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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                 Ciiicii       --!'*"'Jl floor
   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.
                    7

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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.
                            8

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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
                       10

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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.
                      11

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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.
                           12

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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.
                         13

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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.
                            14

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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.
                         15

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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
                          16

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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.
                      17

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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.
                         18

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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.
                               19

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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.
                          20

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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;
                         21

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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.
                             22

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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.
                           23

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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.
                            24

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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.
                           25

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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
                           26

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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:
                           27

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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.
                          28

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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.
                           29

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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
                           30

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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.
                             31

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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

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    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

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        a.  Generic data exemption Statement (EPA Form 8580-3),
            if applicable, or the FIFRA Section 3(c)(2)(B)  Summary
            Sheet, 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

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 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

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I.  DATA APPENDICES
    36

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                            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

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                            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

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                            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

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                            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

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                                                       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

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                                                        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

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                                                          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.

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                                                       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
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                                                            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

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                                                             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.)

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II.   LABELING APPENDICES
             65

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                          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

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                          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

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                          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

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                          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

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                          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

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                          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

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                  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

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                  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

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                             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

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                            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

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                             CONT/DIS-1

                   CONTAINER DISPOSAL INSTRUCTIONS

     The label of each product must bear container disposal
instructions appropriate to the type of container.

     1.     Domestic use products must bear one of the following
container disposal statements:
Container Type
                   statement
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

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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

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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.

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                         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)

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                          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

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IV.      FORMS APPENDICES

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         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

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          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

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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

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                                                                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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