermediate and the fianl product, reaction conditions, the duration of each step
of the process, purification procedures, and quality control measures. In addition, the name and address of the
manufacturer, producer, or supplier of each beginning material used in the manufacture of each product must be
provided, along with information regarding the properties of those materials.
4/ A detailed discussion of all impurities that are or may be present at >0.1% based on knowledge of the beginning
materials, chemical reactions (intended and side) in the manufacturing~prccess, and any contamination during and
after production including post-production reactions among components of the product and its packaging must be
submitted for all manufacturing-use products with the exception of the Pennwalt 86% PI, EPA Reg. No. 4581-355.
V Five or more representative samples of each manufacturing-use product 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 maneb per §e using a method capable of differentiating maneb from interfering (^-liberating
impurities must be quantified. Complete validation data (accuracy and precisian) must be submitted for each
analytical method used.
6/ Upper and lower limits for the active ingredient and each intentionally added inert, and upper limits for each
impurity associated with the active ingredient present at X).l% (w/w) and each "toxicolcgically significant"
impurity associated with the active ingredient present at <0.1% (w/w) must be provided and certified for each
manufacturing-use product. Limits for impurities not associated with the active ingredient need be provided only
if they are considered to be of toxicological significance, regardless of the concentration at which they are
present. Maneb per se must be analyzed by a method capable of differentiating maneb from interfering CS2-
liberating inpirities. An explanation of how each certified limit was established must be provided (e.g. sample
analysis using validated analytical procedures, qualitative estimates based on amounts of ingredients used, etc.).
y Analytical methods must be provided for each product 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
maneb pjer. se from interfering (^-liberating impurities. For (^-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.
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Part 158
Subpart C - Product Chemistry (Continued)
8/ Physicochemical characteristics (color, physical state, odor, density, and storage stability) as required in 40
CFR 158 and more fully described in the Pesticide Assessment Guidelines, Subdivision D, must be submitted for
each formulation intermediate with the exception of the 86% Pi (EPA Reg. No. 4581-355).
9/ Data on pH and corrosiveness are required for each fornulation intermediate.
10/ Data required if the test substance is dispersible in water.
ll/ with the exception of the 86% PI (EPA Reg. No. 4581-355), data are required for each fornulation intermediate
product, if the product contains oxidizing or reducing agents.
12/ With the exception of the 86% PI (EPA Reg. No. 4581-355), data are required for each formulation intermediate
product, if the product contains combustible liquids.
13/ with the exception of the 86% PI (EPA Reg. No. 4581-355), data are required for each formulation intermediate
product if the product is potentially explosive.
14/ Data required if the product is a liquid.
15/ Data required if the product is a liquid and is to be diluted with petroleum solvents.
16/ All nitrosamines must be identified and quantified in six samples; two samples of each must be analyzed
shortly after production and 6 months after production. A method sensitive to 1 ppm of N-nitroso
contaminants must be used.
oc
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APPENDIX II
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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 CPR 156.10(e)J
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 156.10(f)J
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)l
120
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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 Tvoe 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
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)]
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 fc 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 7D. 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 Additional 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))
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)1.
1 2 I -
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SUMMARY-3
Ittm 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)l
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 CPR 156.10(h)(2)tii) 1
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.
122
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SUMMARY-*
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" oust
appear at the top of the front panel of the label. The
statement must be act In type of the sane minimum size
as required for human hazard signal word (see table In 40
CFR
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,
the following statement is required: "For retail salt
to and use only by Certified Applicators or persona
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 cay "split* your registration, i.e., register
two separate products with identical formulations, oct
bearing only unrestricted uses, and the other bearing
restricted uses. To do so, submit two applications for
rereglstratlon, each containing all forms and necessary
labels. Both applications ahould be submitted simul-
taneously. Note that the products will be assigned
separate registration numbers.
Item 9B. MISUSE STATEMENT - All products sjust btar the
misuse statement. "It is a violation of Federal law to use
this product in a Bar.ner inconsistent with ita labeling."
This statement appears at the beginning of the directions
for use. directly beneath the heading of that section.
123
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SUMMARy-5
Ittm 10A. REENTRY STATEMENT - 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.
140 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.
124
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SUMMARY-6
LABELING REQUIREMENTS OP THE PIPRA, AS AMENDED
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
r*ft> ml fMiMtrit~f
Keep Out of Reach
of Children
(Child hazard
warning)
Signal word
APPLICABILITY
OP REQUIREMENT
All products
All products
All products
All products
All products
All products
Liquid products
where dosage
given as Ibs.
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
Req. No.
Immediately
following
product name
Directly below
the main
ingredients
statement
Above signal
word
I (mediately
below child
hazard
1 **at*iaI5i— • ' •*
COMMENTS
If registrant is not the producer, mjst
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.
ro
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SUMMARY-7
ITEM
LABEL ELEMENT
Skull
APPLICABILITY
OP REQUIREMENT
PLACEMENT ON LABEL
REQUIRED
PREFERRED
COMMENTS
6 cross-
bones and word
POISON (in red)
All products
which are Cat-
egory I based
on oral, der-
mal, or inhala-
tion toxicitv
Front panel
Both in close
proximity to
signal word
7D
ro
8A
Statement of
Practical
Treatment or
First Aid
Referral
statement
Side/back panel
precautionary
statements
Hazards to
humans and
domestic
animals
Envi ronmental
hazards
products
in Categories
I, II, and III
All products
where pre-
cautionary
labeling
appears on
other than
front panel.
All products
All products
in Categories
I, II, and III
All products"
Category I:
Front panel
unless refer-
ral statement
is used.
Others:
Grouped with
side panel
precautionary
statements.
Front panel
None
None
None
Front panel
for all.
Top or side
of back panel
preceding
directions
for use
Same as above
Same as above
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.
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SUMMARY-B
ITEM
8C
9A
9B
10A
k
^ 10H
IOC
LABEL ELEMENT
Physical or
chemical
hazards
•
Restricted
block
Misuse
statement
Reentry
statement
Storatje and
disposal block
Directions
for use _
APPLICABILITY
OP REQUIREMENT
All pressurized
products, others
with eiash
points under
150*P
All restricted
products
All products
PR Notice 83-2
or as determined
bv the Aoencv
All products
All products
PLACEMENT ON LABEL
REQUIRED
None
Top center
of front
panel
I mediately
fol lowing
heading of
directions
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
PESTICIDE11 must be sane 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,
OONT/DIS, and PBST/DIS for further
information and required statements.
Hay be in metric as well as U.S. units
-------
Chapter 1—BoTironaental Protection Agency
f156.10 Labeling Requirement*
previously cited aa 1162.10
(a) General—-(1) Contents of the label. Every pesticide
product shall bear a label containing the information specified by
the Act and the 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) of this
section;
(iii) 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) and 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.
Mi) Ail required, label text m«isc*
(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
12b
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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.
(&) 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:
(j.) 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* ?o«* 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;
-------
(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
onco 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 5 162.6(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) 1C the pesticide is solid or seraisol id, viscous or
pressurized, or is a mixture of liquid and solid, the net content
statement shall be in terms 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.*
130
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(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.
(f) 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 o£
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 total
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 J1 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. (i«l»«« t-he ingredient statement i* a complete
analysis of the pesticide, the tern "analysis* shall not be used
as a heading for the ingredient statement.
(2) Position of ingredient statement. (1) 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 froii and must not be placed in the body
of other text.
131
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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-
cent }es 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 psrcentages 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 or chcxic^l 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 siser 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:
132
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Hazard Indicators
Oral ID
Inhalation LC
Darmal LO^
Eya af facts
Skin affacts
I
Up to and
Including
90 *g/kg
Up to and
Including
.2 «g/Mter
Up to and
Including
200 no/kg
Corrosive;
cornea 1 opacity
not ravarstbla
•Ithln 7 days
'
Corrosive
ToKlclty <
II
From 90 thru
900 «g/kg
From .2 thru
2 mg/l Itar
Fro* 200
thru 2000
Cornaal opacity
reversible
•Ithln 7 days;
Irritation
persisting for
7 days
Sava-a Irritation
at 72 hours
:ategerles
III
Fro* 900 thru
9000 «g/kg
F-c* 2 thru
20 •g/lltar
From 2.000 thru
20.000
No cornaaf -opacity;
Irritation
reversible
•Ithln 7 days
Moda-ata Irritation
at 72 hou-s
IV
Greater than
9000 "Q/kg
Graatar than
20 no/liter
Greater then
20.000
No Irritation
e>
1
MUd or sMght
Irritation at|
72 hours
(i) Human hazard signal word.--(A) Toxicit'y Category I. All
pesticide products meeting th« criteria of Toxicity Category X
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.heiaticr. or
front skin and eye local effects) the
in red on a
dermal toxicity (as distinct
word "Poison" shall appear
background of distinctly contrasting color and the
skull and crossbones shall appear in immediate proximity to the
word "poison.*
(B) Toxicity Category
_ II.
criteria of Toxicity Category
the signal word "Warning."
(C) Toxicity Category 111*
criteria of Toxicity Category
the signal word "Caution.*
(D) Toxicity Category IV.
criteria of Toxicity Category
the signal word "Caution."
All pesticide products meeting the
II shall bear on the front panel'
All pesticide
III shall bear
products meeting the
on the front panel
All pesticide products meeting the
IV shall bear on the front panel
133
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(E) Use of signal words. Us* 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
treatment is not required on the front panel except as described
in paragraph (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:
Size of label front panel
in square inches
Points
Requ i red
signal word,
all capitals
6
10
12
14
18
"Keep out
of reach of
Children"
6
6
8
10
12
13.4
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(2) Other required warnings and precautionary statements. The
warnings and precautionary statements as required below shall appear
together on the laoel 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.
Toxlelty
category
Precautionary statements fey toalclty category
Oral, Inhalation, or derwtal tp>lc1t>
Skin and eye local effects
.1
II
ill
IV
Fatal (poisonous) If swallowed (Inflated or
absorbed through sklnl. Do not breath*
vapor (dust! or spray •l»t|. Do not gat
In eyes, on skin, or on clothing I Front
panel statement of practical t-eat»ent
re£u*red.?.
May be fatal if Swallowed (Inhaled or
abso-bed through the sklnl. Do not breathe)
vaps-s (dust or sprat «lst|. Do not get ln|
eyes, on skin, or on clothing. lApproprlate]
first aid statements required.!. |
I
Harmful If s«allowed {Inhaled or absorbed |
through the skin). Avoid breathing vapors |
(dust or spray «1st|. Avoid contact «lth |
shin (eyes or clothlngl. (Appropriate I
first aid statement required.I.
Corrosive, causes eye and skin damage lor
skin Irritation!. Do not get In eyes, on
skin, or on ctotMng. Wear goggles or face
shield and rubber gloves when handling.
Harsful or fatal If swallowed.
(Appropriate first aid statement required.)
Causes eye {and skin} Irritation. Do net
get In eyes, on skin, or on clothing.
Harmful If swallowed. (Appropriate first
aid statement required.1.
Avoid contact with sfln, eyes or clothing.
In case of contact tiwwdlately flush
eyes or skin with plenty of water. Get
•edlcal attention If Irritation persists.
I
I
(No precautionary statements required.I. | (No precautionary statements required.I.
(ii) Environmental hazards. Where a hazard exists to non-
target organisms excluding humans and domestic animals, precautionary
statements are required stating the nature of th« hazard and the
appropriate precautions to avoid potential accident, injury or
135
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damage. Examples of the hazard statements and the circumstances
under which theyrare required follow:
(A) "If a pesticide intended for outdoor use contains an active
ingredient with a mammalian acute oral LDjo °- 100 or less, the
statement "This Pesticide is Toxic to Wildlife" is required.
(B) If a pesticide intended for outdoor use contains an active
ingredient with a fish acute LCgQ of 1 ppm or less, the statement
"This Pesticide is Toxic to Fish" is required.
(C) If a pesticide intended for outdoor use contains an active
ingredient with an avian acute oral LDgo of 100 mg/kg or less, or
a subacute dietary LCgQ 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)1? 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 the
flammability or explosive characteristics of the pesticide are
required as follows:
Flesh point
Required text
(A) PRESSURIZED CONTAINERS
Flesh point at or to low 20*Fj If there It a
flashback at any ••!«• opening.
Flash point above 20*F •** not over |0*F or It
the ftane extension Is •or* than If In. long
at • distance of • In. from the HMO.
Cxfreaely flMMbl*. Contents under pressure.
Keep a«ay fro* lire, sperks, end heated
Surfeees* Do not puncture or Inclnerete
container. Exposure to temperatures above
Fle*
-------
(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.
(iii) 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~bnly 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;
(2) The product will not come into the hands of the general
public except after incorporation into finished products; and
(4) 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:
U) The label clearly states that the product is for use only
by physicians or veterinarians;
(2) The Administrator determines that such directions are not
nece~ssary to prevent unreasonable adverse effects on man or the
environment; and
O) 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:
(1) There is information readily available to the formulators
on Fhe composition, toxicity, methods of use, applicable restrictions
or limitations, and effectiveness of the product for pesticide
purposes;
137
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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
involved;
(2) The product as finally manufactured, formulated, mixed, or
repackaged is registered; and
(.4) The Administrator determines that such directions are not
necessary to prevent unreasonable adverse effects on man or the
environment.
(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."
(ii) 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 § 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)
(£) 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.
138
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(F) Other pertinent information which the Administrator
determines to be necessary for the protection of, man and the
environment.
(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)(l) 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 S 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) classified restricted shall bear statements
of restricted use classification on the front panel as described
below:
(i) Front 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 terms 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 Cor the terms of restriction by regulation,
(k) Advertising. [Reserved]
(40 PR 28268, July 3, 1975; 40 FR 32329, Aug. 1, 1975} 40 FR
38571, Aug. 21, 1975, as amended at 43 FR 5786, Feb. 9, 1978]
139
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PHYS/CHEM-1
Criteria
PHYSICAL/CHEMICAL HAZARDS
Required Label Statement
I. Pressurized Containers
A. Flashpoint at or below
20»Ff 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.
C. All Other Pressurized
Containers
II. Non-Pressurized Containers
A. Flashpoint at or below
20BF.
B. Flashpoint above 20*F
and not over 80*F.
C. Flashpoint over 80*P
and not over 150*F*
0. Flashpoint above
150»F.
Extremely flammable.
Contents under pressure.
Keep away from fire, sparks,
and heated surfaces. 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.
140
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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 ttve 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.
141
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CONT/DXS-1
CONTAINER DISPOSAL INSTRUCTIONS
Tht 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, canst 1ars)
Non-aerosol products
(baqs)
Aerosol products
Do not reuse container (bottle, can, jar).
Rinse thoroughly before discarding 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 instructions,
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 I
for recycling or reconditioning, or puncture
and dispose of in a sanitary landfill* or by
other procedures approved by state and local
authorities.
Triple rinse (or equivalent). Then offet
for recycling or reconditioning, or puncture
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
reused1, 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)
\J Manufacturer may replace this phrase with one indicating
whether and how fiber drum may be reused.
42
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PEST/DIS-1
PESTICIDE DISPOSAL INSTRUCTION;
The label of all products, except those intended solely for domestic
use, nust 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.11
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."
143
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APPENDIX III
-------
BIBGUIDE-1
GUIDE TO USE OF THIS BIBLIOGRAPHY
t
1. CONTENT OF 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 Co be used whenever specific reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier
(MRID), each entry consists of 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.
145
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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 narks, 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 permit
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 la 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.
146
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Maneb Standard
MRID CITATION
00002931 Keppel, G.E. (1971) Collaborative study of the determination of
Dithiocarbamate residues by a modified Carbon disulfide
evolution method. Journal of the AOAC [Association of Official
Analytical Chemists] 54(3):528-531. (Also in unpublished
submission received on unknown date under OF0939; submitted by
Unircyal Chemical, Bethany, Conn.; CDL:094582-G)
00036935 Atkins, E.L.; Greywood, E.A.; Macdonald, R.L. (1975) Toxicity of
Pesticides and Other Agricultural Chemicals to Honey Bees: Labo-
ratory Studies. By University of California, Dept. of Entomolo-
gy. ?: UC, Cooperative Extension. (Leaflet 2287; published
study.)
00040149 Gordon, ?; et al. (1967) [Without title]. Journal of the Associa-
tion of Official Analytical Chemists 50(5):1103-1108. (Incom-
plete article dealing with Ethylenebisdithiccarbamate residues;
also in unpublished submission received Apr 3, 1972 under
2F1258; submitted by Rohm & Haas Co., Philadelphia, Pa.; CDL:
095544-C)
00041799 Lowen, W.K. (1953) Analysis of Manganese ethylenebisdithiocarba-
mate compositions and residues. Journal of the Association of
Official Agricultural Chemists 36(2):484-493. (Also in unpub-
lished submission received Jun 15, 1955 under PP0021; submitted
by E.I. du Pont de Nemours & Co., Inc., Wilmington, Del.; CDL:
090020-D) •
00041800 Lowen, W.K. (1951) Determination of Dithiocarbamate residues on
food crops. Analytical Chemistry 23(12):1846-1850. (Also in
unpublished submission received Jun 15, 1955 under PP0021; sub-
mitted by E.I. du Pont de Nemours & Co., Inc., Wilmington, Del.;
CDL:090020-E)
00088826 Nash, R.G. (1976) Uptake of ethylenebis(dithiocarbamate) fungicides
and ethylenethiourea by soybeans. Journal of Agricultural and
Food Chemistry 24(3):596-601. (Also in unpublished submission
received Dec 9, 1981 under 707-78; submitted by Rohm & Haas
Co., Philadelphia, Pa.; CDL:070528-H)
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)
\f.7
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Maneb Standard
MRID CITATION
00088923 Rhodes, R.C. (1977) Studies with manganese [14:C]ethylenebis(di-
thiocarbamate) (H4:C]maneb) fungicide and [14:C]ethylenethio-
urea ([14:C]ETU) in plants, soil, and water. Journal of Agri-
cultural and Food Chemistry 25(3):528-533. (Also in unpublished
submission received Dec 9, 1981 under 707-78; submitted by Rohm
& Haas Co., Philadelphia, Pa.; CDL:070525-I)
00088931 Fletcher, C.L.; Fries, G.F.; Helling, C.S.; et al. (1973) Research
on Ethylene-bis-dithiocarbamate (EBDC) Fungicides and Ethylene-
thiourea (ETU). Progress rept. II, Feb 21, 1973. (U.S. Agri-
cultural Research Center, Agricultural Environmental Quality
Institute, Pesticide Degradation Laboratory; unpublished study;
CDL:070527-E)
00090132 Rohm & Haas Company (1962) [Residues of Dithane M-45 on Bananas].
Includes method dated Apr 12, 1962 and method 852-2 dated Aug 2,
1955. (Compilation; unpublished study, including letter dated
May 8, 1961 from R.T Schuckert to Dr. Swisher, Mr. Kampmeier,
Dr. Levesque, et al., received Aug 1, 1962 under PP0374; CDL:
090403-C)
00090152 Rohm & Haas Company (1961) Residue and Analytical Method. Includes
method dated Aug 26, 1960. (Compilation; unpublished study
received Jan 9, 1961 under PP0270; CDL:090293-A)
00090174 Pease, H.L. (1957) Determination of dithiocarbamate fungicide res-
idues. Journal of the Association of Official Agricultural
Chemists 40(4):1113-1118. (Also in unpublished submission re-
ceived Oct 20, 1960 under PP0278; submitted by E.I. du Pont de
Nemours & Co., Inc., Wilmington, Del.; CDL:090300-C)
00096318 E.I. du Pont de Nemours annd Company, Incorporated (1982) Product
Chemistry Data Supporting the Registration of du Pont Mancozeh
Composition. Includes methods M 15.755 (R) dated Aug 14, 1980;
M 15.752 (E) dated Oct 3, 1980; M21.852 dated Dec 26, 1963; and
others. (Compilation; unpublished study received Feb 19, 1982
under 352-402; CDL:246838-A)
00096454 E.I. du Pont de Nemours & Company, Incorporated (1982) [Product
Chemistry Data of Maneb]. Includes method M 15.752 (E) dated
Oct 3, 1980; method no. M21.852 dated Dec 26, 1963; method no.
M 20.579 (E) dated Aug 27, 1979; and others. (Compilation; un-
published study received Feb 19, 1982 under 352-517; CDL:
246896-20
148
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Maneb Standard
MRID CITATION
00097198 Rohm & Haas Company (1971) Results of Tests on the Amount of Res-
idue Remaining on or in Bananas, Including a Description of the
Method for Determining Residues: [Maneb]. (Compilation; unpub-
lished study received Sep 23, 1972 under 2F1257; CDL:091788-B)
00097240 McCann, J.A.; Pitcher, F. (1973) [Dithane M-22: Bluegill (Lepomis
macrochirus)]: Test No. 541. (U.S. Environmental Protection
Agency, Pesticides Regulation Div., Animal Biology Laboratory?
unpublished study; CDL:128296-A)
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 Now 16, 1965
under unknown admin, no.; submitted by FMC Corp., Philadelphia,
Pa.; CDL:120299-A)
00098651 Truslow Farms, Incorporated (1975) Final Report: Eight-day Dietary
LC:50—Mallard Ducks: Project No. 112-106. (Unpublished study
received May 9, 1975 under 352-173; submitted by E.I. du Pont
de Nemours & Co., Inc., Wilmington, Del.; CDL:165044-B)
00104264 Fink, R. (1975) Final Report: Eight-day Dietary LC:50—Bobwhite
Quail: Project No. 112-105. (Unpublished study received May
9, 1975 under 352-173; prepared by Truslow Farms, Inc., sub-
mitted by E.I. du Pont de Nemours & Co., Inc., Wilmington, Del.;
CDL:165044-C)
00128936 Terrell, Y.; Bonn, R.; Osattin, M. (1983) Acute Dermal LD50 of
Clean Crop Maneb Plus on New Zealand Albino Rabbits: Project
No. 3F-9102. Final rept. (Unpublished study received Jun 10,
1983 under 34704-240; prepared by Cannon Laboratories, Inc.,
submitted by Platte Chemical Co., Fremont, NB; CDL:250496-A)
00128937 Terrell, Y.; Bonn, R. (1983) The Effect of Clean Crop Maneb Plus
on the Eye Mucosa of New Zealand Rabbits: Project No. 3F-9104.
Final rept. (Unpublished study received Jun 10, 1983 under
34704-240; prepared by Cannon Laboratories, Inc., submitted by
Platte Chemical Co., Fremont, NB; CDL:250496-B)
00128938 Terrell, Y.; Bonn, R. (1983) The Primary Dermal Irritation Study
of Clean Crop Maneb Plus on Abraded and Ncnabraded Skin of New
Zealand Albino Rabbits: Project No. 3F-9103. Final rept. (Un-
published study received Jun 10, 1983 under 34704-240; prepared
by Cannon Laboratories, Inc., submitted by Platte Chemical Co.,
Fremont, NB; CDL:250496-C)
149
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Maneb standard
MRID CITATION
00129749 Terrell, Y.; Bohn, R. (1983) Acute Oral LD50 of Clean Crop Maneb
Plus in Sprague Dawley Rats: Project No. 3F-9102. Final rept.
(Unpublished study received Jun 10, 1983 under 34704-240; pre-
pared by Cannon Laboratories, Inc., submitted by Platte Chemical
CO., Fremont, NB; CDL:250496-D)
00129750 Terrell, Y.; Bohn, R. (1983) Acute Inhalation Toocicity Study of
Clean Crop Maneb Plus in Sprague Dawley Rats: Project No. 3F-
9105. Final rept. (Unpublished study received Jun 10, 1983
under 34704-240; prepared by Cannon Laboratories, Inc., submit-
ted by Platte Chemical Co., Fremont, NB; CDL:250496-E)
00129979 Leuschner, F.; Leuschner, A.; Klie, R.? et al. (1979) Chronic Oral
Tcocicity of Manganese-ethylene-l,2-bis-dithiccarbamate, 90%—
Called for Short—Maneb—in Sprague-Dawley (SIV 50) Rats (with
Special Attention to Carcinogenic Properties). (Unpublished
study received Oct 14, 1980 under unknown admin, no.; prepared
by Labor at or ium fur Pharmakologie und Tcocikologie, W. Ger.,
submitted by Rohm & Haas Co., Philadelphia, PA; CDL:250914-A)
00129980 Leuschner, P.; Leuschner, A.; Schneider, C.; et al. (1977) Oral
Toxicity of Manganese Ethylene-l,2-bis-dithiocarbamate, 90%, In-
ternal No. WF 1172—Called for Short Maneb—in the Rhesus Man-
Key (Repeated Dosage for Six Months). (Unpublished study re-
ceived Oct 14, 1980 under unknown admin, no.; prepared by Labo-
4 ratorium fur Pharmakologie und Toxikologie, W. Ger., submitted
by Rohm & Haas Co., Philadelphia, PA; CDL:250915-A)
00141264 Conine, D. (1984) Delayed Contact Hypersensitivity Study in Guinea
Pigs of Clean Crop 80% Maneb 2% Zinc: Hill Top Research Project
No. 84-0142-21. Unpublished study prepared by Hill Top Research
Inc. 16 p.
00148115 Pennwalt Corp. (1985) Product Chemistry: Maneb 80 Fungicide. Un-
published study. 55 p.
00149570 Ivett, J. (1985) Clastogenic Evaluation of Maneb Technical, Lot
MT 01 (88.1%, a.i.) in the Rat Bone Marrow Cytogenetic Assay:
Final Report: LSI Project No.: 22202. Unpublished study
prepared by Litton Bionetics, Inc. 31 p.
00151415 BASF Wyandotte Corporation (1985) Maneb Product Chemistry Data
Supporting EPA Reg. No. 7969-11. Unpublished compilation.
48 p.
150
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Maneb Standard
MRID CITATION
00153352 Puhl, R. (1985) Metabolism of Radiolabeled Maneb in Rats: Study No.
6181-101. Unpublished study prepared by Hazleton Laboratories
America, Inc. 80 p.
00153475 Puhl, R. (1985) Dermal Absorption of Radiolabelled Maneb in Male
Rats: Final Report: Study No. 6181-100. Unpublished study pre-
pared by Hazleton Laboratories America, Inc. 49 p.
00159847 Weete, J. '(1986) Report to the Maneb Task Force on Metabolism of
[Carbon 14] Maneb in Potato Plants. Unpublished study prepared
by Auburn Univ., Dept of Botany, Plant Pathology, and Microbio-
logy. 40 p.
00159848 Weete, J. (1986) Report to the Maneb Task Force on Metabolism of
[Carbon 14] Maneb in Bean Plants. Unpublished study prepared
by Auburn Univ., Dept of Botany, Plant Pathology, and Microbio-
logy. 40 p.
00159849 Weete, J. (1986) Report to the Maneb Task Force on Metabolism of
[Carbon 14] Maneb in Tomato Plants. Unpublished study prepared
by Auburn Univ., Dept. of Botany, Plant Pathology, and Microbio-
logy. 41 p.
00159850 Weete, J. (1986) Report to the Maneb Task Force on Metabolism of
[Carbon 14] Maneb in Lettuce Plants. Unpublished study prepared
by Auburn Univ., Dept. of Botany, Plant Pathology, and Microbio-
logy. 38 p.
00159851 LeVan, L. (1986) Biodistributicn of [Carbon 14]-Maneb in Lactating
Goats: Final Report: Study No. 6181-102. Unpublished study
prepared by Hazleton Laboratories America, Inc. 87 p.
00159852 LeVan, L. (1986) Biodistributicn of [Carbon 14]-Maneb in Laying
Hens: Final Report: Study No. 6181-103. Unpublished study
prepared by Hazleton Laboratories America, Inc. 76 p.
00161800 BASF Corp. (1986) Maneb Technical: [Product Chemistry]. Unpublish-
ed study. 64 p.
00162084 Ulrich, C. (1986) Thirteen Week Subchrcnic Inhalation Toxicity
Study en Maneb in Rats - Final Report: Study No. 550-001. Un-
published study prepared by International Research and Develop-
ment Corp. 343 p.
00163335 Blair, J. (1986) Anaerobic Aquatic Metabolism of 14C-Maneb. Unpublished
study prepared by Hazel ton Laboratories.
151
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Maneb Standard
MRID CITATION
00164057 Pennwalt Corp. - Agchem Div. (1986) Maneb Technical: Complete
Product Chemistry Data Required under the EPA Data Call-in
Notice of October 19, 1984. Unpublished compilation. 164 p.
00164487 Pennwalt Corp. (1986) Maneb Technical: Storage Stability.
Unpublished study 2 p.
40091301 Thomas, M. (1986) In vitro Sister Chronatid Exchange Assay in
Cultured Chinese Hamster Ovary (CHO) Cells Treated with Techni-
cal Grade Maneb: Final Report: Project No. 850047-30. Unpub-
lished study prepared by American Bicgenics Corp. 19 p.
40091303 Thomas, M. (1986) CHO/HGPRT In vitro Mammalian Cell Mutation Assay
on Technical Grade Maneb: Final Report: Project No. 850047-10.
Unpublished study prepared by American Biogenics Corp. 23 p.
40163901 Loveday, K. (1986) In Vitro Unscheduled DNA Synthesis Assay in Rat
Hepatocytes: The Effect of Technical Grade Maneb: Final Report:
Project No.: 850047-20. Unpublished study prepared by American
Bicgenics Corp. 14 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 [Carbcn 14]-Ethylenethiourea: ABC Final Report No. 36287.
Unpublished study prepared by Analytical Bio-Chemistry Labs.,
Inc. 543 p.
40553401 Kool, P. (1988) Maneb Technical: Product Chemistry: Project ID:
MANEB61. Unpublished compilation prepared by Pennwalt Holland
B.V. 27 p.
15
r.o
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OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Maneb Standard
MRID CITATION
40553402 Kool, p. (1988) Maneb Technical: Product Chemistry: Project ID:
MANEB62. Unpublished compilation prepared by Pennwalt Holland
B.V. 41 p.
40553403 Kool, P. (1988) Maneb Technical: Product Chemistry: MANEB63. Unpu-
blished coirpilaticn prepared by Pennwalt Holland B.V. 10 p.
153
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APPENDIX XV
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FIFKA SECTION 3(C)(2)(B) SUMMARY SHEET
EPA REGISTRATION NO.
PRODUCT NAME
APPLICANTS 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
01. I wOl 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 I will use:
O2. I have entered into an agreement with one or more other registrants under FIFRA section 3(C)(2)(B)Hi) to satisfy the following data
requirements. The tests, and any required protocols, will be submitted to EPA by:
NAME OF OTHER REGISTRANT
D3. 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:
O4. I request that you amend my registration by deleting the following uses (this option is not available to applicants for new products):
OS. I request voluntary cancellation of the registration of this product. (This option is nor mibble to applicants for new products.)
REGISTRANTS AUTHORIZED REPRESENTATIVE
SIGNATURE
DATE
EPA Form 858O-1 (10-82)
155
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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:
11) I have read and am familiar with the terns 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.
t3) 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 .
TV firm will apply for an amendment to the registration prior to'changing the source
of the active Ingrediefit In our product.
(4) I understand, and agree on behalf of my firm, that 1f at any time any portion of
this Statement is no longer true, or if my firm fails to comply with the undertakings made
1n this Statement, my firm's product's registration may be suspended under FIFRA Section
3(c)(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 registrants) who have committed to generate and submit the
required data fall 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 1n 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, 1n
such cases, the Agency generally will not grant a time extension for submitting the data.
Registrant's authorized representative:
(Signature
Dated:
ITypedj
IPA Fora 8570-27 ' \ £>fc
-------
OMB Approval' No.
2070-0057
Expires 11/30/89
IPA Reg. No.
PRODUCT SPECIFIC DATA REPORT
Date
Guidance Document for
"Registration
Guideline No.
Sec. 153.120
PRODUCT
CHEMISTRY
61-1
61-Z
bl-J
62-1
62-2
62-3
63-2
63-3
63-4
63-5
63-6
63-/
63-8
63-9
63-10
63-11
63-12
Name of Test
Identity of
Ingredients
Statement of
composition
Discussion of
formation of
Ingredients
Preliminary
analysis
Certification of
limits
Analytical methods
for enforcement
limits
Color
Physical state
Odor
Melting point
Boiling point
Density, bulk-
density, or
specific gravity
Solubility
Vapor pressure
Dissociation
constant
Test not
required
for my
product
listed
above
(check
below)
Oc ta no l /water j
partition !
coefficient j
pH i
i i
I am complying with !
data requirements by j
citing nkID
Number or
EPA Accession
Number
isubmit-i
ting }
Data ! (For EPA Use Only)
(At- I Accession Numbers
tached) ! Assigned
i
i
• >
•
•
i
•
•
•
•
•
•
!
•
t
•
! ~~
•
•
i
•
•
i
i
*
i
i
•
j
•
i
•
i
•
i
!
!
£PA Form 8580-4
157
-------
OMB Approval No.
2070-0057
Expires 11/30/89
EPA Reg. No.
PRODUCT SPECIFIC DATA REPORT (confd)
Date
Guidance Document for
Registration
Guideline No.
Sec. lbB.120
PRODUCT
CHEMISTRY
(conf d)
63-13
•03-14
63-15
63-16
63- 1/
63-lb
63-19
63-2U
_.
63-21
sec. it>b.i3b
TOXICOLOGY
01-1
01-Z
01-3
01-4
01-5
81-6
01-7
i
! '
!
i
Name of Test
stability
oxi di zi ng/reduci ng
reaction
Flammabi nty
Explodabi nty
Storage stabi Mty
Viscosity
Mi sci bi lity
corrosion
characteristics
Dielectric break-
down voltage
Acute oral
toxlclty. rat
Acute dermal
toxlclty, rabbit
Acute inhalation,
toxlclty, rat
Primary eye
Irritation, rabbit
Primary dermal
Irritation
Dermal sensitiza-
tlon,
Acute Delayed
neurotoxiclty, hen
Test not!
required
for my
product
listed
above
(check
below)
i
i
I am complying with !
data requirements by I
citing NKID J submit-;
Number or Sting J
EPA Accession! Data !(For EPA Use Only)
Number !(At- {Accession Numbers
itached)! As signed
i
i
!.-
i
i
•
•
•
•
•
i
1
1
1
1
•
i
•
i
• *•
i
•
i
i
!
•
1
i
i
•
•
•
•
•
•
i
!
£PA Fora 8580-4 (confd)
-------
OMBN*.«OTO«B7.
fTo qtmfffy. ctrtffvALL four torn*;
CERTIFICATION OF ATTEMPT TO ENTER
INTO AN AGREEMENT WITH OTHER REGISTRANTS
FOR DEVELOPMENT OF DATA
1. I am duly authorized to represent the following firm(s) who are subject to the require-
menu of a Notice under FIFRA Section 3(c)(2)(B) contained in a Guidance Document
to submit data concerning the active ingredient:
GUIDANCE DOCUMENT DATE
ACTIVE INGREDIENT
NAME OF FIRM
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 enter
into an agreement with one or more other registrants to develop jointly, or to share in the cost of developing, the following required
hems or data:
3. My firm tits offered in writing to inter into such in agreement Copies of the offen «re ittiched. That offer was irrevocable and included an offer to bt
bound by an arbitration decision under F IF RA Section 3(c)(2)(B)(iiil if final igreement on all terms could not be reached otherwise. This offer wu mide
to the following firm(s) on the following date(s):
NAME OF FIRM
DATE OF OFFER
However, none of those firm (si accepted my offer.
4. "Wry firm requests that EPA not suspend the registration(s) of my firm's product(s), if any of the firms named in paragraph (3) above
have agreed to submit the data listed in paragraph (2} above in accordance with the Notice. I understand EPA will promptly inform
me whether my firm must submit data to avoid suspension of its registration(s) under FIFRA Section 3(c)(2)(B). (This statement
not apply to applicants for new products.) I give EPA permission to disclose this statement upon request.
TYPED NAME
SIGNATURE
DATE
£PA Form B5SO-6 11O42J
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