United States Office of Prevention, Pesticides
Environmental Protection And Toxic Substances
Agency (H-7508W)
SEPA Reregistration
Eligibility Document
(RED)
Streptomycin and
Streptomycin Sulfate
-------
0 — iJ1
* \ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
30 1992
OFFICE OF
C£/?r/F/ED MAIL
Dear Registrant:
I am pleased to announce that the Environmental Protection Agency (the "Agency") has
completed its reregistration eligibility decision on the pesticide active ingredients streptomycin
and streptomycin sulfate.
Enclosed is a Reregistration Eligibility Document (RED) for the pesticide active
ingredients streptomycin and streptomycin sulfate, hereafter referred to as streptomycin. The
RED is the Agency's evaluation of streptomycin's and streptomycin sulfate's data base, its
conclusions regarding human and environmental risks associated with the current product uses,
and its decisions and conditions under which uses and products will be eligible for
rereregistration. Also enclosed is the EPA RED facts and the Pesticide Reregistration
Handbook which provides instructions to registrants on how to respond to any labeling and data
requirements specified in the RED and how to reregister products.
The RED identifies outstanding product specific data requirements for end-use products
and manufacturingruse products. These requirements are listed on the Requirements Status and
Registrant's Response Form, which, along with the Data Call-In Response Form listing all of
your company's products subject to the RED, is included as an Attachment. Instructions for
completing both forms are contained in the RED package. All product specific data must be
submitted and found acceptable by the Agency before a product can be reregistered.
Generic data requirements usually will have been fulfilled prior to making a reregistration
eligibility decision. However, there may be some instances where additional generic data are
required. If generic data requirements need to be fulfilled, all registrants must complete the
appropriate Data Call-In Response Form and Requirements Status and Registrant's Response
Form. These forms are in the appendices to the RED.
The RED identifies any specific labeling requirements such as restricted use classifica-
tion, groundwater hazard statements, endangered species precautions, etc., necessary for reregis-
tration based on a review of the generic data for the active ingredient. In addition, in order to
HyD Printed on Recycled Paper
-------
be reregistered, all product labeling must be in compliance with format and content labeling as
described in 40 CFR §156.10 and all labeling changes imposed by Pesticide Regulation (PR)
Notices, and any label changes imposed by 'this RED. j
/ '! • . '-"A
The Pesticide Reregistration Handbook contains detailed instructions for compliance with
the RED and must be followed carefully. There are several key points to remember in preparing
your response to the RED:
Within 90 Days of Your Receipt of this Letter
1. For each product which is subject to this RED, you must complete, sign and submit
the data call-in (DCD response forms attached to the RED [Appendix G, Attachments
B and C, has forms for product specific data]. Follow the instructions in Attachments
B and C for completing those forms and submit the forms to the appropriate address
specified in the Data Call-Ins. Note that the DCI forms for generic data are to be
sent to the Special Review and Reregistration Division (use the mailing distribution
code RED-SRRD-0169 for your generic response). The DCI forms for product
specific data are to be sent to the Registration Division (use the mailing distribution
code RED-RD-PM21 for your product specific response).
2. No tune extensions will be granted for submitting the 90-day responses. If the
Agency does not receive a response for a product, it may issue a Notice of Intent to
Suspend (NOIS) for that product.
3. Any requests for data waivers or time extensions to the 8-month deadline must be
submitted as part of your 90-day response. Such requests will generally not be
considered if submitted later than the 90-day response.
Within 8 Months of the Date of this Letter
1. For each product, you must submit a completed Application for Reregistration (EPA
Form 8570-1), five copies of the label and labeling revised as specified by the RED and
in accordance with current requirements, two completed copies of the Confidential
Statement of Formula (CSF) (EPA Form 8570-4), a completed Certification with
Respect to Citation of Data (EPA Form 8570-31), and data or references to data (see
item 2 below).
2. You must submit or cite the required product specific data as part of your commit-
ment for reregistration. For most products, you will probably be citing data which have
already been submitted to the Agency. In these cases, you must submit a list of the
studies and the corresponding EPA identifier numbers (i.e., ACCESSION or MRID
numbers). Before citing these studies, you must make sure that they meet the
Agency's current acceptance criteria (Appendix F, Attachment E). Be sure to follow
-------
data formatting requirements in P.R. Notice 86-5. Failure to adequately comply with
the data requirements specified in this RED may result in the Notice of Intent to Suspend
your product.
3. The labeling and CSF which you submit for each product must comply with P.R. Notice
91-2 (Appendix D). That Notice requires that the amount of active ingredient declared
in the ingredient statement must be stated as the nominal concentration rather than the
lower certified limit. You have two options for submitting a CSF: (1) accept the
standard certified limits (see 40 CFR §158.175) or (2) provide certified limits that are
supported by the analysis of five batches. If you choose the second option, you must
submit or cite the data for the five batches along with a certification statement as
described in 40 CFR §158.175(e).
4. Send your Application for Registration to the Registration Division Product Manager
21 (PM 21) who is assigned to the product, Susan T. Lewis. Use the correct address
shown on page 6 of the enclosed Product Reregistration Handbook (Appendix E). Note
that the mailing distribution code for your response is RED-RD-PM21.
Questions on product specific data requirements and labeling (for both End-use and
Manufacturing-use products) should be directed to the Registration Division Product Manager
21 Team member for streptomycin and streptomycin sulfate, Benjamin C. Chambliss at (703)
305 - 7382. Questions on the generic data requirements should be directed to Theresa A.
Stowe, the Chemical Review Manager in the Special Review and Reregistration Division at
(703) 308 - 8043.
The Agency is prepared to meet with any registrants who have questions about respond-
ing to the streptomycin RED. If you wish to meet with the Agency, you must contact Mr.
Chambliss within two weeks of your receipt of the RED. The Agency intends to have one
combined meeting with interested registrants. If there are any requests for such a meeting, the
Agency will notify all registrants who requested a meeting of the date, location and time.
Requests for a meeting will not extend the 90-day or 8-month response deadlines.
Sincerely yours,
Daniel M. Barolo, Director
Special Review and
Reregistration Division
Enclosures
-------
REREGISTRATION ELIGIBILITY DOCUMENT
STREPTOMYCIN AND STREPTOMYCIN SULFATE
LIST A
CASE 0169
September, 1992
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
SPECIAL REVIEW AND REREGISTRATION DIVISION
WASHINGTON, D.C.
-------
GLOSSARY OF TERMS AND ABBREVIATIONS
ADI
a.i.
ARC
CAS
CSF
EEC
EP
EPA
FIFRA
FFDCA
HDT
LC50
LD
50
LOT
LEL
MP
Acceptable Daily Intake. Also known as Reference Dose or RfD.
Active Ingredient
Anticipated Residue Contribution
Chemical Abstracts Service
Confidential Statement of Formula
Estimated Environmental Concentration. The estimated pesticide concentration
in an environment, such as a terrestrial ecosystem.
End-Use Product
U.S. Environmental Protection Agency
Federal Insecticide, Fungicide, and Rodenticide Act
Federal Food, Drug, and Cosmetic Act
Highest Dose Tested
/"'
Median Lethal Concentration. A statistically derived concentration of a substance
that can be expected to cause death in 50% of test animals. It is usually express-
ed as the weight of substance per weight or volume of water or feed, e.g., mg/1
or ppm.
Median Lethal Dose. A statistically derived single dose that can be expected to
cause death in 50% of the test animals when administered by the route indicated
(oral, dermal, inhalation). It is expressed as a weight of substance per unit
weight of animal, e.g., mg/kg.
Lowest Dose Tested
Lowest Effect Level
Manufacturing-Use Product
-------
GLOSSARY OF TERMS AND ABBREVIATIONS (cont.)
MRID Master Record Identification (number). EPA's system of recording and tracking
studies submitted.
N/A Not Applicable
NPDES National Pollutant Discharge Elimination System
NOEL No Observed Effect Level
OPP Office of Pesticide Programs
PADI Provisional Acceptable Daily Intake
ppm Parts Per Million
RfD Reference Dose
RS Registration Standard
TMRC Theoretical Maximum Residue Contribution
11
-------
TABLE OF CONTENTS
GLOSSARY
EXECUTIVE SUMMARY
I. INTRODUCTION
II. CASE OVERVIEW
A. CHEMICAL OVERVIEW
B. USE PROFILE
C. ESTIMATED USAGE OF THE PESTICIDE STREPTOMYCIN
D. DATA REQUIREMENTS
D. REGULATORY HISTORY
HI. SCIENCE ASSESSMENT OF STREPTOMYCIN
A. PRODUCT CHEMISTRY ASSESSMENT
B. HUMAN HEALTH ASSESSMENT
1. Toxicology Assessment
a. Acute Toxicity
b. Subchronic Toxicity
c. Chronic Toxicity
d. . Developmental Toxicity
e. Reference Dose (RfD) for Chronic Oral Exposure
f. Antibiotic Resistance
g. Human Data
2. Exposure Assessement
a. Dietary Exposure
b. Occupational and Residential Exposure
3. Risk Assessment
in
-------
C. ENVIRONMENTAL ASSESSMENT
1. Environmental Fate
2. Ecological Effects
a. Ecological Hazard
b. Ecological Effects Risk Assessment
IV. RISK MANAGEMENT AND REREGISTRATION DECISION OF
STREPTOMYCIN
A. DETERMINATION OF ELIGIBILITY
1. Eligibility Decision
. . 2. Eligible and Ineligible Uses
B. REGULATORY POSITION
1. Tolerance Reassessment
2- Labeling Rationale
V. ACTIONS REQUIRED BY REGISTRANTS
A. MANUFACTURING-USE PRODUCTS
1. Additional Generic Data Requirements
2. Labeling Requirements for Manufacturing-Use Products
B. END-USE PRODUCTS
1. Additional Product Specific Data Requirements
2. Labeling Requirements for End-Use Products
VI. APPENDICES
APPENDIX A - Table of Use Patterns Subject to Reregistration
APPENDIX B - Table of the Generic Data Requirements and Studies Used to Make the
Reregistration Decision
APPENDIX C - Streptomycin Bibliography: Citations Considered to be Part of the Data
Base Supporting the Reregistration of Streptomycin
iv
-------
APPENDIX D - List of Available Related Documents
APPENDIX E - Pesticide Reregistration Handbook
APPENDIX F - Generic Data Call-In
Attachment A - Generic Chemical Status Sheet
Attachment B - Generic DCI Response Forms (Form A) plus Instructions
Attachment C - Generic DCI Requirements Status and Registrant's Response
Forms (Form B) plus Instructions
Attachment D - List of all Registrant(s) sent the Generic and Product Specific DCI
Attachment E - EPA Acceptance Criteria
Attachment F - Generic DCI Cost Share/Data Compensation Forms
APPENDIX G - Product Specific Data Call-In
Attachment A - Product Specific DCI Chemical Status Sheet
Attachment B - Product Specific DCI Response Forms (Form A) plus Instructions
Attachment C - Product Specific DCI Requirements Status and Registrants'
Response Forms (Form B) plus Instructions
Attachment D - EPA's Grouping of End-Use Products for Meeting Acute
Toxicology Data Requirements
Attachment E - Product Specific Data Call-In Cost Share and Data Compensation
Forms
-------
EXECUTIVE SUMMARY
Streptomycin is a human antibiotic drug which is also currently registered in the United
States for use as an antibiotic bactericide/bacteriostat, fungicide, and algicide. The registrations
containing streptomycin as an active ingredient control bacterial and fungal diseases of selected
fruit, vegetables, seed, specialized field crops, and ornamental crops, and algae in ornamental
ponds and aquaria. This Reregistration Eligibility Document (RED) addresses the eligibility for
reregistration of products containing streptomycin for control of bacteria, fungi and algae. The
formulations of streptomycin are dust, wettable powder, wettable powder/dust, and pelleted/
tableted.
A Registration Standard for streptomycin and streptomycin sulfate, hereafter referred to
as streptomycin, was issued in September, 1988 (NTIS PB89-129738). The Registration
Standard summarized the available data supporting the reregistration of products containing
streptomycin used for the control of bacteria, fungi and algae. The Registration Standard
required additional data to assure that the proper use of the pesticide posed no potential adverse
effects to man or the environment. The Agency has completed its review of the streptomycin
data base including the data submitted in response to the 1988 Registration Standard.
The Agency has determined that the use of streptomycin to control bacteria, fungi and
algae will not cause unreasonable risk to man or the environment and all uses are eligible for
reregistration. However, the Agency is requiring certain other generic data to be submitted.
These data include product chemistry on the technical formulation, a hydrolysis study, and an
invertebrate toxicity study. The Agency regards these data as necessary to confirm the
reregistration eligibility decision put forth in this document. Reregistration of all products will
proceed in the absence of the confirmatory data noted above. Although the Agency does not
anticipate any changes in its regulatory position based on these confirmatory data, if the product
chemistry, hydrolysis, and invertebrate toxicity data identify a risk that requires modification of
the reregistration eligibility decision, the Agency will publish its rationale in the Federal Register
(FR) and notify all affected registrants of its decision.
Before reregistering the applicable products, the Agency is requiring that product specific
data, revised Confidential Statements of Formula (CSF), and labeling be submitted within 8
months of the issuance of this document. These data include product chemistry for each
registration and acute toxicology testing. After reviewing these data and the revised labels, the
Agency will reregister a product based on whether or not that product meets the requirements
in Section 3(c)(5) of FIFRA. Those products which contain other active ingredients will be
eligible for reregistration only when the other active ingredients are determined to be eligible
for reregistration.
-------
I. INTRODUCTION
In 1988, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was
amended to accelerate the reregistration of products with active ingredients registered
prior to November 1, 1984. The amended Act provides a schedule for the reregistration
process to be completed in nine years. There are five phases to the reregistration
process. The first four phases of the process focus on identification of data requirements
to support the reregistration of an active ingredient and the generation and submission
of data to fulfill the requirements. The fifth phase is a review by the U.S.
Environmental Protection Agency (referred to as "the Agency") of all data submitted to
support reregistration.
FIFRA Section 4(g)(2)(A) states that in Phase 5 "the Administrator shall
determine whether pesticides containing such active ingredient are eligible for
registration" before calling in data on products and either reregistering products or taking
"other appropriate regulatory action." Thus, reregistration 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" criterion of FIFRA.
This document presents the Agency's decision regarding the reregistration of
streptomycin. The document consists of six sections. Section I is the introduction.
Section II describes streptomycin, its uses, data requirements and regulatory history.
Section III discusses the human health and environmental assessment based on the data
available to the Agency. Section IV discusses the reregistration decision for
streptomycin. Section V discusses the reregistration requirements for streptomycin.
Section VI is the Appendices which support this Reregistration Eligibility Document.
Additional details concerning the Agency's review of applicable data are available on
request.1
EPA's reviews of data on the set of registered uses
considered for EPA's analysis may be obtained from the
OPP Public Docket, Field Operations Division (H7506C) ,
Office of Pesticide Programs, EPA, Washington, D.C. 20460
-------
CASE OVERVIEW
A. Chemical Overview
The following active ingredients are covered by this Reregistration Eligibility
Document:
Common Name: Streptomycin and Streptomycin Sulfate
Chemical Name: 0-2-Deoxy-2-(methylamino)-5-L-glucopyranosyl-(l-
> 2)-0-5-deoxy-3-C-formyl-5-L-lyxofuranosyl-( 1 -
>4)-N,N'-bis(aminoiminomethyl)-D-streptamine
Chemical Family: Aminoglycoside antibiotic isolated from the
bacterium Streptomyces griseus
CAS Registry Number: 57-92-1 and 3810-74-0 (streptomycin sulfate)
OPP Chemical Code: 006306 and 006310 (streptomycin sulfate)
Empirical Formula: C^Hj^Ou and C42HMN,4O36S3 (streptomycin sulfate)
Trade and Other Names: Agri-Mycin 17®, Agri-Strep®, Plantomycin® and
Streptomycin 3000 Dust®
Basic Manufacturer: Pfizer, Inc.
B. Use Profile
The following is information on the active registered uses with specific use sites
and application methods. A detailed table of both eligible and ineligible uses of
streptomycin is included in Appendix A. In addition, a detailed table of the
methods, application rates and limited use restrictions is included in Appendix A.
Type of Pesticide: Antibiotic bactericide/bacteriostat, fungicide, algicide
Use Sites: Terrestrial food crop use on celery, crabapples,
pears, peppers, and quince;
Terrestrial food and feed crop use on apples, beans,
potatoes, and tomatoes;
Terrestrial non-food crop use on sugar beets (grown
for seed), tobacco, ornamental herbaceous plants,
ornamental woody shrubs and vines;
-------
Terrestrial outdoor residential use on ornamental
herbaceous plants, ornamental woody shrubs and
vines;
Aquatic non-food residential use on ornamental
ponds and aquaria.
Pests: Aquariums
Apples and Pears
Beans
Celery
Chrysanthemums
Cotoneaster
Dieffenbachia
Flowering Crabapple
Flowering Quince
Hawthorne
Peppers
Philodendron
Pyracantha
Potato
Roses
Sugar beets
Tobacco
Tomato
Formulation Types Registered:
For streptomycin: 0.15% and 0.30% dust
For streptomycin sulfate: 0.01% dust, 15.00% pelleted/tableted, 21.20%
wettable powder, 21.1% and 62.6% wettable powder/dust
Algae
Fireblight
Halo blight
Bacterial blight
Bacterial wilt
Fireblight
Bacterial stem rot
Fireblight
Fireblight
Fireblight
Bacterial spot
Bacterial leaf spot
Fireblight
Soft rot, Black leg
Crown gall
Bacterial blight
Blue mold, Wildfire
Bacterial spot
C. Estimated Usage of the Pesticide Streptomycin
This section summarizes the best estimates available for the pesticide uses of
streptomycin. These estimates are derived from a variety of published and
proprietary sources available to the Agency. The data are reported on an
aggregate and site (crop) basis and reflect annual fluctuations in use patterns and
variability in data from information sources. The quantity of pesticides used on
crops that are grown on relatively few acres and the quantity of infrequently used
pesticides are both difficult to ascertain. Non-agricultural uses of pesticides may
also be difficult to quantify. Quantitative data are not available for all sites of
streptomycin application.
3
-------
The domestic basic producer of streptomycin is Pfizer, Inc. Data on production,
sales and distribution are confidential business information and are protected
under Section 7 (d) and Section 10 of FIFRA, as amended, and thus cannot be
disseminated.
Streptomycin is a bactericide registered for foliar treatment of: apples, celery,
crabapples, pears, peppers, tobacco, tomatoes and ornamentals including
anthurium, cotoneaster, flowering crabapple, dieffenbachia, hawthorn,
philodendron, pyracantha, flowering quince and roses. Registered sites for seed,
seed piece or bed treatment includes: beans, celery, potatoes, sugar beets,
tobacco, and tomatoes. Other sites include chrysanthemum (cuttings) and aquaria
water.
The table below summarizes streptomycin use by site, this usage represents a
moderate increase from the previous usage estimate (the 1987 high-end estimate
was 57,000 Ibs. active ingredient). Most sites have a very small percentage of
acreage treated with streptomycin, so small that these figures remain consistent
over time. It is important to note that streptomycin usage may vary greatly from
year to year, depending on weather conditions.
Streptomycin is used primarily on pome fruit (although resistance to streptomycin
has been reported, the total use of streptomycin on pome fruit has increased),
ornamentals and tobacco. Based upon the available data, apples and pears
account for 58%, nursery and landscape uses for 17%, tobacco use for 7%, and
other uses (including celery, potatoes, sugar beets, and ornamentals not included
in landscape and nursery stock) for 15% of the total use of streptomycin. Each
remaining site accounts for no more than 1 % of the total use of streptomycin
(pounds a.i.).
On the major crop, pears, up to 80% of acreage is treated with streptomycin.
Among the other crops, less than 5% of tobacco and pepper acreage are treated,
with each remaining site having less than 1% of its acreage treated with
streptomycin. Usage estimates of seed, seed piece or bed treatments may be
under reported because of sampling methods.
-------
DOMESTIC USAGE OF STREPTOMYCIN AS A PESTICIDE
TYPICAL RECENT YEARS (1987 - 1991)
SITE
Pears'
Apples'
Nursery Stock
Tobacco
Landscape
Maintenance
Tomatoes
Dried Beans and Peas
Peppers
OTHER2
TOTAL
LBS. A.I.
(1,000)
18-60
8-30
5- 15
3-10
<7
<1
<1
<1
<15
<60- <140
% OF
TOTAL USE
39
19
10
7
<7
<1
<1
<1
15
100
% OF SITE
TREATED
<80
<1
NA
<5
NA
<1
<1
<5
NA
STATE USAGE
Western US
East, N. Central
CA data 1990, FL
KY, WV data 1990
CA data, 1990
CA, N. East
CA only 1988 - 1990
OH data, 1990
NA - Not Available
1 Includes bearing and non-bearing acres.
2 Including celery, potatoes, sugar beets, ornamentals (not included in nursery stock and land-
scape maintenance).
D. Data Requirements
Data required in the September 1988 Registration Standard for streptomycin
included studies on product chemistry, ecological effects, environmental fate, and
residue chemistry. These data were required to support the uses listed in the
1988 Registration Standard for streptomycin. Please refer to Appendix B for
details of the complete data base for streptomycin. Appendix B includes all data
requirements identified by the Agency for current use groups that are needed to
support reregistration plus data requirements being imposed as a result of the
Agency's review.
E. Regulatory History
Streptomycin has been used in the United States since the 1940s to treat bacterial
infections in humans and was first registered as a pesticide in the United States
in 1955. At that time, it was used primarily as a bactericide/fungicide on selected
agricultural and non-agricultural crops. Other uses included seed treatment,
residential, and as an algicide for aquaria.
5
-------
A Registration Standard for streptomycin was issued in September, 1988. This
document required data to support the uses identified in the 1988 Registration
Standard.. The Reregistration Eligibility Document reflects a reassessment of all
data submitted in response to the Registration Standard.
There are currently sixteen end-use products containing streptomycin registered
in the United States. No technical or manufacturing-use product is currently
registered.
HI. SCIENCE ASSESSMENT OF STREPTOMYCIN
The Agency has conducted a thorough review of the scientific data base for streptomycin
for the purposes of determining the reregistration eligibility of this pesticide. These
findings are summarized below.
A. Product Chemistry Assessment
Streptomycin, produced by the soil bacterium, Streptomyces griseus. is an
aminoglycoside antibiotic. It may be produced on an industrial scale by aerobic
fermentation, followed by isolation and purification by ion exchange.
There are several product chemistry requirements which are not fully satisfied for
technical streptomycin sulfate. They include the following: Chemical Identity
(GLN 61-1), Formation of Impurities (GLN 61-2b), Preliminary Analysis (GLN
62-1), and Dissociation Constant (GLN 63-10). The Agency regards these data
as necessary to confirm the reregistration eligibility decision put forth in this
document. The physical and chemical properties of the streptomycin sulfate
technical grade of the active ingredient (TGAI) are summarized below:
TGAI Streptomycin sulfate
Molecular Weight 1467.48
Color Light tan
Physical State Solid (STP)
Odor Odorless
Melting Point 168°C
Boiling Point N/A (TGAI is a solid)
Bulk Density 1.78g/ml
Solubility > 200 g/100ml in water
Vapor Pressure Waived
Dissociation Constant Data Gap
Oct./Water Part. Coeff. Waived
pH 5.5 (Ig sample/5ml water)
Stability Not photosensitive; not sensitive to metal or
metal ions. Slightly decreased potency
following 24 months at 37°C.
-------
B. Human Health Assessment
1. Toxicology Assessment
Much of the data available to support the reregistration of streptomycin are
reviews conducted by the Food and Drug Administration on dihydrostreptomycin
(FDA, 1986). Streptomycin is similar in action to dihydrostreptomycin and its
toxicity would not be expected to significantly differ from that of dihydro-
streptomycin. All generic lexicological data requirements for streptomycin have
been waived based on extensive information available from studies conducted in
animals in support of its use as a human drug.
a. Acute Toxicity
The oral LD50 for streptomycin in rats has been reported to be
9,000 mg/kg (Thompson, 1977). The oral LD50 in mice has also
been reported to be 9,000 mg/kg (BCPC, 1972). This is low
toxicity and is classified as Toxicity Category IV.
b. Subchronic Toxicity
FDA concluded that a NOEL of 40 mg/kg/day was obtained in a
90-day study with cats in which the animals were dosed orally with
40 mg/kg/day dihydrostreptomycin, or in some cases, injected
intramuscularly with 75 - 200 mg/kg/day dihydrostreptomycin.
The cats receiving dihydrostreptomycin intramuscularly lost the
righting reflex in 3 weeks whereas those treated orally did not.
Gross pathology and histopathology were unremarkable.
A 90-day study was conducted in guinea pigs. It. was concluded
that 40 mg/kg/day dihydrostreptomycin administered orally
produced no hearing loss.
c. Chronic Toxicity
A 2-year feeding study in rats was conducted employing doses of
0, 1, 5 and 10 mg/kg/day dihydrostreptomycin. Based on the
data, dihydrostreptomycin does not appear to have carcinogenic
potential. The only adverse effect noted was reduced body weight
gain in males in the 10 mg/kg/day group. The NOEL was
determined to be 5 mg/kg/day.
-------
d. Developmental Toxicity
In a developmental toxicity study in rabbits, the animals were
dosed with 5 and 10 mg/kg/day of dihydrostreptomycin from days
6 - 19 of gestation. The FDA review concluded that there were
no teratogenic effects at either dose. The NOEL for teratogenic
effects in the rabbit was 10 mg/kg/day.
e. Reference Dose (RfD) for Chronic Oral Exposure
A provisional ADI (PADI) or RfD for streptomycin of 0.05 mg/kg
bwt/day can be established based on a NOEL of 5.0 mg/kg
bwt/day from a two year feeding study in rats, which demonstrated
as an effect reduced body weight gain, and utilizing an uncertainty
factor of 100. The Joint FAO/WHO Expert Committee on Food
Additives has not established an ADI for streptomycin.
f. Antibiotic Resistance
In a study conducted for FDA, beagle dogs were fed a diet of 0,
2, or 10 /zg/g of dihydrostreptomycin per gram of feed. The 2
/xg/g level was selected to represent a residue level of the
antibiotic. In both treatment groups, administration of the
medicated feed resulted in a shift from a predominantly
dihydrostreptomycin-susceptible coliform fecal population to a
resistant population. An increase in the prevalence of
dihydrostreptomycin resistance was observed after 15 days of
dihydrostreptomycin-supplemented feeding and persisted during the
post-treatment phase of the study. Although it has not been tested
for, the same potential may exist for the development of chemical
resistance in the respiratory flora.
g. Human Data
Streptomycin has been available for use in humans as an antibiotic
for urinary infections since the late 1940s. The usual route of
administration is through intramuscular injection since only minor
quantities are absorbed through the gastrointestinal tract. The total
daily dose varies from 1 to 2 g or 0.5 to 1 g every 12 hours with
treatment usually lasting 7 to 10 days. A variety of allergic
reactions have been observed in sensitive patients treated with
8
-------
streptomycin. These reactions include: erythema, rashes,
urticaria, purpura, drop in blood pressure, headache, nausea and
vomiting. The following effects have been observed after
prolonged therapy for tuberculosis: vertigo, tinnitus, diplopia
after rapid movement of the head, and deafness.
2. Exposure Assessment
a. Dietary
The nature of streptomycin residues in plants and animals is
adequately understood; the residue of concern is streptomycin. In
view of the long use of streptomycin as a drug, and to the low
residues expected in or on RACs, no metabolism data have been
required. No residues were detected in the commodities for which
tolerances have been established when these commodities were
treated according to registered uses.
Currently, tolerances of 0.25 ppm are established in 40 CFR
180.245 for negligible residues of streptomycin (the residue of
concern) in or on the raw agricultural commodities listed below.
The tolerance of 0.25 ppm was based on the limit of detection of
the enforcement method submitted to the Agency.
Commodity
1. Celery, peppers, and tomatoes (treatment of
seedling plants before transplanting)
2. Potatoes (treatment of seed pieces)
3. Pome fruits (apples, crabapples, pears and quince;
foliar application)
Although the Agency finds these tolerances to be acceptable, the
Agency considers the expression "negligible residues" as obsolete
and will revise 40 CFR 180.245 to delete the reference to
"negligible residues."
In addition, the Agency required bean data depicting streptomycin
residues in or on beans, bean vines, and bean hay following seed
treatment according to registered labels. The Agency is requesting
that the registrant propose an appropriate tolerance for strepto-
mycin in or on beans (succulent and dried), based on the
-------
results of the field trials. The available bean data indicate that
tolerances of 0.25 ppm for dry beans, bean forage, bean hay and
bean straw grown from treated seed and at 0.50 ppm for succulent
beans grown from treated seed are needed. No tolerances or data
depicting streptomycin residues in bean cannery waste are
required.
The current SLN (State Local Need) registration, OR850037, calls
for foliar treatment of sugar beets grown for seed. Use restrictions
prevent any livestock/human exposure to treated plants/seeds. The
foliar application rate is 50 to 200 ppm, 250 times less than the
labeled seed treatment rate for beans. Based on the bean data, the
difference in application rates, the interval between seed crop
treatment and root crop harvest, dilution effects, and label
restrictions, no tolerances or supporting residue data are required
to support the SLN registration for streptomycin on sugar beets
grown for seed which the Agency considers to be a nonfood use.
The Agency has adequate data to support registered uses on all the
above RACs and tobacco. There are no proposed or established
CODEX (international) tolerances for streptomycin. There are no
Canadian tolerances, and the Mexican tolerances for streptomycin
are currently harmonized with U.S. tolerances. No other
harmonization issues remain to be resolved. Because streptomycin
is used in veterinary medicine, tolerances for streptomycin residues
have also been established by FDA and USD A.
b. Occupational and Residential Exposure
Streptomycin, as one of the early antibiotic drugs (developed in the
1940s) possesses an accumulation of lexicological data and
knowledge regarding its use as a bactericide for humans. The
totality of this data indicates that streptomycin does not meet the
Agency's toxicity criteria which would trigger the requirement for
occupational/residential exposure monitoring data. Streptomycin,
however, has produced various allergic reactions in some human
patients. Therefore, label statements are required restricting the
reentry into treated fields and specifying the use of certain
protective clothing and equipment (PPE) while handling and
applying end-use products for commercial use on agricultural crops
and ornamentals. For the specific label language, refer to Section
V, Labeling Requirements.
10
-------
3. Risk Assessment
From the late 1940s, streptomycin has been available as an aminoglyco-
side antibiotic for humans. The drug continues today as part of the
arsenal for endocarditis, tularemia, bubonic plague, and tuberculosis. On
account of its low oral absorptivity, the drug is usually administered by
intramuscular injection. Streptomycin is still used in veterinary medicine
to help prevent infections in fowl, calves, and swine. Estimation of
dietary risk by the Dietary Risk Evaluation 'System (ORES) utilized a
Reference Dose (RfD) of 0.05 mg/kg bwt/day, based on a no-observed-
effect level (NOEL) of 5.0 mg/kg bwt/day and an uncertainty factor of
100. The NOEL is taken from a two-year rat feeding study which
demonstrated reduced body-weight gain as the most lexicologically
significant effect. This RfD has been approved by the EPA Health Effects
Division RfD Peer Review Committee (06/18/92)..
The Agency has conducted a dietary risk analyses (DRES) for
streptomycin. Food uses included in the analysis were the established
tolerances (40 CFR 180.245) supported in the reregistration of
streptomycin. All EPA-published food uses for this chemical are being
supported through reregistration. Tolerances on celery, peppers, pome
fruits, potatoes, and tomatoes are established at 0.25 ppm, the limit of
detection of the enforcement method submitted. Residues considered in
the analysis were the published uses previously mentioned and the
proposed tolerances from the use of streptomycin as a seed treatment on
beans (0.25 ppm for dry beans, 0.5 ppm for succulent beans). These
tolerances reflect the limit of detection of the method and actual residue
levels of streptomycin on beans are probably lower.
The DRES chronic exposure analysis used tolerance level residues and
100% crop treated to estimate the Theoretical Maximum Residue
Contribution (TMRC) for the overall U.S. population and 22 population
subgroups. The TMRC for the overall population from the EPA-
published uses of streptomycin is 0.000899 mg/kg bwt/day, which
represents \.%% of the RfD. The proposed use on beans contributes an
additional 0.000167 mg/kg bwt/day of exposure, raising the TMRC for
the general population to 0.001066 mg/kg bwt/day, or 2.1% of the RfD.
The DRES subgroup most highly exposed (non-nursing infants less than
one year old) has a TMRC of 0.003006 mg/kg bwt/day, or 6% of the
RfD. The proposed use on beans raises the exposure to 0.003476 mg/kg
bwt/day, or 7% of the RfD. Because of the assumptions of tolerance
level residues and 100 percent crop treated, it is likely that these values
overestimate the exposure and risk. Even so, the chronic dietary risk
posed by these uses of streptomycin are well below the level at which the
Agency would have concern. Summaries of the residue data used in this
analysis and the analysis itself are included in the streptomycin public
docket.
11
-------
Given the assumptions of tolerance-level residues and 100% crop treated,
as well as the fact that tolerances are set at the limit of detection because
no residues were actually found, these exposure values are most likely
overestimates of exposure. In summary, the dietary risk from
streptomycin appears minimal.
The Agency is aware of data exhibiting the induction by streptomycin of
drug-resistant microflora in the intestine [Sec. III.B.l.f.]. A recent
assessment of the impact of drug residues (in food) on the generation of
"drug resistance" in humans has focused on the relative significance of (1)
the potency of ingested antibiotic residues in food for producing drug-
resistant microflora, and (2) the quantity of drug-resistant microflora
already on or in the food ingested. More research has been suggested in
order to ascertain the relative magnitudes of these two contributions to a
drug-resistant population of microflora in the mammalian intestine. At
present, the Agency has no data showing that food residues of strepto-
mycin possess a significant or even measurable potential for developing
in the human intestine streptomycin-resistant strains of microorganisms at
levels above background levels acquired from the drug-resistant
microorganisms ingested with food.
Workers may be exposed to streptomycin during use. There is a potential
for an allergic response from individuals that are streptomycin-sensitive.
Specific label requirements limiting inhalation exposure would mitigate
this potential risk. These label requirements would also address concerns
for the potential development of streptomycin-resistant microorganisms in
the respiratory tract.
C. Environmental Assessment
1. Environmental Fate
Since there are no ecological or health effects concerns from this naturally
occurring antibiotic, all environmental fate requirements, except for
hydrolysis data (Guideline Reference No. 161-1), are waived. The
hydrolysis study is being called in but the data are considered
confirmatory. The unavailability of the hydrolysis data at this time will
not delay reregistration of eligible products.
Hydrolysis is the only environmental fate data requirement that will be
imposed for streptomycin. All other data requirements were waived based
on the information found in a literature search conducted by the Agency
which led to the following conclusions. Pseudomonas fluorescens
12
-------
degrades streptomycin in water in the pH range of 6-8.1, but not at pH 5.
Also, streptomycin is stable in sterilized soil and degrades in 2-3 weeks
in non-sterilized soil with active P. fluorescens cultures. The lag time for
degradation of streptomycin in soil decreases with later applications,
indicating an inducible response. The major degradate of streptomycin in
both soil and water was methylamine. Another degradation study in water
found that 90% of the labeled streptomycin was found as C02 and cell
materials while 10% was found as urea. Streptomycin (500-1,000 ^g/ml)
did not move beyond 0.5 cm of depth when applied to saturated sandy soil
and exhibited activity at 9 and 32 days when applied at 1,000 and 2,500
Hg/g soil, respectively. Adsorption and consequent immobilization of
streptomycin appears to increase with increasing clay and organic matter
content. Streptomycin was also detected at concentrations of 2.4 - 4.6 and
7.4 - 38 /xg/ml of tomato plant sap when a sandy clay soil was treated
with 1,000 and 2,500 /ig/g soil, respectively.
2. Ecological Effects
The Agency has reviewed the available information for streptomycin and
has determined that all ecological effects data requirements, except for an
Aquatic Invertebrate EC50 study, are satisfied. The Aquatic Invertebrate
EC50 study is being called in but the data are considered confirmatory.
The unavailability of these data at this time will not delay reregistration
of eligible products.
a. Ecological Hazard
I. Effects on Birds
An acute avian oral toxicity study on bobwhite quail
showed that streptomycin has an LD50 > 2,000 mg/kg.
These data indicate that streptomycin is practically non-
toxic to upland bird species on an acute oral basis. In two
subacute avian dietary studies on bobwhite quail and
mallard duck, the LC50 > 5,620 and 4640 ppm, respective-
ly. These data also indicate that streptomycin is practically
non-toxic to birds on a dietary and acute oral basis. These
studies fulfill Agency minimum data requirements to
establish the toxicity of streptomycin in birds.
13
-------
2. Effects on Freshwater Invertebrates
No studies were received on the effects of streptomycin on
freshwater invertebrates, however, a literature search
conducted by the Agency resulted in finding one study that
can be used as supplemental data. This study was
considered supplemental because information on the study
methods was not reported. This study was acceptable for
use in the hazard assessment, but does not fulfill the
guideline requirements for an aquatic invertebrate toxicity
study. These data suggest that streptomycin is practically
non-toxic to freshwater invertebrates. To establish the
toxicity of streptomycin to aquatic invertebrates, a 48-hour
acute study using the technical grade of streptomycin is
required. The test organisms should be first instar Daphnia
magna.
3. Effects on Freshwater Fish
Two 96-hour freshwater fish toxicity studies on rainbow
trout (coldwater species) and bluegill (warmwater species)
were submitted to establish the acute toxicity of strepto-
mycin to freshwater fish. The LC50 is > 180 ppm for both
studies. These data indicate that streptomycin is slightly
toxic to both cold water and warm water species of fish.
The guideline requirements are fulfilled for acute toxicity
testing on freshwater fish.
4. Effects on Non-Target Insects
An acute honey bee study was submitted to establish the
toxicity to honey bees. These data indicate that strepto-
mycin is practically non-toxic to honey bees and fulfills the
Agency's requirements for this study.
5. Effects on Non-Target Plants
No studies have been required for the effects of strepto-.
mycin on non-target plants. However, a literature search
conducted by the Agency resulted in two scientific articles
that demonstrated phytotoxic effects. Although these
studies would not satisfy guideline requirements, they are
sufficient for the purpose of assessing hazard to non-target
plants and no additional data are required.
14
-------
b. Ecological Effects Risk Assessment
Streptomycin is currently registered for use on Terrestrial Food
and Feed Crops; Terrestrial Non-Food Crops; Ornamental and/or
Shade Trees; Ornamental Herbaceous Plants; Ornamental Woody
Shrubs and Vines; and Ornamental Ponds/Aquaria. It is registered
as an algicide, bacteriocide/bacteriostat and a fungicide. The most
common method for foliar application is by ground equipment such
as airblast. Other methods of application include aircraft, duster
attachments or hand-held sprayers.
1. Terrestrial Species
Streptomycin is applied to apple and pear orchards at the
maximum rate of 0.3 Ib ai/A in West Coast States and at
0.50 Ib ai/A in other areas of the United States. Residues
are found on both the crop and surrounding vegetation.
Based on the maximum application rates, the following
maximum residues could occur immediately after a single
application:
Substrate Residues at 0.5 Ib ai/A
Leaves & leafy crops 63
Forage (alfalfa & clover) 29
Fruit 3.5
Streptomycin is applied several times throughout the
growing season. No information is available concerning
the persistence of streptomycin on plant surfaces, therefore,
the potential for residue accumulation, if any, cannot be
determined. The acute LD50 for bobwhite quail is greater
than 2,000 mg/kg and the dietary LC50 for bobwhite quail
and mallard duck is 5,620 ppm and 4,640 ppm, respective-
ly. Based on the maximum expected residues when
compared to the LCJO's, streptomycin should not have an
acute effect on birds.
2. Freshwater Organisms
The available data on streptomycin indicates that it is
practically non-toxic to freshwater organisms including
Daphnia. bluegill sunfish and rainbow trout. The EC50
determined for Daphnia is 650 ppm. The LC50 for both
bluegill and rainbow trout is greater than 180 ppm.
15
-------
Following a direct application to water, the following
residues would result in 6 inches and 6 feet of water.
Application Rate Aquatic Residues (ppb)
(Ib ai/A) 6 inches 6 feet
0.5 367 31
Based on the expected residues when compared to the
aquatic LC50 for fish and the EC50 for Daphnia. strepto-
mycin poses minimal risks to aquatic fauna.
3. Non-Target Insects
An LD50 greater than 100 micrograms was determined for
honey bees. These data indicate that streptomycin is
practically non-toxic to honey bees and adverse effects are
not likely to occur.
4. Non-Target Plants
The studies with species of algae indicate that streptomycin
is toxic to algae. The EC50 was determined to be 0.86
mg/1 for the most sensitive species. Based on the
maximum label application rates and the expected residues
for use on apples and pears, significant adverse impact on
algae could occur if direct application occurred. Strepto-
mycin is also labeled at lower application rates for use in
ornamental ponds, fountains and aquaria to control algae.
Dose levels for the tablet (slow release) form of strepto-
mycin used .in aquatic environments could not be
determined.
5. Endangered Species
The use of streptomycin as described, is not expected to
pose significant risk to threatened and endangered species.
In summary, data indicate that streptomycin is practically non-toxic
to bobwhite quail on an acute oral basis; to bobwhite quail and
mallard ducks on a dietary basis; to coldwater and warmwater fish
species; and to honey bees. No data were submitted for an aquatic
invertebrate acute toxicity study. Scientific literature was used to
support the hazard assessment. This study was deficient for the
16
-------
purposes of an aquatic invertebrate study; however, it did provide
supplemental data that was adequate to support a hazard
assessment. A valid aquatic invertebrate study will be necessary
to confirm the hazard assessment. Because of the demonstrated
effects on aquatic plants, precautionary labeling for all non-aquatic
uses is required. For specific precautionary labeling language,
refer to Section V, Labeling Requirements.
IV. RISK MANAGEMENT
A. Determination of Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission
of relevant data concerning an active ingredient, whether products containing the
• active ingredient are eligible for reregistration. The Agency has previously
identified and required the submission of the generic (i.e. active ingredient
specific) data required to support reregistration of products containing
streptomycin as an active ingredient. The Agency has completed its review of
these generic data, and has determined that the data are sufficient to support
reregistration of all products containing streptomycin. Appendix B identifies the
generic data requirements that the Agency reviewed as part of its determination
of reregistration eligibility of streptomycin, and lists the submitted studies that the
Agency found acceptable.
The data identified in Appendix B were sufficient to allow the Agency to assess
the registered uses of streptomycin and to determine that these uses of
streptomycin can be used without resulting in unreasonable adverse effects to man
and the environment. The Agency therefore finds that all products containing
streptomycin/streptomycin sulfate as the active, ingredients are eligible for
reregistration. The reregistration of particular products is addressed in Section
V of this document.
The Agency made its reregistration eligibility determination based upon the target
data base required for reregistration, the current guidelines for conducting
acceptable studies to generate such data and the data identified in Appendix B.
Although the Agency has found that all uses of streptomycin are eligible for
reregistration, it should be understood that the Agency may take appropriate
regulatory action, and/or require the submission of additional data to support the
registration of products containing streptomycin, if new information comes to the
Agency's attention or if the data requirements for reregistration (or the guidelines
for generating such data) change.
17
-------
1. Eligibility Decision
The Agency has sufficient information on the heaJth effects of
streptomycin and on its potential for causing adverse effects in fish and
wildlife and the environment. The Agency therefore concludes that
products containing streptomycin for all uses are eligible for
reregistration. The Agency has determined that additional data for
product chemistry, ecological effects, and environmental fate are required
for confirmatory purposes.
The Agency has determined that streptomycin products, labeled and used
as specified in this Reregistration Eligibility Document, will not pose
unreasonable risks or adverse effects to humans or the environment.
2. Eligible and Ineligible Uses
The Agency has determined that the uses of streptomycin for beans (seed
treatment); celery, peppers, and tomatoes (treatment of the seedling plants
before transplanting); potatoes (seed piece treatment); pome fruit (foliar
treatment); sugar beets (grown for seed only); selected ornamental shrubs
and trees; and ornamental ponds and aquaria are eligible for reregistration
at this time.
Regulatory Position
The following is a summary of the regulatory positions and rationales for
streptomycin. Where labeling revisions are imposed, specific language is set
forth in Section V of this document.
1. Tolerance Reassessment
The term "negligible residues" is considered by the Agency to be obsolete
and will be deleted from 40 CFR 180.245. Adequate data exist to support
the existing tolerances of 0.25 ppm for residues of streptomycin in or on
the raw agricultural commodities celery, peppers, and tomatoes from
treatment of the seedling plants, before transplanting; potatoes from
treatment of seed pieces; and pome fruits.
Tolerances of 0.25 ppm should be established for streptomycin residues
in or on dry beans, bean forage, and bean hay grown from treated seed
and 0.50 ppm in or on succulent beans grown from treated seed. No
tolerances or data depicting streptomycin residues in bean cannery waste
are required. No residue data are required to support the SLN registration
for streptomycin on sugar beets grown for seed, which is considered by
the Agency to be a nonfood use.
18
-------
There are no proposed or established CODEX (international) tolerances
for streptomycin. There are no Canadian tolerances, and the Mexican
tolerances for streptomycin are currently harmonized with U.S. tolerances.
No other harmonization issues remain to be resolved. Because
streptomycin is used in veterinary medicine, tolerances for streptomycin
residues have also been established by FDA and USDA.
2. Labeling Rationale
a. Because streptomycin has produced various allergic reactions in
some human patients and there may be some potential for the
development of streptomycin resistant microorganisms in the
respiratory tract, the Agency is requiring label statements
restricting the reentry into treated fields and specifying the use of
certain protective clothing and equipment (PPE) while handling
and applying end-use products for commercial use on agricultural
crops and ornamentals. The specific label language is in Section V,
Labeling Requirements.
b. Because streptomycin is used to control algae, products that are
not used as an algicide in ornamental ponds and aquaria must have
appropriate aquatic plant hazard labeling. The specific label
language is in Section V, Labeling Requirements.
V. ACTIONS REQUIRED BY REGISTRANTS
This section is designed to assist the registrant by listing all of the data requirements and
responses necessary for the reregistration of both manufacturing-use and end-use
products.
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregistration of streptomycin
products for the above eligible uses has been reviewed and determined to
be substantially complete. However, some of the product chemistry
guidelines have not been completely fulfilled. All of the product
chemistry data were originally required in the Registration Standard and
are therefore not included in the generic Data Call-In for the RED.
Further, registrants are reminded that any changes, since the Registration
Standard was issued in 1988, in the manufacturing process for the
technical grade of streptomycin, and any detection of new impurities since
that time, must be reported to the Agency.
19
-------
In addition to product chemistry, the Agency has determined that
confirmatory data are required for the Invertebrate Toxicity (GLN 72-2a),
and Hydrolysis (GLN 161-1) studies. These new generic data
requirements are being called in and are listed in Appendix F.
2. Labeling Requirements for Manufacturing-Use Products
No technical or manufacturing-use products are currently registered.
However, if any are registered, they will be required to meet the
requirements of 40 CFR 156.10, this RED, and other current policies.
B. End-Use Products
1. Additional Product-Specific Data Requirements
Based on the reviews of the generic data for the active ingredient strepto-
mycin, the products containing streptomycin with uses for beans (seed
treatment); celery, peppers, and tomatoes (treatment of the seedling plants
before transplanting); potatoes (seed piece treatment); pome fruit (foliar
treatment); sugar beets (grown for seed only); selected ornamental shrubs
and trees; tobacco (seedling; foliar treatment) and ornamental aquaria are
eligible for reregistration. Section 4(g)(2)B) of FIFRA calls for the
Agency to obtain any needed product-specific data regarding the pesticide
after a determination of eligibility has been made. The product specific
data requirements are listed in Appendix G, the Product Specific Data
Call-in Notice.
The product specific data were called in with the issuance of the 1988
Registration Standard. Registrants must review previous data submissions
to ensure that they meet current EPA acceptance criteria (Appendix F;
Attachment E) and if not, commit to conduct new studies. If a registrant
believes that previously submitted data meet current testing standards, then
study MRID numbers should be cited according to the instructions in the
Requirement Status and Registrants Response Form provided for each
product.
2. Labeling Requirements for End-Use Products
The labels and labeling of all products must comply with EPA's current
regulations and requirements as specified in 40 CFR §156.10. Please
follow the instructions in the Pesticide Reregistration Handbook with
respect to labels and labeling.
The Agency has determined that the current label precautions are still
applicable and are required for product reregistration. The following
additional (or revised) label statements are required in the human hazards
section:
20
-------
a. The labels of products registered for commercial use on
agricultural crops and ornamentals must include the following
restricted entry statement: "Entry into treated fields is prohibited
for 12 hours following application."
b. The labels of products registered for commercial use on
agricultural crops and ornamentals must include the following
protective clothing statement: "Prolonged or frequently repeated
skin contact may cause allergic reactions in some individuals. Do
not breathe dust or spray mist. Wear a MSHA/NIOSH approved
TC-21C dust/mist filtering respirator, long sleeved shirt, pants,
shoes, and chemical-resistant gloves while handling or applying
this product. Wash thoroughly after handling or applying."
c. In the environmental hazards section, all products, except for those
used as an algicide in ornamental aquaria and ponds, must have the
following label statement: "This product may be hazardous to
aquatic plants. Do not apply directly to water, areas where surface
water is present or to intertidal areas below the mean high water
mark. Do not contaminate water by cleaning of equipment or
disposal of wastes."
21
-------
APPENDIX A
Table of Streptomycin Use Patterns
Subject to Reregistration
-------
The following table shows the eligible and ineligible uses of streptomycin. It does not show any changes resulting from
the RED review itself. Changes that result from the RED review, e.g. PHI, application rates, etc. are specified in Section
IV.
APPENDIX A- Case 01 69 Chemical 006306 (Streptomycin)
USES
ELIGIBLE
FOR
REREG.
FOOD/
FEED
USES
USES IN-
ELIGIBLE
FOR
REREG.
UMVOV
SH.
Application
tiff**
Fom
Application lyp.
and Application
CtaJpmant
MWn»n
Application Bata
Maunun
Application Rata
Max. 1 Appa.
Ma». •
App.. 9
M.x Rata
M«. htarval
Batv~an App.. 9
Max. R.I.
(Dayal
Raanietad
B*y
kiorval
-------
APPENDIX A- Case 01 69 Chemical 006310 (Streptomycin Sulf ate)
USES
ELIGIBLE
FOR
REREG
FOOD/
FEED USES
USE
CROUP
SITE
A«*c.tioo timing
fam
Apf*c.tiontvi»
«od AepbuIKX
bMxmn
Minimum
Application lbl«
(ppm refers
to strepto-
mycin
content)
Mvjamjm
*wtc.uon H.I.
(ppm refers
to strepto-
mycin
content)
U.»->App.
U»x /
AB». e
MU.RIU
Uin. faurvd
BMWMWI Afpa. 0
Mu. R»W
0>«<1
RMrictod
Ewy
hutvri
(0>yd
C^f^Hc
Uniutiotw
-------
APPENDIX A- Case 01 69 Chemical 006310 (Streptomycin Sulf ate)
use
CROUP
A
A
A. B
A, B
A. B
SITE
Pear
Pepper
Apple
Apple
Bean
Apportion tMng
bloom
foliar
seedling
stage
bloom,
foliar
petal fall
bloom.
petal fall
foliar
seed
—
Fo*m
wettable
powder/
dust
wettable
powder/
dust
wettable
powder
and
wettable
powder/
dust
wettable
powder/
dust
wettable
powder/
dust
Application type
•nd Application
Equipnwnt
dust
(equipment
not on
label)
spray with
sprayer
spray with
sprayer
dust
(equipment
not on
label)
seed
treatment
with slurry-
type seed
treater
Minimum
Application Rite
(ppm refers
to strepto-
mycin
content)
20 Ib ai/ac
200 ppm
.26 Ib ai/ac
(.31 Ib ai/ac
in West
Coast)
20 Ib ai/ac
50,000
ppm
M.»mum
Apptintion Rvt*
(ppm refers
to strepto-
mycin
content)
20 Ib ai/ac
200 ppm
.51 Ib ai/ac
20 Ib ai/ac
50,000
ppm
M.x 1 App.
None
specified
None
specified
None
specified
None
specified
None
specified
M.« »
App.. e
M.>. R.I.
None
specified
None
specified
None
specified
None
specified
None
specified
Mm. hwvil
BM.MOT App*. 9
M.«. R.I.
(Doy.!
5
4
3 to 10
3 to 5
None
specified
RMtricm)
Cntiy
kuwvri
(0>V«>
None
specified
None
specified
None
specified
None
specified
None
specified
Gng»phie
Limil«noni
«_
West
Coast is
identified
None
specified
West
Coast is
identified
West
Coast is
identified
None
specified
DMowxl
None
specified
None
specified
None
specified
None
specified
None
specified
lM.LI.rWt.tion.
30 day
preharvest
interval.
Final
application
should not
exceed 10
weeks
after
bloom.
None
specified
SO day
preharvest
interval
SO day
preharvest
interval
Do not use
treated
seed for
feed or
food
-------
APPENDIX A- Case 0169 Chemical 006310 (Streptomycin Sulf ate)
NONFOOD/
NONFEED
USES
USE
CROUP
A. B
A, B
A. B
SITE
Potato
Potato
Tomato
Acvbc.uoot.nng
i«M»u piectt
seed piece
seedling
stage
fctm
dust
wettable
powder
and
wettable
powder/
dust
wettable
powder
and
wettable
powder/
dust
Appbc.tion typ«
«xiAppUc.uoo
Ew«w*
seed piece
treatment
with duster
soak
(equipment
not on
label)
spray with
sprayer
Mirioum
Applic.ua, B.U
(ppm refers
to strepto-
mycin
content)
1 I!./ ICO IDS
seed (ppm
not
specified)
10O ppm
200 ppm
U.omum
Application RM»
(ppm refers
to strepto-
mycin
content)
1 lb/100
Ibs (ppm
not
specified)
TOO ppm
200 ppm
M.» (App.
None
specified
None
specified
None
specified
Mu.*
AW. e
M.x.R.1.
None
specified
None
specified
None
specified
Min. hunnl
BM~~n App. #
Max. HIM
(D.y.)
None
specified
None
specified
4
B-UK,-
f»*v
hural
(D^>
None
specified
None
specified
None
specified
G~».p*c
UfntBliofM
Mo«~l
None
specified
Maine
and
adjacent
areas are
identified
None
specified
OwalowwJ
None
specified
None
specified
None
specified
UM Lifnuvcro
Do not use
treated
seed
pieces for
food or
feed
purposes
Do not use
treated
seed
pieces for
food or
feed
purposes
None
specified
C
Sugarbeet
foliar
wettable
powder
spray with
sprayer
200 ppm
200 ppm
None
specified
,
1
None
specified
None
specified
None
specified
None
specified
None
specified
Do not
graze or
cut green
forage for
livestock
feed. Do
not feed
aftermath
or
screening
to
livestock.
-------
APPENDIX A - Case 0169 Chemical 006310 (Streptomycin Sulfate)
USE
GROUP
c
c
c
c
c
c
c
SITE
Ornamental
and/or
shade trees
Ornamental
herbaceous
plants
Ornamental
herbaceous
plants
Ornamental
herbaceous
plants
Ornamental
herbaceous
plants
Ornamental
woody
shrubs and
vines
Ornamental
woody
shrubs and
vines
Aptfc.lkm tifritig
bloom
foliar
cutting
cutting
foliar
foliar
bloom
foliar
foliar
Fotm
wettable
powder/
dust
wettable
powder
wettable
powder/
dust
wettable
powder
wettable
powder/
dust
wettable
powder
wettable
powder/
dust
A|»«c«iontvi»
«nd AixiCcMien
Equip™n.
spray with
sprayer
soak
(equipment
not on
label)
soak
(equipment
not on
label)
spray with
hand held
sprayer or
motor
driven
sprayer
spray with
sprayer
spray with
spray
spray with
sprayer
MMmum
AccColion RH>
(ppm refers
to strepto-
mycin
content)
1 00 ppm
50 ppm
200 ppm
2 Ib/A
200 ppm
1OO ppm
SO ppm
M»mun>
Apolic.tion DM.
(ppm refers
to strepto-
mycin
content)
1 00 ppm
50 ppm
200 ppm
None
specified
200 ppm
None
specified
1 0O ppm
M., 1 App..
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
Mix. 1
*ff 9
Mo R>0
None
specified
None
specified
None
specified
None
specified
specified
None
specified
None
specified
BxnMnApp. C
•tax. Rate
(D»^l
7
None
specified
None
specified
5 days
4
3 to 5
5
Eftty
W.rv.1
(O-y.)
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
0~gr«|>Hc
UiriUIKm.
Afevmd
None
specified
None
specified
None
specified
Hawaii is
identified
None
specified
None
specified
None
specified
DMh»~d
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
U» limil.cio™
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
-------
APPENDIX A - Case 0169 Chemical 006310 (Streptomycin Sulfate)
USE
CROUP
C
c
C
c
C. K
C. K
C. K
SITE
Ornamental
woody
shrubs and
vines
Tobacco
Tobacco.
Tobacco
Ornamental
herbaceous
plants
Ornamental
herbaceous
plants
Ornamental
woody
shrubs and
vines
Apptc.uoo Ummg
transplant
seedling
stage
seedling
stage
seedling
stage
foliar
cutting
foliar
bloom and
foliar
Foim
wettable
powder
and
wettable
powder/
dust
wettable
powder
and
wettable
powder/
dust
wettable
powder
wettable
powder/
dust
wettable
powder
wettable
powder
wettable
powder
A«*c«ion typ.
•nd Application
EW-»-«
soak
(equipment
not on
label)
drench
(equipment
not on
label);
spray with
sprayer
spray with
sprayer
spray with
sprayer
soak
(equipment
not on
label)
spray with
sprayer
spray with
sprayer
Mininua
Application R*t*
(ppm refers
to strepto-
mycin
content)
20O ppm
100 ppm
1 00 ppm
1 00 ppm
50 ppm
200 ppm
1 00 ppm
U»»mun.
Appbc.tion R.U
(ppm refers
to strepto-
mycin
content)
None
specified
200 ppm
ZOO ppm
200 ppm
200 ppm
200 ppm
20O ppm
M.x.fApp..
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
M.» <
APP.. e
MM. Rail
None
specified
-None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
Min. hurvd
BM«~«App.. 0
kbx.n.1.
(0«yml
Not
specified
5
5
5 to 7
None
specified
4
3 to 5
nmiicuj
Entry
tawvd
(D-rt
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
G*ov*phic
Ufntctioiw
Alowd
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
OiMllowwd
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
UM Uaiutiom
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
None
specified
-------
APPENDIX A - Case 0169 Chemical 006310 (Streptomycin Sulfate)
USES IN-
ELIGIBLE
FOR
REREG
USE
GBOUP
C, K
G
SITE
Ornamental
woody
shrubs and
vines
Ornamental
pond/
aquaria
Application fining
transplant
when
needed
Fain
wettable
powder
pelleted/
tableted
Application typa
and Application
E4t«|JIIMIII
spray with
sprayer
water
treatment
by hand
Minimum
AppUotion Rata
(ppm refers
to strepto-
mycin
content)
200 ppm
1 tablet/5
gal water
Maomum
Application Rata
(ppm refers
to strepto-
mycin
content)
200 ppm
None
specified
M«. / Appa.
200 ppm
None
specified
Ma«.«
App. 9
M». H.I.
None
specified
None
specified
Batman App*. 0
Max. Ran
(Dayal
None
specified
30 days
Raatriclad
tmr,
•Kwal
(Oaya)
None
specified
None
specified
OooorapMc
LimHatnna
Allomd
None
specified
None
specified
OMIoMvl
None
specified
None
specified
Ua» limhationa
None
specified
None
specified
NONE
A Terrestrial Food G
B Terrestrial Feed K
C Terrestrial Non-Food
Aquatic Non-Food Residential
Residential
-------
APPENDIX B
Table of the Generic Data Requirements
and Studies Used to Make the
Reregistration Decision
-------
GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregistration for
the pesticide streptomycin covered by this Reregistration Eligibility Document. It contains
generic data requirements that apply to streptomycin in all products, including data requirements
for which a "typical formulation" is the test substance.
The data table is organized in the following format:
1. Data Requirement (Column 1). The data requirements are listed in the order in
which they appear in 40 CFR, Part 158. The reference numbers accompanying
each test refer to the test protocols set in the Pesticide Assessment Guidelines,
which are available from the National Technical Information Service, 5285 Port
Royal Road, Springfield, VA 22161 (703) 487 - 4650.
2. Use Pattern (Column 2). This column indicates the use patterns for which the
data requirements apply. The following letter designations are used for the given
use patterns:
A Terrestrial food
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
O Indoor residential
3. Bibliographic citation (Column 3). If the Agency has acceptable data in its files,
this column lists the identifying number of each study. This normally is the
Master Record Identification (MRID) number, but may be a "GS" number if no
MRID number has been assigned. Refer to the Bibliography appendix for a
complete citation of the study.
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Streptomycin
REQUIREMENT
USE PATTERN CITATION
PRODUCT CHEMISTRY
61-1 Chemical Identity
61-2 Start. Mat. & Mnfg. Process
61-3 Formation of Impurities
62-1 Preliminary Analysis
63-2 Color
63-3 Physical State
63-4 Odor
63-5 Melting Point
63-6 Boiling Point
63-7 Density
63-8 Solubility
63-9 Vapor Pressure
63-10 Dissociation Constant
63-11 Octanol/Water Partition
63-12 pH
63-13 Stability
64-1 Submittal of Samples
ABCGK 41445401 - DATA GAP
ABCGK 41445401, 42044701, Pfizer letter (SEE BIBLIOGRAPHY)
ABCGK 41445401, 42044701 - DATA GAP
ABCGK 41445401 - DATA GAP
ABCGK 41445401
ABCGK 41445401
ABCGK 41445401
ABCGK 41445401
ABCGK N/A - TGAI is a solid at room temperature
ABCGK 41445401
ABCGK 41445401
ABCGK N/A - TGAI is a solid
ABCGK DATA GAP
ABCGK N/A - TGAI is polar and water soluble
ABCGK 41445401
ABCGK 41445401, 42044701
ABCGK RESERVED - If samples are required, the Agency will request them
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Streptomycin
REQUIREMENT
USE PATTERN CITATION
ECOLOGICAL EFFECTS
71-1A Acute Avian Oral - Quail/Duck ABCK
71-2A Avian Dietary (LC^ - Quail ABCK
71-2B Avian Dietary (LCgo) - Duck ABCK
72-1A Fish Acute (LCSO) - Bluegill ABCK
72-1C Fish Acute (LCSO) - Trout ABCK
72-2A Aquatic Invertebrate (EC50) ABCK
72-6 Aquatic Organism Accumulation ABCK
123-2 Aquatic Plant Growth ABCK
141-1 Honey Bee Acute Contact ABCK
41777701
41777702
107412
103395
103394
DATA GAP
WAIVED
Articles (SEE BIBLIOGRAPHY)
41777703
TOXICOLOGY
All lexicological data requirements were waived based on existing animal and human data. Toxicological references are listed
in the Bibliography (Appendix C).
81-1 Acute Oral Toxicity - Rat
81-2 Acute Dermal Toxicity -
Rabbit/Rat
81-3 Acute Inhalation Toxicity - Rat
81-4 Primary Eye Irritation - Rabbit
ALL
ALL
ALL
ALL
WAIVED
WAIVED
WAIVED
WAIVED
3
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Streptomycin
REQUIREMENT
USE PATTERN CITATION
TOXICOLOGY
81-5 Primary Dermal Irritation -
Rabbit
81-6 Dermal Sensitization - Guinea
Pig
81-7 Acute Delayed Neurotoxicity -
Hen
82-1A 90-Day Feeding - Rodent
82-1B 90-Day Feeding - Non-rodent
82-2 21-Day Dermal - Rabbit/Rat
82-3 90-Day Dermal - Rodent
82-4 90-Day Inhalation - Rat
82-5A 90-Day Neurotoxicity - Hen
82-5B 90-Day Neurotoxicity - Mammal
83-1A Chronic Feeding Toxicity -
Rodent
83-1B Chronic Feeding Toxicity - Non-
Rodent
83-2A Oncogenicity - Rat
83-2B Oncogenicity - Mouse
ALL
WAIVED
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
4
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Streptomycin
REQUIREMENT USE PATTERN CITATION
TOXICOLOGY
83-2B
83-3A
83-3B
83-4
84-2A
84-2B
84-4
85-1
Oncogenicity - Mouse
Developmental Toxicity - Rat
Developmental Toxicity - Rabbit
2-Generation Reproduction -
Rat
Gene Mutation (Ames Test)
Structural Chromosomal
Aberration
Other Genotoxic Effects
General Metabolism
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
ENVIRONMENTAL FATE
161-1
161-2
161-3
162-1
162-2
163-1
Hydrolysis
Photodegradation - Water
Photodegradation - Soil
Aerobic Soil Metabolism
Anaerobic Soil Metabolism
Leaching/Adsorption/Desorption
ABCK
ABCK
ABCK
ABCK
ABCK
ABCK
DATA GAP
WAIVED
WAIVED
WAIVED
WAIVED
WAIVED
5
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Streptomycin
REQUIREMENT
USE PATTERN CITATION
ENVIRONMENTAL FATE
165-1 Confined Rotational Crop
165-4 Bioaccumulation in Fish
ABCK
ABCK
WAIVED
WAIVED
RESIDUE CHEMISTRY
171-4C Residue Analytical Method -
Plants
171-4K Crop Field Trials
Beans (succulent and dry)
Celery
Peppers
Pome fruits
Potatoes
Tomatoes
AB
AB
00103383, 00103386, 00103390, 00108026
Gustafson Analytical Report (SEE BIBLIOGRAPHY)
00103384, 00108022
00065578, 00103384
00103377, 00103386, 00103390
00103384
00103384, 00108022
-------
APPENDIX C
STREPTOMYCIN BIBLIOGRAPHY
Citations Considered to be Part of the Data Base
Supporting the Reregistration of Streptomycin
-------
GUIDE TO APPENDIX C
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies
considered relevant by EPA in arriving at the positions and conclusions stated elsewhere
in the Reregistration Eligibility Document. Primary sources for studies in this biblio-
graphy have been the body of data submitted to EPA and its predecessor agencies in
support of past regulatory decisions. Selections from other sources including published
literature, in those instances where they have been considered, are 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 submittted. 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 also attempted 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 uniqu^
to the citation, and should be uses whenever a 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 further explanation). In a few cases,
entries added to the bibliography late in the review may be preceded by a nine character
temporary identifying number is also to be used whenever specific reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry
consists of a citation containing standard elements followed, in the case of material
submitted to EPA, by a description of the earliest known submission. Bibliographic con-
ventions used reflect the standard of the American National Standards Institute (ANSI),
expanded to provide for certain special needs.
a. Author. Whenever the author could confidently be identified, the Agency has
chosen to show a personal author. When no individual was identified, the
Agency has shown a identifiable laboratory or testing facility as the author.
When no author or laboratory could be identified, the Agency has shown the first
submitter as the author.
b. Document Date. The date of the study is taken directly from the document.
When the date is followed by a question mark, the bibliographer has deduced the
date from the evidence contained 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 the 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 trail-
ing parentheses include (in addition to any self-explanatory text) the following
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. When authorship is de-
faulted 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", which stands for "Company
Data Library". This accession number is in turn followed by an alpha-
betic suffix which shows the relative position of the study within the
volume.
-------
APPENDIX C
Streptomycin Bibliography
MRID Citation
00065578 Pfipharmecs (1958) [Efficacy of Streptomycin on Peppers, Tomatoes,
Pears, Apples, Tobacco and Chrysanthemums]. (Compilation;
unpublished study, including published data, received May 26,
1954?; November 7, 1955?; January 22, 1954?; February 20,
1958 under 1007-6; CDL: 229886-A).
00103377 Pfipharmecs (1968) [Streptomycin Residue Analyses - Pears]. (Compi-
lation; unpublished study received January 21, 1969 under 1007-
24; CDL: 005381-B).
00103383 Chas. Pfizer & Co., Inc. (1964) Streptomycin Residue Determination on
Apples. (Unpublished study received September 24, 1967 under
8F0693; CDL: 091202-G).
00103384 Interregional Research Project No. 4 (1972) [Streptomycin Residue
Determination in Various Crops, Dairy Products and Animal
Tissues]. (Compilation; unpublished study received on unknown
date under 1E1095; CDL: 093407-A).
00103386 Carroll, V. (1966) Streptomycin Residue Determination on Apples.
(Unpublished study received March 14, 1966 under 1007-24;
submitted by Pfipharmecs, Div. of Pfizer, Inc., New York, NY;
CDL: 101536-A).
00103390 Pfipharmecs (1960) Agri-mycin 100 Spray and Dust Field Trials on
Pears, Apples and Walnuts. (Unpublished study received
December 21, 1960 under 1007-24; prepared by Univ. of
California - Davis, Agricultural Experiment Station; CDL:
119407-B).
00103394 Pitcher, F. (1974) Agri-Strep: Rainbow Trout (Salmo gairdneri):
Test No. 678. (U.S. Environmental Protection Agency,
Pesticides Regulation Div., Animal Biology Laboratory;
Unpublished study; CDL: 129168-A).
00103395 Pitcher, F.; McCann, J. (1974) Agri-Strep: Bluegill (L. macrochi-
rus). (U.S. Environmental Protection Agency, Chemical &
Biological Investigations Branch, Technical Services Div.;
Unpublished study; CDL: 131068-A).
-------
APPENDIX C
Streptomycin Bibliography
MRID Citation
00107412 Fink, R. (1974) Final Report: Eight-Day Dietary LC50 - Mallard
Ducks: Streptomycin Sulfate: Project No. 105-107. (Unpublish-
ed study received March 18, 1974 under 618-28; prepared by
Truslow Farms, Inc., submitted by Merck & Co., Inc., Rahway,
NJ; CDL: 128709-B).
00108022 Interregional Research Project No. 4 (1972) Summary of Merck Strepto-
mycin Trials on Celery, Pepper, Potato and Tomato. (Compila-
tion; unpublished study received October 20, 1972 under
1E1095; CDL: 090855-A).
41445401 Dowd, N.; Defoe, J. (1990) Streptomycin Sulfate Technical - Product
Chemistry Data. Unpublished study prepared by Pfizer, Inc.,
Quality Control Division. 157 p.
41777701 Campbell, S.; Hoxter, K.; Smith, G. (1991) Streptomycin Sulfate
Technical: An Acute Oral Toxicity Study with the Northern
Bobwhite: Lab Project Number: 260-105. Unpublished study
prepared by Wildlife International Ltd. 19 p.
41777702 Long, R.; Hoxter, K.; Smith, G. (1991) Streptomycin Sulfate
Technical: A Dietary LC50 Study with the Northern Bobwhite:
Lab Project Number: 260-104. Unpublished study prepared by
Wildlife International Ltd. 17 p.
41777703 Winter, P.; Hoxter, K.; Smith, G. (1991) Streptomycin Sulfate
Technical: An Acute Contact Toxicity Study with the Honey
Bee: Lab Project Number: 260-106. Unpublished study
prepared by Wildlife International Ltd. 14 p.
42044701 DeFoe, J.; Dowd, N. (1991) Streptomycin Sulfate Technical: Product
Chemistry Data. Unpublished study prepared by Pfizer, Inc.
37 p.
British Crop Protection Council (1968) Pesticide Manual. 3rd ed.,
Worcestershire, England.
Brock, T.D. (1979) Biology of Microorganisms. 3rd ed., Prentice-Hall
Inc., New Jersey.
-------
APPENDIX C
Streptomycin Bibliography
MRID Citation
EPA (1988) Guidance for the Reregistration of Pesticide Products
Containing Streptomycin and Streptomycin Sulfate as the Active
Ingredient. Case No. 0169, 540/RS-88-097, Washington, D. C.
20460.
FDA (1986) Memorandum of R. L. Gillespie to P. Gushing on
Dihydrostreptomycin, dated January 9, 1986.
Fenton, J.; Klein, D. Studies on the Bacterial Degradation of
Streptomycin Using Radioactively-Labeled Compounds.
University of Minnesota, St. Paul.
Gustafson, Inc. (1992) Analytical Reports of Streptomycin Residue in
Beans dated August 20, 1992. (CBRS No. 10453). Gustafson,
Inc., Dallas, Texas.
Harrass, M.; Kindig, A.; Taub, F. (1985) "Responses of Blue-green
and Green Algae to Streptomycin in Unialgal and Paired
Culture". Aquatic Toxicology. 6, p. 1-11.
Kruger, W. (1961) The Activity of Antibiotics in Soils II. Movement,
Stability, and Biological Activity of Antibiotics in Soils and
Their Uptake by Tomato Plan 301-313.ts. South African
Journal of Agricultural Science. 4(3):
Lehninger, A. L. (1975) Biochemistry. 2nd ed., Worth Publishers, New
York.
Merck Index (1983) 10th ed., Merck and Co., New Jersey.
Muller, Hans-Gunther. (1982) "Sensitivity of Daphnia magna Strauss
Against Eight Chemotherapeutic Agents and Two Dyes".
Bulletin of Environmental Contamination Toxicology. 28, p. 1-2.
Physicians Desk Reference (1988) 42nd ed.
Pfizer, Inc. (1992) Letter from S. Bigelow to S. Lewis (EPA) dated
06/30/92.
Pramer, D.; Starkey, R. L. (1961) Determination of Streptomycin in
Soil and the Effect of Soil colloidal Material on its Activity.
New Jersey Agricultural Research Station, Rutgers University.
-------
APPENDIX C
Streptomycin Bibliography
MRID Citation
Pramer, D.; Starkey, R. L. (1972) Decomposition of Streptomycin in
Soil & by an Isolated Bacterium. Soil Science. 114(6): 451-455.
Symposium: Microbiological Significance of Drug Residues in Food.
Animal Health Institute and FDA-Center for Veterinary
Medicine, Rockville, MD, June 8-9, 1992.
Thompson, W. T. (1970) Agricultural Chemicals. Book IV., Thompson
Publications, Fresno, California, p. 35.
World Health Organization (1968) Twelfth Report of the Joint
FAQ/WHO Expert Committee on Food Additives. Geneva, 1-8 July,
1968, Technical Report Series No. 430.
-------
APPENDIX D
List of Available Related Documents
-------
APPENDIX D
The following is a list of available documents related to streptomycin. Its purpose is to provide
a path to more detailed information if it is needed. These accompanying documents are part of
the Administrative Record for streptomycin and are included in the EPA's Office of Pesticide
Programs Public Docket.
1. Health and Environmental Effects Science Chapters
2. Detailed Label Usage Information System (LUIS) Report
3. Streptomycin RED Fact Sheet
4. PR Notice 91-2 (Included in this RED) Pertains to the Label Ingredient Statement
5. Summary of the Residue Data Used in the ORES Analysis and the ORES
Analysis Tables
Federal publications on streptomycin are available and may be purchased from the
National Technical Information Service (NTIS), 5285 Port Royal Road, Springfield, VA 22161.
1. Pesticide Fact Sheet (No. 186) for Streptomycin: NTIS Stock No. PB89-129720.
2. Guidance for the Reregistration of Pesticide Products Containing Streptomycin
and Streptomycin Sulfate as the Active Ingredient (The 1988 Registration
Standard): NTIS Stock No. PB89-129738.
-------
UNfTED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
I-UY 2
OFfCCOF
SUBSTANCES
NOTICE TO MANUFACTURERS, PRODUCERS, FORMULATORS,
AND REGISTRANTS OF PESTICIDES
ATTENTION: Persons Responsible for Federal Registration of
Pesticide Products.
SUBJECT: Accuracy of Stated Percentages for Ingredients
Statement
I. PURPOSE:
The purpose of this notice is to clarify the Office of
Pesticide Program's policy with respect to the statement of
percentages in a pesticide's label's ingredient statement.
Specifically, the amount (percent by weight) of ingredient(s)
specified in the ingredient statement on the label must be stated
as the nominal concentration of such ingredient (s), as that term is
defined in 40 CFR 158.153(i). Accordingly, the Agency has
established the nominal concentration as the only acceptable label
claim for the amount of active ingredient in the product.
II. BACKGROUND
For some time the Agency has accepted two different methods of
identifying on the label what percentage is claimed for the
ingredient(s) contained in a pesticide. Some applicants claimed a
percentage which represented a level between the upper and the
lower certified limits. This was referred to as the nominal
concentration. Other applicants claimed the lower limit as the
percentage of the ingredient(s) that would be expected to be
present in their product at the end of the product's shelf-life.
Unfortunately, this led to a great deal of confusion among the
regulated industry, the regulators, and the consumers as to exactly
how much of a given ingredient was in a given product. The Agency
has established the nominal concentration as the only acceptable
label claim for the amount of active ingredient in the product.
Current regulations require that the percentage listed in the
active ingredient statement be as precise as possible reflecting
good manufacturing practices 40 CFR 156.10(g)(5). The certified
limits required for each active ingredient are intended to
encompass any such "good manufacturing practice" variations 40 CFR
158.175(c)(3).
Printfd ontocycMPip*
-------
2.
The upper and lover certified limit*, which oust be proposed in
connection with a product's registration, represent the amounts of
an ingredient that may legally be present 40 CFR 158.175. The lover
certified limit is used as the enforceable lover limit for the
product composition according to FIFRA section 12(a)(l)(C), while
the nominal concentration appearing on the label vould be the
routinely achieved concentration used for calculation of dosages
and dilutions.
The nominal concentration vould in fact state the greatest
degree of accuracy that is varranted vith respect to actual product
composition because the nominal concentration vould be the amount
of active ingredient typically found in the product.
It is important for registrants to note that certified limits
for active ingredients are not considered to be trade secret
information under FIFRA section 10(b). In this respect the
certified limits vill be routinely provided by EPA to States for
enforcement purposes, since the nominal concentration appearing on
the label may not represent the enforceable composition for
purposes of section 12(a)(1)(C).
ZZZ. REQUIREMENTS
As described belov under Unit V. " COMPLIANCE SCHEDULE," all
currently registered products as veil as all applications for nev
registration must comply vith this Notice by specifying the nominal
"concentration expressed as a percentage by veight as the label
claim in the ingredient(s) statement and equivalence statements if
applicable (e.g., elemental arsenic, metallic zinc, salt of an
acid). In addition, the requirement for performing sample analyses
of five or more representative samples must be fulfilled. Copies of
the raw analytical data must be submitted vith the nominal
ingredient label claim. Further information about the analysis
requirement nay be found in the 40 CFR 158.170. All products are
required to provide certified limits for each active, inert
ingredient, impurities of toxicological significance(i.e., upper
limit (s) only) and on a case by case basis as specified by EPA.
These limits are to be set based on representative sampling and
chemical analysis(i.e., quality control) of the product.
The format of the ingredient statement oust conform to 40 CFR
156-Labeling Requirements For Pesticides and Devices.
After July 1, 1997, all pesticide ingredient statements must
be changed to nominal concentration.
-------
XV. PRODUCTS THAT REQUIRE EFFICACY DATA
All pesticides are required to be efficacious. Therefore,
the certified lover liaits nay not be lover then the ainiaua
level to eehieve efficacy. This is extreaely iaportant for
products vhich are intended to control pests vhich threaten the
public health, e.g., certain antiaicrobial and rodenticide
products. Refer to 40 CFR 158.640.
In those cases where efficacy liaits have been established,
the Agency vill not accept certified lover Units vhich are belov
that level for the shelf life of'the product.
• •
V. COMPLIANCE SCHEDULE
As described earlier, the purpose of this Notice is to Bake
the registration process sore uniform and Bore aanageable for
both the agency and the regulated coaaunity. It is the Agency's
intention to iapleaent the requireaents of this notice as
saoothly as possible so es not to disrupt or delay the Agency's
high priority programs, i.e., reregistration, nev cheaical, or
fast track (FIFRA section 3(c)(3)(B). Therefore,
applicants/registrants are expected to coaply with the
requireaents of this Notice as follovs:
(1) Beginning July 1, 1991, all nev product
registrations subaitted to the Agency
are to coaply vith the requireaents of this
Notice.
(2) Registrants having products subject to
reregistration under FIFRA section 4(a) ere to
coaply vith the requireaents of this Notice vhen
specific products are called in by the Agency
under Phase V of the Reregistration Program.
(3) All other products/applications that are
not subject to (1) and (2) above vill have until
July 1, 1997, to coaply vith this Notice.
Such applications should note •Conversion
to Noainal Concentration" on the application
for*. These types of aaendaents vill not be
handled as "Fast Track" applications but
vill be handled as routine requests.
VI. FOR FURTHER INFORMATION
Contact Tyrone Aiken for inforaatlon or questions concerning
this notice en (703) 557-5024.
Ann* E. Lindsay, Director
Registration Division (R-7505
-------
APPENDIX E
Pesticide Reregistration Handbook
-------
APPENDIX F
Generic Data Call-In
-------
*% af% ', UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
* ^!?2. * WASHINGTON, D.C. 20460
DATA CALL-IN NOTICE
•
CERTIFIED 'MAIL CCD C n IQQ9 PESTCOESANO'Cx .
btr o U iyy£ SCSSTANCES
Dear Sir or Madam:
'This Notice requires you and other registrants of pesticide
products containing the active ingredient identified in
Attachment A of this Notice, the Data Call-In Chemical Status
Sheet, to submit certain data as noted herein to the U.S.
Environmental Protection Agency (EPA, the Agency). These data
are necessary to maintain the continued registration of your
product(s) containing this active ingredient. Within 90 days
after you receive this Notice you must respond as set forth in
Section III below. Your response must state:
1. how you will comply with the requirements set forth in
this Notice and its Attachments A through E; or
2. why you believe you are exempt from the requirements
listed in this Notice and in Attachment C, Requirements
Status and Registrant's Response Form, (see section
III-B); or
3. why you believe EPA should not require your submission
of data in the manner specified by this Notice (see
section XXX-D).
Xf you do not respond to this Notice, or if you do not
satisfy EPA that you will comply with its requirements or should
be exempt or excused from doing so, then the registration of your
product(s) subject to this Notice will b« subject to suspension.
We have provided a list of all of your products subject to this
Notice in Attachment B, Data Call-in Response Fornu as well as a
list of all registrants who were sent this Notice (Attachment D).
Th« authority for this Notice is section 3(c)(2)(B) of the
Federal Insecticide, Fungicide and Rodenticide Act as amended
(FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
information is authorized under the Paperwork Reduction Act by
OMB Approval No. 2070-0107 (expiration data 12-31-92).
-------
This Notice is divided into six sections and five
Attachments. The Notice itself contains information and
instructions applicable to all Data Call-in Notices. The'
Attachments contain specific chemical information and
instructions. The six sections of the Notice are:
Section I - Why You Are Receiving This Notice
Section II - Data Required By This Notice
Section III - Compliance With Requirements Of This
Notice
Section IV - Consequences Of Failure To Comply with
This Notice
Section V - Registrants' Obligation To Report
Possible Unreasonable Adverse Effects
Section VI - Inquiries And Responses To This Notice
The Attachments to this Notice are:
Attachiwnt A - Data Call-In Chemical Status Sheet
Attachment B - Data Call-In Response Form
Attachment C - Requirements Status And Registrant's Response
Form
Attachment 0 - List Of All Registrants Sent This Data
Call-in Notice . .
Attachment E - Cost Share And Data Compensation Forms
SECTION I. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active
ingredient and reevaluated the data needed to support continued
registration of the subject active ingredient. This reevaluation
identified additional data necessary to assess the health and
safety of the continued use of products containing this active
ingredient. You have been sent this Notice because you have
product(s) containing the subject active ingredient.
SECTION II. DATA REQUIRED BY THIS NOTICE
II-A. DATA REQUIRED
The data required by this Notice are specified in
Attachment C, Requirements Status and Registrant's Response Form.
Depending; on the results of the studies required in this Notice,
additional tasting nay be required.
II-B. SCHEDULE FOR SUBMISSION OF DATA.
You ar« required to submit .the data or otherwise satisfy the
data requirement* specified in Attachment C, Requirements status
and Registrant's Response Porn, within the timeframes provided.
-------
II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in
accordance with test standards outlined in the Pesticide Assessment
Guidelines for those studies for which guidelines have been
established.
These EPA Guidelines 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 (40 CFR § 158.70). When
using the OECD protocols, they should be modified as appropriate so
that the data generated by the study will satisfy the requirements
of 40 CFR § 158. Normally, the Agency will not extend deadlines
for complying with data requirements when the studies were not
conducted in accordance with acceptable standards. The OECD
protocols are available from OECD, 1750 Pennsylvania Avenue N.W.,
Washington, D.C. 20006.
All new studies and proposed protocols submitted in response
to this Data Call-in Notice must be in accordance with Good
Laboratory Practices [40 CFR Part 160.3(a)(6)].
II-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3feU21fBl NOTICES
ISSUED BY THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in
anv way supersede or change the requirements of any previous Data
Call-infsi. or any other agreements entered into with the Agency
pertaining to such prior Notice. Registrants oust comply with the
requirements of all Notices to avoid issuance of a Notice of Intent
to suspend their affected products.
SECTION 111. COMPLIANCE WITH REQUIREMENTS OP THIS NOTICE
III-A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice
must be submitted to the Agency within 90 days after your receipt
of this Notice. Failure to adequately, respond to this Notice
within 90 days of your receipt will be a basis for issuing a Notice
of Intent to Suspend (NOIS) affecting your products. This and other
bases for issuance of NOIS due to failure to comply with this
Notice are presented in Section IV-A and IV-B.
-------
III-B. OPTIONS FOR RESPONDING TO THE AGENCY
The options for responding to this Notice are: l) voluntary
cancellation, 2) delete use(s), (3) claim generic data exemption,
(4) agree to satisfy the data requirements imposed by this Notice
or (5) request a data waiver(s).
A discussion of how to respond if you chose the Voluntary
Cancellation option, the Delete Use(s) option or the Generic Data
Exemption option is presented below. A discussion of the various
options available for satisfying the data requirements of this
Notice is contained in Section III-C. A discussion of options
relating to requests for data waivers is contained in
Section III-D.
There are two forms that accompany this Notice of which,
depending upon your response, one or both must be used in your
response to the Agency. These forms are the Data-Call-in Response
•Form. Attachment B an£ the Requirements Status and Registrant's
Response Form. Attachment C. The Data Call-In Response Form must be
submitted as part of every response to this Notice. Please note '
that the company's authorized representative is required to sign
the first page of the Data Call-In Response Form and Requirements
Status and Registrant's Response Forrn (if this form is required)
and initial any subsequent pages. The fonts contain separate
detailed instructions on the response options. Do not alter the
printed material. If you have questions or need assistance in
preparing your response, call or write the contact person
identified in Attachment A.
. 1. Voluntary Cancellation - You may avoid the requirements of
this Notice by requesting voluntary cancellation of your product(s)
containing the active ingredient that is the subject of this
Notice. If you wish to voluntarily cancel your product, you must
submit a completed Data Call-In Response Forn. indicating your
election of this option. Voluntary cancellation is item number 5-
on the Data Call-In Response Form. If you choose this option, this
is the only fora that you are required to complete.
If you chose* to voluntarily cancel your product, further sale
and distribution of your product after the effective date of
cancellation must be in accordance with the Existing Stocks
provision* of this Notice which are contained in Section IV-C.
2. Qaa Delation - You may avoid the requirements of this
Notice by eliminating the uses of your product to which the
requirements apply. If you wish to amend your registration to
delete uses, you must submit the Requirementa status and
Registrant'a Response Form, a completed application for amendment,
a copy of your proposed amended labeling, and all other information
required for processing the application. Use deletion is option-
number 7 on the Requirements status and Registrant's Response For™
You must also complete a Data call-in Response Form by signing the
certification, item number 8. Application forms for amending
-------
registrations nay be obtained from the Registration Support and
Emergency Response Branch, Registration Division, (703) 557_^2126.
If you choose to delete the use(s) subject to this Notice or
uses subject to specific data requirements, further sale,
distribution, or use of your product after one year from the due
date of your 90 day response, must bear an amended label.
3. Generic Data Exemption - Under section 3(c)(2)(D) of
FIFRA, an applicant for registration of a product is exempt from
the requirement to submit or cite generic data concerning an active
'ingredient if the active ingredient in the product is derived
exclusively from purchased, registered pesticide products
containing the active ingredient. EPA has concluded, as an
exercise of its discretion, that it normally will not suspend the
registration of a product which would qualify and continue to
qualify for the generic data exemption in section 3(c)(2)(D) of
FIFRA. To qualify, Ail of the following requirements must be met:
a. The active ingredient in your registered product must be
present solely because of incorporation of another
registered product which contains the subject active
ingredient and is purchased from a source not connected
with you;
b. Every registrant who is the ultimata source of the active
ingredient in your product subject to this DCI must be in
compliance with the requirements of this Notice and must
remain in compliance; and
c. You must have provided to EPA an accurate and current
"Confidential Statement of Formula" for each of your
products to which this Notice applies.
!
To apply for the Generic Data Exemption you must submit a
completed Data Call-In Response Form. Attachment B and all
supporting documentation. The Generic Data Exemption is item
number 6a on the Data Call-In Response Form, if you claim a
generic data exemption you are not required to complete the
Requirements Status and Registrant*a Response Fern. Generic Data
Exemption cannot be selected as an option tor product specific
data, •••-
'•- :* , •
If you are granted a Generic Data Exemption, you rely on the
effort* of other parsons to provide the Agency with. the required
data. If the registrant(•) who have committed to generate and
submit th« required data fail to take appropriate steps to meet the
requirements or ar« no longer in. compliance with this Data Call-In
Notice, the Agency vill consider that both they and you. are not in
compliance and will normally initiate proceedings to suspend the
registrations of both your and their product(s), unless you commit
to submit and do submit the required data within the specified
time. In such cases the Agency generally vill not grant a time
extension for submitting the data.
-------
4. Satisfying the Data Requirements of this Notice There are
various options available to satisfy the data requirements of this
Notice. These options are discussed in Section III-C of this
Notice and comprise options 1 through 6 on the Requirements stat^
and Registrant's Response Form and option 6b and 7 on the Data
Call-in Response Form. If you choose option 6b or 7, you must
submit both forms as well as any other information/data pertaining
to the option chosen to address the data requirement.
5. Request for Data Waivers. Data waivers are discussed in
Section III-D of this Notice and are covered by options 8 and 9 on
the Requirements Status and Registrant's Response Form. If you
choose one of these options, you must submit both forms as well as
any other information/data pertaining to the option chosen to
address the data requirement.
III-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call-in Response Form that you
agree to satisfy the data requirements (i.e. you select option 6b-
and/or 7), then you must select one of the six options on the
Requirements Status and Registrant's Response Form related to data
production for each data requirement. Your option selection
be entered under item number 9, "Registrant Response." The six
options related to data production are the first six options
discussed under item 9 in the instructions for completing the
Requirements Status and Registrant's Response Form. These six
options are listed immediately below with information in
parentheses to guide registrants to additional instructions
provided in this Section. The options are:
(1) I will generate and submit data within the specified
timeframe (Developing Data)
(2) I have entered into an agreement with one or more
registrants to develop data jointly (Cost Sharing)
(3) Z have made offers to cost-share (Offers to Cost
Share)
(4) Z am submitting an existing study that has not been
submitted previously .to the Agency by anyone
(Submitting an Existing Study)
(5) Z an submitting or citing data to upgrade a study
classified by EPA as partially acceptable and
upgradeable (Upgrading a Study)
(6) Z am citing an existing study that EPA has
classified as acceptable or an existing study that
has been submitted but net reviewed by the Agency
(Citing an Existing Study)
-------
Option 1. Developing Data — If you choose to develop the
required data it must be in conformance with Agency deadlines and
with other Agency requirements as referenced herein and in .the
attachments. All data generated and submitted must comply with the
Good Laboratory Practice (GLP) rule (40 CFR Part 160), be conducted
according to the Pesticide Assessment Guidelines (PAG), and be in
conformance with the requirements of PR Notice 86-5. In addition,
certain studies require Agency approval of test protocols in
advance of study initiation. Those studies for which a protocol
must be submitted have been identified in the Requirements Status
and Registrant's Response Form and/or footnotes to the fora. If
you wish to use a protocol which differs from the options discussed
in Section II-C of this Notice, you must submit a detailed
description of the proposed protocol and your reason for wishing to
use it. The Agency may choose to reject a protocol not specified
in Section II-C. If the Agency rejects your protocol you will be
notified in writing, however, you should be aware that rejection of
a proposed protocol will not be a basis for extending the deadline
for submission of data.
A progress report must be submitted for each study within 90
days from the date you are required to commit to generate-or
undertake some other means to address that study requirement, such
as maki ig an offer to cost share or agreeing to share in the cost
of developing that study. A 90-day progress report must be
submitted for all studies. This 90-day progress report must
include the date the study was or will be initiated and, for
studies to be started within 12 months of commitment, the name and
address of the laboratory(ies) or individuals who are or will be
conducting the study.
In addition, if the time frame for submission of a final
report is more than 1 year, interim reports must be submitted at 12
month intervals from the date you are required to commit to
generate or otherwise address the requirement for the study.
In addition to the other information specified in the preceding
paragraph, at a minimum, a brief description of current activity on
and the status of the study must be included as well as a full
description of any problems encountered since the last progress
report.
The time, frames in the Requirements Status and Registrant's
Response Form are the time frames that the Agency is allowing for
the submission of completed study reports or protocols. The noted
deadlines run from the data of the receipt of this Notice by the
registrant. If the data are not submitted by the deadline, each
registrant is subject to receipt of a Notice of Intent to Suspend
the affected registration(s).
Zf you cannot submit the data/reports to the Agency in the
time required by this Notice and intend to seek additional time to
meet the requirements(s), you must submit a request to the Agency
which includes: (1) a detailed description of the expected
difficulty and (2) a proposed schedule including alternative dates
-------
8
for meeting such requirements on a step-by-step basis. You must
explain any technical or laboratory difficulties and provide
documentation from the laboratory performing the testing. While
EPA is considering your request, the original deadline remains.
The Agency will respond to your request in writing. If EPA does
not grant your request, the original deadline remains. Normally,
extensions can be requested only in cases of extraordinary testing
problems beyond the expectation or control of the registrant.
Extensions will not be given in submitting the 90-day responses.
Extensions will not be considered if the request for extension is
not made in a timely fashion; in no event shall an extension
request be considered if it is submitted at or after the lapse of
the subject deadline.
Option 2. Agreement to Share in Cost to Develop Data -r If
you choose to enter into an agreement to share in the cost of
producing the required data but will not be submitting the data
yourself, you must provide the name of the registrant who will be
submitting the data. You must also prov5.de EPA with documentary
evidence that an agreement has been formed. Such evidence may be
your letter offering to join in an agreement and the other
registrant's acceptance of your offer, or a written statement by
the parties that an agreement exists. The agreement to produce the
data need not specify all of the terms of the final arrangement _
between the parties or the mechanism to resolve the terms. Secticfl
3(c)(2)(B) provides that if the parties cannot resolve the terms or
the agreement they may resolve their differences through binding
arbitration.
Option 3. Offer to Share in the Cost of Data Development — If
you have made an offer to pay in an attempt to enter into an
agreement or amend an existing agreement to meet the requirements
of this Notice and have been unsuccessful, you may request EPA (by
selecting this option) to exercise its discretion not to suspend
your registration(s), although you do not comply with the data
submission requirements of this Notice. EPA has determined that as
a general policy, absent other relevant considerations, it will not
suspend the registration of a product of a registrant who has in
good faith sought and continues to seek to enter into, a joint data
development/cost sharing program, but tha other registrant(s)
developing the data has refused to accept your offer. To qualify
for this option, you must submit documentation to the Agency
proving that you hava made an offer to another registrant (who has
an obligation to submit data) to shara in the burden of developing
that data. You must also submit to tha Agency a completed EPA Form
8570-32, Certification of Offar to Cost Share in the Development of
Data, Attachment E. In addition, you must demonstrate that the
other registrant to whom tha offar was mad* has not accepted your
offer to enter into a costsharing agreement by including a copy of
your offar and proof of tha other registrant's receipt of that
offar (such as a cartiflad mail racaipt). Your offar must, in
addition to anything else, offar to share in the burden of
producing the data upon terms to be agreed or failing agreement tc
ba bound by binding arbitration as providad by FXFRA section
-------
3(c)(2)(B)(iii) and must not qualify this offer. The other
registrant must also inform EPA of its election of an option to
develop and submit the data required by this Notice by submitting a
Data Call-in Response Form and a Requirements Status and
Registrant's Response Form committing to develop and submit the
data required by this Notice.
In order for you to avoid suspension under this option, you
may not withdraw your offer to share in the burdens of developing
the data. In addition, the other registrant must fulfill its
commitment to develop and submit the data as required by this
Notice. If the other registrant fails to develop the data or for
some other reason is 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 do submit the required data in the specified time frame. In
such cases, the Agency generally will not grant a time extension
for submitting the data.
Option 4. Submitting an Existing Study --If you choose to
submit an existing study in response to this Notice, you must
determine that the study satisfies the requirements imposed by this
Notice. You may only submit a study that has not been previously
submitted to the Agency or previously cited by anyone. Existing
studies are studies which predate issuance of this Notice. Do not
use this option if you are submitting data to upgrade a study. (See
Option 5).
You should be aware that if the Agency determines that the
study is not acceptable, the Agency will require you to comply with
this Notice, normally without an extension of the required date of
submission. The Agency may determine at any time that a study is
not valid and needs to be repeated.
To meet the requirements of the OCX Notice for submitting an
existing study, all of the following three criteria must be clearly
met;
a. You must certify at the time that the existing study is
submitted that the raw data and specimens from the study are
available for audit and review and you oust identify where
they are available. This must be dona in accordance with
the requirements of the Good Laboratory Practice (GLP)
regulation, 40 CFR Part 160. As stated in 40 CFR 160.3(j)
• '[r]aw data* means any laboratory worksheets, records,
memoranda, notes, or exact copies thereof, that are the result
of original observations and activities of a study and are
necessary for the reconstruction and evaluation of the report
of that study. Zn the event that exact transcripts of raw
data have been prepared (e.g., tapes which have been
transcribed verbatim, dated, and verified accurate by
signature), the exact copy or exact transcript nay be
substituted for the original source as raw data. 'Raw data*
may include photographs, microfilm or microfiche copies,
-------
10
computer printouts, magnetic media, including dictated
observations, and recorded data from automated instruments."
The tern "specimens", according to 40 CFR 160.3(k), means "any
material derived from a test system for examination or
analysis."
b. Health and safety studies completed after May 1984 must
also contain all GLP-required quality assurance and quality
control information, pursuant to the requirements of 40 CFR
Part 160. Registrants must also certify at the time of
submitting the existing study that such CLP information is
available for post-May 1984 studies by including an
appropriate statement on or attached to the study signed by an
authorized official or representative of the registrant.
c. You oust certify that each study fulfills the acceptance
criteria for the Guideline relevant to the study provided in
the FIFRA Accelerated Reregistration Phase 3 Technical
Guidance and that the study has been conducted according to
the Pesticide Assessment Guidelines (PAG) or meets the purpose
of the PAG (both available from NTIS). A study not conducted
according to the PAG may be submitted to the Agency for
consideration if the registrant believes that the study
clearly meets the purpose of the PAG. The registrant is
referred to 40 CFR 158.70 which states the Agency's policy
regarding acceptable protocols. If you wish to submit the
study, you must, in addition to certifying that the purposes
of the PAG are met by the study, clearly articulate the
rationale why you believe the study meets the purpose of the
PAG, including copies of any supporting information or data.
It has been the Agency's experience that studies completed
prior to January 1970 rarely satisfied the purpose of the PAG
and that necessary raw data are usually not available for such
studies.
If you submit an existing study, you must certify that the
study meets all requirements of the criteria outlined above.
If EPA has previously reviewed a protocol for a study you are
submitting, you must identify any action taken by the Agency on the
protocol and must indicate, as part of your certification, the
manner in which all Agency comments, concerns, or issues were
addressed in the- final protocol and study.
If you'know of a study pertaining to any requirement in this
Notice which does not meet the criteria outlined above but does
contain factual information regarding unreasonable adverse effects,
you must notify the Agency of such a study. If such study is in
the. Agency's files, you need only cits it along with the
notification. It not in the Agency's files, you must submit a
summary and copies as required by PR Notice 86-5.
-------
11
Option 5. Upgrading a study — if a study has been classified
as partially acceptable and upgradeable, you may submit data to
upgrade that study. The Agency will review the data submitted and
determine if the requirement is satisfied. If the Agency decides
the requirement is not satisfied, you may still be required to
submit new data normally without any time extension. Deficient,
but upgradeable studies will normally be classified as
supplemental. However, it is important to note that not all
studies classified as supplemental are upgradeable. If you have
questions regarding the classification of a study or whether a
study may be upgraded, call or write the contact person listed in
Attachment A. If you submit data to upgrade an existing study you
must satisfy.or supply information to correct all deficiencies in
the study identified by EPA. You must provide a clearly
articulated rationale of how the deficiencies have been remedied or
corrected and why the study should be rated as acceptable to EPA.
Your submission must also specify the MRID number(s) of the study
which you are attempting to upgrade and must be in conformance with
PR Notice 86-5.
•
Do not submit additional data for the purpose of upgrading a •
study classified as unacceptable and determined by the Agency as
not capable of being upgraded.
This option should also be used to cite data that has been
previously submitted to upgrade a study, but has not yet been
reviewed by the Agency. You must provide the MRID number of the
data submission as well as the MRID number of the study being
upgraded.
The criteria for submitting an existing study, as specified in
Option 4 above, apply to all data submissions intended to upgrade
studies. Additionally your submission of data intended to upgrade
studies must be accompanied by a certification that you comply with
each of those criteria as veil as a certification regarding
protocol compliance with Agency requirements.
Option 6. Citing Existing Studies — If you choose to cite a
study that has been previously submitted to EPA, that study must
have been previously classified by EPA as acceptable or it must b«
a study which has not yet been reviewed by the Agency. Acceptable
toxicology studies generally will have been classified as "core-
guideline* or "core minimum." For ecological effects studies, the
classification generally would be a rating*of "core." For all
other disciplines the classification would be "acceptable." With
respect to any studies for which you wish to select this option you
must provide the MRID number of the study you are citing and, if
the study has been reviewed by the Agency, you oust provide the
Agency's classification of the study.
- If you are citing a study of which you are not the original
data submitter, you oust submit a completed copy of EPA Fora
8570-31, Certification with Respect to Data Compensation,
Requirements.
-------
12
III-D REQUESTS FOR DATA WAIVERS
There are two types of data waiver responses to this Notice.
The first is a request for a low volume/minor use waiver an: the
second is a waiver request based on your belief that the data
requirement(s) are inapplicable and do not apply to your product.
1. Low Volume/Minor Use Waiver — Option 8 on the Requirements
Status and Registrant's Response Form. Section 3(c)(2)(A) of FIFRA
requires EPA to consider the appropriateness of requiring data for
low volume, minor use pesticides. In implementing this provision
EPA considers as low volume pesticides only those active
ingredients whose total production volume for all pesticide
registrants is small. In determining whether to grant a low
volume, minor use waiver the Agency will consider the extent,
pattern and volume of use, the economic incentive to conduct the
testing, the importance of the pesticide, and the exposure and risk
from use of the pesticide. If an active ingredient is used for
both high volume and low volume uses, a low volume exemption will
not be approved. If all uses of an active ingredient are low
volume and the combined volumes for all uses are also low, then an
exemption may be granted, depending on review of other information
outlined below. An exemption will not be granted if any registrant
of the active ingredient elects to conduct the testing. Any
registrant receiving a low volume minor use waiver must remain
within the sales figures in their forecast supporting the waiver
request in order to remain qualified for such waiver. If granted a
waiver, a registrant will be required, as a condition of the
waiver, to submit annual sales reports. The Agency will respond to
requests for waivers in writing.
To apply for a low volume, minor use waiver, you must submit
the following information, as applicable to your product(s), as
part of your 90-day response to this Notice:
a(i). Total company sales (pounds and dollars) of all
registered product(s) containing the active ingredient.
If applicable to the active ingredient, include
foreign sales for those products that are not
.registered in this country but are applied to sugar
(cane or beet), coffee, bananas, cocoa, and other
such, crops. Present the above information by year
for each of the past five years.
ii. Provide an estimate of the sales (pounds and dollars)
of the active ingredient for each major use site.
Present the above information by year for each of the
past five years.
-------
13
b. Total direct production cost of product(s) containing
the active ingredient by year for the past five years.
Include information on raw material cost, direct
labor cost, advertising, sales and marketing, and any
other significant costs listed separately.
c. Total indirect production cost (e.g. plant overhead,
amortized plant and equipment) charged to product(s)
containing the active ingredient by year for the past
five years. Exclude all non-recurring costs that were
directly related to the active ingredient, such as
costs of initial registration and any data development.
d(i). A list of each data requirement for which you seek
a waiver. Indicate the type of waiver sought and
the estimated cost to you (listed separately for
each data requirement and associated test) of
conducting the testing needed to fulfill each of
these data requirements.
ii. A list of each data requirement for which you are not
seeking any waiver and the estimated cost to you
(listed separately for each data requirement and
associated test) of conducting the testing heeded to
fulfill each of these data requirements.
e. For each of the next ten years, a year-by-year fore-
cast of company sales (pounds and dollars) of the
active ingredient, direct production costs of product(s)
containing the active ingredient (following the
parameters in item 2 above), indirect production
costs of product(s) containing the active ingredient
(following the parameters in item 3 above), and
costs of data development pertaining to the active
ingredient.
f. A description of the importance and unique benefits of
the active ingredient to users. Discuss the us*
patterns and the effectiveness of the active ingredient
relative to registered alternative chemicals and
non-chemical control strategies. Focus on benefits
unique to the active ingredient, providing information
that is as quantitative as possible. It you do not
have,quantitative data upon which to base your estimates,
then present the reasoning used to derive your estimates.
To assist the Agency in determining- the degree of
importance of the active ingredient in terns of its
benefits, you should provide information on any of
the following factors, as applicable to your product(s):
(a) documentation of the usefulness of the active
ingredient in Integrated Pest Management, (b) description
of the-beneficial impacts on the environment of use
of the active ingredient, as opposed to its registered
-------
14
alternatives, (c) information on the breakdown of the
active ingredient after use and on its persistence in
the environment, and (d) description of its usefulness
against a pest(s) of public health significance.
Failure to submit sufficient information for the Agency to
make a determination regarding a request for a low volume/minor use
waiver will result in denial of the request for a waiver.
2. Request for Waiver of Data — Option 9 on the Requirements
Status and Registrant's Response Form. This option may be used if
you believe that a particular data requirement should not apply
because the corresponding use is no longer registered or the
requirement is inappropriate. You must submit a rationale
explaining why you believe the data requirements should not apply.
You oust also submit the current label(s) of your product(s) and,
if a current copy of your Confidential Statement of Formula is not
already on file you must submit a current copy.
• .
You will be informed of the Agency's decision in writing. If
the Agency determines that the data requirements of this Notice do'
not apply to your product(s), you will not be required to supply
the data pursuant to section 3(c)(2)(B). If EPA determines thai;
the data ire required for your product(a). you must choose a method
of meeting the requirements of this Notice within the time frame
provided by this Notice. Within 30 days of your receipt of the
Agency's written decision, you must submit a revised Requirements
Status and Registrant's Response Form indicating the option chosen.
IV. . CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE" "
IV-A NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products
subject to this Notice due to failure by a registrant to comply
with the requirements of this Data Call-In Notice, pursuant to
FIFRA section 3(c)(2)(B). Events which may be the basis for
issuance of a Notice of Intent to Suspend include, but are not
limited, to, the following:
1. Failure to respond as required by this Notice within 90
days of your receipt of this Notice. .
2. Failure- to submit on the required schedule an acceptable
proposed or final protocol when such is required to be
submitted to the Agency for review.
3. Failurs to submit on the required schedule an adequate
progress report on a study as required by this Notice.
4. Failure to submit on the required schedule acceptable
data as required by this Notice.
-------
15
5. Failure to take a required action or submit adequate
information pertaining to any option chosen to address the
data requirements (e«9-» any required action or information
pertaining to submission or citation of existing studies or
offers, arrangements, or arbitration on the sharing of costs
or the formation of Task Forces, failure to comply with the
terms of an agreement or arbitration concerning joint data
development or failure to comply with any terms of a data
waiver).
6. Failure to submit supportable certifications as to the
conditions of submitted studies, as required by Section III-C
of this Notice.
7. withdrawal of an offer to share in the cost of developing
required data.
8. Failure of the registrant to whom you have tendered an
offer to share in the cost of developing data and provided
proof of the registrant's receipt of such offer or failure of
a registrant on whom you rely for a generic data exemption
either to: ij*»
a. inform EPA of intent to develop and submit the data
required by this Notice on a Data Call-In Response Form and
a Requirements Status and Registrant's Response Form?
b. fulfill the commitment to develop and submit the data as
required by this Notice; or
c. otherwise take appropriate steps to meet the
requirements stated in this Notice,
unless you commit to submit and do submit the required data in
the specified time frame.
9. Failure to take any required or appropriate steps, not
mentioned above, at any time following the issuance of this
Notice.
IV-B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS
UNACCEPTABLE
The Agency may determine that a study (even if submitted
within the required time) is unacceptable and constitutes a basis
for issuance of a Notice of Intent to Suspend. The grounds for
suspension include, but are not limited to, failure to meet any of
the following:
-------
16
1. EPA requirements specified in the Data Call-in Notice or
other documents incorporated by reference (including, as
applicable, EPA Pesticide Assessment Guidelines, Data
Reporting Guidelines, and GeneTox Health Effects Test
Guidelines) regarding the design, conduct, and reporting of
required studies. Such requirements include, but are not
limited to, those relating to test material, test procedures,
selection of species, number of animals, sex and distribution
of animals, dose and effect levels to be tested or attained,
duration of test, and, as applicable, Good Laboratory
Practices.
2. EPA requirements regarding the submission of protocols,
including the incorporation of any changes required by the
Agency following review.
3. 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 referenced1
or included in this Notice or contained in PR 86-5. All
studies must be submitted in the fora of a final report; a
preliminary report will not be considered to fulfill the
submission requirement.
IV-C EXISTING STOCKS OF SUSPENDED OR CAN^T.T.flp PRODUCTS
EPA has statutory authority to permit continued sale,
distribution and use of existing stocks of a pesticide product
which has been suspended or cancelled if doing so would be
consistent with the purposes of the Act.
The Agency has determined that such disposition by registrants
of existing stocks for a suspended registration when a section
3(c)(2)(B) data request is outstanding would generally not be
consistent with ths Act's purposes. Accordingly, the Agency
anticipates granting registrants permission to sell, distribute, or
use existing stocks of suspended product (s) only in exceptional
circumstance*. Zf you believe such disposition of existing stocks
of your product (s) which may be suspended for failure to comply
with this Notice should be permitted, you have ths burden of
clearly demonstrating to EPA that granting, such permission would be
consistent with ths Act. You must also explain why an "existing
stocks" provision is necessary, including a statement of the
quantity of existing stocks and your estimate of ths time required
for their sals, distribution, and uss. Unless you meet this burden
ths Agency vin not consider any request pertaining to the
continued sals, distribution, or uss of your existing stocks after
suspension.
If you request a voluntary cancellation of your product (s) as
a responss to this Notice and your product is in full compliance
with all Agency requirements, you will have, under most
-------
17
circumstances, on* year from the date your 90 day response to this
Notice is due, to sell, distribute, or use existing stocks.
Normally, the Agency will allow persons other than the registrant
such as independent distributors, retailers and end users to sell,
distribute or use such existing stocks until the stocks are
exhausted. Any sale, distribution or use of stocks of voluntarily
cancelled products containing an active ingredient for which the
Agency has particular risk concerns will be determined on case-by-
case basis.
Requests for voluntary cancellation received after the 90 day
response period required by this Notice will not result in the
Agency granting any additional time to sell, distribute, or use
existing stocks beyond a year from the date the 90 day response was
due unless you demonstrate to the Agency that you are in full
compliance with all Agency requirements, including the requirements
of this Notice. For example,- if you decide to voluntarily cancel
your registration six months before a 3 year study is scheduled to
be submitted, all progress reports and other information necessary
to establish that you have been conducting the study in an
acceptable and good faith manner oust have been submitted to the
Agency, before EPA will consider granting an existing stocks
provision.
SECTION V. REGISTRANTS' OBLISATION TO REPORT POSSIBLE
UNREASONABLE ADVERSE EFFECTS
Registrants are reminded that FZFRA section 6(a)(2) states
that if at any time after a pesticide is registered a registrant
has additional factual information regarding unreasonable adverse
effects on the environment by the pesticide, the registrant shall
submit the information to the Agency. Registrants must notify the
Agency of any factual information they have, from whatever source,
including but not limited to interim or preliminary results of
studies, regarding unreasonable adverse effects on man or the
environment. This requirement continues as long as the products
are registered by the Agency.
SECTION VT. TNODTRTES AND RESPONSES TO THIS NOTICE
• ."• •
If you have any questions regarding the requirements and
procedures established by this Notice, call the contact person
listed in Attachment A* the Data Call-In chemical status Sheet.
All responses to this Notice* (other than voluntary
cancellation requests and generic data exemption claims) Bust
include a completed Pata Call-in Beaponae Fora (Attachment B) and a
completed Requirement* Status and Registrant*a Response Form
(Attachment C) and any other documents required by this Notice, and
should be submitted to the contact person identified in Attachment
A. Zf the voluntary cancellation or generic data exemption option
is chosen, only the Data Call-in Reaponaa Fora need be submitted.
-------
18
The Office of Compliance Monitoring (OCM) of the Office of
Pesticides and Toxic Substances (OPTS), EPA, will be monitoring the
data being generated in response to this Notic«.
Sincarsly,
Danial M. Barolo, Director
Special Review and
Reregistration Division
Attachments
A - Data Call-In Chemical Status Sheet
B - Data Call-in Response Porn
C - Requirements Status and Registrants
Response Form
D — List of Registrants Receiving This Notice
E - Cost Share and Data Compensation Forms
-------
ATTACHMENT A
Generic Data Call-In Chemical Status Sheet
-------
ATTACHMENT A
STREPTOMYCIN: GENERIC DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Generic Data Call-In Notice because you have products contain-
ing streptomycin.
This Generic Data Call-In Chemical Status Sheet, contains an overview of data required
by this notice, and point of contact for inquiries pertaining to the reregistration of streptomycin.
This attachment is to be used in conjunction with (1) the Generic Data Call-In Notice, (2) the
Generic Data Call-In Response Form (Attachment B), (3) the Requirements Status and
Registrant's Form (Attachment C), (4) a list of registrants receiving this DCI (Attachment D),
(5) the EPA Acceptance Criteria (Attachment E), and (6) the Cost Share and Data Compensation
Forms in replying to this Streptomycin Generic Data Call-In (Attachment F). Instructions and
guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the generic database for streptomy-
cin are contained in the Requirements Status and Registrant's Response (Attachment C). The
Agency has concluded that new ecological effects and environmental fate data on technical
streptomycin sulfate are needed. In addition, some of the product chemistry guidelines have not
been completely fulfilled. All of the product chemistry data were originally required in the
Registration Standard and are therefore not included in the generic Data Call-In for the RED.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic data requirements and procedures
established by this Notice, please contact Theresa A. Stowe at (703) 308 - 8043.
All responses to this -Notice for the generic data requirements should be submitted to:
Theresa A. Stowe, Chemical Review Manager
Reregistration Branch, Section I
Special Review and Reregistration Division (H7508W)
Office of Pesticide Programs
U.S. Environmental Protection Agency
401 M Street, S.W.
Washington, D.C. 20460
RE: STREPTOMYCIN
-------
ATTACHMENT B
Generic Data Call-in Response Forms (Form A) plus Instructions
-------
SPECIFIC INSTRUCTIONS FOR
THE DATA CALL-IN RESPONSE FORM
This form is designed to be used to respond to call-ins for
generic and product specific data for the purpose of
reregistering pesticides under the Federal Insecticide Fungicide
and Rodenticide Act. Fill out this form each time you are
responding to a data call-in for which EPA has sent you the form
entitled "Requirements Status and Registrant's Response."
Items 1 -4 will have been preprinted on the form. Items 5
through 7 must be completed by the registrant as appropriate.
Items 8 through 11 must be completed by the registrant before
submitting a response to the Agency.
Public reporting burden for this collection of information
is estimated to average .15 minutes per response, including time
for reviewing instructions, searching existing data sources,
gathering and maintaining the data needed, and completing and
reviewing the collection of information. Send comments regarding
the burden estimate or any other aspect of this collection of
information, including suggesting for reducing this burden, to
Chief, Information Policy Branch, PM-223,- U.S. Environmental
Protection Agency, 401 M St., S.W., Washington, D.C. 20460; and
to the Office of Management and Budget, Paperwork Reduction
Project 2070-0107, Washington, D.C. 20503.
INSTRUCTIONS
Item 1. This item identifies your company name, number .and
address.
Item 2. This item identifies the case number, case name, EPA
chemical number and chemical name.
Item 3. This item identifies the date and type of data call-in.
Item 4. This item identifies the EPA product registrations
relevant to the data call-in. Please note that you are
also responsible for informing the Agency of your
response regarding any product that you believe may be
covered by this data call-in but that is not listed by
the Agency in Item 4. You must bring any such apparent
omission to the Agency's attention within the period
required for submission of this response form.
Item 5. Check this item for each product registration you wish
to cancel voluntarily. If a registration number is
listed for a product for which you previously requested
voluntary cancellation, indicate in Item 5 the date of
that request. You do not need to complete any item on
-------
the Requirements Status and Registrant's Response Form
for any product that is voluntarily cancelled.
Item 6a. Check this item if this data call-in is for generic
data as indicated in Item 3 and if you are eligible for
a Generic Data Exemption for the chemical listed in
Item 2 and used in the subject product. By electing
this exemption, you agree to the terms and conditions
of a Generic Data Exemption as explained in. the Data
Call-in Notice.
If you are eligible for or claim a Generic Data
Exemption, enter the EPA registration Number of each
registered source of that active ingredient that you
use in your product.
Typically, if you purchase an EPA-registered product
from one or more other producers (who, with respect to
the incorporated product, are in compliance with this
and any other outstanding Data Call-In Notice), and
incorporate that product into all your products, you
may complete this item for all products listed on this
form. If, however, you produce the active ingredient
yourself, or use any unregistered product (regardless
of the fact that some of your sources are registered),
you may not claim a Generic Data Exemption and you may
not select this item.
Item 6b. Check this Item if the data call-in is a generic data
call-in as indicated in Item 3 and if you are agreeing
to satisfy the generic data requirements of this data
call-in. Attach the Requirements Status and
Registrant's Response Form that indicates how you will
satisfy those requirements.
Item 7a. Check this item if this call-in is a data call-in as
indicated in Item 3 for a manufacturing use product
(MUP), and if your product is a manufacturing use
product for which you agree to supply product-specific
data. Attach the Requirements status and Registrants'
Response Form that indicates how you will satisfy those
requirements.
Item 7b. Check this item if this call-in is a data call-in for
an end use product (EUP) as indicated in Item 3 and if
your product is a end use product for which you agree
to supply product-specific data. Attach the
Requirements Status and Registrant's Response Form that
indicates how you will satisfy those requirements.
Item 8. This certification statement must be signed by an
authorized representative of your company and the
-------
person signing must include his/her title. Additional
pages used in your response must be initialled and
dated in the space provided for the certification.
Item 9. Enter the date of signature.
Item 10. Enter the name of the person EPA should contact with
questions regarding your response.
Item 11. Enter the phone number of your company contact.
-------
DRAFT COPY
Page 1 of 1
United States Environmental Protection Agency
Washington, D.C. 20460
DATA CALL-IN RESPONSE
Form Approved
(MB No. 2070-0107
Approval Expires 12-31-92
INSTRUCTIONS: Please type or print in ink. Please read carefully the attached instructions and supply the information requested on this form.
Use additional sheet(s) if necessary
1. Company name and Address 2. Case It and Name
SAMPLE COMPANY °169 ****£!****
NO STREET ADDRESS Chemical # and Name 006310
NO CITY, XX 00000 Streptomycin sul fate
4. EPA Product
Registration
NNNNNN-NNNNN
5. 1 wish to
cancel this
product regis-
tration volun-
tarily
6. Generic Data
6a. I am claiming a Generic
Data Exemption because 1
obtain the active ingredient
from the source EPA regis-
tration number listed below.
6b. I agree to satisfy Generic
Data requirements as indicated
on the attached form entitled
"Requirements Status and
Registrant's Response."
3. Date and Type of DCI
GENERIC
SEP 3 0 I992
7. Product Specific Data
7a. My product is an HUP and
I agree to satisfy the HUP
requirements on the attached
form entitled "Requirements
Status and Registrant's
Response."
8. Certification
I certify that the statements made on this form and all attachments are true, accurate, and complete.
I acknowledge that any knowingly false or misleading statement may be punishable by fine, imprisonment
or both under applicable law.
Signature and Title of Company's Authorized Representative
10. Name of Company Contact
.
7b. My product is an EUP and
I agree to satisfy the EUP
requirements on the attached
form entitled "Requirements
Status and Registrant's
Response."
i
9. Date
11.
Phone Number
-------
ATTACHMENT C
Generic Data Call-in Requirements Status and
Registrant's Response Forms (Form B) plus Instructions
-------
SPECIFIC INSTRUCTIONS FOR COMPLETING
THE REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE FORM
Generic Data
• This form is designed to be used for registrants to respond
to call-ins for generic and product-specific data as part of
EPA's reregistration program under the Federal Insecticide
Fungicide and Rodenticide Act. Although the form is the same for
both product specific and generic data, instructions for
completing the forms differ slightly. Specifically, options for
satisfying product specific data requirements do not include (1)
deletion of uses or (2) request for a low volume/minor use
waiver. These instructions are for completion of generic data
requirements.
EPA has developed this form individually for each data call-
in addressed to each registrant, and has preprinted this form
with a number of items. 'DO NOT use this form for any other
active ingredient.
Items 1 through 8 (inclusive) will have been preprinted on
the form. You must complete all other items on this form by
typing or printing legibly.
Public reporting burden for this collection of information
is estimated to average 30 minutes per response, including time
for reviewing instructions, searching existing data sources,
gathering and maintaining the data needed, and completing and
reviewing the collection of information. Send comments regarding
the burden estimate or any other aspect of this collection of
information, including suggesting for reducing this burden, to
Chief, Information Policy Branch, PM-223, U.S. Environmental
Protection Agency, 401 M St., S.W., Washington, D.C. 20460; and
to the Office of Management and Budget, Paperwork Reduction
Project 2070-0107, Washington, D.C. 20503.
-.JJr-.!-^-k ~--..— -. ..;- si- j.u^ij».jj-G ,^t.^»..^«^^^j^ua^«aq^aj;*^»^>i^-; j^
-------
Item i.
Item 2.
Item 3.
Item 4.
Item 5.
Item 6.
This item identifies your company name, number, and
address.
This item identifies the case number, case name, EPA
chemical number and chemical name.
This item identifies the date and type of data call-in.
This item identifies the guideline 'reference numbers of
studies required to support the product(s) being
reregistered. These guidelines, in addition to
requirements specified in the Data Call-In Notice,
govern the conduct of the required studies.
This item identifies the study title associated with
the guideline reference number and whether protocols
and 1, 2, or 3-year progress reports are required to be
submitted in connection with the study. As noted in
Section III of the Data call-in Notice, 90-day progress
reports are required for all studies.
If an asterisk appears in Item 5, EPA has attached
information relevant to this guideline reference number
to the Requirements Status and Registrant's Response
Form.
This item identifies the code associated with the use
pattern of the pesticide. A brief description of each
code follows:
A Terrestrial food
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E - Aquatic non-food outdoor
F Aquatic non-food industrial
•ft Aquatic non-food residential
Greenhouse food
non-food residen
H Greenhouse food
I Greenhouse non-food crop
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
0 Indoor residential
-------
Item 7. ,This item identifies the code assigned to the substance
that must be used for testing. A brief description of
each code follows:
EP
MP
MP/TGAI
PAI
PAI/M
PAI/PAIRA
PAIRA
PAIRA/M
PAIRA/PM
TEP
TEP % .
TEP/MET
TEP/PAI/M
TGAI
TGAI/PAI
TGAI/PAIRA
TGAI/TEP
MET
IMP
DEGR
*
End-Use Product
Manufacturing-Use Product
Manufacturing-Use Product and Technical
Grade Active Ingredient
Pure Active Ingredient
Pure Active Ingredient and Metabolites
Pure Active ingredient or Pure Active
Ingredient Radiolabelled
Pure Active Ingredient Radiolabelled
Pure Active Ingredient Radiolabelled and
Metabolites
Pure Active Ingredient Radiolabelled and
Plant Metabolites
Typical End-Use Product
Typical End-Use Product, Percent Active
Ingredient Specified
Typical End-Use Product and Metabolites
Typical End-Use Product or Pure Active
Ingredient and Metabolites
Technical Grade Active Ingredient
Technical Grade Active Ingredient or
Pure Active Ingredient
Technical Grade Active Ingredient or
Pure Active Ingredient Radiolabelled
Technical Grade Active Ingredient or
Typical End-Use Product
Metabolites
Impurities
Oegradates
See: guideline comment
Item 8. This item identifies the time frame allowed for
submission of the study or protocol identified in
item 2. The time frame runs from the date of your
receipt of the Data Call-in Notice.
Item 9. Enter the appropriate Response Code or Codes to show '
how you intend to comply with each data requirement.
Brief descriptions of each code follow. The Data Call-
in Notice contains a fuller description of each of
these options.
1. .(Developing Data) I will conduct a new study and
submit it within the time frames specified in item
8 above. By indicating that I have chosen this
option, I certify that I will' comply with all the
-------
requirements pertaining to the conditions for
submittal of this study as outlined in the Data
Call-in Notice and that I will provide the
protocols and progress reports required in item 5
above.
. 2. (Agreement to Cost Share) I have entered into an
agreement with one or more registrants to develop
data jointly. By indicating that I have chosen
this option, I certify that I will comply with all
the requirements pertaining to sharing in the cost
of developing data as outlined in the Data Call-in
Notice. .••'.••
3. (Offer to Cost Share) I have made an offer to
enter into an agreement with one or more
registrants to develop data jointly. I am
submitting a 'copy of the form "Certification of
Offer to Cost Share in.the Development of Data"
that describes this offer/agreement. By
indicating that I have chosen this option, I
certify that I will comply with all the
requirements pertaining to making an offer to
share in the cost of developing data as outlined
in the Data Call-in Notice.
4. (Submitting Existing Data) I am submitting an
existing study that has never before been
submitted to EPA. By indicating that I have
chosen this option, I certify that this study
meets all the requirements pertaining to the
conditions for submittal of existing data outlined
in the Data Call-In Notice and I have attached the
needed supporting information along with this
response.
5. (Upgrading a Study) I am submitting or citing data
to upgrade a study that EPA has classified as
partially acceptable and potentially upgradeable.
By indicating that I have chosen this option, I
certify that I have met all the requirements
pertaining to the conditions for submitting or
citing existing data to upgrade a study described
in the Data Call-in Notice. I am indicating on
attached correspondence the Master Record
. Identification Number (MRID) that EPA has assigned
to the data that I am citing as well as the MRID
of .the study I am attempting to upgrade.
6. (Citing a Study) I am citing an existing study
that has been previously classified by EPA as
acceptable, core, core minimum, or a study that
i^'^T^^^^^^'"^^^^**^^^''' '^'*'l'*-t**'*y^'ifc-\:- % y -'•>"•• VWJS^J *m*m- - «*<•.» \*^ _ 7Y7* '*t*^ "--ijT-C^S.;^ .» . . t "'*' '..'* - •—-..- . —•— -^ ~ »—' v-- —JJ«fc"».J
-------
has not yet been reviewed by the Agency. I am
providing the Agency's classification of the
study.
7. (Deleting Uses) I am attaching an application for
amendment to my registration deleting the uses for
which the data are required.
8. (Low Volume/Minor Use Waiver Request) I have read
the statements concerning low volume-minor use
data waivers in the Data Call-In Notice and I
request a low-volume minor use waiver of the data
requirement. I am attaching a detailed
justification to support this waiver request
including, among other things, all information
required to support the request. I understand
that, unless modified by the Agency in writing,
the data requirement as stated in the Notice
governs.
9. (Request for Waiver of Data) I have read the
statements concerning data waivers other than low-
volume minor-use data waivers in the Data Call-in
Notice and I request a waiver of the data
requirement. I am attaching an identification of
the basis for this waiver and a detailed
justification to support this waiver request. The
justification includes, among other things, all
information required to support the request. I
understand that, unless modified by the Agency in
writing, the data requirement as stated in the
Notice governs.
Item 10. This item must be signed by an authorized
representative of your company. The person signing
must include his/her title, and roust initial and date
all other pages of this form.
Item 11. Enter the date of signature.
Item 12. Enter the name of the person EPA should contact with
questions regarding your response.
Item 13. Enter the phone number of your company contact.
-------
DRAFT COPY
Page 1 of 1
United States Environmental Protection Agency
Washington, D.C. 20460
REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE
INSTRUCTIONS: Please type or print in ink. Please read carefully the attached instructions and supply the information requested
Use additional sheet(s) if necessary
1. Company name and Address
SAMPLE COMPANY
NO STREET ADDRESS
NO CITY, XX 00000
4. Guideline
Requirement
Number
72-2 (a) *
161-1 *
5. Study Title
Invertebrate toxi city
Hydrolysis
|
2. Case # and Name
0169 Streptomycin
Chemical # and Name 006310
Streptomycin sulfate
Progress
Reports
1
2
3
6. Use
Pattern
ABCGK
ABCGK
7. Test
Substance
.T.GA.I.
TGAI
10. Certification
I certify that the statements made on this form and all attachments are true, accurate, and complete.
I acknowledge that any knowingly false or misleading statement may be punishable by fine, imprisonment
or both under applicable law.
Signature and Title of Company's Authorized Representative
12. Name of Company Contact
Form Approved
OMB No. 2070-0107
Approval Expires 12-31-92
on this form.
3. Date and Type of DCI
GENERIC
SEP 3 0 I992
8. Time
Frame
12
12
mos.
mos.
9. Registrant
Response
11. Date
13. Phone Number
-------
Page 1 of 1
United States Environmental Protection Agency
Washington, D.C. 20460
* COMMENTS FOR GUIDELINE REQUIREMENTS
Case # and Name
0169 Streptomycin
Chemical # and Name
006310 Streptomycin sulfate
GUIDELINE COMMENT
72-2(a)Sufficient non-guideline information is available to perform a preliminary ecological
hazard assessment. However, the data are insufficient to confirm the reported findings.
A new study will be needed to confirm the freshwater invertebrate hazard assessment.
161-1 All environmental fate data requirements, except for hydrolysis, are waived. Hydrolysis
data at pH's of 5, 7, and 9 are required.
-------
ATTACHMENT D
List of Registrants Receiving the Generic
and Product Specific Data Call-In
-------
List of All Registrants Sent This Data Call-in Notice
Case # and Name
0169 Streptomycin
Chemical # and Name
006310 Streptomycin sulfate
Company Number Company Name
Additional Name
Address
City & State
Zip
000070
000554
000618
001007
002596
007401
D10107
034704
056644
060258
WILBUR-ELLIS COMPANY
AGSCO INC
MERCK & CO INC
PFIZER INC. - SPECIALTY CHEMICALS .
HARTZ MOUNTAIN CORP
VOLUNTARY PURCHASING GROUP, INC.
CORN BELT CHEMICAL COMPANY
WILLIAM M. MAHLBURG
SECURITY PRODUCTS COMPANY OF DELAW
MONROVIA NURSERY COMPANY
AGENT FOR: MERCK & CO INC
AGENT FOR: PLATTE CHEMICAL CO.. IN
BOX 16458
BOX 458
HILLSBOROUGH RD
235 EAST 42ND ST
700 FRANK E. RODGERS BLVD. SO
P. 0. BOX 460
BOX 410
- BOX 667
7801 METRO PARKWAY BOX 59084
18331 EAST FOOTHILL BOULEVARD
FRESNO CA
GRANDFORKS ND
THREE BRIDGES NJ
NEW YORK NY
HARRISON NJ
BONHAM TX
MCCOOK NE
GREELEY CO
MINNEAPOLIS MN
AZUSA CA
93755
58201
08887
10017
07029
75418
69001
80632
55420
91702
-------
ATTACHMENT E
EPA Acceptance Criteria
-------
SUBDIVISION D
Guideline Study Title
Series 61 Product Identity and Composition
Series 62 Analysis and Certification of Product Ingredients
Series 63 Physical and Chemical Characteristics
-------
61 Product Identity and Composition
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Name of technical material tested (include product name and
trade name, if appropriate)
2. Name, nominal concentration, and certified limits (upper and
lower) for each active ingredient and each intentionally-
added inert ingredient
3. Name and upper certified limit for each impurity or each
group of impurities present at > 0.1% by weight and for
certain toxicologically significant impurities (e.g.,
dioxins, nitrosamines) present at <0.1%
4. Purpose of each active ingredient and each intentionally-
added inert
5. Chemical name from Chemical Abstracts index of Nomenclature
and Chemical Abstracts Service (CAS) Registry Number for each
active ingredient and, if available, for each intentionally-
added inert
6. Molecular, structural, and empirical formulas, molecular
weight or weight range, and any company assigned experimental
or internal code numbers for each active ingredient
7. Description of each beginning material in the manufacturing
process
EPA Registration Number if registered; for other
beginning materials, the following:
Name and address of manufacturer or supplier
Brand name, trade name or commercial designation
Technical specifications or data sheets by which
manufacturer or supplier describes composition,
properties or toxicity
8. Description of manufacturing process
Statement of whether batch or continuous process
Relative amounts of beginning materials and order in
which they are added
Description of equipment
Description of physical conditions (temperature,
pressure, humidity) controlled in each step and the
parameters that are maintained
Statement of whether process involves intended chemical
reactions
-------
8. (continued)
Flow chart with chemical equations for each intended
chemical reaction
Duration of each step of process
Description of purification procedures
Description of measures taken to assure quality of final
product
9. Discussion of formation of impurities based on established
chemical theory addressing (1) each impurity which may be
present at > 0.1% or was found at > 0.1% by product analyses
and (2) certain toxicologically significant impurities
(tsee #3)
-------
61 Product Identity and Composition
GUIDANCE FOR SUMMARIZING STUDIES
The following criteria apply to the technical grade of the active
ingredient being reregistered. Items 1, 2, 3, and 5 can be
satisfied for most registered products by submission of the
Certified Statement of Formula Ingredients Page (EPA Form 8570-4).
Items 7 and 8 can be satisfied for most technical grade active
ingredients (TGAIs) by submission of a flow chart with chemical
equations for each intended chemical reaction. The flow chart
.should include complete Chemical structures and names for each
reactant and product of all the reactions.
1. Name of technical material (include product name and trade name,
if appropriate).
2. Description of each active and intentionally-added inert
ingredient, including name, concentration, and certified limits.
3. Name and upper limit for all impurities present at > 0.1% and
those toxicologically significant impurities present at <0.1%.
4. The purpose of each active and intentionally-added inert
ingredient.
5. Chemical name and Registry Number for each active and
intentionally-added inert ingredient (if available).
6. Molecular, structural, and empirical formulas, molecular weight,
and any experimental or internal code number for each active
ingredient.
7. Description of each beginning material in the manufacturing
process.
8. Description of manufacturing process.
9. Discussion of formation of impurities based on established
chemical theory.
-------
62 Analysis and Certification of Product Ingredients
ACCEPTANCE CRITERIA
The following criteria apply to the technical grade of the active
ingredient being reregistered. Use a table to present the
information in items 6, 7, and 8.
Does your study meet the following acceptance criteria?
1. Five or more representative samples (batches in case of
batch process) analyzed for each active ingredient and all
impurities present at >. 0.1%
2. Degree of accountability or closure > ca 98%
3. Analyses conducted for certain trace toxic impurities at
lower than 0.1% (examples, nitrosamines in the case of
products containing dinitroanilines or containing secondary
or tertiary amines/alkanolamines plus nitrites;
polyhalogenated dibenzodioxins and dibenzofurans) [Note
that in the case of nitrosamines both fresh and stored
samples must be analyzed.]
4. Complete and detailed description of each step in analytical
method used to analyze above samples
5. Statement of precision and accuracy of analytical method
used to analyze above samples
6. Identities and quantities (including mean and standard
deviation) provided for each analyzed ingredient
7. Upper and lower certified limits proposed for each active
ingredient and intentionally added inert along with
explanation of how the limits were determined
8._ Upper certified limit proposed for each impurity present at
> 0.1% and for certain toxicologically significant
impurities at <0.1% along with explanation of how limit
determined
9. Analytical methods to verify certified limits of each
active ingredient and impurities (latter not required if
exempt from requirement of tolerance or if generally
recognized as safe by FDA) are fully described
10. Analytical methods (as discussed in #9) to verify certified
limits validated as to their precision and accuracy
-------
62 Analysis and Certification of Product Ingredients
GUIDANCE FOR SUMMARIZING STUDIES
The following criteria apply to the technical grade of the active
ingredient being reregistered.
1. Number of representative samples analyzed for all active
ingredients and all impurities at > 0.1%.
2. Degree of accountability or closure in analyses in item #1.
3. Chemical names of toxic impurities which were analyzed for
levels <0.1%.
4. Brief description(s) of analytical method(s) used to measure
active ingredients and impurities in items #1 and #3.
5. Statement of precision and accuracy of method(s) in item #4.
6. Chemical name and quantities observed (range, mean, standard
deviation) for each ingredient (actives and impurities)
analyzed in item #1.
7. Proposed upper and lower certified limits for each active
ingredient and intentionally added inert with brief explanation
of how limits were determined.
8. Proposed upper certified limit for each impurity present at
>=0.1% and certain toxicologically significant impurities at
<0.1% with brief explanation of how limits were determined.
9. Brief description of analytical method(s) used to verify
certified limits (if same methods as item #4, may reference
latter).
10. statement of precision and accuracy of method(s) in item #9
(may reference item #5 if applicable).
-------
63 Physical and Chemical Characteristics
ACCEPTANCE CRITERIA
The following criteria apply to the technical grade of the active
ingredient being reregistered.
Does your study meet the following acceptance criteria?
63-2 Color
Verbal description of coloration (or lack of it)
Any intentional coloration also reported in terms of
Munsell color system
63-3 Physical State
Verbal description of physical state provided using terms
such as "solid, granular, volatile liquid"
Based on visual inspection at about 20-25° C
63-4 Odor
Verbal description of odor (or lack of it) using terms
such as "garlic-like, characteristic of aromatic
compounds"
Observed at room temperature
63-5 Melting Point
Reported in C°
Any observed decomposition reported
63-6 Boiling Point
Reported in C°
Pressure under which B.P. measured reported
Any observed decomposition reported
63-7 Density, Bulk Density, Specific Gravity
Measured at about 20-25° C
Density of technical grade active ingredient reported in
g/ml or the specific gravity of liquids reported with
reference to water at 20° C. [Note: Bulk density of
registered products may be reported in Ibs/ft or
Ibs/gallon.]
-------
63-8 Solubility
Determined in distilled water and representative polar and
non-polar solvents, including those used in formulations
and analytical methods for the pesticide
Measured at about 20-25° C
Reported in g/100 ml (other units like ppm acceptable if
sparingly soluble)
63-9 Vapor Pressure
Measured at 25° C (or calculated by extrapolation from
measurements made at higher temperature if pressure too
low to measure at 25° C)
Experimental procedure described
Reported in mm Hg (torr) or other conventional units
63-10 Dissociation Constant
.Experimental method described
Temperature of measurement specified (preferably
about 20 - 25° C)
63-11 Octanol/water Partition Coefficient
Measured at about 20-25° C
Experimentally determined and description of procedure
provided (preferred method-45 Fed. Register 77350)
Data supporting reported value provided
63-12 pH
Measured at about 20 - 25° C
Measured following dilution or dispersion in distilled
water
63-13 Stability
Sensitivity to metal ions and metal determined
stability at normal and elevated temperatures
Sensitivity to sunlight determined
-------
63 Physical and Chemical Characteristics
GUIDANCE FOR SUMMARIZING STUDIES
The following criteria apply to the technical grade of the active
ingredient being reregistered.
1. Description of color.
2. Description of physical state.
3. Description of odor.
4. Indication of melting point (in C°).
5. Indication of boiling point (in C°).
6. Indication of density, bulk density, and specific gravity.
7. Indication of solubility.
8. Indication of vapor pressure.
9. Indication of dissociation constant.
10. Indication of octanol/water partition coefficient.
11. Indication of PH.
12. Description of stability.
-------
SUBDIVISION F
Guideline Study Title
81-1 " . Acute Oral Toxicity in the Rat
81-2 Acute Dermal Toxicity in the Rat, Rabbit or Guinea Pig
81-3 Acute Inhalation Toxicity in the Rat
81-4 Primary Eye Irritation in the Rabbit
81-5 Primary Dermal Irritation Study
81-6 Dermal Sensitization in the Guinea Pig
81-7 Acute Neurotoxicity in the Hen
-------
81-1 Acute Oral Toxicity in the Rat
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc)
. 2. At least 5 young adult rats/sex/group
3. Dosing, single oral may be administered over 24 hrs.
4'.*. Vehicle control if other than water.
5. Doses tested, sufficient to determine a toxicity category
or a limit dose (5000 mg/kg).
6. Individual observations at least once a day.
7. Observation period to last at least 14 days, or until all
test animals appear normal whichever is longer.
8. Individual daily observations.
9. Individual body weights.
10. Gross necropsy on all animals.
Criteria marked with a * are supplemental and may not be required
for every study.
-------
81-1 Acute Oral Toxicity in the Rat
GUIDANCE FOR SUMMARIZING STUDIES
1. The form of pesticide tested, e.g. solid, liquid, percent
AI in technical, end-use product, etc.
2. The number of animals/dose/sex tested.
3. Dosing route and regimen.
4. Vehicle used
5. Doses tested and results
6. Individual observations on day of dosing and for at
least 14 days.
7. Summarization of body weights
8. Summarization of gross necropsy
9-. Significance of changes from the Acceptance Criteria
-------
81-2 Acute Dermal toxicity in the Rat, Rabbit or Guinea Pig
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc)
2. At leas.t 5 animals/sex/group
3.jjL Rats 200-300 gm, rabbits 2.0-3.0 kg or guinea pigs 350-
450 gm.
4. Dosing, single dermal.
5. Dosing duration at least 24 hours.
6.*. Vehicle control, only if toxicity of vehicle is unknown.
7. Doses tested, sufficient to determine a toxicity category
or a limit dose (2000 mg/kg).
8. Application site clipped or shaved at least 24 hours
before dosing
9. Application site at least 10% of body surface area.
10. Application site covered with a porous nonirritating cover
to retain test material and to prevent ingestion.
11. Individual observations at least once a day.
12. Observation period to last at least 14 days.
13. Individual body weights.
14. Gross necropsy on all animals.
Criteria marked with a * are supplemental and may not be required
for every study.
-------
81-2 Acute Dermal Toxicity in the Rat, Rabbit or Guinea Pig
GUIDANCE FOR SUMMARIZING STUDIES
1. The form of pesticide tested, e.g., solid, liquid, percent AI
in technical, end-use product, etc.
2. The number of animals/sex/dose
3. Weight range of animals
4. Verification of single, dermal exposure
5. Duration of dermal exposure
6. Statement of vehicle control
7. Doses tested and results
8. Preparation of application site
9. Area of application site (percent body surface)
10. Occlusion of test material on application site
11. Individual observations on day of dosing and for at
least 14 days or until all animals appear normal (whichever is
longer).
12. Summarization of body weights
13. Summarization of gross necropsy
14. Significance of changes from Acceptance Criteria
-------
81-3 Acute Inhalation Toxicity in the Rat
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc)
2. Product is a gas, a solid which may produce a significant
vapor hazard based on toxicity and expected use or contains
particles of inhalable size for man (aerodynamic diameter
15 urn or less).
3. At least 5 young adult rats/sex/group
4. Dosing, at least 4 hours by inhalation.
5. Chamber air flow dynamic, at least 10 air changes/hour, at
least 19% oxygen content.
6. Chamber temperature, 22° C (±2), relative humidity 40-60%.
7. Monitor rate of air flow
8. Monitor actual concentrations of test material in breathing
zone.
9. Monitor aerodynamic particle size for aerosols.
10. Doses tested, sufficient to determine a toxicity category
or a limit dose (5 mg/L actual concentration of respirable
substance).
11. Individual observations at least once a day.
12. Observation period to last at least 14 days.
13. Individual body weights.
14. Gross necropsy on all animals.
-------
81-3 Acute Inhalation Toxicity in the Rat
GUIDANCE FOR SUMMARIZING STUDIES
1. The form of pesticide tested, e.g., solid, liquid, percent AI
in technical, end-use product, etc.
2. Statement of the inhalability of test substance
3. The number of animals/sex/dose
4. Duration of inhalation exposure
5. Number of chamber air changes/hour and the percent oxygen
content of chamber air
6. Ranges for chamber air temperature and relative humidity
7. Air flow rate
8. Analytical concentrations of test material in breathing zone
9. Results of aerosol particle-size determination
10. Doses tested (or limit dose of 5mg/L or highest attainable)
11. Individual observations on day of dosing and for at least 14
days.
12. Summarization of body weights
13. Summarization of gross necropsy
14. Significance of changes from Acceptance Criteria
-------
81-4 Primary Eye Irritation in the Rabbit
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc)
2. Study not required if material is corrosive, causes severe
dermal irritation or has a pH of < 2 or >. 11.5.
3. 6 adult rabbits
4. Dosing, instillation into the conjunctival sac of one eye
per animal.
5.. Dose, 0.1 ml if a liquid; 0.1 ml or not more than 100 mg if
a solid, paste or particulate substance.
6. Solid or granular test material ground to a fine dust.
7. Eyes not washed for at least 24 hours.
8. Eyes examined and graded for irritation before dosing and
at 1, 24, 48 and 72 hr, then daily until eyes are normal or
21 days (whichever is shorter).
9.*. individual daily observations.
Criteria marked with a * are supplemental and may not be required
for every study.
-------
81-4 Primary Eye Irritation in the Rabbit
GUIDANCE FOR SUMMARIZING STUDIES
1. The form of pesticide tested, e.g., solid, liquid, percent AI
in technical, end-use product, etc.
2. State if material is corrosive, cause severe dermal irritation
or has a pH of <2 or >11.5
3. Number of adult rabbits tested
4. State method of dosing, i.e., instillation into the
conjunctival sac of one eye per animal
5. Dose administered
6. Note whether solid or granular test material has been ground to
a fine dust
7. State whether eyes were washed and at what time post
instillation (not less than 24 hours)
8. State whether eyes were examined and graded for irritation
before dosing and at what periods after dosing
9. Individual daily observations afterwards, until eyes are normal
or for 21 days
10. Significance of changes from Acceptance Criteria
-------
81-5 Primary Dermal Irritation Study
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc)
2. Study not required if material is corrosive or has a
pH of <2 or > 11.5.
3. 6 adult animals.
4. Dosing, single dermal.
5. Dosing duration 4 hours.
6. Application site shaved or clipped at least 24 hours prior
to dosing
7. Application site approximately 6 cm.
8. Application site covered with a gauze patch held in place
with nonirritating tape
9. Material removed, washed with water, without trauma to
application site
10. Application site examined and graded for irritation at 1,
24, 48 and 72 hr, then daily until normal or 14 days
(whichever is shorter).
11.*. Individual daily observations.
Criteria marked with a * are supplemental and may not be required
for every study.
-------
81-5 Primary Dermal Irritation Study
GUIDANCE FOR SUMMARIZING STUDIES
1. The form of pesticide tested, e.g., solid, liquid, percent AI
in technical, end-use product, etc.
2. State if material is corrosive, has a pH <2 or >11.5, or has a
dermal LD 50 <200 rog/kg
3. Number of adult animals tested
4. Amount applied
5. Duration of dermal exposure
6. Preparation of application site (shaved or clipped at specified
time before dosing)
7. Area of application site
8. Method for occlusion of application site
9. Note removal of test material and if skin was washed with water
10. State times post application when site was graded for
irritation
11. Individual observations for day of dosing and individual
daily observations thereafter
12. Significance of changes from Acceptance Criteria.
-------
81-6 Dermal Sensitization in the Guinea Pig
ACCEPTANCE CRITERIA
dose your study meet the following acceptance criteria?
1. Identify material tested (technical, end-use product, etc)
2. Study not required if material is corrosive or has a
pH of <2 or > 11.5.
3. One of the following methods is utilized;
Freund's complete adjuvant test
Guinea pig maximization test
Split adjuvant technique
Buehler test
Open epicutaneous test
Mauer optimization test
Footpad technique in guinea pig
4. Complete description of test
5.*. Reference for test.
6. Test followed essentially as described in reference
document.
7. Positive control included (may provide historical data
conducted within the last 6 months)
Criteria marked with a * are supplemental and may not be required
for every study.
-------
81-6 Dermal Sensitization in the Guinea Pig
GUIDANCE FOR SUMMARIZING STUDIES
1. The form of pesticide tested, e.g., solid, liquid, percent AI
in technical, end-use product, etc.
2. State if material is corrosive or has pH <2 or >11.5.
3. State specific method utilized
4. Complete description of specific method
5. Reference for the specific method employed
6. Note adherence of the protocol to that in the reference for
the specific method utilized
7. State the positive control tested
8. Significance of changes from Acceptance Criteria
-------
81-7 Acute Neurotoxicity in the Hen
ACCEPTANCE CRITERIA
Does your study meet the following acceptance criteria?
1. Study performed on an organophosphate cholinesterase
inhibiting compound.
2. .Technical form of the active ingredient tested.
3.± Positive control utilized.
4. Species utilized, domestic laying hen 8-14 months of age.
5. Dosing oral by gavage or capsule (dermal or inhalation
may be used).
6. An acute oral LD is determined.
7. Dose tested equalrto an acute oral LD or a limit test of
5000 mg/kg.
8.*. Dosed animals may be protected with atropine and/or 2-
PAM.
Sufficient test animals so that at least 6 survive.
Negative (vehicle) control group of at least 6 hens
Positive control of at least 4 hens, (if used)
Test dose repeated if no signs of delayed neurotoxicity
observed by 21 days after dosing.
Observation period 21 days after each dose.
Individual daily observations.
Individual body weights.
Individual necropsy not required.
Histopathology performed on all animals. Tissue to be
fixed in sin preferably using whole animal perfusion
techniques. At least three sections of each of the
following tissues:
brain, including medulla oblongata
_spinal cord; upper cervical, mid-thoracic and
"lumbro-sacral regions
_tibial nerve; proximal regions and branches
"sciatic nerve
Criteria marked with a * are supplemental and may not be required
for every study.
-------
ATTACHMENT F
Generic Data Call-in Cost Share and Data Compensation Forms
-------
r/EPA
United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION OF OFFER TO COST
SHARE IN THE DEVELOPMENT OF DATA
Form Approved
OMB No. 2070-0106
Approval Expires 12-31-92
Public reporting burden for this collection of information is estimated to average 15 minutes per response, including
time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and
completing and reviewing the collection of information. Send comments regarding the burden estimate or any other
aspect of this collection of information, including suggestions for reducing this burden, to Chief, Information Policy
Branch, PM-223. U.S. Environmental Protection Agency. 401 M St., S.W., Washington, DC 20460: and to the Office
of Management and Budget, Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Pfease fill In blanks below.
Company Nam*
Company Number
Chemical Name
EPA Chemical Number
I Certify that:
My company is willing to develop and submit the data required by EPA under the authority of the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA), if necessary. However, my company would prefer to
enter into an agreement with one or more registrants to develop jointly or share in the cost of developing
data
My firm has offered in writing to enter into such an agreement. That offer was irrevocable and included an
offer to be bound by arbitration decision under section 3(c)(2)(B)(iii) of FIFRA if final agreement on all
terms could not be reached otherwise. This offer was made to the following firm(s) on the following
date(s):
Name of Flrm(s)
Date of Offer
Certification:
I certify that I am duly authorized to represent the company named above, and that the statements that I have made on
this form and all attachments therein are true, accurate, and complete. I acknowledge that any knowingly false or
misleading statement may be punishable by fine or imprisonment or both under applicable law.
Signature of Company'a Authorized Representative
Oat*
Narrated Title (Pleaae Type or Print)
. — . • '
iPA Form 8570-32 (4*90)
-------
f/EPA
United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION WITH RESPECT TO
DATA COMPENSATION REQUIREMENTS
Form Approved
OMB No. 2070.0106
Approval Ezplrts 12-31-92
Public reporting burden for this collection of information is estimated to average 15 minutes per response, including
time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and
completing and reviewing the collection of information. Send comments regarding the burden estimate or any other
aspect of this collection of information, including suggestions for reducing this burden, to Chief, Information Policy
Branch, PM-223, U.S. Environmental Protection Agency, 401 M St., S.W., Washington, DC 20460; and to the Office
of Management and Budget, Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Please fill In blanks below.
Company Nam*
Chemical Name
Company Number
EPA Chemical Number
I Certify that:
1. For each study cited in support of registration or ^registration under the Federal Insecticide, Fungicide and
Rodenticide Act (FIFRA) that is an exclusive use study, I am the original data submitter, or I have obtained the
written permission of the original data submitter to cite that study.
2. Ibat for each study cited in support of registration or ^registration under FIFRA that is NOT an exclusive use
^•y, I am the original data submitter, or I have obtained the written permission of the original data submitter, or I
have notified in writing the company(ies) that submitted data I have cited and have offered to: (a) Pay
compensation for those data in accordance with sections 3(C)(1)(D) and 3(c)(2)(D) of FIFRA; and (b) Commence
negotiation to determine which data are subject to the compensation requirement of FIFRA and the amount of
compensation due, if any. The companies I have notified are: (check one)
I \ All companies on the data submitters' list for the active ingredient listed on this form (Cite-All
Method or Che-All Option under the Selective Method). (Also sign the General Offer to Pay
below.)
[ 1 The companies who have submitted the studies listed on the back of this form or attached
sheets, or indicated on the attached "Requirements Status and Registrants' Response Form,*
3. That I have previously complied with section 3(c)(1)(D) of FIFRA for the studies I have cited in support of
registration or ^registration under FIFRA.
Signature
Date
Name and Title (Please Type or Print)
GENERAL-OFFER TO PAY: I hereby offer and agree to pay compensation to other persons, with regard to the
registration or ^registration of my products, to the extent required by FIFRA sections 3(C)(1)(D) and 3(c)(2)(D).
Slg^ej^re
Oat*
Name and TlUe (Please Type or Print)
EPA Form 8570*31 (4-90)
-------
ATTACHMENT F
Generic Data Call-In Cost Share and Data Compensation Forms
-------
r/EPA
United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION OF OFFER TO COST
SHARE IN THE DEVELOPMENT OF DATA
Form Approved
OMB No. 2070-0106
Approval Expires 12-31-92
Public reporting burden for this collection of information is estimated to average 15 minutes per response, including
time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and
completing and reviewing the collection of information. Send comments regarding the burden estimate or any other
aspect of this collection of information, including suggestions for reducing this burden, to Chief, Information Policy
Branch, PM-223. U.S. Environmental Protection Agency, 401 M St., S.W., Washington, DC 20460; and to the Office
of Management and Budget, Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Pfease fill in blanks below.
Company Nim»
Company Number
Chemical Name
EPA Chemical Number
I Certify that:
My company is willing to develop and submit the data required by EPA under the authority of the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA), if necessary. However, my company would prefer to
enter, into an agreement with one or more registrants to develop jointly or share in the cost of developing
My firm has offered in writing to enter into such an agreement. That offer was irrevocable and included an
offer to be bound by arbitration decision under section 3(c)(2)(B)(iii) of FIFRA if final agreement on all
terms could not be reached otherwise. This offer was made to the following firm(s) on the following
date(s):
Name of Flrm(s)
Date of Offer
Certification:
I certify that I am duly authorized to represent the company named above, and that the statements that I have made on
this form and all attachments therein are true, accurate, and complete. I acknowledge that any knowingly false or
misleading statement may be punishable by fine or imprisonment or both under applicable law.
Signature of Company'* Authorized Representative
Oat* '
Narn^pid Title (Please Type or Print)
PA Form 8570-32 (4-90)
-------
United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION WITH RESPECT TO
DATA COMPENSATION REQUIREMENTS
Form Approved
OMB No. 2070-0106
Approval Expires 12-31*92
Public reporting burden for this collection of information is estimated to average 15 minutes per response, including
time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and
completing and reviewing the collection of information. Send comments regarding the burden estimate or any other
aspect of this collection of information, including suggestions for reducing this burden, to Chief, Information Policy
Branch, PM-223, U.S. Environmental Protection Agency, 401 M St., S.W., Washington, DC 20460; and to the Office
of Management and Budget, Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Please fill In blanks below.
Company Namo
Chemical Name
Company Number
EPA Chemical Number
I Certify that:
1. For each study cited in support of registration or reregistration under the Federal Insecticide, Fungicide and
Rodenticide Act (FIFRA) that is an exclusive use study, I am the original data submitter, or I have obtained the
written permission of the original data submitter to cite that study.
! for each study cited in support of registration or reregistration under FIFRA that is NOT an exclusive use
Jy. I am the original data submitter, or I have obtained the written permission of the original data submitter, or I
have notified in writing the companyfjes) that submitted data I have cited and have offered to: (a) Pay
compensation for those data in accordance with sections 3(C)(1)(D) and 3(c)(2)(D) of FIFRA; and (b) Commence
negotiation to determine which data are subject to the compensation requirement of FIFRA and the amount of
compensation due, if any. The companies I have notified are: (check one)
[ ] AH companies on the data submitters' list for the active ingredient listed on this form (Cite-All
Method or Cite-All Option under the Selective Method). (Also sign the General Offer to Pay
below.)
[ 1 The companies who have submitted the studies fisted on the back of this form or attached
sheets, or indicated on the attached 'Requirements Status and Registrants' Response Form,"
3. That I have previously complied with section 3(c)(1)(D) of FIFRA for the studies I have cited in support of
registration or reregistration under FIFRA
| Signature
I
Date
Name and Title (Pleaae Type or Print)
(
GENERAL OFFER TO PAY: I hereby offer and agree to pay compensation to other persons, with regard to the
registration or reregistration of my products, to the extent required by FIFRA sections 3(C)(1)(D) and 3(c)(2)(D).
*'*•
Name
Dale
and Title (Please Type or Print)
EPA Form 8570-31 (4-90)
-------
APPENDIX G
Product Specific Data Call-In
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, O.C. 20460
DATA CALL-IN NOTICE
CERTIFIED MAIL
OFFICE Of
.__ _ „ PESTICDES AND TOXIC
SEP 3 0 1992 SUBSTANCES
Dear Sir or Madam:
This Notice .requires you and other registrants of pesticide
products containing the active ingredient identified in
Attachment A of this Notice, the Data Call-In Chemical Status
Sheet. to submit certain product specific data as noted herein to
the U.S. Environmental Protection Agency (EPA, the Agency).
These data are necessary to maintain the continued registration
of your product(s) containing this active ingredient. Within 90
days after you receive this Notice you must respond as set forth
in Section III below. Your response must state:
1. How you will comply with the requirements set forth in
this Notice and its Attachments A through G; or
2. Why you believe you are exempt from the requirements
listed in this Notice and in Attachment C,
Requirements Status and Registrant's Response Form, (see
section III-B); or
3. Why you believe EPA should not require your submission
of product specific data in the manner specified by this
Notice (see section III-D).
If you do not respond to this Notice, or if you do not
satisfy EPA that you will comply with its requirements or should
be exempt or excused from doing so, then the registration of your
product(s) subject to this Notice will be subject to suspension.
We have provided a list of all of your products subject to this
Notice in Attachment B, Data Call-In Response Form, as well as a
list of all registrants who were sent this Notice (Attachment F).
The authority for this Notice is section 3(c)(2)(B) of the
federal Insecticide, Fungicide and Rodenticide Act as amended
r(FIFRA), 7 U.S.C. section 136a(c) (2) (B). Collection of this
information is authorized under the Paperwork Reduction Act by
OMB Approval No. 2070-0107 (expiration date 12-31-92).
Prirwd on Kteyclfd Piper
-------
This Notice is divided into six sections and seven
Attachments. The Notice itself contains information and
instructions applicable to all Data Call-in Notices. The
Attachments contain specific chemical information and
instructions. The six sections of the Notice are:
Section I - Why You Are Receiving This Notice
Section II - Data Required By This Notice
Section III - Compliance With Requirements Of This
Notice
Section IV - Consequences Of Failure To Comply With
This Notice
Section V - Registrants' Obligation To Report
Possible Unreasonable Adverse Effects
Section VI - Inquiries And Responses To This Notice
The Attachments to this Notice are:
A - Data Call-In Chemical Status Sheet
B - Data Call-in Response Form
C - Requirements Status and Registrant's Response Form
D - EPA Grouping of End-Use Products for Meeting Acute
Toxicology Data Requirements for Rereaistration
E - EPA Acceptance Criteria
F - List of Registrants Receiving This Notice
G - Cost Share and Data Compensation Forms, and Product
Specific Data Report Form
SECTION I. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active
ingredient and reevaluated the data needed to support continued
registration of the subject active ingredient. The Agency has
concluded that the only additional data necessary are product
specific data. No additional generic data requirements are being
imposed. You have been sent this Notice because you have
product(s) containing the subject active ingredient.
SECTION II. DATA REQUIRED BY THIS NOTICE
II-A. DATA REQUIRED
The product specific data required by this Notice are
specified in Attachment C, Requirements Status and Registrant's
Response Form. Depending on the results of the studies required in
this Notice, additional testing may be required.
-------
II-B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the
data requirements specified in Attachment C, Requirements Status
and Registrant's Response Form, within the timeframes provided.
II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in
accordance with test standards outlined in the Pesticide Assessment
Guidelines for those studies- for which guidelines have been
established.
These EPA Guidelines are available from the National Technical
Information Service (NTIS) , Attn: Order Desk, 5285 Port Royal Road,
Springfield, Va 22161 (tell 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 (40 CFR § 158.70). When
using the OECD protocols, they should be modified as appropriate so
that the data generated by the study will satisfy the requirements
of 40 CFR § 158. Normally, the Agency will not extend deadlines
for complying with data requirements when the studies were not
conducted in accordance with acceptable standards. The OECD
protocols are available from OECD, 1750 Pennsylvania Avenue N.W. ,
Washington, D.C. 20006.
All new studies and proposed protocols submitted in response
to this Data Call-in Notice must be in accordance with Good
Laboratory Practices [40 CFR Part 160.3 (a) (6) ].
II-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3fcW2UB) NOTICES
ISSUED BY THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in
any way supersede or chance the requirements of any previous Data
Call-ln(s) . or any other agreements entered into with the Agency
pertaining to such prior Notice. Registrants must comply with the
requirements of all Notices to avoid issuance of a Notice of Intent
to Suspend their affected products.
SECTION III. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
III-A. gCffEPVfE fOfli PESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice
for product specific data must be submitted to the Agency within 90
days after your receipt of this Notice. Failure to adequately
respond to this Notice within 90 days of your receipt will be a
basis for issuing a Notice of Intent to Suspend (NOIS) affecting
-------
your products. This and other bases for issuance of NOIS due to
failure to comply with this Notice are presented in Section IV-A
and IV-B.
III-B. OPTIONS FOR RESPONDING TO THE AGENCY
The options for responding to this Notice for product specific
data are: (a) voluntary cancellation/ (b) agree to satisfy the
product specific data requirements imposed by this Notice or (c)
request a data waiver(s).
A discussion of how to respond if you choose the Voluntary
Cancellation option is presented below. A discussion of the
various options available for satisfying the product specific data
requirements of this Notice is contained in Section III-C. A
discussion of options relating to requests for data waivers is
contained in Section III-D.
There are two forms that accompany this Notice of which,
depending upon your response, one or both must be used in your
response to the Agency. These forms are the Data-Call-in Response
Form, and the Requirements Status and Registrant's.Response Form.
Attachment B and Attachment C. The Data Call-in Response Form must
be submitted as part of every response to this Notice. In
addition, one copy of the Requirements Status and Registrant's
Response Form must be submitted for each product listed on the
Data Call-In Response Form unless the voluntary cancellation option
.is selected or unless the product is identical to another (refer to
the instructions for completing the Data Call-in Response Form in
Attachment B). Please note that the company's authorized
representative is required to sign the first page of the Data Call-
in Response Form and Requirements Status and Registrant's Response
Form (if this form is required) and initial any subsequent pages.
The forms contain separate detailed instructions on the response
options. Do not alter the printed material. If you have questions
or need assistance in preparing your response, call or write the
contact person(s) identified in Attachment A.
•
1. Voluntary Cancellation - You may avoid the requirements of
this Notice by requesting voluntary cancellation of your product(s)
containing the active ingredient that is the subject of this
Notice. If you wish to voluntarily cancel your product, you must
submit a completed Data Call-In Response Form, indicating your
election of this option. Voluntary cancellation is item number 5
on the Data Call-in Response Form. If you choose this option, this
is the only form that you are required to complete.
If you choose to voluntarily cancel your product, further sale
and distribution of your product after the effective date of
cancellation must be in accordance with the Existing Stocks
provisions of this Notice which are contained in Section IV-C.
-------
2. Satisfying the Product Specific Data Requirements of this
Notice. There are various options available to satisfy the product
specific data requirements of this Notice. These options are
discussed in Section III-C of this Notice and comprise options 1
through 6 on the Requirements Status and Registrant's Response Form
and item numbers 7a and 7b on the Data Call-in Response Form.
Deletion of a use(s) and the low volume/minor use option are not
valid options for fulfilling product specific data requirements.
3. Request for Product Specific Data Waivers. Waivers for
product specific data are discussed in Section III-D of this Notice
and are covered by option 7 on the Requirements Status and
Registrant's Response Form. If you choose this option, you must
submit both forms as well as any other information/data pertaining
to the option chosen to address the data requirement.
III-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call*In Response Form that you
agree to satisfy the product specific data requirements (i.e. you
select option 7a or 7b), then you must select one of the six '"
options on the Requirements Status and Registrant's Response Form
related to data production for each data requirement. Your option
selection should be entered under item number 9, "Registrant
Response." . The six options related to data production are the
first six options discussed under item 9 in the instructions for
completing the Requirements Status and Registrant's Response Form.
These six options are listed immediately below with information in
parentheses to guide registrants to additional instructions
provided in this Section. The options are:
<1). I will generate and submit data within the specified
timeframe (Developing Data)
(2) I have entered into an agreement with one or more
registrants to develop data jointly (Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been
submitted* previously to the Agency by anyone (Submitting
an Existing Study)
(5) I am submitting or citing data to upgrade a study
classified by EPA as partially acceptable and upgradeable
(Upgrading a Study)
(6) I am citing an existing study that EPA has classified as
acceptable or an existing study that has been submitted
but not reviewed by the Agency (Citing an Existing Study)
Option 1. Developing Data — If you choose to develop the
teguired data it must be in conformance with Agency deadlines and
ith other Agency requirements as referenced herein and in the
attachments. All data generated and submitted must comply with the
Good Laboratory Practice (GLP) rule (40 CFR Part 160), be conducted
according to the Pesticide Assessment Guidelines (PAG), and be in
conformance with the requirements of PR Notice 86-5.
-------
The time frames in the Requirements Status and Registrant's
Response Form are the time frames that the Agency is allowing for
the submission of completed study reports. The noted deadlines run
from the date of the receipt of this Notice by the registrant, if
the data are not submitted by the deadline, each registrant is
subject to receipt of a Notice of Intent to Suspend the affected
registration(s).
If you cannot submit the data/reports to the Agency in the time
required by this Notice and intend to seek additional time to meet
the requirements (s), you must submit a request to the Agency which
includes: (l) a detailed description of the expected difficulty and
(2) a proposed schedule including alternative dates for meeting
such requirements on a step-by-step basis. You must explain any
technical or laboratory difficulties and provide documentation from
the laboratory performing the testing. While EPA is considering
your request, the original deadline remains. The Agency will
respond to your request in writing. If EPA does not grant your
request, the original deadline remains. Normally, extensions can
be requested only in cases of extraordinary testing problems beyond
the expectation or control of the registrant. Extensions will not
be given in submitting the 90-day responses. Extensions will not
be considered if the request for extension is not made in a timely
fashion; in no event shall an extension request be considered if it
is submitted at or after the lapse of the subject deadline.
Option 2. Agree to Share in Cost to Develop Data --Registrants
may only choose this option for acute toxicity data and certain
efficacy data and only if EPA has indicated in the attached data
tables that your product and at least one other product are similar
for purposes of depending on the same data. If this is the case,
data may be generated for just one of the products in the group.
The registration nyi^r of the product for which data will be
submitted must be noted in the agreement to cost share by the
registrant selecting this option. If you choose to enter into an
agreement to share in the cost of producing the required data but
will not be submitting the data yourself, you must provide the name
of the registrant vho will be submitting the data. You must also
provide EPA with documentary evidence that an agreement has been
formed. Such evidence may be your letter offering to join in an
agreement and the other registrant's acceptance of your offer, or a
written statement by the parties that an agreement exists. The
agreement to produce the data need not specify all of the terms of
the final arrangement between the parties or the mechanism to
resolve the terms. Section 3(c)(2)(B) provides that if the parties
cannot resolve the terms of the agreement they may resolve their
differences through binding arbitration.
Option 3. Offer to Share in the Cost of Data Development —
This option only applies to acute toxicity and certain efficacy
data as described in option 2 above. If you have made an offer to
pay in an attempt to enter into an agreement or amend an existing
agreement to meet the requirements of this" Notice and have been
-------
unsuccessful, you may request EPA (by selecting this option) to
exercise its discretion not to suspend your registration(s),
although you do not comply with the data submission requirements of
this Notice. EPA has determined that as a general policy, absent
other relevant considerations, it will not suspend the registration
of a product of a registrant who has in good faith sought and
continues to seek to enter into a joint data development/cost
sharing program, but the other registrant (s) developing the data
has refused to accept your offer. To qualify for this option, you
must submit documentation to the Agency proving that you have made
an offer to another registrant (who has an obligation to submit
data) to share in the burden of developing that data. You must
also submit to the Agency a completed EPA Form 8570-32,
Certification of Offer to Cost Share in the Development of Data,
Attachment G. In addition, you must demonstrate that the other
registrant to whom the offer was made has not accepted your offer
to enter into a costsharing agreement by including a copy of your
offer-and proof of the other registrant's receipt of that offer
(such as a certified mail receipt). Your offer must, in addition
to anything else, offer to share in the burden of producing the.
data upon terms to be agreed or failing agreement to be bound by
binding arbitration as provided by FIFRA section 3(c)(2)(B)(iii)
and must not qualify this offer. The other registrant must also
inform EPA of its election of an option to develop and submit the
data required by this Notice by submitting a Data Call-in Response
Form and a Requirements Status and Registrant's Response Form
committing to develop and submit the data required by this Notice.
In order for you to avoid suspension under this option, you may
not withdraw your offer to share in the burdens of developing the
data. In addition, the other registrant must fulfill its
commitment to develop and submit the data as required by this
Notice. If the other registrant fails to 'develop the data or for
some other reason is 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 do submit the required data in the specified time frame. In
such cases,'the Agency generally will not grant a time extension
for submitting the data.
Option 4. Subjflj^t^no: an Existing Study -— If you choose to
submit an existing study in response to this Notice, you must
determine that the study satisfies the requirements imposed by this
Notice. You may only submit a study that has not been previously
submitted to the Agency or previously cited by anyone. Existing
studies are studies which predate issuance of this Notice. Do not
use this option if you are submitting data to upgrade a study. (See
Option 5).
You should be aware that if the Agency determines that the
study is not acceptable, the Agency will require you to comply with
this Notice, normally without an extension of the required date of
submission. The Agency may determine at any time that a study is
.not valid and needs to be repeated.
-------
8
To meet the requirements of the DCI Notice for submitting an
existing study, all of the following three criteria must be clearly
met;
a. You must certify at the time that the existing study is
submitted that the raw data and specimens from the study are
available for audit and review and you must identify where they
are available. This must be done in accordance with
the requirements of the Good Laboratory Practice (GLP)
regulation, 40 CFR Part 160. As stated in 40 CFR 160.3(j)
" '[r]aw data1 means any laboratory worksheets, records,
memoranda, notes, or exact copies thereof, that are the result
of original observations and activities of a study and are
necessary for the reconstruction and evaluation of the report
of that study. In the event that exact transcripts of raw data
have been prepared (e.g., tapes which have been transcribed
verbatim, dated, and verified accurate by signature), the exact
copy or exact transcript may be substituted for the original
source as raw data. 'Raw data1 may include photographs,
microfilm or microfiche copies, computer printouts, magnetic
media, including dictated observations, and recorded data from
automated instruments." The term "specimens", according to 40
CFR 160.3(k), means "any material derived from a test system
for examination or analysis."
b. Health and safety studies completed after May 1984 must also
contain all GLP-required quality assurance and quality control
information, pursuant to the requirements of 40 CFR Part 160.
Registrants must also certify at the time of submitting the
existing study that such GLP information is available for post-
May 1984 studies by including an appropriate statement on or
attached to the study signed by an authorized official or
representative of the registrant.
c. You must certify that each study fulfills the acceptance
criteria for the Guideline relevant to the study provided in
the FIFRA Accelerated Reregistration Phase 3 Technical Guidance
and that the study has been conducted according to the
Pesticide Assessment Guidelines (PAG) or meets the purpose of
the PAG (both available from NTIS). A study not conducted
according to the PAG may be submitted to the Agency for
consideration if the registrant believes that the study clearly
meets the purpose of the PAG. The registrant is referred to 40
CFR 158.70 which states the Agency's policy regarding
acceptable protocols. If you wish to submit the study, you
must, in addition to certifying that the purposes of the PAG
are met by the study, clearly articulate the rationale why you
believe the study meets the purpose of the PAG, including
copies of any supporting information or data. It has been the
Agency's experience that studies completed prior to January
1970 rarely satisfied the purpose of the PAG and that necessary
raw data are usually not available for such studies.
-------
9
If you submit an existing study, you must certify that the
study meets all requirements of the criteria outlined above.
If you know of a study pertaining to any requirement in this
Notice which does not meet the criteria outlined above but does
contain factual information regarding unreasonable adverse effects,
you must notify the Agency of such a study. If such study is in
the Agency's files, you need only cite it along with the
notification. If not in the Agency's files, you must submit a
summary and copies as required by PR Notice 86-5.
Option 5. Upgrading a Study ~ If a study has been classified
as partially acceptable and upgradeable, you may submit data to
upgrade that study. The Agency will review the data submitted and
determine if the requirement is satisfied. If the Agency decides
the requirement is not satisfied, you may still be required to
submit new data normally without any time extension. Deficient,
but upgradeable studies will normally be classified as
supplemental. However, it is important to note that not all
studies classified as supplemental are upgradeable. If you have
questions regarding the classification of a study or whether a
study may be upgraded, call or write the contact person listed in
Attachment A* If you submit data to upgrade an existing study you
Tnust satisfy or supply information to correct all deficiencies in
the study identified by EPA. You must provide a clearly
articulated rationale of how the deficiencies have been remedied or
corrected and why the study should be rated as acceptable to EPA.
Your submission must also specify the MRID number(s) of the study
which you are attempting to upgrade and must be in conformance with
PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a
study classified as unacceptable and determined by the Agency as
not capable of being upgraded.
This option should also be used to cite data that has been
previously submitted to upgrade a study, but has not yet been
reviewed by the Agency. You must provide the MRID number of the
data submission as well as the MRID number of the study being
upgraded.
The criteria for submitting an existing study, as specified in
Option 4 above, apply to all data submissions intended to upgrade
studies. Additionally your submission of data intended to upgrade
studies must be accompanied by a certification that you comply with
each of those criteria as well as a certification regarding
protocol compliance with Agency requirements.
Option 6. Citing Existing Studies --If you choose to cite a
study that has been previously submitted to EPA, that study must
have been previously classified by EPA as acceptable or it must be
a study which has not yet been reviewed by £he Agency. Acceptable
-------
10
toxicology studies generally will have been classified as "core-
guideline" or "core minimum." For all other disciplines the
classification would be "acceptable." With respect to any studies
for which you wish to select this option you must provide the MRID
number of the study you are citing and, if the study has been
reviewed by the Agency, you must provide the Agency's
classification of the study.
If you are citing a study of which you are not the original
data submitter, you must submit a completed copy of EPA Form
8570-31, Certification with Respect to Data Compensation
Requirements.
Registrants who select one of the above 6 options must meet all
of the requirements described in the instructions for completing
the Data Call-in Response Form and the Requirements Status and
Registrant's Response Form, as appropriate.
III-D REQUESTS FOR DATA WAIVERS
If you request a waiver for product specific data because you
believe it is inappropriate, you must attach a complete
justification for the request, including technical reasons, data
and references to relevant EPA regulations, guidelines or policies.
(Note: any supplemental data must be submitted in the format
required by PR Notice 86-5). This will be the only opportunity to
state the reasons or provide information in support of your
request. If the Agency approves your waiver request, you will not
be required to supply the data pursuant to section 3(c)(2)(B) of
FIFRA. If the Agency denies your waiver request, you must choose
an option for meeting the data requirements of this Notice within
30 days of the receipt of the Agency's decision. You must indicate
and submit the option chosen on the Requirements Status and
Registrant's Response Form. Product specific data requirements for
product chemistry, acute toxicity and efficacy (where appropriate)
are required for all products and the Agency will grant a waiver
only under extraordinary circumstances. You should also be aware
that submitting a waiver request will not automatically extend the
due .date for the study in question. Waiver requests submitted
without adequate supporting rationale will be denied and the
original due date will remain in force.
IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE
IV-A NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products
subject to this Notice due to failure by a registrant to comply
with the requirements of this Data Call-In Notice, pursuant to
FIFRA section 3(C)(2)(B). Events which may be the basis for
issuance of a Notice of Intent to Suspend include, but are not
limited to, the following:
-------
11
1. Failure to respond as required by this Notice within 90
days of your receipt of this Notice.
2. Failure to submit on the required schedule an acceptable
proposed or final protocol if such is required to be submitted
to the Agency for review.
3. Failure to submit on the required schedule an adequate
progress report on a study if required by this Notice.
4 . Failure to submit on the required schedule acceptable
data as required by this Notice.
5. Failure to take a required action or submit adequate
information pertaining to any option chosen to address the data
requirements (e.g., any required action or information
pertaining to submission or citation of existing studies or
offers, arrangements, or arbitration on the sharing of costs or
the formation of Task Forces, failure to comply with the terms
of an agreement or arbitration concerning joint data
development or failure to comply with any terms of a data
waiver) .
6. Failure to submit supportable certifications as to the
conditions of submitted studies, as required by Section III-C
of this Notice.
7. Withdrawal of an offer to share in the cost of developing
required data.
8. Failure of the registrant to whom you have tendered an offer
to share in the cost of developing data and provided proof of
the registrant's receipt of such offer either to:
a. Inform EPA of intent to develop and submit the data
required by this Notice on a Data Call-in Response Form and a
Requirements Status and Registrant's Response Form;
b. Fulfill the commitment to develop and submit the data as
required by this Notice; or
c. Otherwise take appropriate steps to meet the requirements
stated in this Notice, unless you commit to submit and do
submit the required data in the specified time frame.
9. Failure to take any required or appropriate steps, not
mentioned above, at any time following the issuance of this
Notice.
. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS
The Agency may determine that a study (even if submitted within
the required time) is unacceptable and constitutes a basis for
_ft_ ^.... — --....•. --—• - v-riw - . -, x i__ .-. ;-i—-JarMifrM"''-rr; • uyi -V. r.'t -T-LB. ^ '. VTA »J >l ?a i i?i iu ' n~ *•'Yf J fV3 foW1- r>S ^^^•f^J i JPC^IJiLB^!^ yi "iB"-fJ^jSJI^
-------
12
issuance of a Notice of Intent to Suspend. The grounds for
suspension include, but are not limited to, failure to meet any of
the following:
1. EPA requirements specified in the Data Call-in Notice or
other documents incorporated by reference (including, as
applicable, EPA Pesticide Assessment Guidelines, Data Reporting
Guidelines, and GeneTox Health Effects Test Guidelines)
regarding the design, conduct, and reporting of required
studies. Such requirements include, but are not limited to,
those relating to test .material, test procedures, selection of
species, number of animals, sex and distribution of animals,
dose and effect levels to be tested or attained, duration of
test, and, as applicable, Good Laboratory Practices.
2. EPA requirements regarding the submission of protocols (if
applicable), including the incorporation of any changes
required by the Agency following review.
3. 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 86-5. All studies must be submitted
in the form of a final report; a preliminary report will not be
considered to fulfill the submission requirement.
IV-C EXISTING STOCKS OF SUSPENDED OR CANCfl^.T.fln PRODUCTS
EPA has statutory authority to permit continued sale,
distribution and use of existing stocks of a pesticide product
which has been suspended or cancelled if doing so would be
consistent with the purposes of the Act.
The Agency has determined that such disposition by registrants
of existing stocks for a suspended registration when a section
3(°)(2)(B) data request is outstanding would generally not be
consistent with the Act's purposes. Accordingly, the Agency
anticipates granting registrants permission to sell, distribute, or
use existing stocks of suspended product(s) only in exceptional
circumstances. If you believe such disposition of existing stocks
of your product(s) which may be suspended for failure to comply
with this Notice should be permitted, you have the burden of
clearly demonstrating to EPA that granting such permission would be
consistent with the Act. You must also explain 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, distribution, and use. Unless you meet this burden
the Agency will not consider any request pertaining to the
continued sale, distribution, or use of your existing stocks after
suspension.
If you request a voluntary cancellation of your product(s) as a
response to this Notice and your product is in full compliance with
-------
13
all Agency requirements, you will have, under most circumstances,
one year from the date your 90 day response to this Notice is due,
to sell, distribute, or use existing stocks. Normally, the Agency
will allow persons other than the registrant such as independent
distributors, retailers and end users to sell, distribute or use
such existing stocks until the stocks are exhausted. Any sale,
distribution or use of stocks of voluntarily cancelled products
containing an active ingredient for which the Agency has particular
risk concerns will be determined on a case-by-case basis.
Requests for voluntary .cancellation received after the 90 day
response period required by .this Notice will not result in the
Agency granting any additional time to sell, distribute, or use
existing stocks beyond a year from the date the 90 day response was
due unless you demonstrate to the Agency that you are in full
compliance with all Agency requirements, including the requirements
of this Notice* For example, if you decide to voluntarily cancel
your registration six months before a 3 year study is scheduled to
be submitted, all progress reports and other information necessary
to establish that you have been conducting the study in an
acceptable and good faith manner must have been submitted to the
Agency, before EPA will consider granting an existing stocks
provision.
SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLE
UNREASONABLE ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6(a)(2) states that
if at any time after a pesticide is registered a registrant has
additional factual information regarding unreasonable adverse
effects on the environment by the pesticide, the registrant shall
submit the information to the Agency. Registrants must notify the
Agency of any factual information they have, from whatever source,
including but not limited to interim or preliminary results of
studies, regarding unreasonable adverse effects on man or the
environment. This requirement continues as long as the products
are registered by the Agency.
SECTION VI. INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and
procedures established by this Notice, call the contact person(s)
listed in Attachment A, the Data Call-In Chemical Status Sheet.
All responses to this Notice (other than voluntary cancellation
requests) oust include a completed Data Call-In Response Form and a
Completed Requirements Status and Registrant's Response Form
^Attachment B and Attachment C) and any other documents required by
this Notice, and should be submitted to the contact person(s)
identified in Attachment A. If the voluntary cancellation option is
chosen, only the Data Call-In Response Form need be submitted.
-------
14
The Office of Compliance Monitoring (OCM) of the Office of
Pesticides and Toxic Substances (OPTS), EPA, will be monitoring the
data being generated in response to this Notice.
Sincerely yours,
A
B
C
D
E
F
G
Daniel N. Barolo, Director
Special Review and
Reregistration Division
Attachments
Data Call-In Chemical Status Sheet
Data Call-in Response Form
Requirements Status and Registrant's Response Form
EPA Grouping of End-Use Products for Meeting Acute
Toxicology Data Requirements for Rereaistration
EPA Acceptance Criteria
List of Registrants Receiving This Notice
Cost Share and Data Compensation Forms, and Product
Specific Data Report Form
-------
ATTACHMENT A
Product Specific Chemical Status Sheet
-------
ATTACHMENT A
STREPTOMYCIN: PRODUCT SPECIFIC DATA CALL-IN CHEMICAL STATUS
SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-In Notice because you have products
containing streptomycin.
This Product Specific Data Call-In Chemical Status Sheet, contains an overview of data
required by this notice, and point of contact for inquiries pertaining to the reregistration of
streptomycin. This attachment is to be used in conjunction with (1) the Product Specific Data
Call-In Notice, (2) the Product Specific Data Call-In Response Form (Attachment B), (3) the
Requirements Status and Registrant's Form (Attachment C), (4) EPA's Grouping of End-Use
Products for Meeting Acute Toxicology Data Requirements for Reregistration (Attachment D)
(5) a list of registrants receiving this DCI (Attachment E), (6) the Cost Share and Data
Compensation Forms in replying to this Streptomycin Product Specific Data Call-In (Attachment
F). Instructions and guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the product specific database for
streptomycin are contained in the Requirements Status and Registrant's Response (Attachment
C). The Agency has concluded that additional data on streptomycin are needed for specific
products. While product specific data requirements were imposed in the 1988 Registration
Standard, a complete listing is provided in Attachment C. If you, as a registrant of a
streptomycin product, responded to the 1988 Registration Standard and submitted the data
relating to your specific product, simply choose response number 6 and cite the MRID number
that was assigned to your study. Otherwise, these data are required to be submitted to the
Agency within the timeframe listed. These data are needed to fully complete the reregistration
of all eligible streptomycin products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic data requirements of streptomycin, please
contact Theresa A. Stowe at (703) 308 - 8043.
If you have any questions regarding the product specific data requirements and pro-
cedures established by this Notice, please contact Benjamin C. Chambliss (703) 305 - 7382.
-------
All responses to this Notice for the Product Specific data requirements should be
submitted to:
Susan J. Lewis, Product Manager 21
Herbicide and Fungicide Branch
Registration Division (H7505C)
Office of Pesticide Programs
U.S. Environmental Protection Agency
401 M Street, S.W.
Washington, D.C. 20460
RE: STREPTOMYCIN
-------
ATTACHMENT B
Product Specific Data Call-In Response Forms (Form A) plus Instructions
-------
INSTRUCTIONS FOR COMPLETING THE "DATA CALL-IN RESPONSE" FORM FOR
PRODUCT SPECIFIC DATA
Item 1-4. Already completed by EPA.
Item 5. If you wish to voluntarily cancel your product, answer
"yes." If you choose this option, you will not have to
provide the data required by the Data Call-In Notice and
you will not have to complete any other forms. Further
sale and distribution of your product after the effective
date of cancellation must be in accordance with the
Existing Stocks provision of the Data Call-in Notice
(Section IV-C).
Item 6. Not applicable since this form calls in product specific
data only. However, if your product is identical to
another product and you qualify for a data exemption, you
must respond with "yes" to Item 7a (MUP) or 7B (EUP) on
this form, provide the EPA registration numbers of your
source(s); you would not complete the "Requirements
Status and Registrant's Response" form. Examples of such
products include repackaged products and Special Local
Needs (Section 24c) products which are identical to
federally registered products.
Item 7a. For each manufacturing use product (MUP) for which you
wish to maintain registration, you must agree to satisfy
the data requirements by responding "yes."
Item 7b. For each end use product (EUP) for which you wish to
maintain registration, you must agree to satisfy the data
requirements by responding "yes." If you are requesting
a data waiver, answer "yes" here; in addition, on the
"Requirements Status and Registrant's Response" form
under Item 9, you must respond with Option 7 (Waiver
Request) for each study for which you are requesting a
waiver. See Item 6 with regard to identical products and
data exemptions.
Items 8-11. Self-explanatory.
NOTE; You may provide additional information that does not fit
on this form in a signed letter that accompanies this
form. For example, you may wish to report that your
product has already been transferred to another company
or that you have already voluntarily cancelled this
product. For these cases, please supply all relevant
details so that EPA can ensure that its records are
correct.
-------
INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE" FORM FOR PRODUCT SPECIFIC DATA
Item 1-3 Completed by EPA. Note the unique identifier number
assigned by EPA in Item 3. This number must be used in
the transmittal document for any data submissions in
response to this Data Call-In Notice.
Item 4. The guideline reference numbers of studies required to
support the product's continued registration are
identified. These guidelines, in addition to the
- requirements specified in the Notice, govern the conduct
of the required studies. Note that series 61 and 62 in
product chemistry are now listed under 40 CFR 158.155
through 158.180, Subpart C.
Item 5. The study title associated with the guideline reference
number is identified.
* .*•?
Item 6. The use pattern(s) of the pesticide associated with the
product specific requirements is (are) identified. For
most product specific data requirements, all use patterns
are covered by the data requirements. In the case of
efficacy data, the required studies only pertain to
products which have the use sites and/or pests indicated.
Item 7. The substance to be tested is identified by EPA. For
product specific data, the product as formulated for sale
and distribution is the test substance, except in rare
cases.
Item 8. The due date for submission of each study is identified.
It is normally based on 8 months after issuance of the
Reregistration Eligibility Document unless EPA determines
that a longer time period is necessary.
Item 9. Enter only one of the following response codes for each
data requirement to show how you intend to comply with
the data requirements listed in this table. Fuller
descriptions of each option are contained in the Data
Call-in Notice.
1. I will generate and submit data by the specified due date
(Developing Data). By indicating that I have chosen this
option, I certify that I will comply with all the
requirements pertaining to the conditions for submittal
of this study as outlined in the Data Call-in Notice.
2. I have entered into an agreement with one or more
registrants to develop data jointly (Cost Sharing). I am
submitting a copy of this agreement. I understand that
this option is available only for acute toxicity or
certain efficacy data and only if EPA indicates in an
attachment to this Notice that my product is similar
-------
enough to another product to qualify for this option. I
certify that another party in the agreement is committing
to submit or provide the required data; if the required
study is not submitted on time, my product may be subject
to suspension.
3. I have made offers to share in the cost to develop data
(Offers to Cost Share). I understand that this option is
available only for acute toxicity or certain efficacy
data and only if EPA indicates in an attachment to this
Data Call-in Notice that my product is similar enough to
. another product to qualify for this option. I am
submitting evidence that I have made an offer to another
registrant (who has an obligation to submit data) to
share in the cost of that data. I am also submitting a
completed "Certification of Offer to Cost Share in the
Development Data" form. I am including a copy of my
offer and proof of the other registrant's receipt of that
offer. I am identifying the party which is committing to
submit or provide the required data; if the required
study is not submitted on time, my product may be subject
to suspension. I understand that other terms under
Option 3 in the Data Call-in Notice (Section III-C.l.)
apply as well.
4. By the specified due date, I will submit an existing
study that has not been submitted previously to the
Agency by anyone (Submitting an Existing study). I
certify that this study will meet all the. requirements
for submittal of existing data outlined in Option 4 in
the Data Call-In Notice (Section III-C.l.) and will meet
the attached acceptance criteria (for acute toxicity and
product chemistry data). I will attach the needed
supporting information along with this response. I also
certify that I have determined that this study will fill
the data requirement for which I have indicated this
choice.
5. By the specified due date, I will submit or cite data to
upgrade a study classified by the Agency as partially
acceptable and upgradable (Upgrading a Study). I will
submit evidence of the Agency's review indicating that
the study may be upgraded and what information is
required to do so. I will provide the MRID or Accession
number of the study at the due date. I understand that
the conditions for this option outlined Option 5 in the
Data Call-In Notice (Section III-C.l.) apply.
6. By the specified due date, I will cite an existing study
that the Agency has classified as acceptable or an
existing study that has been submitted.but not reviewed
by the Agency (Citing an Existing Study). If I am citing
another registrant's study, I understand that this option
is available only for acute toxicity or certain efficacy
-------
data and only if the cited study was conducted on my
product, an identical product or a product which EPA has
"grouped" with one or more other products for purposes of
depending on the same data. I may also choose this
option if I am citing my own data. In either case, I
will provide the MRID or Accession number(s) for the
cited data on a "Product Specific Data Report" form or in
a similar format. If I cite another registrant's data,
I will submit a completed "Certification With Respect To
Data Compensation Requirements" form.
7. . I request a waiver for this study because it is
inappropriate for my product (Waiver Request). I am
attaching a complete justification for this request,
including technical reasons, data and references to
relevant EPA regulations, guidelines or policies. [Note:
any supplemental data must be submitted in the format
required by P.R. Notice 86-5]. I understand that this is
my only opportunity to state the reasons or provide
information in support of my request. If the Agency
approves my waiver request, I will not be required to
supply the data pursuant to Section 3(c)(2)(B) of FIFRA.
If the Agency denies my waiver request, I must choose a
method of meeting the data requirements of this Notice by
the due date stated by this Notice. In this case, I
must, within 30 days of my receipt of the Agency's
written decision, submit a revised "Requirements Status
and Registrant's Response" Form indicating the option
chosen. I also understand that the deadline for
submission of data as specified by the original data
call-in notice will not change.
Items 10-13. Self-explanatory.
NOTE: You may provide additional information that does not fit
on this form in a signed letter that accompanies this
form. For example, you may wish to report that your
product has already been transferred to another company
or that you have already voluntarily cancelled this
product. For these cases, please supply all relevant
details so that EPA can ensure that its records are
correct.
-------
DRAFT COPY
United States Environmental Protection Agency
Washington, D. C. 20460
DATA CALL-IN RESPONSE
Page 1 of
Form Approved
OMB No. 2070-0107
Approval Expires 12-31-92
INSTRUCTIONS: Please type or print in ink. Please read carefully the attached instructions and supply the information requested on this form.
Use additional sheet(s) if necessary.
1• Company name and Address
SAMPLE COMPANY
NO STREET ADDRESS
NO CITY, XX 00000
2. Case f and Name
0169 Streptomycin
3. Date and Type of OCI
PRODUCT SPECIFIC
SEP 3 0 1992
4. EPA Product
Registration
5. I wish to
cancel this
product regis-
tration volun-
tarily.
6. Generic Data
6a. I am claiming a Generic
Data Exemption because I
obtain the active Ingredient
from the source EPA regis-
tration number listed below.
6b. I agree to satisfy Generic
Data requirements as indicated
on the attached form entitled
"Requirements Status and
Registrant's Response."
7. Product Specific Data
7a. My product is a IMP and
I agree to satisfy the HUP
requirements on the attached
form entitled "Requirements
Status and Registrant's
Response."
7b. My product is an EUPer
I agree to satisfy the EUP
requirements on the attache
form entitled "Requirements
Status and Registrant's
Response."
NNNNNN-NNNNN
N.A.
N.A.
8. Certification
I certify that the statements made on this form and all attachments are true, accurate, and complete.
I acknowledge that any knowingly false or misleading statement may be punishable by fine, imprisonment
or both under applicable law.
Signature and Title of Company's Authorized Representative
9. Date
10. Name of Company Contact
11. Phone Number
-------
ATTACHMENT C
Product Specific Data Call-in Requirements Status and
Registrant's Response Forms (Form B) plus Instructions
-------
8PECX7IC INSTRUCTIONS FOR COMPUTING
TEB R1QOZREXZHTS STATUS AKD REGISTRANT** R2SPONSI FORM
product Specific Pate
This fern is designed to be used for registrants to respond
to call-ins for generic and product-specific data as part of
EPA1* raregistration program under the Federal Insecticide
Fungicide and Rodenticide Act. Although the form is the sane for
both product specific and generic data, instructions for
completing the forms differ slightly. Specifically/ options for
satisfying product specific data requirements do not include (l)
deletion of uses or (2) request for a low volume/minor use
waiver. These instructions are for completion of product
specific data requirements.
EPA has developed this form individually for each data call-
in addressed to each registrant, and has preprinted this form
with a number of items. PQ MOT use this form for any other
active ingredient.
Items 1 through 8 (inclusive) will have been preprinted on
the form. You must complete all other itVms on this form by
typing or printing legibly.
Public reporting burden for this collection of information
is estimated to average 30 minutes per response, including tine
for reviewing instructions, searching existing data sources,
gathering and maintaining the data needed, and completing and
reviewing the collection of information. Send comments regarding
the burden estimate or any other aspect of this collection of
information, including suggesting for reducing this burden, to
Chief, Information Policy Branch, PM-223, U.S. Environmental
Protection Agency, 401 H St., S.W., Washington, O.C. 20460; and
to the Office of Management and Budget, Paperwork Reduction
Project 2070-0107, Washington, D.C. 20503.
-------
INSTRUCTIONS POR COMPLETING THE "REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE" FORM FOR PRODUCT SPECIFIC DATA
Item 1-3 Computed by EPA. Not* the uaique ideatifier number
. • assign** by EPA in Item 3. This number Bust be used in
the traasaittal document for any data submission* in
response to this Data CaU-In Notice.
Item 4. The guideline reference numbers of studies required to
support the product's continued registration are
identified. These guidelines, in addition to the
requirement* specified in the Notice, govern the conduct
of the required studies. Note that series 61 and 62 in
product chemistry are now listed under 40 CFR 158.155
through 158.180, Subpart C.
Item 5. The study title associated with the guideline reference
number is identified.
Item 6. The use pattern(s) of the pesticide associated with the
product specific requirements is (are) identified. For
most product specific data requirements, all use patterns
are covered by tht data requirements. In the case of
efficacy data, the required studies* only pertain to
products which have the use sites and/or pests indicated.
Item 7. The substance to be tested is identified by EPA. For
product specific data, the product as formulated for sale
and distribution is the test substance, except in rare
cases.
Item 8. The due date for submission of each study is identified.
It is normally based on • months, after issuance of the
Reregistratioa Eligibility Document unless EPA .determines
that a longer time period is necessary.
Item 9. Enter enlv one of the following response codes for each
data requirement to show how you iatead to comply with
the data requirements listed ID this table. Fuller
• descriptions of each option are contained in the Data
Call-In Notice.
1. Z will generate and submit data by the specified due date
(Developing Data). By indicating that I have chosen this
option, Z certify that I will comply with all the
requirements pertaining to the conditions for submittal
of this study as outlined in the Data Call-in Notice.
2. Z have entered into an agreement with one or more
registrants to develop data jointly (Cost Sbariag). I
am submitting a eopy of this agreement and a completed
••Certification With Respect To Data Compensation
Requirements" fora. I understand that this option is
available only for acute toxicity or certain efficacy
-------
data and only if EPA indicates in an attachment to this
Notiea that ay product in similar •nough to another
product to qualify for thi« option. Z eartify that
anothar party in tha agreement it committing to submit
or provide tha required data; if tha required atudy is
not aubmittad on time, ay product aay be subj act to
•uspanaion. .
3. Z hava aada offara to ahara in tha coat to davalop data
(Offers to Cost Bbare). Z understand that this option
is available only for acuta toxicity or certain efficacy
data and only if EPA indicates in an attachaant to this
Data Call-in Notiea that ay product is aiailar enough to
anothar product to qualify for this option. I an
submitting evidence that Z hava Bade aa offer to another
registrant (who has an obligation to submit data) to
share in tha cost of that data. Z am also submitting a
completed "Certification of Offer to Cost Share in the
Development Data" fora. Z aa including a copy of ny
offer and proof of the other registrant's receipt of that
offer. Z aa identifying tha party which is committing
to submit or provida tha required data; if tha. required
•tudy is not submitted on time, ay product aay be subject
to suspension. Z understand that other terms under
Option 3 in tha Data Call-In Notice (Section III-C.l.)
apply as vail.
4. By tha specified dua data, Z will submit an existing
•tudy that has not been submitted previously to the
Agency by anyone (Submitting aa Existing Study). I
certify that this study will meet all tha requirements
for submittal of existing data outlined in Option 4 in
tha Data Call-in Notice (Section III-C.l.) and will meet
tha attached acceptance, criteria (for acuta toxicity and
product chemistry data). Z will attach tha needed
supporting information along with this response. I also
eartify that Z have determined that this study will fill
tha data requirement for which Z hava' indicated this
choice.
S. By the spacifiad dua data, Z will submit or cite data to
upgrade a study classified by tha Agency as partially
acceptable and upgradable (Upgrading a study). I will
submit evidence of the Agency's review indicating that
the study Bay be upgraded and what information is
required to do so. Z will provide the KRID or Accession
number of the study at the due date. Z understand that
the conditions for this option outlined Option 5 in the
Data Call-In Notice (Section III-C.l.) apply.
6. By the specified due date, Z will cite an existing study
that the Agency has classified as acceptable or ar.
existing study that has been submitted but not reviewed
by the Agency (Citing aa Existing Study). Zf Z am citir.z
-------
another registrant'* study, X understand that this option
is available only for acute toxieity or certain efficacy
data and only if the cited study was conducted on ay
product, an identical product or a product which EPA has
•grouped" with one or sore other products for purposes
of depending on the sane data. Z nay also choose this
option if z as citing ay own data. In either case, i
will provide the MRID or Accession number(s) for th«
cited data on a "Product Specific Data Report" fora or
in a similar format. If z cite another registrant's
data, Z will submit • completed "Certification with
Respect To Data Compensation Requirements" form.
7. Z request a waiver for this study because it is
inappropriate for ay product (Waiver Request). I aa
attaching a complete justification for this request,
including technical reasons, data and references to
relevant EPA regulations, guidelines or policies. [Note:
any supplemental data oust be submitted in the foraat
required by P.R. Notice 86-5]. Z understand that this
is ay only opportunity to state the reasons or provide
information in support of my request. If the Agency
approves ay waiver request, Z; will aot be required to
supply the data pursuant to Section 3(c)(2)"(B) of FIFRA.
Zf the Agency denies ay waiver request, Z aust choose a
method of meeting the data requirements of this Notice
by the due date stated by this Notice. In this case, I
aust, within 30 days of my receipt of the Agency's
written decision, submit a revised "Requirements Status
and Registrant's Response" Form indicating the option
.. chosen* Z also understand that the deadline for
submission of data as specified by the original data
call-in notice will not change.
Items 10-13. Self-explanatory.
NOTES You aay provide additional information that does not fit
on this form in a signed letter that accompanies this
fora. For example, you may wish to report. that your
product has already been transferred to another company
or that you have already voluntarily cancelled this
product. For these cases, please supply all relevant
detail* so that EPA can ensure that its records are
correct.
-------
DRAFT COPY
Page 1 of 2
United States Environmental Protection Agency
Washington, D. C. 20460
REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE
INSTRUCTIONS: Please type or print in ink. Please read. carefully
Use additional sheet(s) if necessary.
1. Company name and Address
SAMPLE COMPANY
NO STREET ADDRESS
NO CITY, XX 00000
4. Guideline
Requirement
Number
61-1
61-2 (a)
61-2 (b)
62-1
62-2
62-3
63-3
63-7
63-12
63-14
63-15
63-16"
5. Study Title
Prod them - Regular Chemical
Product identity ft compost tion(1)
Deserip of starting mater(als,(1,2)
production ft formulation
proc
Discussion of formation of (1,3)
tmpurltteft
Preliminary analysis (1,4)
Certification of limit* (1,5)
Analytical method (1)
Physical state
Density
pH (9)
Oxidizing or reducing action (10)
Flanmabtlity (11)
Explodability (12)
10. Certification ;
the attached instructions and supply the information requested
2. Case * and Name
0169 Streptomycin
EPA Reg. No. NNNNNN-NNNNN
i
i
i
Progress
Reports
1
*
2
3
6. Use
Pattern
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
7. Test
on this form.
3. Date and
Form Approved
OMB No. 2070-0107
Approval Expires 12-31-92
Type of DCI
PRODUCT SPECIFIC
ID# NNNNNN-RD-NNNN
Substance
MP/EP
MP/EP
MP/EP
MP/EP
MP/EP
EP
EP
EP
EP
MP/EP
EP
EP
1 certify that the statements made on this fora and all attachments are true, accurate, and complete.
1 acknowledge that any knowingly false or misleading statement may be punishable by fine, imprisonment
or both under applicable law.
Signature and Title of Company's Authorized Representative
12. Name of Company Contact
^
11.
13.
SEP 3 0 1992
8. Time
Fran
K
8 mos.
8 mos.
8 mos.
8 mos.
8 mos.
8 mos.
8 mos.
8 mos.
8 mos.
8 mos.
8 mos*
8 mos.
Date
Phone Number
9. Registrant
Response
,.
-------
DRAFT COPY
Page 2 of 2
United States Environmental Protection Agency
Washington, D. C. 20460
REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE
INSTRUCTIONS: Please type or print in ink. Please read carefully
Use additional sheet (s) if necessary.
1. Company name and Address
SAMPLE COMPANY
NO STREET ADDRESS
NO CITY, XX 00000
4. Guideline
Requirement
Number
63-17
63-18
63-19
63-20
81-1
81-2
81-3
81-4
81-5
81-6
5. Study Title
Storage stability (38)
Viscosity (13)
Niscibility
Corrosion characteristics
Acute Toxic - Regular Chemical
Form Approved
OMB No. 2070-0107
Approval Expires 12-31-92
the attached instructions and supply the information requested on this form.
2. Case * and Name
0169 Streptomycin
3. Date and
Type of DCI
PRODUCT SPECIFIC
ID# NNNNNN-RD-NNNN
EPA Reg. No. NNNNNN-NNNNN
Acute oral toxicity-rat (1,36,37)
Acute dermal <1,2,37>
toxicity-rabbit/rat
Acute inhalation toxicity-rat (3)
Primary eye irri tat ion- rabbit (2)
Primary dermal irritation (1,2)
Dermal sensittzation (4)
Progress
Reports
1
2
5
6. Use
Pattern
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
Initial to indicate certification as to information on this page
(full text of certification is on page one).
7. Test
Substance
EP
EP
EP
MP/EP
MP/EP and TGAI
MP/EP and TGAI
MP/EP and TGAI
MP/EP
MP/EP
MP/EP
8. Time
Frame
8 mos.
8 mos.
8 mos.
8 mos.
8 mos.
8 mos.
8 mos*
8 mos.
8 mos.
8 mos.
9. Registrant
Response
Date
-------
DRAFT COPY Page 1 of 2
United States Environmental Protection Agency
Washington, D. C. 20460
FOOTNOTES AND KEY DEPUTATIONS FOR GUIDELINE REQUIREMENTS
Case I and name: 0169 Streptomycin
Kay: MP • Manufacturing-use product; EP • end-use product; provided formulstors purchase their active ingredlent(s) from a registered source, they need not submit or cite
data pertaining to the purchased product. (NOTE: If a product is a 100 percent repackage of another registered product that is purchased, and any use for the product does
not differ fro» those of the purchased and registered source, users are not subject to any data requireMsnts Identified In the tables.); TEP • typical end-use product;
TGAI • technical grade of the active ingredient; PAI • "pure" active Ingredient; PAIRA • "pure" active Ingredient, radlolabeled.
Use Catagorfea Key:
A - Terrestrial food crop 0 - Terrestrial food feed crop C - Terrestrial nonfood crop D - Aquatic food crop E - Aquatic nonfood outdoor
F • Aquatic nonfood Industrial G - Aquatic nonfood residential N - Greenhouse food crop I - Greenhouse nonfood crop J - Forestry
K - Residential outdoor L • Indoor food M - Indoor nonfood N - Indoor Medical 0 - Indoor residential
Footnotes: (The following notes are referenced In column two (5. Study Title) of the REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE fora.]
Prod dwjM - Regular Chearicml
1 RequircMents pertaining to product Identity, composition, analysis, and certification of ingredients are detailed further In the following sections: *158.155 for
product identity and composition (61-1); •158.160. 158.162, and 158.165 for description of starting Materials and Manufacturing process (61-2); "158.167 for
discussion of formation of Impurities (61-3); "158.170 for preliMinary analysis (62-1); *158.175.for certification of limits (62-2); and •158.160 for enforcement
analytical Methods (62-3).
2 A schematic dlagraM and/or brief description of the production process will suffice If the pesticide is not already under full scale production and an experimental
use pensit la being sought.
3 If the pesticide is not already under full scale production and an experimental use pensit Is sought, a discussion of unintentional Ingredients shall be submitted to
the extent this information la available.
4 Required to support the registration of each manufacturing-use product (Including registered TGAIs) as well as end-use products produced by an Integrated system.
Data on other end-use products will be required on a case-by-case basis. For pesticides in the development state, a rudimentary product analytical Method and data
will suffice to support an experimental use permit.
5 Certified Units are not required for inert ingredients in products proposed for experimental use.
9 Required if test substances are dispersible with water.
10 Required if product contains an oxidizing or reducing agent.
11 Required if product contains combustible liquids.
12 Required if product is potentially explosive.
13 Required If product is a liquid.
M Required If product Is an emulslfiable liquid and la to be diluted with petroleum solvents.
M Btotage Stability Data required foe a minimum of 12 months at 20 OBUIHBB or 25 degrees C. an! if the package
IB puimiinhln, at relatiw humidity of SOI oc under Non-house conditions which reflect the expected storage
«.» . _ _ f ••*__ • — -* — * * *- ^F^
Toxic • Regular CtMarfcal
J Z r-ojIrS !! S3 MM U Jo^roaJv.''^!^^^^ l«. than 2 or greater than 11.5; such a product will b. classlfl-d a. Toxiclty Category I on th. b».l.
1 jlqu^Jad'if1 tJITpJ^^Utrofl^ISe^ondltlon. of us. will result In. an Irt.lable Material (e. g.. gas, volatile Stance., or a^ol/partlculate).
4 Required unless repeated dermal exposure does not occur underJ-°"dlt
-------
DRAFT COPY . Page 2 of 2
United States Environmental Protection Agency
Washington, D. C. 20460
FOOTNOTES AND KEY DEFINATIONS FOR GUIDELINE REQUIREMENTS
Case i and Name: 0169 Streptomycin
Footnotes (cont.):
prior to Initiation of studies.
37 Testing of the EP dilution Is required If It can be reasonably anticipated that the results of such testing nay *eet the criteria for restriction to use by certified
applicators specified In 40 CFR 152.170(b) or the criteria for initiation of special review specified in 40 CFR 154.7 (a)(1).
-------
ATTACHMENT D
EPA's Grouping of End-Use Products for Meeting Acute
Toxicology Data Requirements for Reregistration
-------
ATTACHMENT D
EPA'S BATCHING OF STREPTOMYCIN AND STREPTOMYCIN SULFATE END-USE
PRODUCTS FOR MEETING ACUTE TOXICITY DATA REQUIREMENTS FOR
REREGISTRATION
In an effort to reduce the time, resources and number of animals needed to fulfill the
acute toxicity data requirements for reregistration of end-use products containing the active
ingredients streptomycin and streptomycin sulfate, the Agency has batched products which can
be considered similar for purposes of acute toxicity. Factors considered in the sorting process
include each product's active and inert ingredients (identity, percent composition and biological
activity), type of formulation (e.g., emulsifiable concentrate, aerosol, wettable powder, granular,
etc.), and labeling (e.g., signal word, use classification, precautionary labeling, etc.). Note that
the Agency is not describing batched products as "substantially similar" since some products
within a batch may not be considered chemically similar or have identical use patterns.
Batching has been accomplished using the readily available information described above.
Frequently acute toxicity data on individual end-use products has been found to be incomplete.
Notwithstanding the batching process, the Agency reserves the right to require, at any time,
acute toxicity data for an individual end-use product should the need arise.
Registrants of end-use products within a batch may choose to cooperatively generate,
submit or cite a single battery of six acute lexicological studies to represent all the products
within that batch. It is the registrant's option to participate in the process with all the other
registrants, only some of the other registrants, or only their own products within a batch, or to
generate all the required acute lexicological studies for each of their own products. If a
registrant chooses to generate the data for a batch, he/she must use one of the products within
the batch as the test material. If a registrant chooses to rely upon previously submitted acute
toxicity data, he/she may do so provided that the data base is complete and valid by today's
standards (see acceptance criteria in Appendix F, Attachment E), the formulation tested is
considered by EPA to be similar for acute toxicity, and the formulation has not been significant-
ly altered since submission and acceptance of the acute toxicity data. Regardless of whether new
data is generated or existing data is referenced, registrants must clearly identify the test material
by EPA Registration Number.
In deciding how to meet the product specific data requirements, registrants must follow
the directions given in the Data Call-In Notice and its attachments appended to the RED. The
DCI Notice contains two response forms which are to be completed and submitted to the Agency
within 90 days of receipt. The first form, "Data Call-In Response", asks whether the registrant
will meet the data requirements for each product. The second form, "Requirements Status and
Registrant's Response", lists the product specific data required for each product, including the
standard six acute toxicity tests. A registrant who wishes to participate in a batch must decide
whether he/she will provide the data or depend on someone else to do so. If a registrant
supplies the data to support a batch of products, he/she must select one of the following options:
1
-------
Developing Data (Option 1), Submitting an Existing Study (Option 4), Upgrading an Existing
Study (Option 5) or Citing an Existing Study (Option 6). If a registrant depends on another's
data, he/she must choose among: Cost Sharing (Option 2), Offers to Cost Share (Option 3) or
Citing an Existing Study (Option 6). If a registrant does not want to participate in a batch, the
choices are Options 1, 4, 5 or 6. However, a registrant should know that choosing not to
participate in a batch does not preclude other registrants in the batch from citing his/her studies
and offering to cost share (Option 3) those studies.
Table I contains three different batches with each one containing two products.
TABLE I
BATCH#
1
2
3
EPA REG.
NO,
618-101
34704-577
618-72
34704-425
618-28
56644-31
%
ACTIVE
21.20
21.20
62.60
0.30
21.20
21.20
ACTIVE INGREDIENTS
Streptomycin sulfate
Streptomycin sulfate
Streptomycin sulfate
Streptomycin
Streptomycin sulfate
Streptomycin sulfate
FORMIC
LAT10N
Powder
Powder
Powder
Powder
Powder
Powder
-------
Ten products (Table II) were either considered not to be similar for purposes of acute
toxicity or the Agency lacked sufficient information for decision making and were not placed
in any batch. Registrants of these products are responsible for meeting the acute toxicity data
requirements for each product.
TABLE H
EPA REG. M>,
70-259
554-108
618-100
2596-41
7401-311
10107-94
10107-98
34704-156
34704-338
34704-675
% ACTIVE
21.20
8.00
0.01
62.50
15.00
21.20
7.30
0.01
7.30
0.01
7.33
0.01
0.15
7.33
0.01
ACTIVE INGREDIENTS
Streptomycin sulfate
Maneb
Streptomycin sulfate
Streptomycin sulfate
Streptomycin sulfate
Streptomycin sulfate
Captan
Streptomycin sulfate
Captan
Streptomycin sulfate
Captan
Streptomycin
Streptomycin
Captan
Streptomycin
FORMULATION
Powder
Powder
Powder
Tablet
Powder
Powder
Powder
Powder
Powder
Powder
-------
ATTACHMENT E
Product Specific Data Call-in
Cost Share and Data Compensation Forms
-------
EPA
United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION WITH RESPECT TO
DATA COMPENSATION REQUIREMENTS
Form Approved
OMB No. 2070-0106
Approval Expire* 12-31-92
Public reporting burden for this collection of information is estimated to average 15 minutes per response, including
time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and
completing and reviewing the collection of information. Send comments regarding the burden estimate or any other
aspect of this collection of information, including suggestions for reducing this burden, to Chief, Information Policy
Branch, PM-223, U.S. Environmental Protection Agency, 401 M St., S.W., Washington, DC 20460; and to the Office
of Management and Budget, Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Please fill In blanks below.
Company Nam*
Product Name
EPA Reg. No.
I Certify that:
1. For each study cited in support of registration or reregistration under the Federal Insecticide, Fungicide and
Rodenticide Act (FIFRA) that is an exclusive use study, I am the original data submitter, or I have obtained the
written permission of the original data submitter to cite that study.
2. That for each study cited in support of registration or reregistration under FIFRA that is NOT an exclusive use
study, I am the original data submitter, or I have obtained the written permission of the original data submitter, or I
have notified in writing the company(ies) that submitted data I have cited and have offered to: (a) Pay
compensation for those data in accordance with sections 3(c)(1)(D) and 3(c)(2)(D) of FIFRA: and (b) Commence
negotiation to determine which data are subject to the compensation requirement of FIFRA and the amount of
compensation due, if any. The companies I have notified are:
[ ] The companies who have submitted the studies listed on the back of this form or attached
sheets, or indicated on the attached •Requirements Status and Registrants' Response Form,*
3. That I have previously complied with section 3(c)(l )(D) of FIFRA for the stydies I have cited in support of
registration or reregistration under FIFRA.
Signature
Oat*
Nam* and Title (Please Type or Print)
GENERAL OFFER TO PAY: I hereby offer and agree to pay compensation to other persons, with regard to the
registration or reregistration of my products, to the extent required by FIFRA sections 3(c)(1)(D) and 3(c)(2)(D).
Signature
Date
Name and Title (Pleaa* Type or Print)
- , j<+-
EPA Form 8570-31 (4-90)
-------
r/EPA
United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION OF OFFER TO COST
SHARE IN THE DEVELOPMENT OF DATA
Form Approved
OMB No. 2070-0106
Approval Expire* 12-31-92
Public reporting burden for this collection of information is estimated to average 15 minutes per response, including
time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and
completing and reviewing the collection of information. Send comments regarding the burden estimate or any other
aspect of this collection of information, including suggestions for reducing this burden, to Chief, Information Policy
Branch, PM-223, U.S. Environmental Protection Agency, 401 M St.. S.W.. Washington, DC 20460; and to the Office
of Management and Budget, Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Please fill In blanks below.
Company Nam*
Product Name
EPA Reg. No.
I Certify that:
My company is willing to develop and submit the data required by EPA under the authority of the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA), if necessary. However, my company would prefer to
enter into an agreement with one or more registrants to develop jointly or share in the cost of developing
data.
My firm has offered in writing to enter into such an agreement. That offer was irrevocable and included an
offer to be bound by arbitration decision under section 3(c)(2)(B)(iii) of FIFRA if final agreement on all
terms could not be reached otherwise. This offer was made to the following firm(s) on the following
date(s):
Nam* of Firm(a)
Dal* of Offer
Certification:
I certify that I am duly authorized to represent the company named above, and that the statements that I have made on
this form and all attachments therein are true, accurate, and complete. I acknowledge that any knowingly false or
misleading statement may be punishable by fine or imprisonment or both under applicable law.
Signature
Nam* and
of Company's Authorized Representative
Till* (Pleas* Type or
Oat*
Print)
EPA Form 8570-32
-------
US Environmental Protection Agency Registration Standard (or:
Washington, DC 20460
AFPA Product Specific
wui r\ Dgta ReDQrt
Registration
Guideline No.
Sec. 158.120
Product
Chemistry
61-1
61-2 (a )
61-2 (b)
62-1
62-2
62-3
63-2
63-3
63-4
63-5
63-6
63-7
63-8
63-9
63-10
63-11
63-12
63-13
63-14
63-15
63-16
63-17
63-18
63-19
63-20
63-21
Sec. 158.135
Toxicology
81-1
81-2
81-3
81-4
81-5
81-6
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
Octanol/water partition coefficient
PH
Stability
Oxidizing/reducing reaction
Flammability
Explodability
Storage stability
Viscosity
Miscibility
Corrosion Characteristics
Dielectric breakdown voltage
Acute oral toxicity, rat
Acute dermal toxicity, rabbit /rat /g . pig
Acute inhalation toxicity, rat
Primary eye irritation, rabbit
Primary dermal irritation
Dermal sensitization
Testing not
required for my
product listed
above
(Check below)
„
EPA Registration Number
1 am complying with
Data Requirements by •
Citing MR ID No.
Submitting Data
(Attached)
(Check below)
:orm Approved
OMB #2070-0057
•xpires 11-30-89
(For EPA Use
Only)
Accession
numbers
assigned
Certification
1 certify that the statements 1 have made on this form and all attachments thereto are
true, accurate, and complete. 1 acknowledge that any knowingly false or misleading
statement may be punishable by fine or imprisonment or both under applicable law.
Typed Name and Title
Signature
Date
EPA Form 8580-4 (Rev. 5-88) Previous edition is obsolete.
------- |