United SURM
Environmental Protection
Agency
Off tea of
Pesticide* and Toxic StiUtaneM
WMhington DC 20460
Pesticide*
vvEPA
540/RS-89-Q18
Guidance for the
Reregistration of
Pesticide Products
»
Containing
OXYTETRACYCLINE
DXYTETRACYCLINE HYDROCHLORID
OXYTETRACYCLINE
CALCIUM COMPLEX
as the Active Ingredient
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OMB Control NO. 2070-0057
Expires November 1989
GUIDANCE FOR THE
REREGISTRATION OF PESTICIDE PRODUCTS
CONTAINING
OXYTETRACYCLINE
[006304]
[CASE NUMBER 0655]
[CAS NUMBER 79-57-2]
OXYTETRACYCLINE HYDROCHLORIDE
[006308]
OXYTETRACYCLINE CALCIUM COMPLEX
[006321]
AS THE ACTIVE INGREDIEKTB
DECEMBER 1988
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ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
WASHINGTON, D.C. 20460
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TABLE OF CONTENTS
I. Introduction 1
II. Chemical(s) Covered by this Standard
A. Description of Chemical
B. Use Profile
C. Mode of Activity
III. Agency Assessment 8
A. Summary
B. Science Assessment
C. Tolerance Reassessment
D. Data Gap Summary
IV. Regulatory Position and Rationale 17
A. Regulatory Positions
B. Criteria for Registration
C. Acceptable Ranges and Limits
D. Required Labeling
V. Products Subject to this Standard 23
VI. Requirement for Submittal of Generic Data 25
A. What are generic data? .....'
B. Who must submit generic data?
C. What generic data must be submitted?. . . .
D. How to comply with DCI requirements ....
E. Registrant requests regarding data
requirements and Agency responses
F. Test protocols and standards
G. Procedures for requesting a change in protocol
H. Procedures for requesting extensions of time
I. Data Format and Reporting Requirements. . . .
J. Existing stocks provisions upon suspension or
cancellation
VII. Requirement for Submittal of Product-Specific Data. .31
VIII. Requirement for Submittal of Revised Labeling ... .32
IX. Instructions for Submittal 32
A. Manufacturing use products (sole active)
B. Manufacturing use products (multiple active)
C. End use products (sole active)
D. End use products (multiple active)
E. Intrastate Products
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APPENDICES
I. DATA APPENDICES
Guide to Tables
. Table A
Table B
Table C
II. LABELING APPENDICES
Summary of label requirements and table
40 CFR 156.10 Labeling Requirements
Physical/Chemical Hazards Labeling Statements
Storage Instructions
Pesticide Disposal Instructions
Container Disposal Instructions
III. BIBLIOGRAPHY APPENDICES
Guide to Bibliography
Bibliography
IV. FORMS APPENDICES
EPA Form 8580-1 FIFRA 3(c)(2)(B) Summary Sheet
EPA Form 8580-3 Generic Data Exemption Statement
EPA Form 8580-4 Product Specific Data Report
EPA Form 8580-6 Certification of Attempt to Enter
Into an Agreement with Other
Registrants for Development of
Data
11
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GLOSSARY OF TERMS AND ABBREVIATIONS
ADI Acceptable Daily Intake. Also known as the
Reference Dose or RfD.
a.i. Active ingredient
ARC Anticipated Residue Contribution
CAS Chemical Abstracts Service
CSF Confidential Statement of Formula
EEC Estimated Environmental Concentration. The
estimated pesticide concentration in an
environment, such as a terrestrial ecosystem.
EP End Use Product
EPA U.S. Environmental Protection Agency
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
LC50 Median lethal concentration - a statistically
derived concentration of a substance that can be
expect.ed to cause death in 50% of test animals. It
is usually expressed as the weight of substance per
weight or volume of water or feed, e..g. , mg/1 or
ppm.
LD50 Median lethal dose - a statistically derived single
dose than 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.
LEL Lowest Effect Level
MPI Maximum Permissible Intake
MRID Master Record Identification (number). EPA's
system of recording and tracking studies submitted
to the Agency.
MP Manufacturing Use Product
NPDES National Pollutant Discharge Elimination System
iii
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NOEL No Observed Effect Level
OPP Office of Pesticide Programs
OES Office of Endangered Species, U.S. Fish and
Wildlife Service
PADI Provisional Acceptable Daily Intake
ppm Parts per million
RfD Reference Dose
TMRC Theoretical Maximum Residue Contribution
IV
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I. INTRODUCTION
EPA has established the Registration Standards program
in order to provide an orderly mechanism by which pesticide
products containing the same active ingredient can be
reviewed and standards set for compliance with FIFRA. The
standards are applicable to reregistration and future
applications for registration of products containing the same
active ingredient. Each registrant of a product containing an
active ingredient subject to this Standard who wishes to
continue to sell or distribute that product must bring his
product and labeling into compliance with FIFRA, as
instructed by this Standard.
The Registration Standards program involves a thorough
review of the scientific data base underlying a pesticide's
registration. The purpose of the Agency's review is to
reassess the potential hazards arising from the currently
registered uses of the pesticide; to determine the need for
additional data on health and environmental effects; and to
determine whether the pesticide meets the "no unreasonable
adverse effects" criteria of FIFRA. In its review EPA
identifies:
1. Studies that are acceptable to support the data
requirements for the currently registered uses of the
pesticide.
2. Additional studies necessary to support continued
registration. The additional studies may not have been
required when the product was initially registered or may be
needed to replace studies that are now considered inadequate.
3. Labeling revisions needed to ensure that the product
is not misbranded and that the labeling is adequate to
protect man and the environment.
The detailed scientific review, which is not contained
in this document, but is available upon request,1 focuses on
the pesticide active ingredient. The scientific review
primarily discusses the Agency's evaluation of and
conclusions from available data in its files pertaining to
the pesticide active ingredient. However, during the review
of these data the Agency is also looking for potential
hazards that may be associated with the end use products that
contain the active ingredient. The Agency will apply the
provisions of this Registration Standard to end use products
if necessary to protect man and the environment.
1The scientific reviews and Compendium of Acceptable
Uses may be obtained from the National Technical Information
Service (NTIS), Attn: Order Desk, 5285 Port Royal Road,
Springfield., VA 22161. Telephone (703) 487-4650.
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EPA's reassessment results in the development of a
regulatory position, contained in this Registration Standard,
on the pesticide and each of its registered uses. See
Section IV - Regulatory Position and Rationale. Based on its
regulatory position, the Agency may prescribe a variety of
steps to be taken by registrants to maintain their
registrations in compliance with FIFRA. These steps may
include:
1. Submittal of data in support of product
registration;
2. Modification of product labels;
3. Modifications to the manufacturing process of the
pesticide to reduce the levels of impurities or contaminants;
4. Restriction of the use of the pesticide to certified
applicators or other specially trained individuals;
5. Modification of uses or formulation types; or
6. Specification of packaging limitations.
Failure to comply with these requirements may result in
the issuance of a Notice of Intent to Cancel or a Notice of
Intent to Suspend (in the case of failure to submit data).
In addition, in cases in which hazards to man or the
environment are identified, the Agency may initiate a special
review of the pesticide in accordance with 40 CFR Part 154 to
examine in depth the risks and benefits of use of the
pesticide. If the Agency determines that the risks of the
pesticide's use outweigh the benefits of use, the Agency may
propose additional regulatory actions, such as cancellation
of uses of the pesticide which have been determined to cause
unreasonable adverse effects on the environment.
EPA has authority under the Data Call-in (DCI)
provisions of FIFRA sec. 3(c)(2)(B) to require that
registrants submit data to answer our questions regarding the
chemical, toxicological, and environmental characteristics
and fate of a pesticide. This Registration Standard lists the
data EPA believes are necessary to resolve our concerns about
this pesticide. These data are listed in the Tables A, B, and
C in Appendix I. Failure to comply with the DCI requirements
enumerated in this Registration Standard may result in
issuance by EPA of a Notice of Intent to Suspend the affected
product registrations.
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Registrants are reminded that FIFRA sec. 6(a)(2)
requires them to submit factual information concerning
possible unreasonable adverse effects of a pesticide at any
time that they become aware of such information. Registrants
must notify the Agency of any information, including interim
or preliminary results of studies, if that information
suggests possible adverse effects on man or the environment.
This requirement is independent of the specific time
requirements imposed by EPA for submittal of completed
studies called in by the Agency and continues as long as the
products are registered under FIFRA.
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II. CHEMICALS COVERED BY THIS STANDARD 2
A. Description of Chemical
The following chemicals are covered by this
Registration Standard:
1. Common Name: Oxytetracycline
Chemical Name: 4-(Dimethylamino)-
1,4,4a,5,5a,6,11,12a-octahydro-3,5,6,10,12,12a
-hexahydro-6-methyl-l,ll-dioxo-2
-naphthacenecarboxamide.
Other Chemical Nomenclature: 2-
Naphthacenecarboxamide , 4(dimethylami no ) -
l,4,4a,5,5a,6,ll,12a-octahydro-3,6,
10,13,12a-pentahydroxy-6-methyl-l,11-dioxo.
Trade Names: Glomycin, Terrafungine, Riomitsin,
Hydroxytetracycline, Berkmycin, Biostat, Impercin,
Oxacycline, Oxatets, Oxydon, Oxydumocycline,
Oxymycin, Oxypan, Oxytetracid, Ryomycin, Stevacin,
Terraject, Terramycin, Tetramel, Tetran, Vendarcin,
and Vendracin.
Chemical Class: Antibiotic (produced by the actino-
mycete Streptomyces rimosus)
Empirical Formula: C22H24N2°9
Molecular Weight: 460.44
Molecular Structure:
CAS Registry No.: 79-57-2
OPP Shaughnessy Nos.: 006304
Physical/chemical properties: Data gap.
2 Information was obtained from the following sources:
The Merck Index, 10th ED., p 6849, Farm Chemicals
Handbook*88 r p. C218, and the Toxic Substances
Control Act Chemical Substances Inventorv. r>. 1070.
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2. Common Name: Calcium oxytetracycline
Chemical Name: [4-(Dimethylamino)
1,4,4a,5,5a,6,11,12a-octahdyro-3,5,6,10,12,12a
-hexahydro-6-methyl-l,11-
dioxo-2-naphthacenecarboxamide] calcium complex.
Trade Name: Agricultural Terramycin, Mycoshield.
Chemical Class: Antibiotic (produced by the
actinomycete streptomvces rimosus)
Empirical Formula: C22H22N2°9 <-a
Molecular Weight: 498.52
CAS Registry No.: 7179-50-2
OPP Shaughnessy Nos.: 006321
Physical/chemical properties:
Color: Tan to dark brown
Physical State: Data gap
pH: 7.5-10.5
3. Common Name: Oxytetracycline hydrochloride
Chemical Name: 2-Naphthacenecarboxamide,
4(dimethylamino)-l,4,4a,5,5a,6,ll,12a-octahydro
-3,6,10,13,12a-pentahydroxy-6-methyl-l,ll-dioxo -
monohydrochloride.
Trade Names: Biosolvomycin, Hydrocyclin,
Liquamycin, Otetryn, Oxlopar, 5-Hydroxytetracycline
Hydrochloride, Terramycin Hydrochloride.
Chemical Class: Antibiotic (produced by the
actinomycete Streptomyces rimosus)
Empirical Formula: C22H24N2°9 HCL
Molecular Weight: 496.9
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CAS Registry No.: 2058-46-0
OPP Shaughnessy Nos.: 006308
Physical/chemical properties:
Color: yellow
Physical State:
Odor: Data gap.
Boiling Point: Data gap
Density: Data gap.
Solubility: Soluble in water (1 g/ml), in
absolute alcohol (12 mg/ml). Insoluble in
ether, petroleum ether and benzene.
Vapor Pressure: Data gap.
pH: 2.0-3.0
B. Regulatory History-
Initial Date of Registration: August 1974
Basic Producer: Pfizer, Inc.
End-Use Registrants: 2
Number of Registrations: The Agency has issued 5
Section 3 registrations and 16 Special Local Need
registrations under FIFRA section 24(c).
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C. Use Profile;
Type of Pesticide: Plant Fungicide/Bactericide and
Algicide.
Pests Controlled: Bacterial and fungal diseases
and slime-forming microorganisms.
Registered Uses:
1. Calcium oxytetracycline [17% WP]:
Nectarines, peaches, pears, and creeping
Bentgrasses.
2. Oxytetracycline hydrochloride [21.6%
soluble concentrate/solid]
-(Tree Trunk Injection) pears, peaches, and
ornamental palms)
- Marine antifoulant paint additive.
3. Oxytetracycline hydrochloride [21.6%
soluble concentrate/solid]
Formulation Intermediate for Marine
antifoulant additive.
Predominant Uses: Pears and peaches (98%).
Minor Uses: Ornamental palms and Bentgrasses.
Annual Usage: 21,350 pounds/ai
Method of Application: Foliar, tree injection, and
brush on (marine use).
•
D. Mode of Activity:
Inhibition of protein synthesis.
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III. AGENCY ASSESSMENT
The Agency has reviewed all data in Agency files as of
August 1988 supporting the registration of oxytetracycline.
Data received by the Agency after this date have not been
reviewed for the purposes of this standard. This section
discusses the Agency's scientific findings and conclusions
based on these data.
A. SUMMARY
1. A review of the oxytetracycline hydrochloride
oncogenicity data indicated equivocal evidence of
oncogenicity in male and female rats. The Agency concluded
that although the findings were termed "equivocal" by the
National Toxicology Program, they do not represent positive
evidence of carcinogenicity in the rat. A similar study in
mice indicated no evidence of oncogenicity.
2. Tolerances for oxytetracycline are limited to peaches
(which includes nectarines) and pears, 0.1 ppm and 0.35 ppm
respectively. A Reference Dose (RfD) of 1.0 mg/kg/day has
been established based on several chronic studies. The
Theoretical Maximum- Residue Contribution (TMRC) for the U.S.
population is 0.000065 mg/kg/day, corresponding to 0.006% of
the RfD. A proposed increase in the peach tolerance from 0.1
to 0.35 ppm would result in a TMRC of 0.000118 mg/kg/day.
The largest subgroups, nursing and non-nursing infants,
represent 0.061% and 0.076% respectively of the current RfD. •
3. The potential for development of oxytetracycline
resistance due to increase background levels from pesticidal
uses to applicators and field workers appears minimal.
4. The Agency is unable to assess the potential for
oxytetracycline to contaminate ground water because the
environmental fate of oxytetracycline is uncharacterized.
However, because of its extensive history of antibiotic use
in humans and low exposures, the Agency does not believe that
pesticide uses of oxytetracyline use will pose a human hazard
via ground water contamination.
5. The Agency is unable to assess the ecological effects
of oxytetracycline on terrestrial or aquatic wildlife,
because no data are available.
As a result of this Registration standard review, the
Agency has identified missing data required to fully evaluate
the environmental and ecological risks associated with the
use of oxytetracycline as an fungicide/bactericide and
algicide. These data must be developed in order to maintain
registrations of existing products or to register any new
products containing oxytetracycline.
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A summary of these data gaps are given in Section D.
Please note that this is only a summary and complete details
can be obtained by referring to the data tables in Appendix I
The regulatory position and rationale section of this
Registration Standard discusses the Agency's position on each
regulatory issue concerning oxytetracycline, and the required
labeling sections contains the specific wording specified for
each labeling provision.
B. SCIENCE ASSESSMENT
l. Health Effects
a. Adverse Effects from Drug Uses
In humans, oxytetracycline is administered orally and
intravenously to treat infectious diseases caused by a wide
variety of microorganisms such as rickettsial, mycoplasma
pneumoniae, spirochetes, gram-negative bacteria (Bartonella
bacilliformis, Pasteurella pestis, Brucella sp.), and gram-
positive bacteria (Streptococcus sp. , Staphylococcus aureus,
Neisseria gonorrhea). The oral dose for adults ranges from 1
to 2 grams per day (orally or intravenously). The usual
daily dose for children is 25 to 50 mg/kg.
A variety of adverse effects in humans have been reported
from the use of oxytetracycline. The major adverse effects
are:
(i). Toxic and Irritative Effects—The antibiotic may
cause gastrointestinal irritation. Epigastric burning and
distress, abdominal discomfort, nausea, vomiting and diarrhea
may occur. Intravenous administration may produce thrombo-
phlebitis. Long-term therapy may produce changes in the
peripheral blood. Leukocytosis, atypical lymphocytes, toxic
granulation of granulocytes and thrombopenia purpura may
occur. A phototoxic reaction may occur, sometimes
accompanied by onycholysis and pigmentation of the nails.
Liver injury and a delay in blood coagulation may occur.
Children under 7 years of age may develop a brown
discoloration of the teeth. Treatment of pregnant females
may also produce discoloration of the teeth of infants.
Oxytetracycline is deposited in the skeleton of fetuses
and children which can produce depression of bone growth
which is readily reversible when the period of exposure to
the drug is sho'rt.
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(ii). Hypersensitivity—Various skin reactions such as
morbilliform rashes, urticaria and generalized dermatitis
may occur. Angioedema and anaphylaxis may develop. Other
effects which may occur are burning of the eyes, cheilosis,
brown or black coating of the tongue, atrophic or
hypertrophic glossitis, pruritus ani or vulvae or vaginitis,
fever and eosinophilia.
(iii). Other Biological Effects—Administration of
oxytetracycline to undernourished adults results in weight
loss,increased urinary but not fecal nitrogen excretion,
negative nitrogen balance and elevated serum nonprotein
nitrogen concentrations. Administration of oxytetracycline,
like most antibiotics, may lead to the development of super
infections by strains of bacteria or yeasts resistant to the
agent.
These effects have been observed from the drug uses of
oxytetracycline by oral and intravenous routes of exposure.
The pesticide uses have substantially less exposure
(virtually no exposure in cases where the pesticide is
applied by injection to trees). The exposures are not by
the intravenous route and exposure by the oral route is
limited to ingestion of fruit from treated trees at levels
substantially below those used for drug use.. Therefore the
Agency does not believe that the adverse effects observed
from drug use are of concern from the pesticide uses.
b. Chronic Toxicity
Two 2-year chronic toxicity studies were conducted in
rats. In one study, weanling male Osborne-Mendel rats were
fed diets containing 0 (180 rats), 100.(100 rats), 1000 (130
rats) and 3000 ppm (100 rats), approximately 0, 5, 50, and
150 mg/kg/body weight/day, oxytetracycline hydrochloride in
the diet for a period of 24 months. The NOEL was determined
to be 3000 ppm, approximately 150 mg/kg/body weight/day,
highest dose tested. In a second study, groups of weanling
Sprague Dawley rats (20/sex/group) were -fed diets containing
0,100, and 1000 ppm (approximately 0, 5, and 50 mg/kg/day)
oxytetracycline hydrochloride in the diet for a period of 24
months. The NOEL for oxytetracycline hydrochloride was 1000
ppm, 50 mg/kg/day, highest dose tested.
Two chronic toxicity studies were conducted in dogs. In
the first study each group contained eight male dogs (4
beagles, 4 mongrels). The dogs were fed diets containing 0,
100, 3000, and 10000 ppm, approximately 0, 2.5, 75, and 250
mg/kg/day, oxytetracycline hydrochloride in the diet for a
period of 24 months. A yellow discoloration of the long
bones and brownish discoloration of the thyroid was observed
in all dosed animals at necropsy. The NOEL was determined to
be 10000 ppm, approximately 250 mg/kg/day, highest dose
tested. In a second study, groups of mongrel dogs/sex were
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fed diets containing 0, 5000, and 10000, approximately 0,-125
and 250 mg/kg/day, of oxytetracycline hydrochloride in the
diet for a period of 12 months. The NOEL was determined to
be 10000 ppm, approximately 250 mg/kg/day, highest dose
tested.
These studies were judged to be supplementary because
too few animals survived to study termination, and/or too
few tissues were examined histologically and/or data were
summarized. However, this data requirement is waived based
upon availability of both animal and human data from oxy-
tetracycline 's drug uses.
c. NCI/NTP Oxytetracycline Oncoaenicity Study in the
F344N/Rat
In this study, oxytetracycline hydrochloride (purity
98.8%) was administered to groups of F344/N rats fed 0,
25000, and 50000 • ppm, approximately 0, 1250 and 2500
mg/kg/day, in the diet for a period of 103 weeks. Fatty
metamorphosis of the liver was increased in rats in the 1250
mg/kg group. The National Toxicology Program's Peer Review
Committee concluded that " there was equivocal
evidence3 of carcinogenicity for male F344/N rats as
indicated by increased incidences of pheochromocytomas of the
adrenal gland. There was equivocal evidence of carcinogen-
icity for female F344/N rats as indicated by increased
incidences of adenomas of the pituitary gland in the high
dose g.roup."
d. NCI/NTP Oxytetracycline Oncooenicity Study in the
B6C3F1 Mouse
In this study, oxytetracycline hydrochloride (purity
98.8%) was administered to groups of B6C3F1 mice fed 0, 6300,
and 12500 ppm, approximately 0, 945, and 1875 mg/kg/day, in
their diet for a period of 103 weeks. Body weights were
decreased in mice in the 1875 mg/kg group when compared to
controls. The National Toxicology Program's Peer Review
Committee concluded that "... there was no evidence of
carcinogenicity for male or female B6C3F1 mice fed diets
containing 6300 or 12500 ppm of oxytetracycline hydrochloride
for 2 years."
3 The NCI/NTP uses five levels of interpretative
evaluations in animal carcinogenesis studies; in decreasing
order of strength (not potency or mechanism) of the
experimental evidence, these are: (i) clear evidence of
carcinogenicity (ii) some evidence of carcinogenicity, (iii)
equivocal evidence of carcinogenicity, (iv) no evidence of
carcinogenicity, and (v) inadequate study of carcinogenicity.
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e. Teratogenic ity
Thirty-six female Charles River CD (COBS) rats were
dosed during days 6 through 15 of gestation with 1200, 1350,
and 1500 mg/kg of oxytetracycline hydrochloride. Thirty-
seven control dams received corn oil during days 6 through 15
of gestation. There were dose-related decreases in maternal
survival and body weight gain, and increases in the incidence
of respiratory difficulties and rough coat. In addition,
there were significant dose-related decreases in the percent
of treated dams found pregnant. There was also a dose-related
decrease in fetal body weight. The high incidence of
maternal deaths and the fetotoxicity noted in all dose levels
tested did not allow for an establishment of a NOEL. The LEL
was 1200 mg/kg/day (lowest dose tested).
The significant findings discussed in this study can be
attributed to the excessive dose levels used, and the overly
stressing of the treated dams.
Groups of 42 female CD-I mice were dosed during day 6
through 15 of gestation with 0, 1325, 1670, and 2100 mg/kg
oxytetracycline hydrochloride. No adverse effects were
demonstrated, due probably to the low dose levels used. The
NOEL for maternal and developmental toxicity in this study
was 2100 mg/kg (highest dose tested)
f.-Antibiotic Microbial Resistance
Mature beagles were fed a ground-meal diet containing
0, 2, or 10 ppm, approximately 0, 0.05, or 0.25 mg/kg/day, of
oxytetracycline for 44 days. The 10 ppm '(0.25 mg/kg/day)
diet resulted in a shift from a predominantly drug-
susceptible population of enteric lactose-fermenting
organisms to a multiple antibiotic-resistant population. A
shift to drug-resistance did not occur in the group fed 2 ppm
approximately 0.05 /mg/kg/day. NOEL was 0.05 mg/kg/day.
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C. TOLERANCE REASSESSMENT
Tolerances have been established for residues of
oxytetracycline in two raw agricultural commodities (40 CFR
180.337). Use of oxytetracycline as a drug in food animals
is regulated by the FDA according to 21 CFR 520, 522, 524,
and 558. The FDA has established tolerances for oxytetra-
cycline in or on meat, fat, meat byproducts, and in uncooked
edible tissues of salmonoid fish and catfish (21 CFR
556.500). EPA has evaluated the residue and toxicology data
supporting tolerances, and has made the following regulatory
determinations:
o Whether the current tolerances and food additive
regulations are sufficient to cover the actual residues
resulting from use (including uses registered under FIFRA
sec. 24(c) and intrastate uses).
o Whether group tolerances can be established in
accordance with 40 CFR I80.34(f).
o Whether, in the absence of tolerances, restrictions on
use, grazing, or feeding of treated commodities are
necessary.
o Whether the tolerances are expressed accurately and in
current terminology.
o The current tolerances are sufficient to cover the
actual residues resulting from foliar applications only.
o The regulatory determinations resulting from EPA's
review are set out in Section IV.A, Regulatory Positions and
Rationales.
1. Residue Data
a. Nature of the Residue in Plants
No data are available to evaluate the nature of the
residue of oxytetracycline in plants. The Agency has
assessed the need for data reflecting the metabolism of
oxytetracycline in plants and has concluded that these data
are not required because of oxytetracycline drug uses.
b. Nature of the Residue in Animals
No data are available to evaluate the nature of the
residue of oxytetracycline in animals. Data on the
metabolism of oxytetracycline in food animals are not
required, because the exposure of livestock to residues of
oxytetracycline is unlikely since there are no registered
uses of feed items at the present time.
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c. Analytical Methods
The available microbiological assay method for the
determination of oxytetracycline residues in or on peaches,
nectarines and pears is adequate for data collection and for
tolerance enforcement. The Agency will not require any
additional analytical methods at this time. The method is
similar to Final Action Microbiological Methods I and II in
the AOAC Official Methods of Analysis (1984;42.293-42.298).
d. Storage Stability
Available data indicate that oxytetracycline is stable
in or on peaches, nectarines, and pears stored at -20 C for
up to 90 days.
e. Magnitude of the Residue in Plants
Tolerances for residues in or on plant commodities are
adequate.
1. Peaches/Nectarines: The available residue data
support the tolerance for foliar application; however, tree
injection applications exceed the current established
tolerance for peaches.
2. Pears: The available residue data support the
established tolerance and are sufficient to assess the
adequacy of the label use directions.
2. Toxicology Data
The toxicology data considered in support of the
tolerances include:
Study Type Species
Chronic Toxicity Rat
Chronic Toxicity Rat
Chronic Toxicity Dog
Chronic Toxicity Dog
NOEL
150 mg/kg/day (HOT)4
50 mg/kg/day (HOT)
250 mg/kg/day (HOT)
250 mg/kg/day (HOT)
The Reference Dose (RfD) is based upon a estimated NOEL
of 100 mg/kg derived from a comprehensive evaluation of the
studies listed. None of the studies listed are of sufficient
quality to be used as the critical study in defining the RfD;
however, taking all the data together and using a safety
factor of 100, the RfD was determined to be 1.0 mg/kg/day.
4 (HOT)-Highest Dose Tested.
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The Theoretical Maximum Residue Contribution for the
U.S. population was determined to be 0.000065 mg/kg/day,
occupying 0.006% of the RfD. The dietary exposure for other
subgroups ranged from a low of 0.003% ( males 20 years and
older) to a high of 0.08% (non-nursing infants less then 1
year of age) of the RfD.
3. Tolerances Issued
Tolerances have been established for residues of
oxytetracycline in or on peaches, including nectarines5, (0.1
ppm) and pears (0.35 ppm) and are expressed in terms of
oxytetracycline (40 CFR 180.337). The use of oxytetracycline
as a drug in food animals is regulated by the FDA according
to 21 CFR 556.500. The FDA has established the following
tolerances for residues of oxytetracycline in or on animal
commodities: (i) 3 ppm in uncooked kidney and 1 ppm in
uncooked muscle, liver, fat and skin of chickens and
turkeys;(ii) 0.1 ppm in uncooked edible tissues of swine;
(iii) 0.1 ppm in uncooked edible tissues of cattle, beef
calves, nonlactating dairy cattle, and dairy calves; and (iv)
0.1 ppm for negligible residues of oxytetracycline in
uncooked edible tissues of salmonoid fish and catfish.
Codex MRLs have not been established or proposed for
residues of oxytetracycline in or on any food/feed commodity.
52 Federal Register 33238 defines the crop
term "peaches" to include both peaches and
nectarines.
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D. DATA GAP SUMMARY
The Agency has identified missing data required to fully
evaluate the human and environmental risk associated with
the use of oxytetracycline. Complete data gaps details may
be obtained by referring to the tables in Data Appendices I.
(Please refer to the data tables in Appendix I for detailed
information regarding these requirements).
ENVIRQNMFJfTAT. FATE/EXPOSURE;
Hydrolysis
Photodegradation in water and in soil
Metabolism Studies (lab)
-Aerobic Soil
-Anaerobic Soil
-Anaerobic Aquatic
-Aerobic Aquatic
Leaching and Adsorption/Desorption
Dissipation Studies (field)
-Soil
-Aquatic (Sediment)
FISH & WILDLIFE;
Avian Acute Oral LD50
Avian Dietary LC50
Freshwater Fish LC50 (TGAI)6
Freshwater Invertebrate (TGAI)
PRODUCT CHEMISTRY
All product chemistry studies
6 TGAI: Technical grade of the active ingredient
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IV. REGULATORY POSITION AND RATIONALE
A. REGULATORY POSITIONS AND RATIONALES
Based on review and evaluation of all available data and
other relevant information on oxytetracycline the Agency has
made the following determinations:
1. Special Review
Oxytetracycline does not meet the criteria for Special
Review.
Rationale; Based on available toxicity data and past
use of oxytetracycline as a human drug, the Agency has
determined that oxytetracycline does not meet nor does it
exceed the criteria specified in 40 CFR 154.7.
2. Restricted Use
Oxytetracycline uses are not being restricted at this
time.
Rationale; Section 3(d)(l)(C) of FIFRA provides that
some or all uses of a pesticide will be classified for
restricted use if the Administrator determines that without
such restriction the pesticide "may generally cause
unreasonable adverse effects in man or the environment."
The Agency has determined that oxytetracycline does not meet
any of the risk criteria of 40 CFR 152.170 restricted use
classification.
3. New Food Uses
The Agency will continue to grant new uses and new
tolerances for oxytetracycline. Existing tolerances for
oxytetracycline are adequately supported and will protect the
public health.
Rationale; No data gaps exist for plant and animal
metabolism, storage stability and residue in the raw
agricultural commodities. No data gaps exist in the area of
toxicology testing. In addition, the TRMC only occupies
0.006% of the RfD.
4. Adequacy of Current Tolerances
Current tolerances are sufficient to cover the actual
residues resulting from foliar applications and tree
injection in pears. The Agency will propose that the
tolerance level for peaches (including nectarines) be
increased from 0.1 ppm to 0.35 ppm.
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Rationale; Available data indicate that the
established tolerance for peaches would be exceeded as a
result of the tree trunk injection uses. An increase of this
tolerance by 0.25 ppm would be adequate to cover these uses.
The proposed increase, 0.35 ppm, would result in an TRMC of
0.000118 mg/3cg/day occupying 0.012% of the RfD.
5. Group Tolerances
The Agency will not propose the establishment of group
tolerance for Pome Fruit or Stone Fruit.
Rationale; Group tolerances are not appropriate at the
present time because oxytetracycline is currently registered
for use in only one member from two of the representative
fruit groups (i.e., Pome Fruits: pears and Stone Fruits:
peaches).
6. Groundwater Contamination
The Agency is deferring its decision concerning
oxytetracycline potential for contaminating groundwater
until information on its environmental characteristics and
fate have been evaluated. Based on its lack of chronic
effects, and use as a human drug, the Agency does not
believe that oxytetracycline will pose a hazard to human
health via ground water contamination.
Rationale; The Agency is unable to assess the potential
for oxytetracycline to contaminate groundwater because the
environmental fate of this chemical is uncharacterized. The
Agency will4 assess oxytetracycline potential for groundwater
contamination after receipt and review of environmental fate
data.
7. Acute and Subchronic Toxicity Testing
The Agency has waived data requirements for acute and
subchronic toxicity testing at this time.
Rationale; The Agency believes that there are no
toxicological issues pertaining to the use of oxytetra-
cycline as an fungicide on raw agricultural commodities or
as an algicide for the prevention of barnacle growth on ship
hulls. Although a number of adverse effects have been
identified in susceptible humans as an result of its human
drug use, these effects are usually seen only after pro-
longed treatment with oxytetracycline at relatively high
dosages.
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8. Applicators/Field Workers
The Agency believes that the potential for development
of resistant microorganisms in applicators and/or field
workers as an result of exposure are negligible.
Rationale: Oxytetracycline is used primarily on pears
in the Western growing region, peaches in the Eastern growing
region, and on palms, mainly in Florida and Texas. All of
the palm applications and some of the pear applications are
by injection for which there will be no human exposure. For
the remaining applications, approximately 15 percent of peach
acreage and 25 to 30 percent of pear acreage (some of which
is treated by injection) is treated by foliar spray.
Application is made only as needed to prevent disease which
is more prevalent in the wet weather. The maximum number of
applications are 8 to 10 at 4 to 6 day intervals for pears
and 7 day intervals for peaches. Oxytetracycline is applied
only when leaves are on the trees. Pears may not be treated
after 60 days before harvest and peaches may not be treated
after 21 days before harvest. This discontinuous and limited
exposure is not likely to produce the constant selective
pressure necessary to induce antibiotic resistance in the
bacterial flora of the applicators or field workers. In
addition, many of the bacterial and rickettsial pathogens
that are primarily treated by oxytetracycline would not be
infective by dermal or pulmonary routes.
9. Dietary Exposure
Potential for development of oxytetracycline-resistant
microorganisms in the diet due to increased background levels
from pesticidal uses are minimal.
Rationale; In a previously summarized study, beagle dogs
were feed various levels of oxytetracycline in the diet.
This study demonstrated that oxytetracycline at 0.05
mg/kg/day did not induce drug resistance to enteric bacteria.
Using this NOEL, 0.05 mg/kg/day, as the RfD (reference
dose) and applying it to the proposed tolerance increase in
peaches, the Theoretical Maximum Residue Concentration would
be 0.000024 mg/kg/day occupying 0.05% of this RfD which
allows for a 2,083 margin of exposure7. The Agency believes
that this margin of exposure will protect against the
Maximum amount of exposure producing no measurable
adverse effects in animals (or studied humans)
divided by the actual amount of human exposure in
a population. Previously called the margin of
safety.
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development of oxytetracycline-resistant microorganisms
in the diet due to increase background levels.
10. Priority Review of Data
The Agency will not give priority review to any studies
required by this Standard. Data that are flagged under 40
CFR 158.34 for potential adverse effects, or that may be
submitted under FIFRA sec. 6(a)(2), however, will receive
immediate review upon receipt.
Rationale; Based upon the available data, the Agency
has not identified any human health or environmental concerns
that would warrant early review of data.
11. Continuation of Current Registrations
While the required data are being developed, currently
registered manufacturing-use products (MPs) and end-use
products (EPs) containing oxytetracycline may be sold,
distributed, formulated and used subject to the terms and
conditions specified in this Standard. Registrants must
provide or agree.to develop and provide additional data, as
specified in the Data Appendices in order to maintain
existing registrations.
Rationale; Under FIFRA, the Agency does not normally
cancel or withhold registration because data are missing or
are inadequate [see FIFRA section 3(c)(2)(B) and 3(c)(7)].
Issuance Of thi's Standard provides a mechanism for identify^
ing data needs. These data will be reviewed and evaluated,
after which the Agency will determine if additional regula-
tory actions are necessary.
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B. CRITERIA FOR REGISTRATION
To be registered or reregistered under this Standard,
products must contain oxytetracycline, bear required
labeling, and conform to the product composition, acute
toxicity limits, and use pattern requirements listed in this
section.
C. ACCEPTABLE RANGES AND LIMITS
1. Product Composition Standard
To be registered or reregistered under this Standard,
manufacturing-use products (MPs) must contain this
pesticide. Each MP formulation proposed for registration
must be fully'described with an appropriate certification of
limits, stating maximum and minimum amounts of the active
ingredient and inert ingredients which are present in
products, as well as impurities-found at greater than 0.1
percent.
2. Acute Toxicity Limits
The Agency will consider registration of technical grade
and manufacturing-use products containing this pesticide
provided that the product labeling bears appropriate
precautionary statements for the acute toxicity category in
which each product is placed.
3. Use Patterns
To be registered under this Standard, manufacturing-use
products may be labeled for formulation into end-use products
only for the commodities listed in the EPA Compendium of
Acceptable Uses (for availability, see page 1). The EPA
Compendium lists all registered uses, as well as approved
maximum application rates and frequencies.
The use patterns currently registered are as
follows:
Terrestrial Food Crop;
Terrestrial Nonfood Crop;
Aquatic Nonfood Crop;
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D. LABELING
In order to remain in compliance with FIFRA, products
must bear appropriate labeling as specified in 40 CFR 156.10
and this Standard, or must be revised to conform to those
specifications. Appendix II contains information on label
requirements.
No pesticide product containing this pesticide may be
released for shipment by the registrant after December 15,
1989, unless the product bears an amended label which
complies with the requirements of this Standard.
No pesticide product containing this pesticide may be
distributed or sold after December 15, 1990, unless the
product bears an amended label which complies with the
requirements of this Standard.
The following specific information must appear on the
labeling in order for products to remain in compliance with
FIFRA:
1. Ingredients Statement
The ingredient statement for products must list the
active ingredient as:
ACTIVE INGREDIENT
Oxytetracycline Calcium complex . %
or
Oxytetracycline hydrochloride %
(20% Oxytetracycline)
2. Use Pattern Statements
All manufacturing-use products must state that they are
intended for formulation into end-use products for acceptable
use patterns. Labeling must specify sites, which are listed
in the EPA Compendium of Acceptable Uses (for availability,
see page 1). However, no use may be included on the label
where the registrant fails to agree to comply with the data
requirements in TABLE A for that use pattern.
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V. PRODUCTS SUBJECT TO THIS STANDARD
All products containing one or more of the pesticides
identified in Section II.A. are subject to certain
requirements for data submittal or changes in composition,
labeling or packaging of the product. The applicable
requirements depend on whether the product is a manufacturing
or end use product and whether the pesticide is the sole
active ingredient or one of multiple active ingredients.
Products are subject to this Registration Standard as
follows:
A. Manufacturing use products containing this pesticide as
the sole active ingredient are subject to:
1. The restrictions (if any1) upon use, composition, or
packaging listed in Section IV, if they per.tain to
the manufacturing use product.
2. The data requirements listed in Tables A and B8
3. The labeling requirements specified for
manufacturing use products in Section IV.
4. Administrative requirements (application forms,
Confidential Statement of Formula, data compensation
provisions) associated with reregistration-.
B. Manufacturing use products containing this pesticide as
one of multiple active ingredients are subject to:
1. The data requirements listed in Table A.
2. The labeling requirements specified for manufacturing
use products in Section IV.
8Data requirements are listed in the three Tables in
Appendix I of this Registration Standard. The Guide to Tables in
that Appendix explains how to read the Tables.
Table A lists generic data requirements applicable to all
products containing the pesticide subject to this Registration
Standard. Table B lists product-Specific data applicable to
manufacturing-use products. The data in Tables A and B need not
be submitted by an end-use producer who is eligible for the
generic data exemption for that active ingredient.
Table C lists product-specific data applicable to end-use
products. The Agency has decided that, in most cases, it will
not require the submittal of product-specific data for end-use
products at this time. Therefore, most Registration Standards do
not contain a Table C.
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C. End use products containing this pesticide as the sole
active ingredient are subject to:
1. The restrictions (if any) upon use, composition, or
packaging listed in Section IV if they pertain to
the end use product.
2. If eligible for the generic data exemption9, the
data requirements listed in Table C.
3. If not eligible for the generic data exemption, the
data requirements listed in Table A and the data
requirements listed in Table C.
4. The labeling requirements specified for end use
products in Section IV.
D. End use products containing this pesticide as one of
multiple active ingredients are subject to:
1. If not eligible for the generic data exemption, the
data requirements listed in Tables A and C.
2. If eligible for the generic data exemption, the data
requirements listed in Table C.
3. The labeling requirements specified for end use
' products in Section IV.
9If you purchase from another producer and use as the source
of your active ingredient only EPA-registered products, you are
eligible for the generic data exemption for generic data
concerning that active ingredient (Table A) and product-specific
data for the registered manufacturing use product you purchase
(Table B).
Two circumstances nullify this exemption:
1) If you change sources of active ingredient to an
unregistered product, formulate your own active ingredient, or
acquire your active ingredient from a firm with ownership in
common with yours, you individually lose the exemption and become
subject to the data requirements in Table A.
2) If no producer subject to the generic data requirements
in Table A agrees to submit the required data, all end-use
producers lose the exemption, and become subject to the data
requirements in Table A.
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VI. REQUIREMENT FOR SUBMISSION OF GENERIC DATA
This portion of the Registration Standard is a notice
issued under the authority of FIFRA sec. 3(c)(2)(B). It
refers to the data listed in Table A, which are required to
be submitted by registrants to maintain in effect the regis-
tration of products containing this active ingredient.10
A. What are generic data?
Generic data pertain to the properties or effects of a
particular active ingredient. Such data are relevant to an
evaluation of all products containing that active ingredient
regardless of whether the product contains other ingredients
(unless the product bears labeling that would make the data
requirement inapplicable).
Generic data may also be data on a "typical formulation"
of a product. "Typical formulation" testing is often
required for ecological effects studies and applies to all
products having that formulation type. These are classed as
generic data, and are contained in Table A.
B. Who must s"bppt generic data?
All current registrants are responsible for submitting
generic data in response to a data request under FIFRA sec.
3(c)(2)(B) (DCI Notice). EPA has 'decided, however, not to
require a registrant who qualifies for the formulator's
exemption {FIFRA sec. 3(c)(2)(D) and 40 CFR 152.85) to submit
generic data in response to a DCI notice if the registrant
who supplies the active ingredient in his product is
complying with the data request.
If you are granted a generic data exemption, you rely on
the efforts of other persons to provide the Agency with the
required data. If the registrants who have committed to
generate and submit the required data fail to take
appropriate steps to meet the requirements or are no longer
in compliance with this data requirements notice, the Agency
will consider that both they and you are not in compliance
and will normally initiate proceedings to suspend the
registrations of both your product (s) and their product (s)
unless you commit to submit and submit the required data in
the specified timeframe. In such cases, the Agency
generally will not grant a time extension for submitting the
data.
10Registrations granted after issuance of this Standard will
be conditioned upon submittal or citation of the data listed in
this Registration Standard.
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If you are not now eligible for a generic data
exemption, you may qualify for one if you change your source
of supply to a registered source that does not share
ownership in common with your firm. If you choose to change
sources of supply, the Confidential statement of Formula must
identify the new source(s) and you must submit a Generic Data
Exemption Statement.
If you apply for a new registration for products
containing this active ingredient after the issuance of this
Registration Standard, you will be required to submit or cite
generic data relevant to the uses of your product if, at the
time the application is submitted, the data have been
submitted to the Agency by current registrants. If the
required data have not yet been submitted, any new
registration will be conditioned upon the new registrant's
submittal or citation of the required data not later than the
date upon which current registrants of similar products are
required to provide such data. See FIFRA sec. 3(c)(7)(A).
If you thereafter fail to comply with the condition of that
registration to provide data, the registration may be
cancelled (FIFRA sec. 6(e)).
C. What generic data must be submitted?
You may determine which generic data you must submit by
consulting Table A. That table lists the generic data needed
to evaluate current.uses of all products containing this
active ingredient,, the uses for which such data are required,
and the dates by which the data must be submitted to the
Agency.
D. How to comply with PCI requirements.
Within 90 days of your receipt of this Registration
Standard, you must submit to EPA a completed copy of the form
entitled "FIFRA Section 3(c)(2)(B) Summary Sheet" (EPA Form
8580-1, enclosed) for each of your products. On that form
you must state which of the following six methods you will
use to comply with the DCI requirements:
1. You will submit the data yourself.
2. You have entered into an agreement with one or more
registrants to jointly develop (or share in the cost of
developing) the data, but will not be submitting the data
yourself. If you use this method, you must state who will
submit the data on which you will rely. You must also
provide EPA with documentary evidence that an agreement has
been formed which allows you to rely upon the data to be
submitted. Such evidence may be: (1) your letter offering to
join in an agreement and the other registrant's acceptance of
your offer, (2) a written statement by the parties that an
agreement exists, or (3) a written statement by the person
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who will be submitting the data that you may rely upon its
submittal. The Agency .will also require adequate assurance
that the person whom you state will provide the data is
taking appropriate steps to secure it. The agreement to
produce the data need not specify all of the terms of the
final arrangement between the parties or a mechanism to
resolve the terms.
If you and other registrants together are generating or
submitting requested data as a task force or consortium, a
representative of the group should request a Joint Data
Submitter Number, as part of your 90-day response. The
request must include the following information:
a. A list of the members of the consortium;
b. The name and address of the designated
representative of the consortium, with whom EPA
will correspond concerning the data;
c. Identity of the Registration Standard containing the
data requirement;
d. A list of the products affected (from all members of
the consortium); and
e. Identification of the specific data that the
consortium will be generating or submitting.
The Agency will assign a number to the consortium, which
should be used on all data submittals by the consortium.
3. You have attempted to enter into an agreement to
jointly develop data, but no other registrant has accepted
vour offer. You request that EPA not suspend your
registration for non-compliance with the PCI. EPA has
determined that, as a general policy, it will not suspend the
registration of a product when the registrant has in good
faith sought and continues to seek to enter into a data
development/cost sharing program, but the other registrants
developing the data have refused to accept its offer. [If
your offer is accepted, you may qualify for Option 2 above by
entering into an agreement to supply the data.]
In order to qualify for this method, you must:
a. File with EPA a completed "Certification of Attempt
to Enter into an Agreement with other Registrants for
Develop-ment of Data" (EPA Form 8580-6, enclosed).
b. Provide us with a copy of your offer to the other
registrant and proof of the other registrant's receipt of
your offer (such as a certified mail receipt). Your offer
must, at a minimum, contain the following language or its
equivalent:
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[Your company name] offers to share in the burden
of producing the data required pursuant to FIFRA
sec.3(c)(2)(B) in the [name of active ingredient]
Registration Standard upon terms to be agreed or
failing agreement to be bound by binding
arbitration as provided by FIFRA
section 3(c)(2)(B)(iii).
The remainder of your offer may not in any way attempt to
limit this commitment. If the other registrant to whom your
offer is made does not accept your offer, and if the other
registrant informs us on a DCI Summary Sheet that he will
develop and submit the data required under the DCI, then you
may qualify for this option. In order for you to avoid
suspension under this method, you may not later withdraw or
limit your offer to share in the burden of developing the
data.
In addition, the other registrant must fulfill its
commitment to develop and submit the data as required by this
Notice in a timely manner. If the other registrant fails to
develop the data or for some other reason would be subject to
suspension, your registration as well as that of the other
registrant will normally be subject to initiation of
suspension proceedings, unless you commit to submit and
submit the required data in the specified timeframe. In such
cases, the Agency generally will not grant a time extension
for submitting the data.
4.' You request a waiver of the- data requirement. If
you believe that a data requirement does not (or should not)
apply to your product or its uses, you mu'st provide EPA with
a statement of the reasons why you believe this is so. Your
statement must address the specific composition or use
factors that lead you to believe that a requirement does not
apply. Since the Agency has carefully considered the
composition and uses of pesticide products in determining
that a data require-ment applies, EPA does not anticipate
that many waivers will be granted. A request for waiver does
not extend the time-frames for developing required data, and
if your waiver request is denied, your registration may be
suspended if you fail to submit the data. The Agency will
respond in writing to your request for a waiver.
5. You request that EPA amend your registration by
deleting the uses for which the data are needed. You are not
required to submit data for uses which are no longer on your
label.
6. You request voluntary cancellation of the
registration of your product(s) for which the data are
needed.
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E. Registrant Requests Regarding Data Requirements and
Agency Responses
All requests for modification of data requirements
(inapplicability, waiver), approval of protocols or protocol
changes, or time extensions must be submitted in writing. The
original requirement remains in effect unless the Agency has
notified you in writing that it has agreed to a change in the
requirement. While being considered by the Agency, such
requests for changes in the requirements do not alter the
original requirements or extend the time allowed for meeting
the r equ i r ement.
F. Test Protocols and Standards
All studies required under this Notice must.be conducted
in accordance with test standards outlined in- the Pesticide
Assessment Guidelines, unless other protocol or standards are
approved for use by the Agency in writing. All testing must
be conducted in accordance with applicable Good Laboratory
Practices regulations in 40 CFR Part 160.
The Pesticide Assessment Guidelines, which are referenced
in the Data Tables, are available from the National Technical
Information Service (NTIS), Attn: Order Desk, 5285 Port Royal
Road, Springfield, VA 22161 (tel: 703-487-4650).
Protocols approved by the Organization for Economic
Cooperation and Development (OECD) are also acceptable if the
OECD-recommended test standards conform to those specified in
the Pesticide Data Requirements regulation (Part 158.70).
Please note, however, that certain OECD standards (such as
test duration, selection of test species, and degradate
identification which are environmental fate requirements) are
less restrictive than those in the EPA Assessment Guidelines
listed above. When using the OECD protocols, they should be
be modified as appropriate so that the data generated by the
study will satisfy the requirements of Part 158. Normally,
the Agency will not extend deadlines for complying with data
requirements when the studies were not conducted in accord
with acceptable standards. The OECD protocols are available
from OECD, 1750 Pennsylvania Avenue, N.W., Washington, D.C.
20006.
G. Procedures for requesting a change in test protocol.
If you will generate the required data and plan to use
test procedures which deviate from EPA's Pesticide Assessment
Guidelines or the Reports of Expert Groups to the Chemicals
Group, Organization for Economic Cooperation and Development
(OECD) Chemicals Testing Programme, you must submit for EPA
approval the protocols you propose to use.
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You should submit your protocols before beginning
testing, because the Agency will not ordinarily accept as
sufficient studies using unapproved protocols. A request for
protocol approval will not extend the timeframe for submittal
of the data, nor will extensions generally be given to
conduct studies due to submittal of inappropriate protocols.
The Agency will respond in writing to your request for
protocol approval or change.
H. Procedures for requesting extensions of time.
If you think that you will need more time to generate
the data than is allowed by EPA's schedule, you may submit a
request for an extension of time.
EPA will view failure to request an extension before the
data submittal response deadline as a waiver of any future
claim that there was insufficient time to submit the data.
While EPA considers your request, you must strive to meet the
deadline for submitting the data.
The extension request should state the reasons why you
believe that an extension is necessary and the steps you have
taken to meet the testing deadline. Time extensions normally
will not be granted due to problems with laboratory capacity
or adequacy of funding, since the Agency believes that with
proper planning these can be overcome. The Agency will
respond in writing to any requests for extension of time.
I. Data Format and Reporting Requirements
All data submitted in response to this Notice must comply
with EPA requirements regarding the reporting of data,
including the manner of reporting, the completeness of
results, and the adequacy of any required supporting (or raw)
data, including, but not limited to, requirements referenced
or included in this Notice or contained in PR Notice 86-5
(issued July 29, 1986). All studies must be submitted in the
form of a final report; a preliminary report will not be
considered to fulfill the submittal requirement.
J. Existing stocks provision upon suspension or cancellation.
The Agency has determined that if a registration is
suspended for failure to respond to a DCI request under FIFRA
sec. 3(c)(2)(B), an existing stocks provision for the registrant
is not consistent with the Act. Accordingly, the Agency does not
anticipate granting permission to sell or distribute existing
stocks of suspended product except in rare circumstances. If you
believe that your product will be suspended or cancelled and that
an existing stocks provision should be granted, you have the
burden of clearly demonstrating to EPA that granting such
permission would be consistent with the Act. The following
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information must be included in any request for an existing
stocks provision:
1. Explanation of why an existing stocks provision is
necessary, including a statement of the quantity of existing
stocks and your estimate of the time required for their sale
or distribution; and
2. Demonstration that such a provision would be consis-
tent with the provisions of FIFRA.
VII. REQUIREMENT FOR SUBMISSION OF PRODUCT-SPECIFIC DATA
Under its DCI authority, EPA has determined that certain
product-specific data are required to maintain your registrations
in effect. Product-specific data are derived from testing using
a specific formulated product, and, unlike generic data,
generally support only the registration of that product. All such
data must be submitted by the dates specified in. this
Registration standard.
If you have a manufacturing use product, these data are
listed in Table B. If you have an end use product, the data are
listed in Table C. As noted earlier, the Agency has decided that
it will not routinely require product-specific data for end use
products at this time. Therefore, Table C may not be contained
in this Registration Standard; if there is no Table C, you are
not required to submit the data at this time.
In order to comply with the product specific data require-
ments, you must follow the same procedures as for generic data.
See Section VI.D through J. You should note, however, that
product chemistry data are required for every product, and the
only acceptable responses are options VI.D.I. (submit data) or
VI.D.6.(cancellation of registration).
Failure to comply with the product-specific data require-
ments for your products will result in suspension of the
product's registration.
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VIII. REQUIREMENT FOR SUBMITTAL OF REVISED LABELING
FIFRA requires each product to be labeled with accurate,
complete and sufficient instructions and precautions, reflecting
the Agency's assessment of the data supporting the product and
its uses. General labeling requirements are set out in 40 CFR
156.10 (see Appendix II - LABELING and SUMMARY). In addition,
labeling -language specific to products containing this pesticide
is specified in Section IV.D of this Registra-tion standard.
Responses to this Registration Standard must include draft
labeling for Agency review.
Labeling must be either typewritten text on 8-1/2 x 11 inch
paper or a mockup of the labeling suitable for storage in 8-1/2 x
11 files. Draft labeling must indicate the intended colors of the
final label, clear indication of the front panel of the label, and
the intended type sizes of the text.
If you fail to submit revised labeling as required, which
complies with 40 CFR 156.10 and the specific instructions in
Section IV.D., EPA may seek to cancel the registration of your
product under FIFRA sec. 6.
IX. INSTRUCTIONS FOR SUBMITTAL
All submittals in response to this Registration Standard
must be sent to the following address:
Office of Pesticide Prograjns
OPP Mailroom (TS-767C)
Environmental Protection Agency
401 M St., SW
Washington, B.C. 20460
Attn: Oxytetracyline Registration Standard
A. Manufacturing Use Products (MUPs) containing the subject
pesticide as sole active ingredient.
1. Within 90 days from receipt of this document, you must
submit for each product subject to this Registration Standard:
a. Generic Data Exemption Statement (EPA Form 8580-3),
if applicable, or the "FIFRA Section 3(c)(2)(B) Summary
Sheet" (EPA Form 8580-1), with appropriate attachments.
b. Confidential Statement of Formula (EPA Form 8570-4).
c. Evidence of compliance with data compensation
requirements of FIFRA sec. 3(c)(l)(D). Refer to 40 CFR
152.80-152.99.
32
-------
2. Within 9 months from receipt of this document you must
submit:
a. Application for Pesticide Registration (EPA Form
8570-1).
b. Two copies of any required product-specific data
(See Table B).
c. Three copies of draft labeling, including the
container label and any associated supplemental
labeling.
d. Product Specific Data Report (EPA Form 8580-4).
3. Within the times set forth in Table A. you must submit
all generic datar, * unless you are eligible for the generic data
exemption. If for any reason any test is delayed or aborted so
that the schedule cannot be met, immediately notify the Agency of
the problem, the reasons for the problem, and your proposed
course of action.
B. Manufacturing Use Products containing the subject pesticide
in combination with other active ingredients.
1. Within 90 days from receipt of this document, you must
submit:
a. Generic Data Exemption Statement (.EPA Form 8580-3), .
if applicable, or the'FIFRA sec. 3(c)(2)(B) Summary Sheet, with
appropriate attachments (EPA Form 8580-1).
b. Confidential Statement of Formula (EPA Form 8570-4)
2. Within 9 months of receipt of this document, you must
submit:
Three copies of draft labeling, including the container
label and any associated supplemental labeling.
3. Within the time frames set forth in Table A. you must
submit all generic data, unless you are eligible for the generic
data exemption. If for any reason any test is delayed or aborted
so that the schedule cannot be met, immediately notify the Agency
of the problem, the reasons for the problem, and your proposed
course of action.
C. End Use Products containing the subject pesticide as sole
act ive ingredi ent.
1. Within 90 days from receipt of this document, you must
submit:
33
-------
a. Generic data exemption Statement (EPA Form 8580-3),
if applicable, or the FIFRA Section 3(c)(2)(B) Summary
Sheet, with appropriate attachments (EPA Form 8580-1).
b. Confidential Statement of Formula (EPA Form 8570-4).
2. Within 9 months from receipt of this document you must
submit:
a. Two copies of any product-specific data, if required
by Table C.
b. Product Specific Data Report (EPA Form 8580-4) ,
if Table C lists required product-specific data.
c. Three copies of draft labeling, including the
—- „ — . container label and any associated supplemental
labeling.
•
3. Within the times set forth in Table A. you must submit
all generic data, unless you are eligible for the generic data
exemption. If for any reason any test is delayed or aborted so
that the schedule cannot be met, immediately notify the Agency of
the problem, the reasons for the problem, and your proposed
course of action.
D. End Use Products containing the subject active ingredient
as one of multiple active ingredients
1. Within 90 days from receipt of this document, you must
submit:
a. Generic data exemption Statement (EPA Form 8580-3) ,
if applicable, or the FIFRA Section 3(c)(2)(B)
Summary Sheet, with appropriate attachments (EPA Form
8580-1).
b. Confidential Statement of Formula (EPA Form 8570-4).
2. Within 9 months from the receipt of this document, you
must submit:
Three copies of draft labeling, including the container
label and any associated supplemental labeling.
3. Within the times set forth in Table A. you must submit
all generic data, unless you are eligible for the generic data
exemption. If for any reason any test is delayed or aborted so
that the schedule cannot be met, immediately notify the Agency of
the problem, the reasons for the problem, and your proposed
course of action.
34
-------
E. Intrastate Products
Applications for full Federal registration of intrastate
products were required to be submitted no later than July 31,
1988. Unless an application for registration was submitted by
that date, no product may be released for shipment by the
producer after July 31, 1988.
35
-------
I. DATA APPENDICES
36
-------
TGUIDE-1
GUIDE TO TABLES
Tables A, B, and C contain listings of data requirements
for the pesticides covered by this Registration standard.
Table A contains generic data requirements that apply
to the pesticide in all products, including data
requirements for which a "typical formulation" is the
test substance.
Table B contains product-specific data requirements that
apply only to a manufacturing use product.
«
Table c contains product-specific data requirements that
apply only to an end use product.
The data tables are generally organized according to 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 out in the Pesticide Assessment Guidelines, which
are available from the National Technical Information Service,
5285 Port Royal Road, Springfield, VA 22161.
2. Test Substance (Column 2). This column lists the
composition of the test substance required to be used for the
test, as follows:
TGAI = Technical grade of the active ingredient
PAI = Pure active ingredient
PAIRA = Pure Active ingredient, radio labeled
TEP = Typical end use formulation
MP = Manufacturing use product
EP = End use product
Any other test substances, such as metabolites, will be
specifically named in Column 2 or in footnotes to the table.
37
-------
TGUIDE-2
3. Use pattern (Column 3). This column indicates the use
patterns to which the data requirement applies. Use patterns
are the same as those given in 40 CFR Part 158. The following
letter designations are used for the given use patterns:
A = Terrestrial, food
B = Terrestrial, non-food
C = Aquatic, food
D = Aquatic, non-food
E = Greenhouse, food
F = Greenhouse, non-food
G = Forestry
H = Domestic outdoor
I = Indoor
•
Any other designations will be defined in a footnote to the
table.
4. Does EPA have data? (Column 4). This column indicates one
of three answers:
YES - EPA has data in its files that completely
satisfy this data requirement. These data may be
cited by other registrants in accordance with data
compensation requirements of Part 15.'2, Subpart E.
PARTIALLY - EPA has some data in its files, but such
data do not fully satisfy the data requirement. In
some cases, the Agency may possess data on one of two
required species or may possess data on one test
substance but not all. The term may also indicate that
the data available to EPA are incomplete. In this
case, when the data are clarified, or additional
details of the testing submitted by the original data
submitter, the data may be determined to be acceptable.
If this is the case, a footnote to the table will
usually say so.
38
-------
TGUIDE-3
NO - EPA either possesses no data which are sufficient
to fulfill the data requirement, or the data which EPA
does possess are flawed scientifically in a manner that
cannot be remedied by clarification or additional
information.
5. Bibliographic citation (Column 5). If the Agency has
acceptable data in its files, this column lists the identifying
number of each study. This normally is the Master Record
Identification (MRID) number, but may be a GS number if no MRID
number has been assigned. Refer to the Bibliography Appendices
for. a complete citation of the study.
6. Must additional data be J-JUbpiitteft? (Column 6). This column
indicates whether the data must be submitted to the Agency. If
column 3 indicates that the Agency already has data, this column
will usually indicate NO. If column e indicates that the Agency
has only partial data or no data, this column will usually
indicate YES. In some cases, even though the Agency does not
have the data, EPA will not require its submission because of the
unique characteristics of the chemical; because data on another
chemical can be used to fulfill the data requirement; or because
the data requirement has been waived or reserved. Any such
unusual situations will be explained in a footnote to the table.
39
-------
TGUIDE-4
7. Timeframe for submission (Column 7). If column t requires
that data be submitted, this column indicates when the data are
to be submitted, based on the issuance date of the Registration
Standard. The timeframes are those established either as a
result of a previous Data Call-in letter, or standardized
timeframes established by PR Notice 85-5 (August 22, 1985).
8. Footnotes (at the end of each table). Self-explanatory.
40
-------
Table A
GENERIC DATA REQUIREMENTS FOR OmEIRACTCLINE
Data Requirement
Composition
Does EPA
Have Data to
Satisfy This
Regui rement?
Must Additional
Data Be Submitted Timeframe
Bibliographic Under FIFRA Section for
Citation 3(cH2)(B)? Submission
Part 158, Subpart c,
Chemistry
Product Identity and Composition
61-2 - Description of Beginning
Materials and Manufac-
turing Process
61-3 - Discussion of Formation
of Impurities
Analysis and Certification of
Product Ingredients
62-1 - Preliminary Analysis
of Product Samples
Physical and Chemical Characteristics
63-2 - Color
63-3 - Physical State
63-4 - Odor
63-5 - Melting Point
63-6 - Boiling Point
63-7 - Density, Bulk Density
or Specific Gravity
TGAI
TOM
NO*/
NO*/
TGAI
No*/
TGAI
TGAI
TGAI
TGAI
TGAI
TGAI
No*/
Yes2/
Yes3/
Yes4/
9 Months
9 Months
12 Months
Yes5/
Yes5/
Yes5/
Yes5'6/
Yes5'7/
Yes5/
9 Months
9 Months
9 Months
9 Months
9 Months
9 Months
-------
Table A
GENERIC DATA REQUIREMENTS FCR OXyjETRACYCLINE
Does EPA
Have Data to
Huit Additional
Data Be Submitted Timeframe
. Satisfy This Bibliographic Under FIFRA Section for
Data Requirement Comtosition Recruirement? Citation 3(c)(2)(B)? Submission
part 158
Physical
63-8 -
63-9 -
63-10 -
63-11 -
63-12 -
, Subpart Cf Profliy^t Hlfinustry (cont'd)
and Qiaucal
ristjcs (cont'd)
Solubility TGAI or PAI
Vapor Pressure TGAI or PAI
Dissociation Constant TGAI or PAI
Octanol/Water PAI
Partitioning coefficient
pH TGAI
63-13 - Stability TGAI
Qt-iier Retirements;
Nb1/
Nol/
No1/
No1/
No1/
Nb1/.
«
Yes5/ 9 Months
Yes5/ 9 Months
Yes5/ 9 Months
Yes5'8/ 9 Months
yes5,9/ 9 Months
Yes5/ 9 Months
64-1 - Sutmittal of Sanples
N/A
N/A
N/A
No
-------
TABLE A
GENERIC DATA REQUIREMENTS FOR CXVIETRACYCLINE
Part 158. Submit C. Product Chemistry - Footnotes
M Although product chemistry may have been submitted in the past, the Agency has determined that these data roust be
resubmitted for each pesticide. New data requirements have been introduced and previously submitted data must be
updated. Therefore, bibliographic citations for the old data are not applicable.
2/ complete information must be provided regarding the nature of the process (batch or continuous), the relative amounts
of beginning materials and the order in which they are added, the chemical equations for each intended reaction,
equipment used to produce each intermediate and the final product, reaction conditions, the duration of each step of
the process, purification procedures, and quality control measures. In addition, the name and address of the
manufacturer, producer, or supplier of each beginning material must be provided, along with information regarding
the properties of each beginning material used to manufacture each product.
3/ A detailed discussion of all impurities that are or may be present at >0.1%, based on knowledge of the beginning
materials, chemical reactions (intended and side) in the manufacturing process, and any contamination during and
after production must be submitted.
4/ Five or more representative samples must be analyzed for the amount of active ingredient and each impurity for whicJ
a certified limit is required. Complete validation data (accuracy, precision) must be submitted for each analytical
method used.
5/ Physicochemical characteristics (color, physical state, odor, melting point, specific gravity, solubility, vapor
pressure, dissociation constant, partition coefficient, pH, and stability) as required in 40 CFR 158.190 and more fuir
described in the Pesticide Assessment Guidelines, Subdivision D, must be submitted.
£/ Data required if the technical chemical is a solid at room temperature.
I/ Data required if the technical product is a liquid at room temperature.
S/ Data required if the technical product is organic or nonpolar.
9/ Data required if the technical substance is dispersible in water.
-------
Table A
Generic Data Requirements for Qxytetracycline
Data Requirement Composition
S158.24Q
171-2 -
171-3 -
171-4 -
171-4 -
171-4 -
171-4 -
Residue Chemistry
Chemical Identity!/
Directions for Use
Nature of the Residue
(Metabolism)
- Plants PAIRA
- Livestock PAIRA
Residue Analytical Methods TGAI
Storage Stability Data TEP
Magnitude of the residue
in plants
Pome Fruits
- pears TEP
Does EPA Must Additional
Have Data to Data Be Submitted Timeframe
Satisfy This Bibliographic Under FIFRA Section For Data
Reouirement? Citation 3
-------
TABLE A
GENERIC DMA REQUIREMENTS FOR Qxytetracycline
S158.24Q Residue Chemistry - Footnotes
A/ The same chemical identity data are required as under S 158.740, with emphasis on impurities that could
constitute residue problems. Refer to Product Chemistry Data Requirements tables.
2/ Data were not submitted regarding the nature of the residues of oxytetracycline in plants. The Agency has
assessed the need for data reflecting the metabolism of •oxytetracycline in plants and has concluded that these data
are not required.
3/ Data on the metabolism of oxytetracycline in food animals are not needed because the exposure of livestock to
residues of oxytetracycline is highly improbable since there are no registered uses on feed items at the present
time.
4/ The term peaches is defined to include both peaches and nectarines (40 CFR 180.1(H)).
5/ Presently, there is no potential for livestock consumption of oxytetracycline residues because oxytetracycline is
registered for use only on commodities (pears and peaches) that are not used for animal feeds.
c.n
-------
Table A
Generic Data Requirements for Calcuim oxytetracycline
45k
Does EPA Must Additional
Have Data to Data Be Submitted Timeframe
Use Satisfy This Bibliographic Under FIFRA Section For Data
Data Requirement Composition Patterns Recruirement? Citation 3(c)(2)(B)? submission
Sec. 158
DpqTQCljjl't"
161-1 -
Photodeo
161-2 -
161-3 -
161-4 -
Metaboli
162-1 -
162-2 -
162-3 -
lfi?-4 -
.290 Environmental Fate
ion Studies — Lab
Hydrolysis TGAI or PAIRA A,B,D No
ra.cld.tiQn
In Water TGAI or PAIRA A,B,D No
Cn Soil TGAI or PAIRA A No
In Air TGAI or PAIRA A -No
Aerobic Soil TGAI or PAIRA A,B No
Anaerobic Soil TGAI or PAIRA A No
Anaerobic Aquatic TGAI or PAIRA D No
Aerobic Aouatic TGAI or PAIRA D No
Yes 9 Months
Yes 9 Months
Yes 9 Months
Yes 9 Months
Yes 27 Months
Yes 27 Months
Yes 27 Months
Yes 27 Months
-------
Table A
Generic Data Requirements for Calcuim oxytetracycline (cont'd)
Data Requir<3nSTlf
Sec. 158.290 Environmental Fate
Mobility Studies
163-1 - Leaching and TGAI
Adsorption/Desorption
163-2 - Volatility (Lab)
163-3 - Volatility (Field)
Dissipation studies - Field
164-1 - Soil
164-2 - Aquatic (Sediment)
164-3 - Forestry
164-4 - Combination and
Composition
(cont»d)
or PAIRA
TEP
TEP
TEP
TEP
TEP
TEP
Use
Patterns
A,B
A
A
A,B
D
N/A •
N/A
Does EPA
Have Data to
Satisfy This
Requirement?
No
No
No
No
No
Must Additional
Data Be Submitted
Bibliographic Under FIFRA Section
Citation 3(c)(2MB)?
Yes
Reserved^/
Reserved^/
Yes
Yes
Timeframe
For Data!/
Submission
12 Months
*
27 Months
27 Months
Tank Mixes
164-5 - Soil, Long-Term
TEP
No
Reserved^/
-------
Table A
Generic Data Requirements for Calcuim oxytetracycline (cont'd)
Data
Does EPA
Have Data to
Use Satisfy TJiis
Composition Patterns Requirement?
Must Additional
Data Be Submitted Timeframe
Bibliographic Under FIFRA Section For Data
Citation 3(cU2Hm?
Submission
Sec. 158.290 Environmental Fate (cont'd)
Accumulation Sf'XliftS
FAIRA
165-1 - Rotational Crops
(Confined)
165-2 - Rotational Crops
(Field)
165-3 - Irrigated Crops
165-4 - In Fish
165-5 - In Aquatic Nbntarget
Organisms
TEP A
TEP N/A
TGAI or FAIRA 'A,D .
HP D
NO
NO
NO
NO
Yes
Reserved^/
12 Months
I/ The need for laboratory and field volatility studies will be reassessed upon evaluation of an acceptable vapor
pressure study.
2/ May be required pending the receipt and review of data under 162-1 (metabolism:aerobic soil) and 164-1
(dissipation field:soil).
j/ Use sites will not involve rotated crops.
4/ May be required pending receipt and review of data under 165-4 (fish accumulation study).
-------
Table A
Generic Data Requirements for Calcuim oxytetracycline (cont'd)
Data Reouirement
Does EPA
Have Data to
Use Satisfy This
Composition Patterns Requirement?
Must Additional
Data Be Submitted Timeframe
Bibliographic Under FIFRA Section For Data*/
Citation 3(c)(2HB)? Submission
Sec. 158.290 Environmental Fate (cont'd)
Mobility S
163-1 - Leaching and TGAI or PAIRA A,B
Adsorption/Desorption
163-2 - Volatility (Lab)
163-3 - Volatility (Field)
Dissipation Studies - Field
164-1 - Soil
164-2 - Aquatic (Sediment)
164-3 - Forestry
164-4 - Combination and
Tank Mixes
164-5 - Soil, Long-Term TEP
No
TEP
TEP
TEP
TEP
TEP
TEP
A
A
A,B
D
N/A
N/A
NO
NO
NO
NO
Yes
Reserved^/
Reserved^/
Yes
Yes
No
Reserved^/
12 Months
27 Months
27 Months
-------
Table A
Generic Data Requirements for Calcuim oxytetracycline
Data Reomrpmeni-
Does EPA
Have Data to
Satisfy This
Conuosition Patterns Requirement?
Sec. 158.390 Reentry Protection
132-1 - Foliar Dissipation TEP
132-2 - Soil Dissipation TEP
132-3 - Dermal Exposure TEP
132-4 - Inhalation Exposure TEP
Sec. 158.440 Spray Drift
201-1 - Droplet Size Spectrum N/A
202-1 - Drift Field Evaluation N/A
A,B
A,B
A,B
A,B
No
No
No
No
Must Additional
Data Be Submitted Timeframe
P: liographic l&ider FIFRA Section for
w»lation 3(cW2WBl? Sutmission
Nbi/
Nbi/
I/Qxytetracycline does not meet the criteria of 40 CFR 158.390 for requiring reentry data (i.e., oxytetracycline has a
low mammalian toxicity and there is no epidemiological evidence of adverse effects to humans from its pesticidal
uses).
-------
Table A
Generic Data Requirements for Qxytetracycline
Data
S158.
81-1
81-2
81-3
81-4
81-5
81-6
L/1 81-7
O
Requirement Con?
340 Toxicology
- Acute Oral - Rat
- Acute Dermal
- Acute Inhalation
- Eye Irritation
- Dermal Irritation
- Dermal Sensitization
- Acute Delayed
Neurotoxicity
osition
TGAI
TGAI
TGAI
TGAI
TGAI
TGAI
TGAI
Use
Patterns
A,B
A,B
A,B
A,B
A,B
A,B
A,B
Does EPA
Have Data to
Satisfy This
Requi rement ?
No
No
No
No
No
No
No
Must Additional
Data Be Submitted Timeframe
Bibliographic Under FIFRA Section For Data
Citation 3(c)(2)(B)? Submission
Nbl/
Nol/
Nol/
Noi/
Nol/
Nol/
No2/
Subchronic Testing
82-1
- 90-Day Feeding -
Rodent
Non-rodent
TGAI
TGAI
A,B
A,B
.-
NO
NO
Nol/
NO^/
-------
Table A
Generic Data Requirements for Qxytetracycline (cont'd)
CJl
Data Requirement
s 158.340 Toxicology
Subchronic Testing (cont'd)
82-2 - 21-Day Dermal
82-3 - 90-Day Dermal
82-4 - 90-Day Inhalation
82-5 - 90-Day Neurotoxicity
Chronic Testing
83-1 - Chronic Testing
-Rodent
-Nonrodent
83-2 - Cocogenicity
-Rat
-Mouse
83-3 -Teratogenicity
-Rat
-Mouse
Compositioi
TGM
TGM
TGM
TGM
TGM
TGM
TGM
TGM
TGM
TGM
Use
n Patterns
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
A,B
Does EPA
Have Data to
Satisfy This
. Requirement?
No
No
No
No
No
No
Yes
Yes
Yes
Yes
Must Additional
Data Be Submitted
Bibliographic Under FIFRA Section
Citation 3(c)(2)(B)?
Nbi/
No«/
No*'
Nb2/
Nbi/
00159856 No
00159856 No
00132391 Nb
00132392 No
Timeframe
For Data
Submission
-------
Table A
Generic Data Requirements for Qxytetracycline (cont'd)
Data Requirement
Does EPA
Have Data to
Use Satisfy This
Composition Patterns Requirement?
Must Additional
Data Be Submitted Timeframe
Bibliographic Under FIFRA Section For Data
Citation 3(C)(2)(B)? Submission
un
fV>
S 158.340 Toxicology
Chronic Testing (cont'd)
83-4 - Reproduction
MUtagenicity Testing
84-2 - Gene Mutation
84-2 - Chromosome Aberration
84-4 - Other Mechanisms of
MUtagenicity
Special Testing
85-1 - General Metabolism
Antibiotic Resistance
TGAI
FAI or
FAIRA
A,B
TGAI
TGAI
TGAI
A,B
A,B
A,B
NO
. No
.NO
A,B
. NO
Yes
40840101
No
-------
Table A
Generic Data Requirements for Qxytetracycline (cont'd)
s 158.340 Toxicology Footnotes
I/ These data requirements are waived based on the availability of human and/ or animal data found in the public
literature (Grollman, A. and Grollman, E.F. (1970) Pharmacology and Therapeutics (7th ed.) Lea and Febiger,
Philadelphia, PA.; Modern Drug Encyclopedia and Therapeutic Index-A Compendium (1977) New York: Yorke Medical Books,
Donnelly Publishing Co.; Physicians Desk Reference (PDR) (1980) Oradell, NJ: Medical Economics Co., pp.1372-1373.;
Shulman, J.A. and Sellers, T.F., Jr. (1971) Chemotherapy of Bacterial Infections VII: Other Important Antibiotics. In
DiPalma, J.R. (ed) Drill's Pharmacology in Medicine. 4th ed. McGraw-Hill Books Co., Inc., New York, pp. 1729-1754.;
Weinstein, L. The Tetracyclines. In Goodman, L., and Gilman, A. (eds). (1970) The Pharmacological Basis of
Therapeutics. 4th ed. Macmillan Publishing Co., pp. 1240-1244.)
2/ This test is required only for compounds which are "organophosphate inhibitors of cholinesterase, or related to
such inhibitors or metabolites of such inhibitors. Oxytetracycline is not an organophosphate, therefore a study is
not required.
3y These data are not required due to use pattern.
en
-------
Table A
Generic Data Requirements for Oxytetracycline
Data Requirement
Does EPA Have
Data to Satisfy
This Require-
Use ment? (Yes,
Composition Pattern No. Partially)
Must Additional
Data Be Submitted Timeframe
Bibliographic Under FIFRA Section For Data
Citation 3(c)(2)(B)? Submission
CJ1
s 158,490 - Wildlife and Aquatic Organisms
Avian and Manroalian Testing
71-1 -Avian Acute Oral Toxicity
- Upland game bird TGAI
71-2 - Avian Dietary ££50
- Upland Game Bird
- Waterfowl
71-3 - Wild Manroal Toxicity
71-4 - Avian Reproduction
- Upland Game Bird
- Waterfowl
71-5 - Actual Field Testing
for Birds and
Manuals
TEP
A,B,D
TGAI
TGAI
TGAI
TGAI
TGAI
A,B,D
A,B,D
A,B,D
A.B.D
A,B,D
NO
No
NO
NO
NO
A,B,D
No
Yes
Reserved
Reserved
No
9 Months
Yes
Yes
No I/
9 Months
9 Months
-------
Table A
Generic Data Requirements for Qxytetracycline (cont'd)
c_n
Data
5158.
Acfli^t
72-1
72-2
72-3
Does EPA Have
Data to Satisfy Must Additional
This Require- Data Be Submitted Timeframe
Use ment? (Yes, Bibliographic IMer FIFRA section For Data 1
Requirement Comoosition Pattern No. Partially) Citation 3(c)(2HB)? Submission
490 - Wildlife and ftouatic Organisms
•ic Organism Testing
- Freshwater Fish LC5Q
- Warmwater TGAI A,B,D No
TEP A,B,D No
- coldwater TGAI A,B,D No
TEP A,B,D No
- Freshwater
Invertebrate LC50 TGAI A,B,D No
TEP A,B,D NO
- Estuarine and Marine
Organisms LC5o
_ pish TGAI A,B,D No
TEP A,B,D NO
Yes 9 Months
Reserved -3/
Yes 9 Months
Reserved -3/
Yes 9 Months
Reserved -27
Reserved 4/
Reserved ^/
-------
Table A
Generic Data Requirements for Oxytetracycline (cont'd)
Does EPA Have
Data to Satisfy
This Require-
Use ment? (Yes,
Must Additional
Data Be Submitted Timeframe
Bibliographic Under FIFRA Section For Data I/
iJcu-Q
S158,
72-3
ixo-tn.i.i.aiKaii- '^«-«'T^>-"-' -^ ^- J-"" *MWWV*H >1V< — i \l» W«M*»J I -V«MT
- Estuarine and Marine
Organisms LC5Q
- Shrimp TGM A,B,D No
TEP A,B,D NO
- Oyster TGM A,B,D No
TEP A,B,D NO
Reserved 4/
Reserved ^/
Reserved 4/
Reserved ^/
72-4 - Fish Early Life Stage
and Invertebrate
Life Cycle
- Freshwater
- Fish
- Invertebrates
TGM
A,B,D
A,B,D
NO
NO
Reserved
Reserved
-------
Table A
Generic Data Requirements for Oxytetracycline (cont'd)
Does EPA Have
Data to Satisfy Must Additional
This Require- Data Be Submitted Timeframe
Use ment? (Yes, Bibliographic Under FIFRA Section For Data I/
Composition Pattern Kb. Partially) Citation 3(c)(2)(B)? Submission
Data Reouirement
•"•158.490 - Wildlife and Aquatic Organisms
72-5 - Fish Life Cycle TGAI A,B,D
72-6 - Aquatic Organisms TGAI A,B
Accumulation
Nb
Nb
Reserved -I/
Reserved 4/
72-7 - Simulated or Actual
Field Testing
-Aquatic Organisms
TEP
A,B
N0
Reserved
I/ Nb requirement currently exists.
2/ Reserved pending evaluation of appropriate environmental fate data needed, such as a field and aquatic sediment
dissipation study to better define expected residues.
-2/ Formulated product testing for acute toxicity to aquatic estuarine and marine organisms is reserved pending the
results of testing with the technical grade (TGAI).
4/ Reserved pending evaluation of acute toxicity data on warmwater fish species and freshwater aquatic invertebrates
along with appropriate environmental fate information (ie., hydrolysis and photolysis in water). These data are
needed to determine if hazardous concentrations of oxytetracycline will reach the aquatic environment when products
are used as directed.
-------
Table A
Generic Data Requirements for Qxytetracycline
Data Requirement
Does EPA Most Additional
Have Data to Data Be Submitted Timeframe
Use Satisfy This Bibliographic Under FIFRA Section For Data
Composition Patterns Requirement? citation 3(c)(2)(B)? Submission
S158.590 Nontarget Insects
oo
141-1 - Honey Bee Acute
Contact LD50
TGM
141-2 - Honey Bee - Toxicity TEP
Residues on
Foliage
A,B,D
A,B,D
141-4 - Honey Bee Subacute
Feeding Study
141-5 - Field Testing for
pollinators
Reserved^/
TEP A,B,D
TMSETT TESTTMT - AQUATIC INSECTS
TEP A,B,D
142-1 - Acute Toxicity to
Aquatic Insects
142-2 - Aquatic Insect
Life Cycle Study
142-3 - Simulated or
Actual Field
Testing for
Aquatic Insects
TEP
TEP
A,B,D
A.B.D
143-1
thru
143-3
TNSBCT TESTTNr - PREDATORS AMP PARASITES
Reserved3-/
No
No
No
No
Yes
No!/
9 Months
No3/
No3/
NO3/
-------
Table A
Generic Data Requirements for Qxytetracycline (cont'd)
S158.590 - Montarget Insects Footnotes
I/ Requirements deferred pending evaluation of data from the acute contact LD50 study.
2/ This requirement is reserved pending development of test methodology.
3/ This requirement is reserved pending Agency decision as to whether the data requirement should be established.
ui
-------
Table B
Product-Specific Data Requirements for Manufacturing-Use Products Containing Cbcytetracycline
Data Requirement
Composition!/
Does EPA
Have Data to
Satisfy This
Requirement?
Must Additional
Data Be Submitted Timeframe
Bibliographic Under FIFRA Section for
Citation 3(c)(2)(B)? submission2/
ON
O
Part 158 f Subpart C. Product
Chemistry
Product Identity and Composition
61-1 - Product Identity and
Disclosure of Ingredients
61-2 - Description of Beginning
Materials and Manufac-
turing Process
61-3 - Discussion of Formation
of Impurities
is and Certification of
Product Ingredients
62-1 - Preliminary Analysis
of Product Samples
62-2 - Certification of Ingredient
Limits
62-3 - Analytical Methods to Verify
Certified Limits
Physical and Chemical
63-2 - Color
63-3 -
MP
MP
MP
MP
MP
MP
NO^/
No3-/
Yes6-/
Yes?/
•NO3-/
NO3-/
No3-/
Yes2/
9 Months
9 Months
9 Months
12 Months
12 Months
12 Months
9 Months
9 Months
-------
Table B
Product-Specific Data Requirements for Manufacturing-Use Products Containing Qxytetracycline
Ddtil Requirement
Part 158
Physical
t Subpart C. Product Chemistry
and Chemical
Composition
(cont'd)
'Does EPA Must Additional
Have Data to Data Be Submitted Timeframe
Satisfy This Bibliographic Under FIFRA Section for
Requirement? Citation 3(c)(2)(B)? Submission!
QlflTd/Tt eristics (cont'd)
63-4 -
63-7 -
63-12 -
63-14 -
63-15 -
63-16 -
63-17 -
63-18 -
63-19 -
Odor
Density, Bulk Density
or Specific Gravity
pH
Oxidizing or Reducing
Agent
Flammability
Explodability
Storage Stability
Viscosity
Miscibility
corrosion Characteristics
MP
MP
MP
MP
MP
MP
MP
MP
MP
MP
No3/
NO3/
NO3/
NO3/
Nb3/
NO3-/
No3/
Nb3/
NO3/
NO3/
Yes7-/ 9 Months
Yes-7-/ 9 Months
YesZ'H/ 9 Months
Yes1^'-^/ 9 Months
YeslQ,!3-/ 9 Months
YosLQilA/ 9 Months
YeslR/ 15 Months
YeslQ^lS/ 9 Months
YeslQ'l6-/ 9 Months
YeslQ/ 15 Months
nt-her Requirements;
64-1 - Sutmittal of Samples
N/A
No
-------
• Table B
Product-Specific Data Requirements for Manufacturing-Use Products Containing Qxytetracycline
Data Requirement
Part 158
Physical
, SvtfTPfirt C. Pfnrtiirt Chemistry
and Chemical
Does EPA Must Additional
Have Data to Data Be Submitted Timeframe
Satisfy This Bibliographic Under FIFRA Section for
Composition Requirement? Citation 3(c)(2)(B)? Submission^
(cont'd)
i
(Tlfl rflfTter i st ics (cont'd)
63-4 -
63-7 -
63-12 -
63-14 -
63-15 -
63-16 -
63-17 -
63-18 -
63-19 -
63-20 -
Other Re
Odor
Density, Bulk Density
or Specific Gravity
PH
Oxidizing or Reducing
Agent
Flammability
Explodability
Storage Stability
Viscosity
Miscibility
Corrosion Characteristics
:jui rements :
MP NO3/
MP NO3/
MP NO3/
MP NO3/
MP NO3/
MP No3-/
MP NO3/
MP NO3/
MP NO3/
MP No3/
Yes7-/ 9 Months
Yes7-/ 9 Months
Ye&2«ll/ 9 Months
Yes^Q'^2/ 9 Months
Yesl0-,^3-/ 9 Months
Yesl°-»A4/ 9 Months
YesAQ/ 15 Months
Yes-1^,-^5/ 9 Months
YeslQ'^6-/ 9 Months
YeSl°-/ 15 Months
64-1 - Submittal of Samples
N/A
N/A
No
-------
TABLE B
PRODUCT-SPECIFIC DA3A RBQUIREMEMS FOR MANUFACTURING USE PRODUCTS CCMIAINING QmEIRACYCLINE
Part 158 . Suboart C. Prnrhy^-
i
J-/ Formulation intermediates are also included in the category of manufacturing-use products (MP) .
2/ Due dates refer to the number of months following receipt of this Registration Standard, unless otherwise indicated.
M Although product chemistry nay have been submitted in the past, the Agency has determined that these data must be
resubmitted for each pesticide. New data requirements have been introduced and previously submitted data must be
updated. Therefore, bibliographic citations for the old data are not applicable.
4/ The chemical name, nominal concentration. Chemical Abstracts (CAS) Registry Number, and purpose of the active
ingredient in each intentionally added inert must be provided. For the active ingredients, the following must also be
provided: the product, common and trade names; the molecular, structural, and empirical formulas; the molecular weight <
weight range; and any experimental or internally assigned code numbers.
5/ Complete information must be provided regarding the nature of the process (batch or continuous), the relative amount
of beginning materials and the order in which they are added, the chemical equations for each intended reaction,
equipment used to produce each intermediate and the final product, reaction conditions, the duration of each step of
the process, purification procedures, and quality control measures. In addition, the name and address of the
manufacturer, producer, or supplier of each beginning material must be provided, along with information regarding
the properties of each beginning material used to manufacture each product.
£/ A detailed discussion of all impurities that are or may be present at >0.1%, based on knowledge of the beginning
materials, chemical reactions (intended and side) in the manufacturing process, and any contamination during and
after production must be submitted.
^/ Five or more representative samples must be analyzed for the amount of active ingredient and each impurity for which
a certified limit is required. Complete validation data (accuracy, precision) must be submitted for each analytical
method used.
fl/ Upper and lower limits for the active ingredients and each intentionally added inert, and upper limits for each
impurity present at > 0.1% (w/w) and each "toxicologically significant" impurity present at <0.1% (w/w) must be provided
and certified. Also^ an explanation of how each certified limit was established must be provided (e.g. , sample analysis
using validated analytical procedures, quantitative estimate based on amounts of ingredients used, etc.). Limits for .
impurities not associated with the active ingredient need be provided only if they are considered to be of toxicological
significance, regardless of the concentration at which they are present. Certification must be submitted on EPA form 857
Rev. 2-85.
-------
TABLE B
PRODUCT-SPECIFIC DMA REQUIREMENTS FOR MANUFACTURING USE PRODUCTS CONTAINING OmMRACYCLINE
Part 158, Subpart C, prrrhirrh Chemistry - Footnotes (cont'd)
27 Analytical methods must be provided to determine the active ingredient, and each toxicologically significant inpurity
and intentionally added inert for which certified limits are required. Each method most be accompanied by validation
studies indicating its accuracy and precision. These methods most be suitable for enforcement of certified limits.
Physiochemical characteristics (color, physical state, odor, melting point, specific gravity, solubility, vapor
pressure, dissociation constant, partition coefficient, pH, and stability) as required in 40 CFR 158.190 and more fully
described in the Pesticide Assessment Guidelines, Subdivision D, most be submitted.
Data required if the test substance is dispersible in water.
Data require t the product contains an oxidizing or reducing agents.
137 Data required if the product contains combustible liquids.
147 Data required if the product is potentially explosive.
157 Data required if the product is a liquid.
Data required if the product is a liquid and is be diluted with petroleum solvents.
-------
Table B
Product-specific Data Requirements for Manufacturing-Use Products Containing Oxytetracycline
Use
Composition Patterns
S 158.340 Toxicology
Acute Testing
81-1 - Acute Oral - Rat
81-2 - Acute Dermal
81-3 - Acute Inhalation - Rat
MP
MP
81-4 - Eye Irritation - Rabbit MP
81-5 - Dermal Irritation
-Rabbit MP
81-6 - Dermal Sensitization
- Guinea Pig MP
A,B
A,B
A,B
A,B
A,B
A,B
Does EPA
Have Data to
Satisfy This
Must Additional
Data Be Submitted Timeframe
Bibliographic Under FIFRA Section For Data
Citation 3(cH2HB>?
No
No
No
No
No
No
Nb2/
Nb2/
Nb2/
I/ Formulation intermediates are also included in the category of manufacturing-use products.
2/ These data requirements are waived based on the availability of human and/ or animal data found in the public
literature (Grollman, A. and Grollman, E.F. (1970) Pharmacology and Therapeutics (7th ed.) Lea and Febiger,
Philadelphia, PA.; Modern Drug Encyclopedia and Therapeutic Index-A Compendium (1977) New York: Yorke Medical Books,
Donnelly Publishing Co. ; Physicians Desk Reference (PDR) (1980) Oradell, NJ: Medical Economics Co., pp. 1372-1373. ;
Shulman, J.A. and Sellers, T.F., Jr. (1971) Chemotherapy of Bacterial Infections VII: Other Important Antibiotics. In
DiPalma, J.R. (ed) Drill's Pharmacology in Medicine. 4th ed. McGraw-Hill Books Co., Inc., New York, pp. 1729-1754.;
Weinstein, L. The Tetracyclines. In Goodman, L., and Gilman, A. (eds). (1970) The Pharmacological Basis of
Therapeutics. 4th ed. Macmillan Publishing Co., pp. 1240-1244.)
-------
II. LABELING APPENDICES
65
-------
SUMMARY-1
LABEL CONTENTS
40 CFR 156.10 requires that certain specific labeling
statements appear at certain locations on the label. This is
referred to as format labeling. Specific label items listed
below are keyed to the table at the end of this Appendix.
Item 1. PRODUCT NAME - The name, brand or trademark is
required to be located on the front panel, preferably
centered in the upper part of the panel. The name of a
product will not be accepted if it is false or misleading.
Item 2. COMPANY NAME AND ADDRESS - The name and address
of the registrant or distributor is required on the label.
The name and address should preferably be located at the
bottom of the front panel or at the end of the label text.
•
Item 3. NET CONTENTS - A net contents statement is
required on all labels or on the container of the pesticide.
The preferred location is the bottom of the front panel
immediately above the company name and address, or at the end
of the label test. The net contents must be expressed in the
largest suitable unit, e.g., "1 pound 10 ounces" rather than
"26 ounces." In addition to English units, net contents may
be expressed in metric units. [40 CFR 156.10(d)]
Item 4. EPA REGISTRATION NUMBER -• The registration
number assigned to the pesticide product must appear on the
label, preceded by the phrase "EPA Registration No.,11 or "EPA
Reg. No." The registration number must be set in type of a
size and style similar to other print on that part of the
label on which it appears and must run parallel to it. The
registration number and the required identifying phrase must
not appear in such a manner as to suggest or imply
recommendation or endorsement of the product by the Agency.
[40 CFR 156.10(6)]
Item 5. EPA ESTABLISHMENT NUMBER - The EPA
establishment number, preceded by the phrase "EPA Est." is
the final establishment at which the product was produced,
and may appear in any suitable location on the label or
immediate container. It must also appear on the wrapper or
outside container of the package if the EPA establishment
number on the immediate container cannot be clearly read
through such wrapper or container. [40 CFR 156.10(f)]
66
-------
SUMMARY-2
Item 6A. INGREDIENTS STATEMENT - An ingredients
statement is required on the front panel. The ingredients
statement must contain the name and percentage by weight of
each, active ingredient and the total percentage by weight of
all inert ingredients. The preferred location is immediately
below the product name. The ingredients statement must run
parallel with, and be clearly distinguished from, other text
on the panel. It must not be placed in the body of other
text. [40 CFR 156.10(g)]
Item 6B. POUNDS PER GALLON STATEMENT - For liquid
agricul- tural formulations, the pounds per gallon of active
ingredient must be indicated on the label.
Item 7. FRONT LABEL PRECAUTIONARY STATEMENTS - Front
panel precautionary statements must be grouped together,
preferably within a block outline. The table below shows the
minimum type size requirements for various size labels.
Size of Label Signal Word "Keep Out of Reach
on Front Panel Minimum Type Size of Children"
in Square Inches All Capitals Minimum Type Size
5 and under 6 point 6 point
above 5 to 10 10 point 6 point
above 10 to 15 12 point 8 point
above 15 to 30 14 point 10 point
over 30 18 point 12 point
Item 7A. CHILD HAZARD WARNING STATEMENT - The statement
"Keep Out of Reach of Children" must be located on the front
panel above the signal word except where contact with
children during distribution or use is unlikely.
[40 CFR 156.10(h)(1)(ii)]
Item -7B. SIGNAL WORD - The signal word (DANGER,
WARNING, or CAUTION) is required on the front panel
immediately below the child hazard warning statement.
[40CFR 156.lO(h)(l)(i)].
Item 7C. SKULL 5, CROSSBONES AND WORD "POISON" - On
products assigned a toxicity Category I on the basis of oral,
dermal, or inhalation toxicity, the word "Poison" shall
appear on the label in red on a background of distinctly
contrasting color and the skull and crossbones shall appear
in immediate proximity to the word POISON.
[40 CFR 156.10(h)(1)(i)].
Item 7D. STATEMENT OF PRACTICAL TREATMENT - A statement
of practical treatment (first aid or other) shall appear on
the label of pesticide products in toxicity Categories I, II,
and III. [40 CFR 156.10(h)(1)(iii)]
67
-------
SUMMARY- 3
Item 7E. REFERRAL STATEMENT - The statement "see Side
(or Back) Panel for Additional Precautionary Statements" is
required on the front panel for all products, unless all
required precautionary statements appear on the front panel.
[40 CFR I56.10(h) (l) (iii) ].
Item 8. SIDE/BACK PANEL PRECAUTIONARY LABELING - The
precautionary statements listed below must appear together on
the label under the heading "PRECAUTIONARY STATEMENTS." The
preferred location is at the top of the side or back panel
preceding the directions for use, and it is preferred that
these statements be surrounded by a block outline. Each of
the three hazard warning statements must be headed by the
appropriate hazard title. [40 CFR 156. 10 (h) (2) ]
Item 8A. HAZARD TO HUMANS AND DOMESTIC ANIMALS - Where
a hazard exists to humans or domestic animals, precautionary
statements are required indicating the particular hazard, the
route(s) of exposure and the precautions to be taken to avoid
accident, injury or damage. [40 CFR 156. 10 (h) ( 2) ( i ) ]
Item 8B. ENVIRONMENTAL HAZARD - Where a hazard exists
to non-target organisms excluding humans and domestic
animals, precautionary statements are required stating the
nature of the hazard and the appropriate precautions to avoid
potential accident, injury, or damage. [40 CFR
Item 8C. PHYSICAL OR CHEMICAL HAZARD - FLAMMABILITY
Precautionary statements relating to flammability of a
product are required to appear on the label if it meets the
criteria in the PHYS/CHEM Labeling Appendix. The requirement
is based on the results of the flashpoint determinations and
flame extension tests required to be submitted for all
products. These statements are to be located in the
side/back panel precautionary statements section, preceded by
the heading "Physical/Chemical Hazards." Note that no signal
word is used in conjunction with the flammability statements.
Item 9A. RESTRICTED USE CLASSIFICATION - FIFRA S6C .
3(d) requires that all pesticide formulations/uses be
classified for either general or restricted use. Products
classified for restricted use may be limited to use by
certified applicators or persons under their direct
supervision (or may be subject to ether restrictions that may
be imposed by regulation) .
In the Registration Standard, the Agency has (1)
indicated certain formulations/uses are to be restricted
(Section IV indicates why the product has been classified for
restricted use); or (2) reserved any classification decision
until appropriate data are submitted.
68
-------
SUMMARY- 4
The Regulatory Position and Rationale states whether
products containing this active ingredient are classified for
restricted use. If they are restricted the draft label(s)
submitted to the Agency as part of your application must
reflect this determination (see below).
If you do not believe that your product should be
classified for restricted use, you must submit any
information and rationale with your application for
reregistration. During the Agency's review of your
application, your proposed classification determination will
be evaluated in accordance with the provisions of 40 CFR
162.11(c). You will be notified of the Agency's
classification decision.
Classification eing Reuirements
If your product has been classified for restricted use,
the following label requirements apply:
1. All uses restricted.
a. The statement "Restricted Use Pesticide" must
appear at the top of the front panel of the label.
The statement must be set in type of the same
minimum size as required for human hazard signal
word (see table in 40 CFR 156. 10(h) UMiv) .
b. Directly below this statement on the front
panel , a summary statement of the terms of
restriction must appear (including the reasons for
restriction if specified in Section I). If use is
restricted to certified applicators, the following
statement is required: "For retail sale to and use
only by Certified Applicators or persons under
their direct supervision and only for those uses
covered by the Certified Applicator's
Certification."
2. Some but not all uses restricted. If the
Regulatory Position and Rationale states that some uses are
classified for restricted use, and some are unclassified,
several courses of action are available:
a. You may label the product for Restricted use.
If you do so, you may include on the label uses
that are unrestricted, but you may not distinguish
them on the label as being unrestricted.
69
-------
SUMMARY-5
b. You may delete all restricted uses from your
label and submit draft labeling bearing only
unrestricted uses.
c. You may "split" your registration, i.e.,
register two separate products with identical
formulations, one bearing only unrestricted uses,
and the other bearing restricted uses. To do so,
submit two applications for reregistration, each
containing all forms and necessary labels. Both
applications should be submitted simultaneously.
Note that the products will be assigned separate
registration numbers.
Item 9B. MISUSE STATEMENT - All products must bear the
misuse statement, "It is a violation of Federal law to use
this product in a manner inconsistent with its labeling."
This statement appears at the beginning of the directions.for
use, directly beneath the heading of that section.
Item 10A. REENTRY STATEMENT - If a reentry interval has
been established by the Agency, it must be included on the
label. Additional worker protection statements may be
required in accordance with PR Notice 83-2, March 29, 1983.
70
-------
SUMMARY- 6
Item 10B. STORAGE AND DISPOSAL BLOCK - All labels are
required to bear storage and disposal statements. These
statements are developed for specific containers, sizes, and
chemical content. These instructions must be grouped and
appear under the heading "Storage and Disposal" in the
directions for use. This heading must be set in the same
type sizes as required for the child hazard warning. Refer
to Appendix II, STOR, PEST/DIS, and CONT/DIS to determine the
storage and disposal instructions appropriate for your
products.
Item IOC. DIRECTIONS FOR USE - Directions for use must
be stated in terms which can be easily read and understood by
the average person likely tot sue or to supervise the use of
the pesticide. When followed, directions must be adequate to
protect the public from fraud and from personal- injury and to
prevent unreasonable adverse effects on the environment. [40
CFR 156.10]
COLLATERAL
Bulletins, leaflets, circulars, brochures, data sheets,
flyers, or other written or graphic printed matter which is
referred to on the label or which is to accompany the product
are termed collateral labeling. Such labeling may not bear
claims or representations that differ in substance from those
accepted in connection with registration of the product. It
should be made part of the response to this notice and
submitted for review.
71
-------
SUlfftRY-7
IABEUNG REQUIREMENTS OF THE FIFRA, AS AMENDED
ITEM
1
2
3
4
5
6A
6B
7
7A
7B
TARFT. FLFWFNT
Product name
Company name
and address
Net contents
EPA Reg. NO.
EFA Est. No.
Ingredients
statement
Pounds/gallon
statement
Front panel
precautionary
statements
Keep Out of Reach
of Children
(Child hazard
warnina)
Signal word
APPLICABILITY
OF REOJIREMEOT
All products
All products
All products
All products
All products
All products
Liquid products
where dosage is
given as Ibs.
ai/unit area
All products
All products
All products
PLATW'Ttfr
RE^n^FD
Front panel
None
None
None
None
Front panel
Front panel
Front panel
Front panel
Front panel
i
(^f T^RF^
PREt>;»RFn
Center front
oanel
Bottom front
panel or end
of label text
Bottom front
panel or end
of label text
Front panel
Front panel
immediately
before or
following
Rea. No.
Immediately
following
prryhirt name
Directly below
the main
ingredients
statement
Above signal
word
Imnediately
below child
hazard
warpina
If registrant
be qualified
"Distributed
May be in met
U.S. units.
Must be in si
parallel to o
May appear on
the label.
Text must run
on the panel.
All front pan
must be group
blocked.
Note type siz
Note type siz
72
-------
SOVMftRY-8
TARET.TKT; RETHTREMENTS OF THE FIFRA. AS AMENDED (cont'
ITEM
7C
7D
7E
8
8A
8B
T^RFJ, TjUffB'!^
Skull & cross-
bones and word
POISCN (in red)
Statement of
Practical
Treatment or
First Aid
Referral
statement
Side/back panel
precautionary
statements
Hazards to
humans and
domestic
flnjjpaj-3
Environmental
ft^Pl*
APPLICABILITY
(ft RECmREMENT
All products
which are Cat-
egory I based
on oral, der-
mal, or inhala-
tion toxicitv
All products
in Categories
I, II, and III
All products
where pre-
cautionary
labeling
appears on
other than
front oanel
All products
All products
in Categories
I, II, and III
All products
prArTT/iHJM1 r
REOtriRED
Front panel
Category I;
Front panel
unless refer-
ral statement
is used.
Others:
Grouped with
side panel
precautionary
statements.
Front panel
None
None
None
rrj ranFT.
f KEfc'K^WhJ )
Both in close
proximity to
signal word
Front panel
for all
Top or side
of back panel
preceding
directions
for use
Same as above
Same as above
Must be group
8A, 8B, and 8
Most be prece
word.
1
Environmental
caution where
73
-------
sovraRY-9
TARFT.T]V1G REQUIREMENTS OF THE t'lb'KA. AS AMENDED (cont*
| APPLICABILITY
PLACEMENT CM LABEL
8C
9A
9B
10A
10B
IOC
Physical or
chemical
hazards
Restricted
block
Misuse
statement
Reentry
statement
Storage and
disposal block
0
Directions
for use
IAII pressurized
* I products , others
jwith flash
j points under
llSO^F
(All restricted
I products
1
(All products
1
1
1
|PR Notice 83-2
|or as determined
bv the Aaencv
|A11 products
1
1
1
1
|A11 products
1
None
Top center
of front
panel
Immediately
following
heading of
directions
for use
In the
directions
for use
In the
directions
for use
None
Same as above
Preferably
blocked
Immediately
after misuse
statement
Immediately
before
specific
directions
for use or
at the end of
directions
for use
None
Refer to Appe
PHYS/CHEM
Includes a st
restriction.
PESTICIDE" mu
Jj^qn^l word.
Required stat
"It is a v
to use th
inconsist
Must be set a
guishable fro
for use.
Refer to Appe
CCNT/DIS, and
information a
May be in met
74
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PHYSICAL-CHEMICAL HAZARDS
Criteria
I. Pressurized Containers
A.
Flashpoint at or below
20°F; or if there is a
flashback at any valve
opening.
B.
Flashpoint above 20°F
and not over 80°F; or
if the flame extension
is more than 18 inches
long at a distance of
6 inches from the
valve opening.
ALL OTHER PRESSURIZED
CONTAINERS
II. Non-Pressurized Containers
A. Flashpoint at or below
20°F.
B. Flashpoint above 20°F
and not over 80°F.
C. Flashpoint over 80°F
and not over 150°F.
D. Flashpoint above
150°F.
Required Label Statement
Extremely flammable.
Contents under pressure.
Keep away from fire,
sparks, and heated
surfaces. Do not
puncture or incinerate
container. Exposure to
temperatures above 130°F
may cause bursting.
Flammable. Contents
under pressure. Keep
away from heat, sparks,
and flame. Do not
puncture or incinerate
container. Exposure to
temperatures above 130°F
may cause bursting.
Contents under pressure.
Do not use or store near
heat or open flame. Do
not puncture or incine-
rate container. Exposure
to temperatures above
130°F may cause bursting.
Extremely flammable.
Keep away from fire,
sparks, and heated
surfaces.
Flammable, keep away
from heat and open flame.
Do not use or store near
heat and open flame.
None required.
75
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STOR-1
STORAGE INSTRUCTIONS FOR PESTICIDES
Heading;
All products are required to bear specific label instructions
about storage and disposal. Storage and disposal instructions
must be grouped together in the directions for use portion of the
label under the heading STORAGE AND DISPOSAL. Products intended
solely for domestic use need not include the heading "STORAGE AND
DISPOSAL."
Storage Instructions:
All product labels are required to have appropriate storage
instructions. Specific storage instructions are not prescribed.
Each registrant must develop his own storage instructions,
considering, when applicable, the following factors:
1. Conditions of storage that might alter the composition or
usefulness of the pesticide. Examples could be temperature
extremes, excessive moisture or humidity, heat, sunlight,
friction, or contaminating substances or media.
2. Physical requirements of storage which might adversely
affect the container of the product and its ability to
continue to function properly. Requirements might include
positioning of the container in storage, storage or damage
due to stacking, penetration of moisture, and ability to
withstand shock or friction.
3. Specifications for handling the pesticide container,
including movement of container1 within the storage area,
proper opening and closing procedures (particularly for
opened containers), and measures to minimize exposure while
opening or closing container.
4. Instructions on what to do if the container is damaged in
any way, or if the pesticide is leaking or has been spilled,
and precautions to minimize exposure if damage occurs.
5. General precautions concerning locked storage, storage in
original container only, and separation of pesticides during
storage to prevent cross-contamination of other pesticides,
fertilizer, food, and feed.
6. General storage instructions for household products should
emphasize storage in original container and placement in
locked storage areas.
76
-------
PEST/DIS-1
PESTICIDE DISPOSAL INSTRUCTIONS
The label of all products, except those intended solely for
domestic use, must bear explicit instructions about pesticide
disposal. The statements listed below contain the exact wording
that must appear on the label of these products:
1. The labels of all products, except domestic use, must
contain the statement, "Do not contaminate water, food, or feed
by storage or disposal."
2. Except those products intended solely for domestic use, the
labels of all products that contain active ingredients that are
Acute Hazardous Wastes or are assigned to Toxicity Category I on
the basis of oral or dermal toxicity, or Toxicity Category I or
II on the basis of acute inhalation toxicity must bear the
following pesticide disposal statement:
"Pesticide wastes are acutely hazardous. Improper disposal
of excess pesticide, spray mixture, or rinsate is a
violation of Federal Law. If these wastes cannot be
disposed of by use according to label instructions, contact
your State Pesticide or Environmental Control Agency or the
Hazardous Waste representative at the nearest EPA Regional
Office for guidance."
3. The labels of all products, except those intended for
domestic use, containing active or inert ingredients that are
Toxic Hazardous Wastes or meet any of the criteria in 40 CFR 261,
Subpart C for a hazardous waste must bear the following pesticide
disposal statement:
"Pesticide wastes are toxic. Improper disposal of excess
pesticide, spray mixture, or rinsate is a violation of
Federal Law. If these wastes cannot be disposed of by use
according to label instructions, contact your State
Pesticide or Environmental Control Agency, or the Hazardous
Waste representative at the nearest EPA Regional Office for
guidance."
4. Labels for all other products, except those intended for
domestic use, must bear the following pesticide disposal
statement:
"Wastes resulting from the use of this product may be
disposed of on site or at an approved waste disposal
facility."
5. Products intended for domestic use only must bear the
following disposal statement: "Securely wrap original container
in several layers of newspaper and discard in trash."
77
-------
CONT/DIS-1
CONTAINER DISPOSAL INSTRUCTIONS
The label of each product must bear container disposal
instructions appropriate to the type of container.
1. Domestic use products must bear one of the following
container disposal statements:
Container Type
statement
iNon-aerosol products |Do not reuse container (bottle, can, jar).
((bottles, cans. Jars)I Rinse thoroughly before discardina in trash
|Non-aerosol products |Do not reuse bag.
I (baas)
Discard bag in trash.
(Aerosol products
I •
Replace cap and discard containers in
trash. Do not incinerate or puncture.
2. All other products must bear container disposal
instructions, based on container type, listed below:
Container Type
Statement
Metal
containers
(non- aerosol)
Plastic containers
•
Glass containers
Fiber drums
with liners
'
-
Paper and
plastic bags
Compressed gas
cylinders
V Manufacturer may re]
and how fiber drum i
Triple rinse (or equivalent). Then offer
for recycling or reconditioning, or puncture
and dispose of in a sanitary landfill, or by|
other procedures approved by state and local
authorities.
Triple rinse (or equivalent). Then offer
for recycling or reconditioning, or puncture
and dispose of in a sanitary landfill, or
incineration, or, if allowed by state and
local authorities, by burning. If burned,
stay out of smoke.
Triple rinse (or equivalent) . Then dispose
of in a sanitary landfill or by other
approved state and local procedures .
Completely empty liner by shaking and
tapping sides and bottom to loosen clinging
particles. Empty residue into application
equipment. Then dispose of liner in a
sanitary landfill or by incineration if
allowed by state and local authorities.
If drum is contaminated and cannot be
reused^/, dispose of in the same manner.
Completely empty bag into application
equipment. Then dispose of empty bag in
a sanitary landfill or by incineration,
or, if allowed by State and local
authorities, by burning. If burned, stay
out of smoke.
Return empty cylinder for reuse (or
similar wordina) .
place this phrase with one indicating whether
nay be reused.
78
-------
III. BIBLIOGRAPHY APPENDICES
-------
Guide to Use of This Bibliography
1. CONTENT OF BIBLIOGRAPHY. This bibliography contains
citations of all studies considered relevant by EPA in arriving at
the positions and conclusions stated elsewhere in the Standard'
Primary sources for studies in this bibliography have been the
body of data submitted to EPA and its predecessor agencies in
support of past regulatory decisions. Selections from other
sources including the published literature, in those instances
where they have been considered, will be included.
2. UNITS OF ENTRY. The unit of entry in this bibliography is
called a "study." In the case of published materials, this
corresponds closely to an article. In the case of unpublished
materials submitted to the Agency, the Agency has sought to
identify documents at a level parallel to the published article
from within the typically larger volumes in which they were
submitted. The resulting "studies" generally have a distinct
title (or at least a single subject), can stand alone for purposes
of review, and can be described with a conventional bibliographic
citation. The Agency has attempted also to unite basic documents
and commentaries upon them, treating them as a single study.
3. IDENTIFICATION OF ENTRIES. The entries in this bibliography
are sorted numerically by" "Master Record Identifier," or MRID,
number. This number is unique to the citation, and should be used
at any time specific reference is required. It is not related to
the six-digit "Accession Number" which has been used to identify
volumes of submitted studies; see paragraph 4(d)(4) below for a
further explanation. In a few cases, entries added to the
bibliography late in the review may be preceded by a nine-
character temporary identifier. These entries are listed after
all MRID entries. This temporary identifier number is also to be
used whenever specific reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier
(MRID), each entry consists of a citation containing standard
elements followed, in the case of material submitted to EPA, by a
description of the earliest known submission. Bibliographic
conventions used reflect the standards of the American National
Standards Institute (ANSI), expanded to provide for certain
special needs.
a. Author. Whenever the Agency could confidently
identify one, the Agency has chosen to show a
personal author. When no individual was
identified, the Agency has shown an identifiable
laboratory or testing facility as author. As a
last resort, the Agency has shown the first
submitter as author.
8C
-------
b. Document Date. When the date appears as four
digits with no question marks, the Agency took it
directly from the document. When a four-digit
date is followed by a question mark, the
bibliographer deduced the date from evidence in
the document. When the date appears as (19??),
the Agency was unable to determine or estimate the
date of the document.
c. Title. In some cases, it has been necessary for
Agency bibliographers to create or enhance a
document title. Any such editorial insertions are
contained between square brackets.
d. Trailing Parentheses. For studies submitted to
the Agency in the past, the trailing parentheses
include (in addition to any self-explanatory text)
the 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, following the phrase "submitted
by." When authorship is defaulted to the
submitter, this element is omitted.
(4) Volume Identification (Accession Numbers).
The final element in the trailing parentheses
identifies the EPA accession number of the
volume in which the original submission of
the study appears. The six-digit accession
number follows the symbol "CDL," standing for
"Company Data Library." This accession
number is in turn followed by an alphabetic
suffix which shows the relative position of
the study within the volume. For example,
within accession number 123456, the first
study would be 123456-A; the second, 123456-
B; the 26th, 123456-Z; and the 27th, 123456-
AA.
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Oxytetracycline Standard
MRID Citation
00039917 California, Department of Food and Agriculture (1972) Residue Re-
sults: [Terramycin. (Unpublished study; CDL:093760-D)
00049096 Pfipharmecs (1973) [Residue Study of Terramycin in Pears], (Compi-
lation; unpublished study received Mar 25, 1974 under unknown
admin, no.; CDL:223547-G)
00058254 Pfizer, Incorporated (19??) Microbiological Agar Diffusion Assay
for Oxytetracycline in Fruit Extract: Report No. 0 12.14. Un-
dated method. (Unpublished study received Apr 1, 1975 under
5E1611; submitted by California, Dept. of Food & Agriculture,
Sacramento, Calif.; CDL:095168-G)
00064602 Bly, B. (1980) Letter sent to Eugene Wilson dated Aug 27, 1980
[Residues of terramycin in peaches]. (California, Dept. of
Food and Agriculture; unpublished study; CDL:243793-A)
00081151 Wood, R.T. (1977) Letter sent to V.J. Carroll dated Sep 13, 1977:
Oxytetracycline stability in fresh peach and pear extracts (QCSA
71886). (Unpublished study received on unknown date under
6E1700; prepared by Biological Control Laboratories, submitted
by Interregional Research Project No. 4, New Brunswick, N.J.;
CDL:097771-A)
00081153 Carroll, V.J. (1975) Determination of Terramycin (Oxytetracycline)
Residues in Peaches. Includes undated standard test procedure
no. 0 12.4. (Unpublished study received Oct 31, 1975 under
6E1700; prepared by Pfizer, Inc., submitted by Interregional
Research Project No. 4, New Brunswick, N.J.; CDL:097771-G)
00081266 Carroll, V.J. (1974) Determination of Terramycin (Oxytetracycline)
Residues in Pears. (California, Dept. of Food & Agriculture;
unpublished study; CDL:095187-D)
00093605 Chas. Pfizer & Company (1966) [Determination of Terramycin Residues
in Peaches]. (Compilation; unpublished study received Mar 20,
1967 under 7G0584; CDL:090748-D)
00132391 Wolkowski-Tyl, R.; Jones-Price, C.; Ledoux, T.; et al. (1983) Tera-
tologic Evaluation of Oxytetracycline Hydrochloride (CAS
2058-46-0) in CD Rats: RTI Project No. 31U-2077. (Unpublished
study received Oct 26, 1983 under 1007-79; prepared by Research
Triangle Institute, submitted by Pfipharmecs Div., Pfizer, Inc.,
New York, NY; CDL:251603-A)
-------
OFFICE OF PESTICIDE PROGRAMS
REGISTRATION STANDARD BIBLIOGRAPHY
Citations Considered to be Part of the Data Base Supporting
Registrations Under the Oxytet racyc line Standar'd
MRID Citation
00132392 Wolkowski-Tyl, R.; Jones-Price, C,; Ledoux, T.; et al (1982)
Teratologic Evaluation of Oxytetracycline Hydrochloride
(CAS 2058-46-0) in CD-I mice: By RTP and NCI for Toxicological
Research, Perinatal and Postnatal Evaluation Branch. Jefferson,
AK: NCTR. (Contract NO. 222-80-2031 (C); study code no. Mi81-OX;
available from NTIS, Springfield, VA 22151; also in unpublished
submission received October 26, 1983 under 1007-79; submitted by
Pfipharmecs Div., Pfizer, Inc., New York, NY; CDL:251603-F)
00135300 Interregional Research Project No. 4 (1977) The Results of Tests on
the Amount of Terramycin Remaining in or on Peaches Including
Description of the Analtytical Method Used. (Compilation; un-
published study received Dec 3, 1976 under 7E1894; CDL:097772-A)
00159856 US Public Health Service (1986) Toxicology and Carcinogenesis
Studies of Oxytetracycline Hydrochloride (Cas No.' 2058-46-0) in
F344/N Rats and B6C3F1 Mice: (Feed Studies): Technical Report
Series No. 315: :NIH Publication No. 86-2571:: Draft. Unpub-
lished study prepared in cooperation with Physiological Research
Laboratories and Midwest Research Institute and others. 194 p.
00162260 Beutel, J. (1980) Letter sent to V. Carroll dated Nov 3, 1980:
:Summary of procedure used to secure the Terramycin residue sam-
ples from 12 year old Bartlett pear trees in the University of
California orchards at Davis, California, during the 1980 sea-
son:. Prepared by Univ. of California, Pomology Dept. 11 p.
40840101 Rollins, L.; Gaines, S.; et al. (1975) Animal Model for Determining
the No-Effect Level of Antimicrobial Drug on Drug Resistance in
the Loctose-Fermenting Enteric Flora. Antimicrobial Agents and
Chemotherapy, p. 661-665.
8
-------
IV. FORMS APPENDICES
-------
EPA Form 8580-1
OMB Approval No. 2070-0057
Expires 11/30/89
FIFHA SECTION 3« rtquirtmtnt to tubmit "jentrie" dttt impottd by tht FIFHA action 3(C)(2)(B) nonet conttmtd m ih« refcrtnctd
Guidtnct Oocumtnt. I *m rtspondmg m tht following manner:
C 1. I will tubmit dttt in t timtty mtnntr to maty tht following rtquirtmtnii If tfit tnt proctdurn I will u« dtviftc from (or tri not
totcifwd m) tht Rtginrttion Guidtlintt or tnt Protoeoll contnntd in tht Rtponi of Eiptn Groupt to tnt Ch«mc*i Group, OECO
Chtmicali Tttting Progrtmmt, I tnciow tht protocol! thtt I will \im:
Attach separate page with a list of the data requirements your
company agrees to satisfy.
O 2, I htvt tnnrtd into an tgrttmtnt with ont or mort ethtr rtgotnntt undtr FIFRA ttction 3(C)(2)(8)lii) to atiity Cit following dtta
rtquinmtnn. Tht ttm. tnd tny rtquirtd protocolt. will bt tubmmtd to EPA by:
NAME OF OTHER REGISTRANT
Attach list of data requirements
O 3. I tnctOM t compltttd "Ctrtificttien of Antmpt to Enttr Into in Agrttmtnt with Othtr Rtcutrenu for Otvtlopmtnt of Otu" with
rtsptct to tht following dan nquirtmtnu:
. I rtquai tntt you tmtnd my rtgwtntion by dtitting tht following uati (thit option * not tvultolt to acplicants for ntw proflucts):
O 5. I rtqutn voluntary ctnctllttion of tht rtgistration of thit product. (Thit option i* not avtUtblt to applictnu for n*w product!.)
REGISTRANT-S AUTHORIZED REPRESENTATIVE
SIGNATURE
DATE
-------
EPA Form 8580-6
OMB Approval No. 2070-0057
Expires 11/30/89
(To QiMlify. artitvALL four ittmtl
CERTIFICATION OF ATTEMPT TO ENTER
INTO AN AGREEMENT WITH OTHER REGISTRANTS
FOR DEVELOPMENT OF DATA
1. I am duly authorized to represent the following firm(s) who «re subject to the require-
ment! of i Notice under FIFRA Section 3(cl(2l(8) contained in a Guidance Document
to submit data concerning the active ingredient:
GUIDANCE DOCUMENT DATE
ACTIVE INGREDIENT
NAME Of FWM
EPA COMPANY NUMBER
(This firm or group of firm* is referred to below as "my firm".)
2. My firm is willing to develop and submit the data as required by that Notice, if necessary. However, my firm would prefer to enter
into an agreement with one or more other registrants to develop jointly, or to share in the cost of developing, the following required
items or data:
3. My firm has offered in writing to enter into such an aereement. Copies of the offers art trtachtd. That offer was imvocablt and included an ottir w b«
bound by an ertrtmion daemon under FIFRA Section 3(e)(2)(B)(iii) H final agreement on all arms eould not be reached otherwise. This offtr was made
to thi following firrn(t) on tht following dated):
NAME Of PIMM
OATEOFOFFE*
However, none of those firm(s) accepted my offer.
4. My firm requests that EPA not suspend the registration(s) of my firm's product(s). if any of the firms named in paragraph (3) above
have agreed to submit the data lined in paragraph (2) above in accordance with the Notice. I understand EPA will promptly inform
me whether my firm mun submit data to avoid suspension of its registration(s) under FIFRA Section 3(c)(2)(B). (This statement
does not apply to applicants for new producti.) I give EPA permission to disclose this statement upon request.
TYPED NAME
SIGNATURE
DATE
-------
US environmental p'raiecson Agency Registration oianaara :or:
Wasnmgton, OC 20460
V^ERA, Product Specific
Data Renort
Registration
Guideline No.
Sec. 153.120
Product
Chemistry
81-1
61-2
81-3
82-1
82-2
82-3
83-2 .
530
53-*
83-5
834
83-7
83-a
83-9
83-10
83-11
83-12
83.13
83-14
53.13
53-18
83.17
53-18
83-19
83-20 J
83-21
Sec 158.135
Toxicology
81-1
81-2
81-3
8l-»
81 -S
81-8
Testing not
required for my
product listed
Name of Test aoove
(Cbacit fietowl
Identity of Ingredients
crA Registration Numoer
1 am complying witn
Cata Psouirements 3v -
Gting MR 10 No.
SuOmitQng Cata
iCAee* Oe/owl
Statement of comoosition
Discussion of formation of ingredients
P*«iimmarv anaivsts
Certification of limits
Analytical metnoos for enforcement limits
Color
Pnvstcal state
Cdor
Meiting gotnt
Soiling oomt
Censitv. auik-densitv. or soeofie gravity
SoluOilitv
Vaoor oressure
Dissociation constant
Form Aooroved
CMB *207C-CCS7
Expires 11-30-59
(For EPA Use
Only)
Accession
numcers
assiqnea
I
Cetanol /water oarntton coefficient
OM
Siaoiiify _
Oxidizing/reducing reeenon
Rammaoility
Exoiooaoiiifv |
Storage naoilify 1
Viseositv I
MfSaoilitV
Corrosion Characteristics
Oielectnc breakdown voltage
Acute oral toncity. rat
Acute dermal toiictty. raoort '
Acute innalarion toxicrty. rat
Pnmary eye irritation, raoort
Pfimary daimal imtaoon 1
Cermai senssttiatioti r 1
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 Nam* and Tide Signature
Oa»
EPA Form »5aO-» (He*. 5-U) Previous ediaon ie ootoiew.
87
-------
CMB Approval No. 2070-005
Expiration Date 11/30/89
GENERIC DATA EXEMPTICN STATEMENT
EFA Product Registration Number:
Registrant's Name and Address:
As an authorized representative of the registrant of the product identified above, I
certify that:
(1) I have read and am familiar with the terms of the Notice from EFA dated
concerning a requirement for submission of "generic" data on the active
ingredient named under FIFRA Section 3(c) (2) (B).
(2) My firm requests that EPA not suspend the registration of our product, despite
our lack of intent to submit the generic data in question, on the grounds that the product
contains the active ingredient solely as the result of the incorporation into the product
of another product which contains that active ingredient, which is registered under FIFRA,
Section 3, and which is purchased by us from another producer.
(3) An accurate confidental Statement of Formula (CSF) for the above-identified
product is attached to this statement. That formula statement indicates, by company name
registration number, and product name, the source of the subject active ingredient in my
firm's product, or
Hie CSF dated on file with ETA is complete, current and .accurate an
contains the information requested on the current CSF Form 8570-4. The registered
source(s) of the above named active ingredient in my prcduct(s) is/are .
and their registration number(s) is/are .
My firm will apply for an amendment to the registration prior to changing the source
of the active ingredient in our product.
(4) I understand, and agree on behalf of my firm, that if at any time any portion 01
this Statement is no longer true, or if my firm fails to comply with the undertakings made
in this Statement, my firm's product's registration may be suspended under FIFRA Section
3(c)(2)(B).
(5) I further understand that if my firm is granted a generic data exemption for th<
product, my firm relies on the efforts of other persons to provide the Agency with the
required generic data. If the registrant(s) who have committed to generate and submit tf
required data fail to take appropriate steps to meet requirements or are no longer in
compliance with this Notice's data requirements, the Agency will consider that both they
and my firm are not in compliance and will normally initiate proceedings to suspend the
registrations of my firm's product (s) and their product (s), unless my firm commits to
submit and submits the required data in the specified time frame. I understand that, in
such cases, the Agency generally will not grant a time extension for submitting the data.
Registrant's authorized representative:.
(Signature
Dated:
(Typed)
EPA Form 8570-27
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