United States
Environmental Protection
Agency
Office of
Pesticides and Toxic Substances
Washington DC 20460
September 1980
Pesticides
               Avitirol
Pesticide  Registration
Standard

-------
           4-Aminopyridine

   Pesticide Registration Standard
 Jane Schwemley, Project Manager (SPRD)
 Charlotte Blalock, Chemist (HED)
 Henry Appleton, Environmental Chemist (HED)
 Lionel Richardson, Environmental Chemist (HED)
 Roland Gessart, Toxicologist (HED)
 R.W. Cook, Residue Chemist (HED)
 Bill Jacobs, Product Manager (RD)
          Acknowledgements

  Jerry Moore, Section Head (SPRD)
  Juanita Wills, Section Head (SPRD)
  Mary Wyman, Project Manager (SPRD)
             September, 1980

Office of Pesticides and Toxic Substances
     Environmental Protection Agency
          401 !Mf Street, S.W.
        Washington, D.C.  204060

-------
                               TABLE OF CONTENTS

I.     How to Register Under a Registration Standard

            Organization of the Standard  ....	  1
            Purpose of the Standard  	  1
            Requirement to Re-register Under the Standard   	  3
            Product Specific Data and Generic Data  	  3
            Data Compensation Requirements Under FIFRA 3(c)(1)(D)   	  4
            Obtaining Data to Fill "Data Gaps",  FIFRA 3(c)(2)(B)  	  5
            Amendments to the Standard  	  5

II.    Regulatory Position

            Manufacturing-Use 4-Aminopyridine  	  8
            4-Aminopyridine Formulated Products  	 10

III.   Product Chemistry

            Introduction  	' 17
            Topical Discussions
                Chemical Identity	 17
                Manufacturing Process  	 18
                Percentages of Components in Pesticide Products  	 18
                Product Analytical Methods and Data  	 18
                Physical/Chemical Properties  	 18
            Disciplinary Review
                Chemistry Profile  	 20
                Generic Data Gaps  	 20
                Required Labeling  	 21
            Bibliography  	 22

IV.    Environmental Fate

            Use Profile  	 23
            Topical Discussions
                Physico-Chemical Transformation	 24
                Soil Metabolism	 24
                Microbial Metabolism  	 26
                Mobility  	 27
                Field Dissipation  	 29
                Accumulation  	 29
            Disciplinary Review
                Environmental Fate Profile		. 30
                Exposure Profile  	 31
            Bibliography  	 32

V.     Ecological Effects

            Topical Discussions
                Birds  	 3o
                Fish  	 35
                Wild Mammals  	,	 33
                Plants  	 33

-------
            Disciplinary Review
             .   Ecological Effects Profile	  38
                Ecological Effects Hazard Assessment   	  39
                Required Labeling  	  40
            Bibliography	  42
VI.    Toxicology
            Topical Discussions
                Acute Effects and Neurotoxicity  	  44
                Local Irritation	,	  46
                Sensitization  	  48
                Subchronic Effects and Neurotoxicity  	  48
                Chronic Effects  	  49
                Oncogenicity  	  49
                Reproduction  	49
                Teratology	  49
                Mutagenicity  	  50
                Pharmacological Effects  	  50
                Clinical Effects	  51
            Disciplinary Review
                Toxicology Profile	  53
                Toxicology Hazard Assessment  	  54
                Generic Data Gaps  	  55
                Required Labeling	  55
            Bibliography	  56
VII.   Residue Chemistry
            Topical Discussions
                Metabolism in Plants  	 	 59
                Metabolism in Animals	 60
                Analytical Methodology	 60
                Residue Data  	 62
            Disciplinary Review
                Residue Chemistry Profile  	 64
                Tolerance Reassessment  	 64
                Generic Data Gaps  	 64
                Required Labeling  	'. 65
            Bibliography  	 56
VIII.  Regulatory Rationale
            Data Gaps	,. 60
            Products to be Covered Under this Standard
                Manufacturing-Use Products  	 68
                Formulated Products  	 	 68
            Hazards to Wildlife
                Manufacturing-Use Products  	 69
                Formulated Products  	 	 53
            Hazards to Humans and Domestic Animals Formulated
                Formulated Products  	,	 70

            Appendix A
                Chemical Data Sheets  	 72
                                        11

-------
            Appendix B
                Summary of Label Ingredient Statements   	 73
IX.    Bibliography

-------
                            I.   HOW TO  REGISTER
                        UNDER  A REGISTRATION  STANDARD
Organization of the Standard
Purpose of the Standard
Requirement to Re-register Under  the Standard
"Product Specific" Data and "Generic" Data
Data Compensation Requirements under FIFRA  3(c)(1)(D)
Obtaining Data to Fill "Data Gaps"; FIFRA 3(c)(2)(B)
Amendments to the Standard
Organization of the Standard

    This first chapter explains the purpose of a Registration Standard and
summarizes the legal principles involved in registering or re-registering under
a Standard.  The second chapter sets forth the requirements that must be met  to
obtain or retain registration for products covered by this particular
Registration Standard.  In the remaining chapters, the Agency reviews the
available data by scientific discipline, discusses the Agency's concerns with
the identified potential hazards, and logically develops the conditions and
requirements that would reduce those hazards to acceptable levels.


Purpose or the Standard

    Section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA) provides that "no person in any State may distribute, sell, offer for
sale, hold for sale, ship, deliver for shipment, or receive (and having so
received) deliver or offer to deliver, to any person any pesticide which is not
registered with the Administrator [of EPA]."  To approve the registration of a
pesticide, the Administrator must find, pursuant to Section 3(c)(5) that:
    "(A) its composition is such as to warrant the proposed claims for it;
     (B) its labeling and other material required to be submitted comply with
         the requirements of this Act;
     (C) it will perform its intended function without unreasonable adverse
         effects on the environment; and
     (D) when used in accordance with widespread and commonly recognized
         practice it will not generally cause unreasonable adverse effects on
         the environment."
    In making these findings, the Agency reviews a wide range of data which
registrants are required to submit, and assesses the risks and benefits
associated with the use of the proposed pesticide.  But the established
approach to making these findings has been found to be defective on two counts:
    First, EPA and its predecessor agency, the United States Department of
Agriculture (USDA), routinely reviewed registration applications on a 'product
by product' basis, evaluating each product-specific application somewhat
independently.  In the review of products containing similar components, there
was little opportunity for a retrospective review of the full range of
pertinent data available in Agency files and in the public literature.  Thus
the 'product by product' approach was often inefficient and sometimes resulted
in inconsistent or incomplete regulatory judgments.

                                    - 1  -

-------
    Second, over the years, as a result of inevitable and continuing advances
in scientific knowledge, methodology, and policy, the data base for many
pesticides came to be considered inadequate by current scientific and
regulatory standards.  Given the long history of pesticide regulation in
several agencies, it is even likely that materials may have been lost from the
data files.  When EPA issued new requirements for registration in 1975  (40 CFR
162) and proposed new guidelines for hazard testing in 1978 (43 FR 29686, July
10, 1973 and 43 FR 37336, August 2, 1973), many products that had already been
registered for years were being sold and used without the sane assurances of
human and environmental safety as was being required for new products.  Because
of this inconsistency, Congress directed EPA to re-register all previously
registered products, so as to bring their registrations and their data bases
into compliance with current requirements [See FIFRA Section 3(g)L
    Facing the enormous job of re-reviewing and calling-in new data for the
approximately 35,000 current registrations,  and realizing the inefficiencies of
the 'product by product1 approach, the Agency decided that a new, more
effective method of review was needed.
    A new review procedure has been developed.  Under it, EPA publishes
docunents called Registration Standards, each of which discusses a particular
pesticide active ingredient.  Each Registration Standard summarizes all the
data available to the Agency on a particular active ingredient and its current
uses, and sets forth the Agency's comprehensive position on the conditions and
requirements for registration of all existing and future products which contain
that active ingredient.  These conditions and requirements, all of which must
be met to obtain or retain full registration or re-registration under Section
3(c)(5) of FIFRA, include the submission of needed scientific data which the
Agency does not now have, compliance with standards of toxicity, conposition,
labeling, and packaging, and satisfaction of the data compensation provisions
of FIFRA Section 3(c)(1)(D).
    The Standard will also serve as a tool for product classification.  As part
of the registration of a pesticide product,  EPA may classify each product for
"general use" or "restricted use" [FIFRA Section 3(d)].  A pesticide is
classified for "restricted use" when some special regulatory restriction is
needed to ensure against unreasonable adverse effects to man or the
environment.  Many such risks of unreasonable adverse effects can be lessened
if expressly-designed label precautions are strictly followed.  Thus the
special regulatory restriction for a "restricted use" pesticide is usually a
requirement that it be applied only by, or under the supervision of, an
applicator who has been certified by the State or Federal government as being
competent to use pesticides safely, responsibly, and in accordance with label
directions.  A restricted-use pesticide can  have other regulatory restrictions
[40 CFR 162.11(c)(5)] instead of, or in addition to, the certified applicator
requirement.  These other regulatory restrictions may include such actions as
seasonal or regional limitations on use, or a requirement for the monitoring of
residue levels after use.  A pesticide classified for "general use," or not
classified at all, is available for use by any individual who is in compliance
with State or local regulations.  The Registration Standard review compares
information about potential adverse effects of specific uses of the pesticide
with risk criteria listed in 40 CFR 162.11(c), and thereby determines whether a
product needs to be classified for "restricted use."  If the Standard does
classify a pesticide for "restricted use," this determination is stated in the
second chapter,

                                 - 2 -

-------
Requirement £o Re-register Under  the Standard

    FIFRA Section  3(g), as amended  in  1978, directs EPA to  re-register  all
currently registered products as  expeditiously as  possible.   Congress also
agreed that re-registration should  be accomplished by the use of  Registration
Standards.
    Each registrant of a currently  registered product to which  this  Standard
applies, and who wishes to continue to sell or distribute his product in
commerce, must apply for re-regisration.  His application must  contain  proposed
labeling that complies with this  Standard.
    EPA will issue a notice of intent to cancel the registration  of  any
currently registered product to which this Standard applies if  the registrant
fails to comply with the procedures for re-registration set forth in the
Guidance Package which accompanies  this Standard.


"Product Specific" Data and "Generic" Data

    In the course of developing this Standard, EPA has determined the types of
data needed for evaluation of the properties and effects of products to which
the Standard applies, in the disciplinary areas of Product  Chemistry,
Environmental Fate, Toxicology, Residue Chemistry, and Ecological Effects.
These determinations are based primarily on the data Guidelines proposed in
1978 (43 FR 29686, July 10, 1978, and 43 FR 37336, August 2,  1978), as applied
to the use patterns of the products to which this Standard applies.  Where it
appeared that data from a normally applicable Guidelines requirement was
actually unnecessary to evaluate  these products, the Standard indicates that
the requirement has been waived.  On the other hand, in some  cases studies not
required by the Guidelines may be needed because of the particular composition,
or use pattern of products the Standard covers;  if so, the Standard explains
the Agency's reasoning.  Data guidelines have not yet been proposed  for the
Residue Chemistry discipline, but the requirements for such data  have been in
effect for some time and are, the Agency believes, relatively familiar  to
registrants.  Data which we have  found are needed to evaluate the
registrability of some products covered by the Standard may not be needed for
the evaluation of other products, depending upon the composition, formulation
type, and intended uses of the product in question.  The Standard states which
data requirements apply to which product categories.  (See the second chapter.)
    The various kinds of data normally required for registration  of a pesticide
product can be divided into two basic groups:

    (A)  data that is "product specific," i.e., data that relates only to
         the properties or effects of a product with a particular composition
         (or a group of products  with closely similar composition); and
    (B)  "generic" data that pertains to the properties or effects of a
         particular ingredient, and thus is relevant to an evaluation of the
         risks and benefits of all products containing that ingredient  (or all
         such products having a certain use pattern), regardless  of any such
         product's unique composition.

    The Agency requires certain "product specific" data for each  product to
characterize the product's particular composition and physical/chemical
properties (Product Chemistry), and to characterize the product's acute
toxicity (which is a function of  its total composition).  The applicant for
registration or re-registration of any product, whether it  is a manufacturing-
use or end-use product, and without regard to its intended use  pattern, must

                            - 3 -

-------
 submit  or  cite  enough  of this  kind of data to allow EPA to evaluate the
 product.   For such purposes, "product specific" data on any product other than
 the  applicant's is irrelevant,  unless the other product is closely similar in
 'composition to  the applicant's.  (Where it has been found practicable to group
 similar products for purposes  of evaluating,  with a single set of tests, all
 products in the group,  the  Standard so indicates.)   "Product, specific" data on
 the  efficacy of particular  end-use products is also required where the exact
 formulation may affect efficacy and where failure of efficacy could cause
 public  health problems.
    .All other data needed to evaluate pesticide products concerns the
 properties or effects  of a  particular ingredient of products (normally a
 pesticidally active ingredient,  but in some cases a pesticidally inactive, or
 "inert," ingredient).   Some data in this "generic"  category are required to
 evaluate the properties  and effects of all products containing that ingredient
 [e.g.,  the acute LD-50 of the  active ingredient in its  technical or purer
 grade;  see proposed 40 CFR  I63.8l-1(a),  43 FR 37355].
     Other  "generic" .data are required to evaluate all products which both
 contain a  particular ingredient and are intended for certain uses (see,  e.g.,
 proposed 40 .CFR 163.82-1, 43 FR 37363,  which  requires subchronic oral testing
 of the  active ingredient with  respect to certain use patterns only).  Where a
 particular data requirement is  use-pattern dependent, it will apply to each
 end-use product which  is to be  labeled for that use pattern (except where such
 end-use product is formulated  from a registered manufacturing-use product
 permitting such formulations)  and to each manufacturing-use product with
 labeling that allows it  to  be used to make end-use  products with that use
 pattern.   Thus,  for example, a  subchronic oral dosing study is needed to
 evaluate the safety of any  manufacturing-use  product that legally could  be used
 to make an end-use, food-crop  pesticide.   But if an end-use product's label
 specified  it was  for use only in ways that involved no  food/feed exposure and
 no repeated human exposure, the subchronic oral dosing  study would not be
 required to evaluate the product's safety; and if  a manufacturing-use
 product's  label states that the product  is for use  only in making end-use
 products not involving food/feed use or  repeated  human  exposure,  that
 subchronic  oral study would not  be relevant to the  evaluation of the
 manufacturing-use  product either.
     If  a registrant of a currently registered manufacturing-use or end-use
 product wishes  to  avoid  the costs  of data compensation  [under FIFRA Section
 3(c)(1)(D)]  or  data generation  [under Section 3(c)(2)(B)]'for "generic"  data
 that is required only with  respect  to  some  use  patterns,  he may elect to delete
 those use  patterns  from  his labeling at  the time  he re-registers his product.
 An applicant for  registration of a  new product  under this  Standard  may
 similarly request  approval  for  only certain use patterns.


 Data Compensation Requirements under FIFRA  3(c)(1)(D)

    Under FIFRA Section  3(c)(1)(D),  an applicant  for registration,  re-
 registration, or amended registration must  offer  to pay compensation for
certain existing data the Agency has used  in  developing  the Registration
 Standard.   The data for which compensation  must be  offered  is all data which is
described by all the following criteria:

    (1)  the data were first submitted to  EPA  (or to its  predecessor agencies,
         USDA or FDA),  on or after  January  1,  1970;
    (2)  the data were submitted to  EPA (or USDA or  FDA)  by some other
         applicant or registrant in  support of an application  for an

                                   -4-

-------
         experimental use permit, an amendment adding a new use to a
         registration, or for re-registration, or to support or maintain  in
         effect an existing registration;
    (3)  the data are relevant to the Agency's decision to register or  re-
         register the applicant's product under the Registration Standard,
         taking into account the applicant's product's composition and  intended
         use pattern(s);
    (4)  the data are determined by EPA to be valid and usable in reaching
         regulatory conclusions; and
    (5)  the data are not those for which the applicant has been exempted by
         FIFRA Section 3(c)(2)(D) from the duty to offer to pay compensation.
         (This exemption applies to the "generic" data concerning the safety of
         an active ingredient of the applicant's product, not to "product
         specific" data.  The exemption is available only to applicants whose
         product is labeled for end-uses for which the active ingredient  in
         question is present in the applicant's product because of his  use of
         another registered product containing that active ingredient which he
         purchases from another producer.)

    An applicant for re-registration of an already registered product under
this Standard, or for registration of a new product under this Standard,
accordingly must determine which of the data used by EPA in developing  the
Standard must be the subject of an offer to pay compensation, and must  submit
with his application the appropriate statements evidencing his compliance with
FIFRA .Section 3(c)(1)(D)'.
    An applicant would never be required to offer to pay for "product specific"
data submitted by another firm.  In many, if not in most cases, data which are
specific to another firm's product will not suffice to allow.EPA to evaluate
the applicant's product, that is, will not be useful to the Agency in determin-
ing whether the applicant's product is registrable.  There may be cases,  how-
ever, where because of close similarities between the composition of two  or
more products, another firm's data may suffice to allow EPA to evaluate some or
all of the "product specific" aspects of the applicant's product.  In such a
case, the applicant may choose to cite that data instead of submitting  data
from tests on his own product, and if he chooses that option, he would have to _
comply with the offer-to-pay requirements of Section 3(O(1)(D) for that  data.
    Each applicant for registration or re-registration of a manufacturing-use
product, and each applicant for registration or re-registration of an end-use
product, who is not exempted by FIFRA Section 3(c)(2)(D), must comply with the
Section 3(c)(1)(D) requirements with respect to each item of "generic" data
that relates to his product's intended uses.
    A detailed description of the procedures an applicant must follow in
applying for re-registration (or new registration) under this Standard is found
in the Guidance Package for this Standard.


Obtaining Data to Fill "Data Gaps"; FIFRA 3(c)(2)(B)

    Some of the kinds of data EPA needs for its evaluation of the properties
and effects of products to which this Standard applies have never been
submitted to the Agency (or, if submitted, have been found to have deficiencies
rendering them inadequate for making registrability decisions) and 'nave not
been located in the published literature search that EPA conducted as part of
preparing this Standard.  Such instances of missing but required data are
referred to in the Standard as "data gaps".

                                  -5-

-------
     FIFRA  Section 3(c)(2)(B)f. added to FIFRA by the Congress in 1978,
 authorizes EPA to require registrants to whom.a data requirement applies to
 generate  (or  otherwise  produce)  data to fill such "gaps" and submit those data
 to  EPA.   EPA  must allow a reasonably sufficient period for this to be
 accomplished.  If a registrant fails to take appropriate and timely steps to
 fill the data gaps identified by a section 3(c)(2)(B)  order, his product's
 registration  may  be suspended until the data are submitted.   A mechanism is
 provided whereby  two or more  registrants may agree to share  in the costs of
 producing  data for which they- are both responsible.
     The Standard  lists, in its summary second chapter, the '^generic" data gaps
 and notes  the classes of products to .which these data gaps pertain.  The
 Standard also points out that to be registrable under the Standard, a product
 must be supported by certain  required "product  spe::fic" data.  In some cases,
 the Agency may possess  sufficient "product specific" data on one currently
 registered product,  but may lack such data on another.  Only those Standards
 which apply to a  very small number of currently registered products will
 attempt to state  definitively the "product specific" data gaps on a 'product by
 product' basis.   (Although the Standard will in some cases note which data that
 EPA does possess  would  suffice to satisfy.certain "product specific" data
 requirements  for  a category of products with closely similar composition
 characteristics.)
     As part of the process of re-registering currently registered products, EPA
 will issue Section 3(c)(2)(B)  directives requiring the registrants to take
 appropriate steps to fill all identified data gaps —.whether that'data in
 question is "product specific" or "generic" —  in accordance with a schedule.
     Persons who wish to obtain registrations for new products under this
 Standard will be  required to  submit (or cite) sufficient "product specific"
 data before their applications are approved. Upon registration,  they will be
 required under Section  3(c)(2)(B) to take appropriate  steps  to submit data
 needed to  fill "generic" data gaps.  (We expect they will respond to this
 requirement by entering into  cost-sharing agreements with other registrants who
 previously have been told they must furnish the data.)  The  Guidance Package
 for  this Standard  details the  steps that must be. taken by registrants to comply
 with .Section  3(c)(2)(B).
Amendments to the Standard

    Applications for registration which propose uses or  formulations  that are
not presently covered by the Standard, or which present  product compositions,
product chemistry data, hazard data, toxicity levels, or labeling  that do not
meet the requirements of the Standard, will automatically be considered by the
Agency to be requests for amendments to the Standard.  In response to such
applications, the Agency may request additional data to  support the proposed
amendment to the Standard, or may deny the application for registration on the
grounds that the proposed product would cause unreasonable adverse effects to
the environment.  In the former case, when additional data have been
satisfactorily supplied, and providing that the data do  not indicate  the
potential for unreasonable adverse effects, the Agency will then amend the
Standard to cover the new registration.
    Each Registration Standard is based upon all data and information available
to the Agency's reviewers on a particular date prior to  the publication date.
Tnis "cut-off" date is stated at the beginning of the second chapter.  Any
subsequent data submissions and any approved amendments  will be incorporated
into the Registration Standard by means of addenda, which are available for
inspection at EPA in Washington,  D.C., or copies of which may be requested from

                                  -6-

-------
he Agency.  When all the present "data gaps" have been filled and the
ubmitted data have been reviewed, the Agency will revise the Registration
tandard.  Thereafter, when the Agency determines that the internally
aintained addenda have significantly altered the conditions for registration
nder the Standard, the document will be updated and re-issued for publication.
   While the Registration Standard discusses only the uses and hazards of
roducts containing the designated active ingredient(s), the Agency is also
oncerned with the potential hazards of some inert ingredients and impurities.
ndependent of the development of any one Standard, the Agency has initiated
he evaluation of some inert pesticide ingredients.  Where the Agency has
dentified inert ingredients of concern in a specific product to which the
tandard applies, these ingredients will be pointed out in the Guidance Package.
                                  -7-

-------
            II.   Regulatory Position

This chapter presents the Agency's decision on what Standards of
product composition, toxicity, use, labeling, and packaging are
required for the pesticide active ingredient in question.  The
decision complies with the rules and regulations (40 CFR 162)
used to implement the Federal Insecticide, Fungicide, and
Rodenticide Act, as amended (FIFRA), and with the Agency's
present regulatory policies.  There are different requirements
for manufacturing-use chemicals and for each type of end-use
formulation which present a significantly different set of
hazards.  This Registration Standard is based upon all data and
information on 4-aminopyridine available to the Agency's
reviewers as of December 23, 1979.

Two companies have submitted data in support of their
registration of 4-aminopyridine products:  Phillips Petroleum
Company of Bartlesville,  Okla.  and Avitol Corporation of Tulsa,
Okla.  These data may be cited by other registrancs or
applicants for registration, when appropriate,  to support the
registration(s) of their own product(s)  provided  they have
offered and agreed to pay compensation as required by FIFRA
Sections 5(c)(1)(d)  and 3(c)(2)(d).  Anyone wishing to cite data
submitted by Avitrol Corporation or Phillips Petroleum Company
must offer and agree to pay compensation to Avitrol Corporation
since Phillips Petroleum Company sold all 4-aminopyridine
registration rights  to Avitrol Corporation in 1972 and has
requested not to receive compensation offers.

Manufacturing-Use

The Agency has reviewed all data available to it.  Although
incomplete, these data indicate that manufacturing-use 4-
aminopyridine is suitable for registration because it does not
meet or exceed the risk criteria leading to a Rebuttable
Presumption Against  Registration [Chapter 40, Section 1o2.119a)
of the Code of Federal Regulations].  Data gaps have been
identified; when these data are supplied, the Agency will again
review the registration status of this compound.

In order to be covered under this Standard, a manufacturing-use
4-aminopyridine product must comply with the following
standards.  A manufacturing-use 4-aminopyridine product
must contain 4-aminopyridine as an  active ingredient.
Intentionally added  inerts present in quantities  greater than
0.10/&,  by weight of  the total  product, must consist of food or
feedstuffs only.  Manufacturing-use 4-aminopyridine products may
fall into Toxicity Categories  I through IV for  the following
acute effects:
                              -  8  -

-------
         Acute Oral Toxicity;

         Acute Dermal Toxicity;

         Acute Inhalation Toxicity;
                                                •'••
         Primary Eye Irritation;  and

         Primary Dermal Irritation

Labels for manufacturing-use products must include the
following:

    1.  The intended end-use of products formulated from
    manufacturing-use products  must  be stated on the
    manufacturing-use products' label.  All manufacturing-use 4-
    aminopyridine products must therefore carry the following
    statement on the label:  For  Formulation into End-Use
    Products Intended only for  Bird  Control.

    2.  All manufacturing-use 4-aminopyridine products must
    carry the following warning on the label, under the "Hazards
    to Wildlife" section:

         This pesticide is toxic  to  birds and fish.
         Do not discharge into  lakes,  streams,  ponds
         or public water unless in accordance with
         an NPDES permit.   For  guidance  contact your
         Regional Office of the EPA.

    3.   All manufacturing-use  4-aminopyridine  products must
    carry the following statement of practical  treatment on the
    label.

         If swallowed:
         If the patient is unconcious, maintain
         breathing and  heartbeat  (CPR:
         cardiopulmonary resuscitation).   Contact
         your local Poison Control Center,
         hospital of physician  immediately.

         If patient is  conscious,  induce  vomiting
         with syrup of  ipecac  (if not  available
         stimulate the  back of  the throat with
         finger).   Never give  anything by mouth
         to an unconscious person.   Contact  your
         local Poison Control Center,  hospital
         or physician immediately.
                         -9-

-------
    4.  Manufacturing-use product labels must comply with the
    requirements of 40 CFR 162.10 regarding toxicity hazard
    warnings, first aid statements,  and label format,  including
    placment of hazard warnings on the label, type size and
    color, etc.

To be covered under this Standard, all applicants for
registration or re-registration of technical and formulation
intermediate products must agree to cite or submit the following
information on the physical/chemical composition of each
proposed product.  Listed after each' data gap is the section of
of the Proposed Guidelines which describes that type of data and
when it is required [43 FR, No. 132, 29696 of July 10,  1978; and
43 FR, No. 163, 37336 of August 22,  1978].

Product Chemistry                         Guideline Section
   For All Manufacturing-Use Products
    1. Density or specific gravity          163.61-8Cc)(8)
   For Technical
    2. Chemical Identity                    163.61-3
         Process
    4.  Product Analytical Methods          163.61-7
         and Data
    5.  Solubility                          163.6l-8(c)(4 )
    6.  Octanol/Water Partition             163.61-8(c)(6)
         Co-efficient
    7.  pH-Aqueous solution                 163.6l-8(c)(11)
4-Aminopyridine Formulations

In order to be covered under this Standard, an end-use, ready-to-
use bait or dust 4-aminopyridine product must contain  4-
aminopyridine as an active ingredient.  All 4-aminopyridine
ready-to-use bait and dust products, regardless of the Toxicity
Categories assigned for acute effects, are classified  as
restricted use pesticides and must consequently bear the label
statement:  "For sale to and use only by Certified Applicators
or persons under their direct supervision."

In addition, 4-aminopyridine formulated products must  comply
with the following standards.

    Ready-to-use Baits
    1.  Intentionally added inerts present in quantities greater
    than Q.10%, by weight of the total product, must consist of
    food or feedstuffs only.
    2.  When registered for use in agricultural crops, the
    product must not exceed 0.03%, by weight of the total
    product, 4-aminopyridine.  The product may consist of 3.02
    or less 4-aminopyridine per treated granule if it  is
    diluted, prior to packaging, at a ratio of  1 treated
    granule to 99 untreated granules.
                             -10-

-------
    3.  When registered for the control of house sparrows,
    cowbirds, blackbirds, or pigeons at nesting and roosting
    structures, the product must not exceed 0.52,  by weight of
    the total product, 4-aminopyridine.
    4.  When registered for the control of crows at nesting and
    roosting structures or for the control of starlings in
    cattle feedlots, the product must not exceed 1.05»,  by
    weight of the total product, 4-aminopyridine.

    Dusts

    1.  Intentionally added inerts must consist of food or  feed
    stuffs only.
    2.  When registered for the control of Herring gulls at
    nesting and roosting structures and at sanitary landfills,
    the product must not exceed 25%,  by weight, 4-aminopyridine.
    3.  When registered for the control of starlings in cattle
    feedlots, the product must not exceed 50%,  by  weight, 4-
    aminopyridine.

Labels for 4-aminopyridine formulated products  must include the
following:

    1.  All 4-aminopyridine formulated products must bear the
    following statement of practical  treatment  on  the front
    panel of the label:

         If swallowed:
         If the patient is unconcious, maintain
         breathing  and heartbeat (CPR:
         cardiopulmonary resuscitation).   Contact
         your local Poison Control Center,
         hospital or physician immediately.

         If patient is conscious,  induce  vomiting
         with syrup or ipecac  (if  not available
         stimulate  the back of the throat with
         finger).   Never give  anything by mouth
         to an  unconscious person!   Contact  your
         local  Poison Control  Center,  hospital
         or physician immediately.

    2.  Each 4-aminopyridine formulated product must carry  on
    the label toxicity hazard  warnings and  first aid statements
    appropriate to  the Toxicity Categories  assigned to  that
    product for acute effects  [refer  to 40 CFR  162.10]  with the
    following exception.   If registrants  of  4-aminopyridine dust
    products do not agree  to provide  or cite  data  on the
    teratogenic or  mutagenic potential of 4-aminopyridina [Refer
    to Toxicology Chapter],  all 4-aminopyridine dust products,
                             -11-

-------
regardless of the Toxicity Categories assigned for acute
inhalation toxicity and acute dsrmal toxicity, must require
applicators to wear protective clothing including long
sleeves, gloves, and respirators.

3.  4-aminopyridine formulated products must include the
following warnings under the "Hazards to Wildlife" section:

     a.   For all products
         This product is toxic to birds and fish.  Do not
         contaminate water by cleaning of equipment or
         disposal of wastes.
     b.   For products intended for, use in agricultural
         crops.
         Do not  allow bait to remain in unprotected places
         after control measures are completed.
     c.   For ready-to-use bait products containing greater
         than". 3.0% (per treated granule) 4-aminopyridine
         and all dust products.
         Pick up and dispose of dead birds by burial.

4.  All  4-aminopyridine formulated products must include the
following under  the section for Use Restrictions:

     a.   For all products
         Before  application in your .area, consult endangered
         species personnel of the U.S. Fish and Wildlife
         Service to ensure that endangered and rare bird
         species are not likely be adversely affected by use
         of this product.

     b.   For, all products except those intended for the
         control of. Herring gulls
         Investigate local laws that may prohibit the use of
         any toxic chemical in bird control.

         For all products
         LProduct Name]Is a poison with flock alarming
         properties used for the control of
         (type of birds) in such a way that a. part of a
         flock may react and frighten the rest away.  Birds
         that react and alarm a flock usually die.

         Do not  use where food (grain or meat) might become
         contaminated.

     d.   For all products, intended, for use in agricultural
         crops
              This product must be applied in accordance
              with 40 CFR Part 170.
                         -12-

-------
         Registrants may amplify the above statement on
         labels or labeling by stating the requirements of
         40 CFR Part 170 or additions thereto if they
         choose.

         For pretreated baits
         Do not feed to livestock or poultry.
         Do not mix with grain for livestock or poultry.

         For dust products
         Keep away -from livestock, poultry, and pets.

         For products intended for, use in cattle
         feed lots
         Keep bait off the ground, out of reach of
         cattle.
5.  All formulated 4-aminopyridine products must specify al'.
prebaiting methods on the label, under the section
"Prebaiting Directions".  If the product is intended for us<
at sanitary landfills or at target species' nesting and
roosting sites the directions must include the following
statement.

     This product must not be applied where
     nontarget birds feed.  Careful
     observation of the birds'  feeding habits
     must therefore be made to establish
     proper feeding locations and to
     determine that no nontarget birds
     are feeding on the prebait.

6.  All 4-aminopyridine ready-to-use bait products intended
for use in agricultural crops must specify all application
methods and rates on the label,  under the section "Baiting
Directions".  Baiting directions must include the following
statement:
     Confine treatment to areas 50 feet in from field edge.

No application rate in excess of .0144 ounces 4-
aminopyridine per acre on the portion being treated may be
recommended.  Directions may not recommend more than four
applications per crop season for corn or more than five
applications per crop season for sunflowers.

If the product is intended for use at sanitary landfills,
cattle feed lots, or nesting and roosting sites,  baiting
directions must include the following:
                           13-

-------
     To obtain minimal mortality the
     distribution of [PRODUCT NAME] should be
     limited to scattered spot placements
     that will provide feeding opportunities
     only for the necessary number of target
     birds.  After the birds' feeding pattern
     has been established through prebaiting,
     replace untreated bait with diluted
     treated bait only at sites where target
     birds are actively feeding.  Do not
     apply treated bait to inactive feeding
     sites.  Pick up and destroy untreated
     bait at the end of each day.

7.  All 4-aminopyridine dust products must specify all bait
preparation methods on the label under the section "Bait
Preparation Directions".  Bait preparation directions  must
include the following statement.

     "Materials resembling human food'must be altered  in
     form by crushing,  balling,  or pelleting so that they
     are not readily recognizable as human food."

8.  All 4-Aminopyridine products except ready-to-use baits
intended for use on agricultural crops must specify all
dilution methods and rates on the label under the  section
"Dilution Directions."  Recommended dilution ratios must
comply with the following:

     If the product is intended for the control of pigeons
     near nesting and roosting sites,  no dilution  ratio less
     than 1 part treated bait to 9 parts treated bait  may
     be recommended.  A dilution ratio of 1 part treated
     bait to 29 parts untreated bait should be recommended
     for normal use (i.e.  situations where other bird  food
     is plentiful).

     If the product is intended for the control of sparrows,
     blackbirds,  cowbirds, or crows in nesting or  roosting
     structures,  or for use in cattle feedlots, no dilution
     ratio less than 1 part treated bait to 9 parts
     untreated bait may be recommended.

     If the product is intended  for the control of Herring
     gulls at sanitary landfills or nesting and roosting
     sites,  no dilution ratio less than 1 part treated bait
     to 10 parts untreated bait may be recommended.
                        -14-

-------
    9.  Labels for 4-Aminopyridine formulated products must
    comply with the requirements of 40 CFR 162.10 regarding
    label format, including placement of hazard warnings on the
    label, type size and color, etc.

To be covered under this Standard, all applicants for
registration or reregistration of 4-aminopyridine ready-to-use
bait and dust products must agree to submit or cite the
following information on the physical/chemical composition of
each proposed product.  Listed after each data gap is the
section in the Proposed Guidelines  which describes that type of
data and when it is required [43 FR, No. 132, 19696 of July 10,
1973; and 43 FR, No. 162,37336 of August  22, 1978].

    Product Chemistry                       Guideline Section
    1.  Color                                 163.51-dCc)(1)
    2.  Odor                                  I63.61-8(c) (2)
    3.  Density                               163.61-8(c) (3)
    4.  Storage Stability                     163.61-8(c)(12)
    5.  Formation of Unintentional
          Ingredients                         163.61-5
    6.  Percentages of Compounds              163.61-6
          Pesticid-. Products

    All applicants for registration or re-registration of dust
    products must also agree to provide or cite an acute
    inhalation toxicity study (163.81-3) on a dust formulation.
    Two toxicology data requirements for 4-Aminopyridine dust
    products are contingent upon label restrictions.   Applicants
    for registration or re-registration of dust products must
    require applicators, by the label, to wear protective
    clothing including long sleeves, gloves,  and respirators  or
    they must agree to provide or cite the following  studies:

  Toxicology

    Teratogenicity                            163.83-3
    Mutagenicity                              163.34-111,2,2,4

Although certain 4-aminopyridine products are used to control
birds at public facilities the Agency does not consider this  use
a public health use.  The Agency is therefore waiving all
efficacy requirements.   In support of this waiver, when 4-
aminopyridine products are used to control nuisance birds at
public facilities,  the user can readily see the results of the
intended action of the pesticide,  thereby eleminating the need
for efficacy data.
                           -15-

-------
Applicants are hereby advised that if the Agency does not
receive commitments, within the specified time period, from
manufacturing-use producers to fill data gaps identified for
the manufacturing-use material, the registrations of the
manufacturing-use products will be suspended.  Formulators m
then bear the burden of supplying the data if they want the
manufacturing use product to be available.
                               -16-

-------
                             III.   Product Chemistry

Product Chemistry  Introduction

FIFRA  3(c)(2)(A) requires  the Agency to  establish  guidelines  for  registering
pesticides  in the  United States.   Registrants  are  required to provide
quantitative data  on  all added  ingredients,  active and  inert,  which  are  equal
to or  greater than 0. U of the  product by weight.

To establish the composition of products proposed  for registration,  the  Agency
requires data and  information not  only on the  manufacturing and formulation
processes,  but  also a discussion on  the  formation  of manufacturing impurities
and other product  ingredients,  intentional and unintentional.  Further,  to
assure that the composition  of  the product as  marketed  will not vary from the
composition evaluated at the time  of registration,  applicants .are required to
submit a statement  certifying upper  and  lower  composition limits  for the added
ingredients, or upper limits only  for sane unintentional ingredients.  Subpart D
suggests specific  precision  limits for ingredients based on the percentage of
ingredient  and  the  standard  deviation of the analytic method.

In addition to  the  data on product composition, the Agency also requires data
to establish the physical  and chemical properties  of both the  pesticide  active
ingredient  and  its  formulations.   For example, data are needed concerning the
identity and physical state  of  the active ingredient (e.g., melting  and  boiling
point  data, vapor  pressure and  solubility).  Data  are also required  on the
properties  of the  formulated product to  establish  labeling cautions  (e.g.,
flammability, corrosivity  or storage stability).   The Agency  uses these  data to
characterize each pesticide  and to determine its environmental and health
hazards.

The number  in parenthesis  next  to  the subheadings  in the Product Chemistry
Topical Discussions corresponds to the number of the section  in the  "Proposed
Guidelines  for  Registering Pesticides in the United States" (43 FR 29696)
which  fully explains the minimum product chemistry  data requirements.

Topical Discussions

Chemical. Identity. .(163..6.1 -3)


At present  there is no acceptable  common name  for  the bird repellent, 4-
aminopyridine (3th Collective Index,   1973).  Other  chemical names for the.
compound include 4-pyridinamine (9th Collective Index,  1977),  gamma-
aminopyridine,   and p-aminopyridine.   "4-AP" is a commonly used abbreviation
while  "Avitrol", "Avitrol 200", "Compound 1861", and "Phillips 1861" are all
trade names.

The Phillips Petroleum Company  (no date, 00004019)  speculated  that 4-
aminopyridine may also exist as a tautoneric form.  However,  Craig (1968,
05010341) presented an NMR spectral study 'which confirmed the  amino  structure.
Baer (1943,  05006181)  also confirmed  the amino structure with  U.V. absorption
spectra data.  Further characterization of 4-aminopyridine is noted  in Appendix
A, Chemical Data Sheet.
                                    -.17-.

-------
Manufacturing, Process (l63.6l:-4)

The Phillips Petroleum Company (Hyden, 1968, 00004143) submitted a description
of the manufacturing process (Appendix B, Manufacturing Process, Confidential)
in 1968.  However, Phillips sold its 4-aminopyridine patents to Avitrol
Corporation in 1972.  The Agency has no information on the present commercial
method of manufacture, which is conducted solely by Avitrol Corporation.

Two methods of preparing 4-aminopyridine have been discussed in the literature
(Baer, 1943, 05006181).  One method involves preparation from chelidonic acid,
through 4-chlorpyridine-2,6-dicarboxylic acid.  The second method involves
preparation from pyridylpyridinium dichloride.  It is uncertain whether either
of these methods is currently used for coranercial manufacture.

Formation of Unintentional. Ingredients 063.61-5,)

The Phillips Petroleum Company submitted information (Hyden, 1968, 00004148) on
the contaminants of technical 4-aminopyridine but did not support the
information with analytical data (Appendix B, Manufacturing Process,
Confidential).  In addition, no information is available on the contaminants
which result from the current manufacturing process of 4-aminopyridine.
Additional data on the formation of unintentional ingredients are therefore
required.

Active Ingredient Limits .in Pesticide Products (163.61-6.)

The technical chemical prepared by Phillips Petroleum Company contained a
minimum of 98£ active ingredient (Hyden, 1968, 00004148).  The confidential
formula of the manufacturing use product is described in Appendix C,
Formulation Processes, (Confidential).  The formulas of nine products which
appear on the labels are listed in Appendix B, Summary of Label Ingredient v
Statements.  Certification of active and inert ingredients is not possible at
this time due to a lack of information on the currently used manufacturing
process for 4-Aminopyridine and the length of time which has passed since the
original submission of formulas for registered products.

Product Analytical Methods and. Data ,(,163.6.1-7,)

Phillips Petroleum (1962, 00003978, 1920, 00004020) submitted a method for
analysis, by U.V. spectrophotometry, of grain seed impregnated with 0.1$ - 3.02
4-aminopyridine.  This method was also used to assay their analytical
standard.  The EPA Manual (1976) describes a similar U.V. method for use on
solid formulations.  This method is adequate for the characterization of 4-
aminopyridine.  However, if impurities in the technical material were to be
identified, analytical methods would also be needed for their assay.

Physical/Chemical Properties (.153.61-8.)

Tne following information (Phillips, 00004019, 00004112) applies to the
technical compound except where otherwise noted.
                                       -18-

-------
Color;  White  (purified).
        Off-white  (technical grade).
        No color reported for  formulated products.

Odor:  None  (purified).
       Slightly musty  (technical).
       No odor reported for formulated products.

Melting point:  158.9°C,  (purified).
                155-158 C. (technical).

Solubility:  Water —  given as both 3% and  12%  (free base).
                   —  50% (HC1 salt).
             Acids —  soluble  as the salts.
             Acetone — moderately to very  soluble.
             Methanol  — soluble.
             Ether —  soluble.
             Benzene — soluble.
             Soluble in most polar solvents.

These data are not adequate to assess the solubility of 4-aminopyrid^ne.
Solubilities must be expressed in quantitative terms, (g/100ml at 20 C,
or ppm).

Stability:  The free base9is moderately stable to light.  An aqueous
solution of free base  darkens slowly in light.  The hydrochloride salt is
light stable.

Qctanol/Water Partition Coefficient:  Mone  reported.

Physical State:  Crystalline solid (technical).  The formulation
intermediate is a granular (impregnated grain).  The formulated products
consist of granulars (impregnated grains),  dusts and pelletized
baits.

Density or Specific Gravity:   Not reported.

Boiling. Point:  273-274°C (760 mm Hg, technical).
                Not applicable for formulated products.

Vapor Pressure:  None  reported (technical).

jg£:  Basic in reaction (technical).

Storage Stability:   Four 0.25% 4-aminopyridine formulations of different
impregnated grains were studied over a period of eight months at 82 F and
140-150T after storage in four different kinds of containers.  No 4-
aminopyridine loss was reported.   Actual use experiments were carried out
for over a year on four 0.5/5 formulations with the same four impregnated
grains.  No loss of 4-aminopyridine was reported in the samples stored in
completely protected feeders.   There was a  40-50% loss of 4-aminopyridine
in samples partly exposed to the weather.
                               -19-

-------
    Flammability:  Not applicable.

    Oxidizing or Reducing Action:   Not reported.

    Explosiveness:   Not reported.

    Miscibility:  Not applicable.

    Viscosity:  Not applicable. .

    Corrosion Characteristics:  Not reported.


DISCIPLINARY REVIEW
Product Chemistry Profile
Data Gaps
Required Labeling


Product Chemistry. Profile

"Avitrol" is a well-known trade name for 4-aminopyridine.  "4-AP" is a commonly
used abbreviation.   The technical  compound is an off-white crystalline solid
with a slightly musty odor.  The hydrochloride salt is stable in light and
soluble in water, acids, and most  organic solvents.  The°technical compound is
manufactured by the Avitrol Corporation in an integrated formulation system
to produce a 0.3J impregnated grain formulation intermediate and end-use
products.

The manufacturing-use product produced by Avitrol is reformulated into
additional products by the Woodbury Chemical Company and the Huge' Company.
All 4-aminopyridine is ultimately formulated into baits.  Most of the end-use
products are ready-to-use baits in which 4-aminopyridine is mixed with a
variety of foodstuffs such as corn, wheat, sorghum, and mixed grains.  The
remaining end-use products are dust concentrates consisting of cornstarch
and 25* or 50% 4-aminopyridine.  These dusts are used to coat bread or french
fries in order to make finished baits.

Data. Gaps

Listed below are Product Chemistry data needed to obtain registration or
reregistration for 4-aminopyridine products.  Listed after each data gap is the
number of the section in the Proposed Guidelines (July 10, 1978, 43 FR, No.
132,29696) which describes that type of data and when it is required.
                                    -20-

-------
    For Technical

    1) Chemical Identity —
         Complete identification of all impurities
         and reaction compounds (if any) in the
         technical chemical.
    2) Manufacturing Process —
          Complete description of the present-day
          manufacturing process, including type of
          process, equipment, quality control
          measures, etc.
    3) Product Analytical Methods and Data —
          Methods of analysis for identifiable
          impurities (if any) in the technical compound.
    4) Solubility — in quantitative terms
    5) Octanol/Water Partition Coefficient
    6) pH — aqueous solution

    For Manufacturing.-use. Product:
    7) Density

    For Formulations .(Readyrto-Use Baits and Dusts,):
    8) Color
    9) Odor
   10) Density
   11) Storage Stability (dust and pellets only)
   12) Formulation of Unintentional Ingredients —
         Theoretical discussion of the formation
         of each substance, aside from the active
         ingredient and intentionally added inert
         ingredients, that might reasonably be
         identifiable as being present in the
         pesticide product.
   13) Percentages of Components in Pesticide Products —
         Declaration/certification of limits for all
         active and inert ingredients.
Guideline Section

   163.61-3
   163.61-4
   163.61-7
   163.61-3(0)
   163.61-8(c)(6)
   163.61-8(c)(8)
   I63.61-8(c)(1)
   I63.61-8(c) (2)
   163.61-8(c)(8)
   163.61-8(0)(12)
   163.61-5
   163.61-6
Required Labeling


The ingredient statement will list the active ingredient as:

                     4-aminopyridine	 ...._%

Additional labeling may be.required following review of physical/chemical
properties data provided at the time of registration or reregistration.
                                  -21-

-------
                        Product Chemistry Bibliography
05006181   Baer, J.E. (19*18) Alkyl Polysulfide and 4-aminopyridine and
               Related Compounds [Doctoral Dissertation].  Philadelphia, Pa:
               University of Pennsylvania. (Twenty-one unpaged figures)
05010341   Craig, J.C.,  Jr.; Pearson, D.E. (1968) NMR proof of the structure
               of 4-aminoquinolines and pyridines.  Journal of Heterocyclic
               Chemistry 5(5):631-637.
00004143   Hyden, S. (1968) Bird Management Process: LDG-123-68P.   (Unpub-
               lished study received Jul 17,  1968 under unknown admin, no.;
               prepared by Nepera Chemical Co.,  submitted by Phillips Petro-
               leum Co., Bartlesville, Okla.; CDL:103068-A)
00004112   Phillips Petroleum Company (no date)  Technical Data Sheet: Phillips
               Avitrol 200 (1861).  (Unpublished study received 1968 under un-
               known admin, no.; CDL:221959-B)
00004019   Phillips Petroleum Company (no date)  [Identity,  Physical and
               Chemical Properties, and Formulations of Avitrol].   (Unpublished
               study received Jul 13, 1970 under 1F1013; CDL:093322-D)
00003978   Phillips Petroleum Company (1962)  Determination of 4-aminopyridine
               in Grain Seed:  Ultraviolet Spectrophotonetric Method.  Method
               PK-62R dated Jan 12, 1962.  (Unpublished study received Aug 13,
               1963 under 224-EX-1; CDL: 122741^A)
00004020   Phillips Petroleum Company (1970)  Determination of 4-aminopyridine
               in Grain Seed Ultraviolet Spectrophotonetric Method.
               (Unpublished study including letter dated Jun 26,  1970 from
               A.M. Schnitzer to U.S. Food and Drug Administration, Pesticides
               Branch, Reference Standards Section, received July 13, 1970
               under 1F1013; CDL:093322-F)

                              Standard. References

           Chemical Abstracts Service (1973)  Chemical Abstracts 8th collective
               index, Vols 66-75 (1967-1971), American Chemical Society.
           Chemical Abstracts Service (1977)  Chemical Abstracts 9th collective
               index, Vols 76-85 (1972-1976), American Chemical Society.
           U.S. Environmental Protection Agency (1976) Manual of chemical
               methods for pesticides and devices.  Washington, D.C.
           U.S. Environmental Protection Agency (1978) Proposed Guidelines for
               the registering of pesticides  in the United States.
               Federal Register., 43 (132) 29696 - (July 10, 1978).
                                     -22-

-------
                    IV.  Environmental Fate

Use Profile

4-aminopyridine is the active ingredient in several federally
registered pesticide products.  It is currently registered for
the control of nuisance and depredatory birds such as
blackbirds, crows, cowbirds, starlings, gulls, and common
grackles.  Application sites include field corn, sweet corn, and
sunflower fields,  and urban and agricultural premises.  Between
330 and 350 pounds of 4-aminopyridine are produced yearly
(Avitrol, 1980, personal communication).   Approximately 104
pounds are used on agricultural crops and approximately 240
pounds are used on agricultural premises  and in urban areas.

All 4-aminopyridine is ultimately formulated into baits.  The
baits are placed in areas where large numbers of nuisance or
depredatory birds congregate.  The baits work by causing the
birds that eat them to utter distress calls which serve to scare
the rest of the flock away.  Birds that eat the treated bait
usually die.

Registered 4-aminopyridine products which are .used on crops
are 3% pretreated  baits.  The baits are mixed prior to
application at a ratio of one treated particle to 99 untreated
particles.  The mixture actually applied  therefore contains
0.032 4-aminopyridine.  Current label directions call for the
application of one pound of bait per total acre applied to one-
third of an acre at a time, resulting in  a rate of 3 Ibs/acre on
the treated portion.   When applied to sunflowers,  only areas of"
15 or more acres are treated.  Succeeding applications are made
on previously untreated areas so that the material is eventually
spread over the entire area.  Labels direct product users to
make applications  to corn fields "when bird damage becomes
apparent" and to make applications to sunflower fields "when
bird damage reaches 200 freshly damaged heads,  or when at least
200 feeding target birds are observed in  a field".  Treatments
are made a maximum of four times per season in corn fields and a
maximum of five times per season in sunflowers.

Other registered formulations include 50% and 252 4-
aminopyri.dine dusts and pretreated bait formulations containing
from 0.022 to 1 % active ingredient.  These formulations are used
for the control of nuisance birds at urban nesting and roosting
sites, cattle feedlots and sanitary landfills.   Current use
directions call for scattered spot placements of untreated bait
followed by placements of treated bait after feeding patterns at
the bait sites have been established. Labels for 4-aminopyridine
products used at urban facilities direct  applicators to place
the baits at the appropriate feeding sites, in high locations
on buildings and ledges.   Labels for 4-aminopyridine products
used at cattle feedlots direct applicators to place the bait in
elevated feeders,  out of reach of farm animals.

Products containing 4-aminopyridine are restricted use
pesticides registered for sale to and use only by certified
applicators or persons under their direct supervision.  These


                             -23-

-------
products are not for sale to the general public.

Topical. Discussions

Numbers in parentheses next to topical discussion subheadings
correspond to the number of the section in the proposed
Guidelines (U.S. Environmental Protection Agency, 1978) which
explains the minimum data requirement of that topic.

                           AVITROL 200R
                         4-Aminopyridine

Physico-Chemical. Transformation (1 63.. 62.-7.)

(A) Hydrolysis. 1.63.62-7(b)

Hydrolysis data are required in most cases, to support the
registration of manufacturing-use products, regardless of the
intended end uses of products formulated from the manufacturing-
use product.  These data are not required for 4-aminopyridine,
however, because the chemical is a minor use pesticide with a
total yearly production of less than 350 pounds.   Should yearly
production of 4-aminopyridine reach 25,000 pounds, hydrolysis
data on the technical chemical will be required.

(B) Photolysis 163..62-7(c)

Photodegradation studies in water are required, in most cases,
to support the registration of formulated products intended for
terrestrial uses.  Studies in soil are required in most cases to
support the registration of formulated products intended for
crop uses.  These studies are not required for 4-aminopyridine,
however, because residues of 4-aminopyridine are  not expected to
reach significant levels in soil or water as a result of
application of 4-amiminopyridine formulated products (Metabolism-
Soil and Exposure Profile below).

Metabolism, 163.62.-8

Data on metabolism are required to determine the  nature of
pesticide residues and their availability to rotational crops,
to help in the assessment of potential disposal and reentry
hazards, and to assist in predicting the persistence and extent
of residue accumulation.

(A) Soil l63.62-8(b,c.)1

Aerobic metabolism studies are required to support the
registration of all formulated 4-aminopyridine products intended
for terrestrial uses.  Anaerobic soil metabolism  studies are

                          -2'4-

-------
required to support the registration of all formulated products
intended for field and vegetable crop uses.

Of three soil metabolism studies submitted, two were considered
valid.  Starr and Cunningham (1975, 05003185) investigated the
degradation of 4-aminopyridine, as measured by   COp
evolution, in various soil types (loamy sand, sandy loam,  loam,
and sandy clay loam) under aerobic and flooded conditions.  In
alkaline soil under aerobic conditions, 4-aminopyridine,  when
applied at 10 ppm, exhibited half-lives ranging from 3 months in
loamy sand to 32 months in sandy clay loam.  Extensive
degradation to C02 occurred after a lag period of over 7
days.  However, under flooded conditions, very little «Q.5%)
[  C] 4-aminopyridine degradation was detected within the same
period.
                        14
Rates of metabolism of [  C] 4-aminopyridine in soil under
aerobic conditions increased with increasing organic matter.
When metabolized in two^slightly acidic (pH 5.6-5.8) loam soils
containing 16£ clay, [  C] 4-aminopyridine was degraded to
  COp faster (t 1/2 = 8 months) in the soil with 5.0% of
organic matter than it was in the soil with 2.9% organic
matter (t 1/2 = 22 months).

Rates of metabolism also increased with increasing soil pH.   The
amount of   COp recovered over a 3-month period was minute
(0.352) for a highly acidic loam (pH 4.1), but was much greater
(4.88X) for an alkaline sandy clay loam with similar levels  of
organic matter and clay.  In these l^sts, degradation of  4-
aminopyridine was measured only by   COp recovery.  No
attempt was made to identify intermediate degradation products.

Bettf§ et al.  (1976, 05003407) investigated the degradation of
[2-  C] 4-aminopyridine (10 ppm) in sandy loam,  fine loamy
sand, and clay soils under aerobic and flooded conditions.
Under aerobic conditions, the half-lives of 4-aminopyridine
ranged from 8 months in the clay soil to 32 months in the  sandy
loam soil.  A lag period of 20 days occurred before extensive
degradation to COp was observed.  Under flooded conditions,
the half-lives of 4-aminopyridine ranged from 8 months in  the
clay soil to approximately 10 months in the sandy loam soil.
These half-lives are based on   CC^ evolution.  No
intermediate degradation products were detected in extracts  from
soils under either aerobic or flooded conditions.

The studies by Betts et. al (1976, 05003407) and Starr and
Cunningham (1975,  05003135) show that 4-aminopyridine residues
would be fairly persistent in soil, but they do not fully
characterize 4-aminopyridine soil metabolism.  No additional
studies are needed, however,  because of the following:

1)  Only a small amount (approximately 104 Ibs)  of 4-
    aminopyridine is used on crops yearly.  Accumulation  in
    soil, based on the maximum allowable use, together with
    available data, should not exceed 1.6 mg per square
    meter.

                             -25-

-------
2)  When applied at cattle feedlots, 4-aminopyridine
    treated baits will be placed off the ground, out of
    reach of cattle.  Therefore, very little direct-soil
    contact is expected.

3)  Similarly, no significant direct-soil contact is expected
    from urban uses.

4)  Since the total amount of 4-aminopyridine applied yearly in
    all landfills is less than  10 Ibs, residue levels in
    soil resulting from this use are expected to be very small.
    In addition, at the site of application, any residues
    which might accumulate would not be expected to be available
    to rotational crops.

In summary, the lack of significant 4-aminopyridine residues
available to rotational crops eliminates the need for fully
assessing 4-aminopyridine soil metabolism.

(B) Microbiological. Studies. 163 .62-8.(f.)

Data on the effects of microbes on pesticide degradation and the
effects of pesticides on microbes are required in most cases to
support the registration of formulated products intended for
terrestrial use.

(1 )  MicrpbiologicalrEffeots of Microbes on. Pesticides. 163^.2.-
One study (Betts, et al, 1976, 05003407) on the ability of soil
microorganisms to metabolize 4-aminopyridine was reviewed.  In
the study, pure cultures of Asperg.illus n.iger , Pseudpmonas
f luorescens, Ent.erobac.ter aerogenes „ Streptomyces griseus, and
Agrobacterium tumefaciens failed to metabolize 4-aminopyrdine
when incubated in the presence of the compound at concentrations
of 10 and 100 ug/ml for 5-6 days.  Microbiological rates in the
pure cultures were not retarded by the pesticide.  These data
cannot be considered conclusive however, because too few species
of microorganisms were examined and culture conditions were not
varied enough.

(2)  Microbiological, - Effects of. Pesticides on Microbes 163.62-
8,(f.).(77                       '

Preliminary data on the effects of 4-Aminopyridine on microbes
were reviewed.  The study by Betts et. al. (1976, 05003407)
indicated that the growth of A_^ nig.er , P^ f luorescens, E_.
aerogenes, S_._ griseus. and A^ tumefaciens was not retarded
when incubated in the presence of 4-aminopyridine at
concentrations of 10 or 100 ug/ml for 5-6 days.  These data
cannot be considered conclusive,  however,  because too few
species of microorganisms were examined.

Although the data discussed above are inconclusive,  no
additional microbiological studies are required because 4-
aminopyridine soil residues potentially available to rotational
crops are expected to be insignificant (Metabolism-Soil above)

                           -26-

-------

-------
Table I.  Leaching of I  CH-Aminopyr Id ine (10 ppm) from soil  columns after  elution with 7  Inches of water over 20 days.3
Soil

A
B

C
D

E
F
G
H
Sol 1 type

Loamy sand
"i Sandy clay loam
f ,
?"•'" Sandy clay loam
* Loam

Loam
Loam
__ Sandy loam
[" Loam
(paste)

7.8
7.7

7.6
7.6

5.8
5.6
5.6
4.1
Organic
matter
(*>

2.9
4.0

1.9
2.5

2.9
5.0
4.0
1.4
Sand
(*>
Alkal Ine sol Is
77
61

47
59
Acidic soils
46
50
53
31
Silt
<*>

16
19

27
30

38
34
33
44
Clay
(%)

7
20

26
11

. 16
16
14
25
Radioactivity
recovered from
leachate
<*>

0.18
0.02

0.09
0.01

<0.01
—
—
—
Radioactivity
remaining in
upper Inch oi
- so 1 1 co 1 umn

95
99

98
— c

>99
>99
>99
>99
a  Adapted fifom Starr and Cunningham (MRID 05003185; KRID 00004001).




   Percent ofe'total recovered from soil columns.




c  Not measured.
                                                                                -28-

-------
immobile in soils.

Because the experimental soils were leached with less than half
the amount of water recommended by the Proposed Guidelines,
these studies would not be considered adequate to assess the
leaching potential of a major crop use chemical.  However, since
the total amount of 4-aminopyridine applied yearly is quite
small, residue levels in soil are expected to be insignificant
(See 2A above).  Therefore, no additional data on the leaching-
potential of 4-aminopyridine are required.

(B) Adsorption/Desorption. 165.62.-9(d.)

A laboratory study using radioisotopic or nonradioisotopic
analytical techniques is required, in most cases, to support the
registration of products intended for terrestrial uses.  These
data are not required for 4-aminopyridine because accumulation
of 4-aminopyridine in soil is expected to be insignificant.

(C) Terrestrial Field. Dissipation 1 63 .62-.VO(b)

A field dissipation study under actual use conditions is
required, in most cases to support the registration of
formulated products intended for terrestrial uses.  This study
is not required for 4-aminopyridine because accumulation of 4-
aminopyridine in soil is expected to be insignificant.

Accumulat.ion 163 . 62-J 1

Data on accumulation are required to determine accumulation in
food webs.

(A) Rotational Crops. 1 63 .62-11 (b )

Rotational crop studies are required,  in most cases,  to support
the registration of formulated products intended for
field/vegetable uses.  4-Aminopyridine residue levels in
soil available to rotational crops are expected to be
insignificant (approximately 1.6 mg/m ).  Consequently, no
significant residues of 4-aminopyridine are expected to occur in
rotational crops, thus eliminating the need for 4-aminopyridine
rotational crop studies.

(B) Fish l63.62-1.1.(d,)

This laboratory study employing radioisotopic or nonradioiso-
topic analytical techniques is  required in most cases to support
the registration of formulated  products intended for terrestrial
and field/vegetable crop uses.   A fish accumulation  study is not
required for 4-aminopyridine, however,  because residues in
aquatic systems are not expected to result from current uses of
the formulated products.
DISCIPLINARY REVIEW
Environmental Fate Profile
Exposure Profile


                            -29-

-------
Environmental, Fate Profile

Residue levels of 4-aminopyridine in soil resulting from
terrestrial application of 4AP formulated products are expected
to be very low.  The following discussion characterizes the
fate of 4-aminopyridine in soil were it to accumulate in soil.

4-aminopyridine is fairly persistent in soil.  Under aerobic
conditions, 4-aminopyridine exhibited half-lives ranging from 3
months to 32 months in a variety of soils.  A lag period of 7-20
days was required before extensive degradation to carbon dioxide
occurred.  Under flooded conditions half-lives ranged from 3
months in clay soil to 10 months in sandy loam soil.

The rate of aerobic soil metabolism of 4-aminopyridine increases
with increasing organic matter.  Of two slightly acidic loam
soils studied, the soil with 5% organic matter degraded the
compound to carbon dioxide almost three times faster than
the soil with 2.95£ organic matter.  Soil pH also influences 4-
aminopyridine metabolism.  Recovered carbon dioxide was almost
negligible for a highly acidic loam (pH 4.1) but was somewhat
greater for alkaline sandy clay loam with similar levels of
organic matter and clay.  Degradation of 4-aminopyridine was
measured only by carbon dioxide recovery; no attempt was made to
identify intermediate degradation products.

The rate of microbial degradation of 4-aminopyridine appears to
be slow.  Several common soil microorganisms, Aspergillus niger,
P.seudomonas fluorescens., Strep.tomyces griseus, and Agrobacterium
tumefaciens, were unable to degrade the chemical within 120
hours.  4-aminopyridine appears to have no effect on microbial
growth.  Microbial growth rates in pure cultures were not
retarded by the pesticide at concentrations of 10 and 100
micrograms/ml.  These results are inconclusive however, and the
ability of microorganisms to degrade 4-aminopyridine as well as
the effect of the pesticide on microbes remains uncertain.
Available data on the mobility of 4-aminopyridine suggest that
the compound does not leach significantly in soil.  When soil
columns containing acidic loam or sandy loam soils (pH 4.1-5.8)
were eluted with water over a 20-day period, greater than 99J of
the applied compound remained in the top inch of soil.  Low
quantities of 4-aminopyridine were found in the leachate of one
of the acidic soils (less than 0.01& of the initial application)
and in all of the alkaline soils (0.09-0.18%).

Because 4-aminopyridine strongly adsorbs to the soil,  it will
remain near the soil surface, where maximim microbial
degradation is likely to occur.  However, the rate of microbial
degradation is, at best, rather slow.  Therefore, any 4-
aminopyridine residues present in soil will probably persist for
a considerable period.  Because 4-aminopyridine appears to be
tightly held to soil under most or all circumstances examined,
migration of the chemical from the site of application will be
minimal.

                                -30-

-------
Exposure Profile

For persons involved in the dilution, mixing, and application of
4-aminopyridine products, there is little chance of oral
exposure except through accidental ingestion.  4-Aminopyridine
is registered for use on food crops but 4-aminopyridine residue
levels in the crops should be insignificant, so there is
very little possibility of dietary exposure to 4-aminopyridine
for the general public.

Because 4-aminopyridine ready-to-use bait formulations consist.
of grains, such as corn and wheat, impregnated with 4-
aminopyridine during the manufacturing process, no occular or
inhalation exposure to these formulations should occur.  There
is a chance of dermal exposure, but applicators would be exposed
to only very small amounts of active ingredient.  Applicators
who handle dust formulations, may receive dermal and inhalatlonal
exposure because the bait preparation process involves manual
mixing of the active ingredient with bait material.  The use of
protective clothing, including long sleeves, gloves,  and
respirators during the handling of dust formulations, will
essentially eliminate all but accidental dermal, occular,  and
inhalation exposure to dust products.

Due to the nature of 4-aminopyridine formulations,  the potential
for contamination of nontarget sites by drift is negligible.
The extremely low rates at which 4-aminopyridine is applied to
crops and to sanitary landfills, and the lack of direct soil
contact with formulations applied to cattle feedlots  and urban
areas should prevent significant 4-aminopyridine accumulation in
soil.   4-Aminopyridine is not expected to be present  in ground
water or surface water as a result of terrestrial application of
4-aminopyridine formulated products.

The potential for exposure to 4-aminopyridine formulations is
greatest for nontarget wildlife, specifically,  grain-feeding
birds.  The greatest risk to migratory birds will occur during
the fall migration period when finches and  other small seed-
feeding birds may ingest lethal doses of the pretreated baits
applied to corn and sunflower fields.  Observations (McCann,
1980,  //0015005) indicate,  however, that in  areas where 4-amino-
pyridine is most often used (the midwest) most  migratory birds
will pass through after the corn is harvested.   In  addition,
field'reports (Besser and Cummings, 1975 #0000479)  indicate that
in a year of normal maturation of sunflowers baiting  will  be
completed before most finches,  sparrows and other birds  migrate.
                                 -31-

-------
              Environmental Fate Bibliography

00004079  Besser, J.F.; Cummings,  J.L. (1975)..Avitrol FC Corn
              Chops - 99 Baits for protecting sunflower from
              blackbirds in North Dakota, Minnesota, and South
              Dakota: (Report of study #59, work unit DF-
              102.3).  (Unpublished study received Nov. 11,  1975
              under 11649-15; prepared by U.S.  Fish and Wildlife
              Service, Denver Wildlife Research Center,
              submitted by Avitrol Corp., Tulsa, Okla.; CDL
              223451-1)
05003407  Betts, P.M.; Giddings, C.W.; Fleeker,  J.R. (1976)
              Degradation of 4-aminopyridine in  soil.  Journal
              of Agricultural and Food Chemistry 24(3):571-574.
GS0015005 McCann, J.A. (1980) Registration standards Phase I
              qualitative use assessment for 4-aminopyridine.
              U.S.  Environmental Protection Agency, Office of
              Pesticide Programs (Internal document)
00004001 Starr,  R.I.; Cunningham,  D.J. (1970) Translocation and
              Degradation of 4-Aminopyridine in  Corn Plants—Its
              Movement and Degradation in Soil  Systems:  .[Third
              Periodic Report, Avitrol Concentrate].
              (Unpublished study received April  24, 1970
              under 224-EX-3; prepared by U.S.  Fish and Wildlife
              Service, Denver Wildlife Research  Center,
              submitted by Phillips Petroleum Co.,
              Bartlesville, Okla.;  CDL: 12.2744-H)
05003185  Starr, R.I.; Cunningham,  D.J.  (1975}4Leaching and
              degradation of 4-aminopyridine   C in several
              soil  systems.  Archives of Environmental
              Contamination and Toxicology 3(1):72-83.


                       Standard Reference

         U.S.  Environmental Protection Agency (1973) Proposed
              Guidelines for Registering Pesticides in the
              United  States.  Federal Register,  43 (132) 29696
              (July 10,  1978)
                             -32-

-------
                            V.  Ecological Effects

Ecological Effects Topical. Discussions


Effects on Avian Species (163.7.1-1,2,4.5)

Effects on avian species can be measured by acute,  subacute,  reproduction,  and
field studies.  The. studies required for a particular chemical depend upon the
use pattern of the chemical and the results of particular tests.

    Acute Effects:  The minimum data required for establishing the acute
    toxicity of 4-aminopyridine are results from avian single-dose oral ID™
    studies using technical 4-aminopyridine.   Test  species should be either
    wild waterfowl (preferably the mallard duck) or upland game birds
    (preferably the bobwhite quail or the ring-necked pheasant).

    Two valid studies on the acute effects of 4-aminopyridine on  a variety of
    species were available for review.   Table 1 summarizes the results of these
    studies.

                 Table 1.    Studies on  the Acute Toxicity
              £f Technical 4-Aminopyridine t£> Avian Species
    Author

    Schafer,
     et al,
     1975   '
    (05003186)
    Schafer
     et al, •
     1973
    (0500319D
Species

Blackbilled
  magpie
Yellowbilled
  magpie
Sparrow hawks

 Quelea
 House Sparrow
 Red-winged
 blackbird
Test
Substance

Technical

Technical

Technical

Technical
Technical
Technical
Results
Oral LD5Q =2.4 mg/kg

Oral LD5Q =2.4 mg/kg

Oral LDco =5.6 mg/kg
  (4.2 iu7.5 mg/kg)
Oral LDqn   =5.6 mg/kg
 50
30
Oral LE£n =7.5 mg/kg
Oral LDg = 2.4 mg/kg
    While  neither  of these studies  alone  fulfills  the  Proposed Guideline
    (US. Environmental  Protection Agency,  1978) requirement  for the  avian
    single dose oral ID™,  the  studies  taken  together  provide sufficient
    information to characterize 4-aminopyridine as highly toxic to avian
    species.  Consequently,  no further acute avian  toxicity studies are required.

    Subacute  Effects:   The minimum data  required  for  establishing the subacute
    toxicity  of 4-aminopyridine in birds  are  as follows:  Avian dietary LCC
    studies  for one wild waterfowl species  (preferably the mallard duck)
    one  upland gamebird species  (preferably the bobwhite quail or the ring-
    neck pheasant).
                                  -33-

-------
Three valid studies were available for review on this topic.
summarizes the available subacute data.

             Table 2.   Studies _on the Subacute Toxicity
             of Technical 4-Aminopyridine Jto A vian Species
                                            Table 2
                               Test
Author

Schafer
 et al,
 1975
(05003186)
Schafer &
Ma-king, 1974
(00004083)

Fink & Reno
   1976
(GS-0015-004)
Species

Coturnix
  Quail
Mourning
  Dove
Coturnix
  Quail
Coturnix
  Quail
Mallard
  Duck
Substance

Technical

Technical

Technical

Technical

Technical
 Results

.LCqn = 447 ppm
   t239 - 714 ppm)
 LCr.n = 316 ppm
   T100 - 1000 ppm)
 LCq0 = 479 ppm
   ^354 - 645 ppm)
 LC50 > 316 ppm

 LCen = 722 ppm
   X547.3 - 952.5 ppm)
Based on this .information, 4-aminopyridine can be characterized as
moderately toxic to upland game birds and waterfowl.

Avian. Reproduction:  Avian reproduction toxicity studies on technical
4-aminopyridine are necessary if the pesticide is persistent in the
environment, if it is stored or accumulated in plant or animal tissues, if
its use is such that nontarget birds may be exposed repeatedly or
continuously to sublethal doses (especially before breeding season), or
if available test information indicates that avian reproduction may be
adversely affected by use of the pesticide.

Schafer et. al. (1975, 05003186) conducted an avian reproduction study on
coturnix quail.  The effects of chronic and single-dose exposures were
studied.  In the chronic feeding test, 4-aminopyridine was incorporated
into the diet at concentrations of 31.6, 100, and 316 ppm.  No significant
differences in egg production or hatchability were found through the F1
generation.  Further generations were not studied.  In the single exposure
study,  a dose of 5.66 mg/kg 4-aminopyridine did not affect egg production
or hatchability.

The preferred test species was not used in this study nor was egg shell
thickness measured.  In addition,  the study was carried out for only four  .
weeks instead of the preferred ten week period, only three concentrations
were administered instead of the preferred four,  and fewer birds than the
preferred number were tested.  Despite these deficiencies, the study
demonstrated for coturnix quail that no adverse reproductive effects will
result from a chronic dose of 316 ppm or a single dose of 5.62 mg/kg. In
view of these results, the high acute avian toxicity of the compound, and
                                    -34-

-------
the method of use of the compound (distribution of discrete bait granules),
it is unlikely that birds would consume sublethal doses that would
adversely affect reproduction.  No additional avian reproduction studies
are required.

Special Studies :  Several special toxicity studies on both technical 4-
aminopyridine and formulated products were available for review.
Schafer et al. (1970, 00003998) found no observable effects at 31.6 and
100 ppm dietary levels after 30 days of feeding 4-aminopyridine to mourning
doves.  However, at the next level, 316 ppm, 5Q% mortality occurred.  This
study further confirms previous LCcQ studies.

Schafer et al. (1973, 05003191) also conducted a study to determine the
acute dermal LDcn for quelea and house sparrow.  The value determined was
greater than 100 mg/kg for both birds.  This LDcn value indicates that 4-
aminopyridine is only slightly toxic when applied dermally to birds.

Several avian feeding studies on the formulated product were available for
review for 4-aminopyridine.  Table 3 summarizes these results.

                   Table 3.   Avian Feeding Studies
                       on. the Formulated Product

Author       Species           Results

Schafer &    Mourning          Both 2% and 3% baits were lethal after a 7
 Lockyer       Doves             day feeding period.  The baits were
 no date,                        diluted at a ratio of 1:99.
(00003999)

Besser,      Bobwhite          No toxic .effects were seen at 1:99 dilution
 1963          Quail             ratio of the 3% active ingredient bait.
(00004101)

Schafer &    Bobwhite          All birds died at the 1:29 dilution ratio of
Marking,  1974  Quail             the 3% active ingredient bait.
(00004033)

Schafer &    Starlings         LCc-n > 1.78 mg/kg/day
Marking,  1974                    ou
(0004033)

Schafer et al. (1974, 00003965) designed a secondary poisoning study which
included blackbilled magpies,  sharp-shinned hawks,  red-tailed hawks,  and
American kestrels.  The birds exhibited no symptoms of intoxication, nor
any gross pathological changes when fed birds killed with 3% baits.
Secondary poisoning toxicity appears to be nonexistent for 3% (per treated
granule)  products.  However,  no data were available to determine the
potential for secondary poisoning of avian predators from 25% or 50% dusts
or from pretreated baits containing greater than 3% (per treated granule)
4-aminopyridine.
                                  -35-

-------
    Besser and Currming  (1975, 00004079) conducted a field study in which
    searches for dead nontarget and target birds were made in North Dakota,
    Minnesota and South Dakota sunflower fields treated with 4-aminopyridine.
    In one part of the study, two relatively small areas (35.65 and 51.5A) were
    searched intensively, along with nearby shelter belts and pastures.  During
    the search, 253 target and 42 nontarget birds were found dead.  Crackles
    and redwings accounted for 231 (902) of the dead target birds.  Slate-
    colored juncos and Harris sparrows accounted for 26  (62%) of .the dead non-
    target birds.

    The second part of the study involved an 18,000 acre area of which only 128
    acres were searched.  The search in this area disclosed a total of 32 dead
    birds: 29 target birds (all black birds), 2 nontarget birds (1 mourning
    dove and 1 song sparrow) and 1 unidentified birti.  The authors reported
    that the ratio of target to nontarget species found closely agreed with
    findings of searches made in heavily damaged fields during the previous six
    years.  (Besser and Cummings, 1975, (00004079).

Effects on Aquatic Organisms. (163.72-1,2,3,4,5,5)

Effects on aquatic organisms are measured by a variety of tests,  including fish
acute LCCQ'S, acute toxicity tests on aquatic invertebrates and estuarine and
marine organisms, and embryolarvae and life cycle studies.  The types of tests
required depend on the pesticide use pattern and the results of previous
tests.

    Fish Acute LQt-n:   The minimum data required, in most cases, for  •
establishing the acute toxicity of 4-aminopyridine to fish are results from
96 hour exposure studies on one coldwater species (preferably rainbow trout)
and one warm water species (preferably bluegill), using technical 4-
aminopyridine.  Valid data on two species were available for review on this
topic.  The acceptable acute toxicity data are summarized in Table 4.
                                      -36-

-------
                  Table 4.   Studies on the Acute Toxicity
              of Technical 4-Aminopyridine _to Fr-eshwater Fish
Author

Schafer &
Marking,
 1974
(00004033)
Schafer 4
Marking,
  1974
(00004033)
Warmwater
Fish
Species

Channel
Catfish
                           17°C

                           22°C
Bluegill
                           17°C

                           22°C
Hardness

very soft

soft

hard

very hard

soft

soft

very soft

soft

hard

very hard

soft

soft
Results

LC5Q=4ppm
(3.2-5. Oppm)
LC(-Q=4ppm
(3T4-4.7ppm)
LCc0=4ppm
(3?6-4.5ppm)
LC.or2.43
(2?2-2.8ppm)
LCqn=4.36ppm
(3.9-4.8ppm)
LC(-0=5.80ppm
(5T2-6.4ppm)
LCcrQ=3.40ppm
(3.0-3.9ppm)
LC53=4.41ppm
(3.3-5. 1ppm)
                                       cn-
                                     (2?3-3.5ppm)
                                     LC«-Q=3.20ppm
                                     (2?7-3.8ppm)
                                     LCc-Q=5.60ppm
                                     (4T80-6.5ppm)
                                     LCcQ=7.56ppm
                                     (6?3-9.1ppm)
Based on these results, 4-aminopyridine can be characterized as moderately
toxic to warmwater fish.  Although no- data on coldwater fish were submitted,
none are required for 4-aminopyridine formulated products because 4-
aminopyridine residues should not occur in water as a result of application of
the formulated products.  In addition,  because 4-aminopyridine is a minor use
pesticide that has a total yearly production of less than 350 pounds, an
acute toxicity study on coldwater fish  is not required for manufacturing-use 4-
aminoyridine.  In further support of this data waiver, a valid study was
available on warmwater fish species which provides sane basis for determining
the toxicity of 4-aminopyridine to fish.  However, should yearly production of
4-aminopyridine reach 25,000 pounds, an LCcQ for coldwater fish will be
required to support the registration of manufacturing-use 4-aminopyridine
products.
                                   -37-

-------
 Effects on Mammals

Special mammalian toxicity studies on technical 4-aminopyridine can be required
under circumstances described in Sec. 163.71(d) of the Proposed Guidelines.  .

One valid study was available on this topic.  Schafer (1971, 00003965) designed
a secondary poisoning study in which a beagle-coyote hybrid, one beagle, and
ten white laboratory rats were fed redwing blackbirds contaminated with 4-
aminopyridine.  The largest dose consumed by a rat in these experiments was 1
redwing blackbird which had been dosed at a rate equal to 300 mg/kg.  The 300
mg/kg dose fed to the blackbird was equal to 57 mg/kg or 3.4 LDcg doses for
the rat.  The highest dose given to a dog was 10 redwings which had been dosed
at a rate of  150 mg/kg.  The dose given to the 10 redwings was equal to 3.22
mg/kg, twice  the dogs' LD50dose.  Neither the rats nor the dogs exhibited
symptoms of intoxication Or any gross pathological changes.  This study
indicates that the hazard to mammals from secondary poisoning is minimal.

Phytotoxici.ty

Two valid studies (Starr and Cunningham, 00004037; 1974, 05003440) on phyto-
toxicity were available for review.  Data from the studies showed that corn
germination was unaffected at 1 ppm (the highest level tested), and that both
corn and sorghum growth were unaffected in a 100 ppm solution of technical 4-
arainopyridine.

Acute Toxicity .to Aquatic Invertebrates (l63:.72-2)

A determination of the EC™ or LC,-g for an aquatic invertebrate is
required, in most cases, to support the registration of all manufacturing-use
products.  These data are not currently required for 4-aminopyridine, however,
because it is a minor use pesticide (refer to above discussion on Fish Acute

"V-

DISCIPLINARY REVIEW
Ecological Effects Profile
Ecological Effects Hazard Assessment
Data Gaps
Required Labeling

Ecological Effects Profile

Acute oral LA-g and dietary LCcn data indicate that 4-aminopyridine is
acutely toxic to several avian species including magpies, sparrowhawks, house
sparrows, and red-winged black birds.  It is moderately toxic to upland
gamebirds and wild waterfowl.  Results of an avian reproduction study suggest
that adverse avian reproductive effects resulting from ingestion of sublethal
doses are unlikely.

LCj-Q values for two warmwater fish species indicate that 4-aminopyridine is
moderately toxic to these species.  Cold water species were not tested.
                                      -38-

-------
 Available  data  on  the  effects  of  feeding  birds  contaminated  with  4-
 arainopyridine to avian predators  and  mammals  suggests  that secondary poisoning
 of mammals is unlikely to  result  fron use of  this compound and  secondary
 poisoning  of avian species is  unlikely to result from  use of 52 or  less
 pretreated baits.   The only phytotoxicity data  available indicate that 4-
 aminopyridine is not significantly  toxic  to corn or  sorghum.  One ppm does  not
 affect seed germination in corn and a 100 ppm solution does  not affact the
 growth of  corn  or  sorghum.

 Ecological, Effects Hazard  Assessment

 Although 4-aminopyridine is acutely toxic to  some bird species  and  at least
 moderately toxic "to others, the hazard  to* nontarget migratory birds from 3.03
 (per treated granule)  4-aminopyridine ready-to-use baits applied  to
 agricultural crops is  slight.  Most nontarget migratory birds are expected  to
 pass through corn  areas after  the crop is harvested.   In addition,  in a year of
 normal maturation  of sunflowers,  all  sunflower  baiting will  have  been completed
 prior to the period during which  most nontarget birds  migrate.  Migratory
 nontarget  birds  may still  be killed occasionally however, due to  variations in
 the time of. migration  and  in the  time of  crop harvest.

 Mourning doves  and bobwhite quails, which are nonmigratory species, may
 potentially be  exposed  after each application of ready-to-use baits to corn and
 sunflower  fields.   However, when  the  3% (per treated granule) baits are applied
 to fields  at a  ratio of one treated granule to  99 untreated  granules, the
 likelihood  of a  nontarget  bird picking  up more  than  1  treated granule is small.
 At the 1:99 dilution ratio and the  current application rate, only about 200
 treated granules per acre  are applied to  corn and sunflower  fields.   One
 3.0& 4-aminopyridine granule is not expected to be lethal to either doves
 or quails.   In  addition, 28-40 day-  LCcg dietary studies show that
 4-aminopyridine  has no  cummulative  toxic  effect; several sublethal  doses have
 no greater  effect  than  a single sublethal dose.  Therefore,   it  appears that in
 the field,  the  1:99 dilution ratio  reduces the  hazard  to doves  and  quails
 although sublethal doses may intoxicate these and other birds,  leaving them
 more vulnerable  to predation.  Available  data indicate, however,  that if a  1:29
 dilution ratio were used in the field, high dove and quail mortality  could
 result (see  Table  3).

 The hazard  to nontarget  birds from 4-aminopyridine pretreated bait  and dust
 products applied to cattle  feedlots, sanitary landfills,  and urban  buildings
 should be slight,  since  these formulations are  restricted to use  only in areas
 where target birds are feeding.   Secondary poisoning of mammals is  not
 expected to occur  as a result of  application of any 4-aminopyridine product.
 Neither is secondary poisoning of avian predators expected to occur as a result
of application of  3.0£ or  less (per treated granule) 4-aminopyridine  ready-to-
use baits.    Due to a lack of data, however,  the potential for secondary
poisoning of avian predators from ready-to-use  baits containing greater than
 ~3.Q% 4-aminopyridine (per treated granule) and  from dust products,  cannot be
 determined.  Adverse avian reproductive effects resulting from sublethal doses
of 4-aminopyridine are unlikely.
                                   -39-

-------
4-aminopyridine residues in water, resulting from terrestrial application of
4-AP formulated products, are expected to be insignificant.  But assuming the
"worst possible case" (i.e. direct application to water which is prohibited by
label restrictions), at the current maximum application rate of .0144 oz. per
acre the amount expected in an acre of water six inches deep is well below the
•LCcQ of 2.43 ppm and 2.82 ppm for channel catfish and bluegill sunfish.
Thas  4-no
Thas, 4-aminopyridine formulated products do not present a hazard to fish.

As indicated by the Environmental Fate Chapter, residues of 4-aminopyridine in
soil are expected to be insignificant.  Therefore, terrestrial plants including
corn and .sunflowers, are not expected to be adversely affected by application
of 4-aminopyridine formulated products.

Required Labeling

The following labeling requirements are made on the basis of the available
ecological effects data:

Manufacturing, 4-aminopyridine:

Do not discharge into lakes, streams, ponds or public waters unless in
accordance with an NPDES permit.  For guidance, contact your regional office of
EPA.

For All Formulations:

For use only by certified applicators or persons under their direct
supervision.

This pesticide is toxic to birds and fish.  Wildlife feeding on treated bait
may be killed.

Do not contaminate water by cleaning of equipment or disposal of waste.

Before application in your area, consult endangered species personnel of the
U.S. Fish and Wildlife Service to ensure that endangered and rare bird species
are not likely to be adversely affected by use of this product.

For Pre-treated Baits

Do not allow this material to remain in unprotected places after control
measures are completed.

For Ready-to-Use Bait Products Containing Greater than 3% (per-treated
particle) 4-aminopyridine and For All Dust Products

Pick up and dispose of dead birds by burial.
                                         -40-

-------
For Products Intended for Use at Sanitary. Landfills, Cattle Feed Lots,  or
Nesting and Roosting Sites;

This product must not be applied where nontarget birds feed.  Careful
observation of birds feeding habits must be made to establish proper feeding
locations and to determine that no nontarget birds are feeding on prebait.

Pick up and destroy uneaten bait at the end of each day.

For Products Intended for the Control of Herring Gulls
(Larus argentatus)

Herring Gulls ( Larus argentatus ) are protected by law and treaty.   Both
Federal and State permits are required to control these birds.

For All Products Intended for Use in Agricultural Crops

Confine treatment to areas 50 feet in from field edge.
                                       -41-

-------
                 Ecological Effects Bibliography
00004101   Besser, J.F.  (1968) Compilation of Information on the Chronic
               Toxicity  of 4-aminopyridine to Pheasant, Cxiail and Starlings.
               (Unpublished study received Mar 2, 1973 under 11649-12; prepared
               by U.S. Fish and Wildlife Service, Denver Wildlife Research
               Center, submitted by Avitrol Corp., Tulsa, Okla.; CDL:120117-A)
00004079   Besser, J; Cummings, J.L. (1975) Antrol FC Corn Chops -  99 Baits
               for protecting Sunflowers from Blackbirds in North Dakota,
               Minnesota, and South Dakota (Report of Study No. 59,  Work Unit
               DF-102.3).  Unpublished study received November 11, 1975 under
               11649-15; prepared by U.S. Fish and Wildlife Serviced, Denver
               Wildlife  Research Center, submitted by Avitrol Corp,  Tulsa,
               Ckla; (DL:223451)
GS0015004  Fink,  R.; Reno, F.E. (1976) Eight-day dietary LC™ - Mallard.
               duck. (Unpublished study received February 9, 1980 under 11649-
               12; pepared by  Hazleton Laboratories America, Inc.,  submitted
               by Avitrol Corp., Tulsa, Qkla.; (DL:223451-I)
05003186   Schafer, E.W.; Brunton, R.B.; Lockyer, N.F. (1975)
               The effects of subacute and chronic exposure to
               4-aminopyridine on reproduction in coturnix quail.  Bulletin of
               Environmental Contamination and Toxicology 13(6):758-764.
00003999   Schafer, E.W.; Lockyer, N. (no date)  The Effects of DRC-1327 Baits
               on Mourning Doves.  (Unpublished  study received Dec 18, 1970
               under 224-EX-3; prepared by U.S.  Fish and Wildlife Service,
               Denver Wildlife Research Center,  submitted by Phillips Petroleum
               Co., Bartlesville, Okla.; CDL:122744-E)
00003998   Schafer, E.W., Jr.; Brunton, R.B.;  Lockyer, N. (1970) The Chronic
               Toxicity of DRC-1327 to Mourning  Doves: Preliminary Report
               No. 16--W. J. DF-T02.2.  .(Unpublished study received  Dec 18,
               1970 under 224-EX-3; prepared by  U.S. Fish and Wildlife Ser-
               vice, Denver Wildlife Research  Center, submitted by Phillips
               Petroleum Co.,  Bartlesville, Okla.; CDL:122744-D)
00003965   Schafer, E.W., Jr.; Brunton, R.B.;  Lockyer, N.F. (1974) Hazards to
               animals feeding on blackbirds killed with 4-aminopyridine baits.
               Journal of Wildlife Management  38(3):424-426.  (Also  in unpub-
               lished submission received Apr  10,  1975 under 11649-10; submit-
               ted by Avitrol Corp.,  Tulsa, Okla.; CDL.-115276-B)
05003191   Schafer, E.W., Jr.; Brunton, R.3.;  Lockyer, N.F.; De Grazio, J.W.
               (1973) Comparative toxicity of  seventeen pesticides to
               the Quelea , house sparrow, and red-winged blackbird.
               Toxicology and Applied Pharmacology 26(1):154-157.
00004033   Schafer, E.W., Jr.; Marking, L.L.  (1974) Long Term Effects of 4-
               Aminopyridine Exposure to Birds and Fish.  (Unpublished study
               received Nov 11,  1975 under 11649-15; prepared by U.S. Fish and
               Wildlife Service,  Wildlife Research Center in cooperation with
               Fish Control Laboratories, submitted by Avitrol Corp., Tulsa,
               Okla.; CDL:225255-C)
                                        -42-

-------
00004057   Starr, R.I.; Cunningham, D.J. (no date) Phytotoxicity.  (Unpublished
               study received Jan 3,  1973 under 1F1013; prepared by U.S. Fish
               and Wildlife Service,  Denver Wildlife Research Center,  submitted
               by Phillips Petroleum Co., Bartlesville, Okla.; CDL:091757-R)
05003440   Starr, R.I.; Cunningham, D.J. (1974) Phytotoxicity, absorption,
               and translocation of 4-aminopyridine in corn and sorghum
               growing in treated nutrient cultures and soils.  Journal of
               Agricultural and Food Chemistry 22(3):409-413.
00003985   U.S. Fish and Wildlife Service,  Denver Research Laboratory (no date)
               Toxicity of Avitrol to Bluegill and Channel Catfish at Selected
               Water Qualities and Temperatures:  Table.  (Unpublished study
               received May 18,  1971  under 224-EX-3; prepared in cooperation
               with La Crosse Fish Control Laboratory,  submitted by Phillips
               Petroleum Co.,  Bartlesville, Okla.; CDL:122743-F)

                              Standard Reference

           U.S.  Environmental Protection Agency  (1978) Proposed Guidelines for
               Registering Pesticides in the United States.   Federal Register,
               43 (132), 19696.
                                  -43-

-------
                           VI.  Toxicology
Toxicology Topical. Discussions

The following topical discussions describe available toxicity data on technical
4.-aminopyridine and its formulations and state whether the data are adequate
for Agency regulatory purposes.  Agency acceptance depends on the adequacy of
test substances used to represent a product on which toxicity data are required
and on the adequacy of the toxicity test procedures used to satisfy Agency
requirements.

Because 4-aminopyridine ready-to-use bait and dust formulations are dilutions
of the technical chemical with foodstuffs, the toxicity of a particular
formulation depends directly on the concentration of the active ingredient
present in that formulation.  Therefore, when no data specific to formulations
were available, toxicity categories were based on extrapolation from data
available on the technical chemical.

Test procedures in several toxicity tests submitted for 4-aminopyridine did not
meet proposed Agency guideline requirements.  Some of those tests were
determined to be adequate, however, for Agency regulatory purposes.  The
judgments made are included in the following topical discussions.

Numbers in parentheses next to topical discussion subheadings correspond to the
number of the section(s) in the Proposed Guidelines of August 22, 1978 (U.S.
Environmental Protection Agency,  1978) which explain(s) the minimum data that
the Agency usually requires in order to adequately assess a pesticide's
toxicology.

Acute Oral Toxicity (163.81-1)

The minimum data requirement for testing acute oral toxicity (LDc-n) of 4-
aminopyridine is one test on the technical chemical, preferably using the
laboratory rat.

Technical;  Ives (1962,  00004024) conducted a study in which laboratory rats
    and dogs were administered 4-aminopyridine hydrochloride, in capsule form
    by gavage.  The LD5Q was 28.7 mg/kg(S.D. =0.6 mg/kg) for the rat and 3.7
    mg/kg (S.D. =0.6 mg/kg) for the dog; both species showed very steep dose
    response curves.  This study meets Agency requirements for an acute oral
    toxicity test and is adequate to place technical 4-aminopyridine in
    Toxicity Category I, indicating.a very high acute oral toxicity hazard.


Formulations:  Ives (1962, 00004024) conducted a second acute oral toxicity
    study in which a .53% granular formulation was administered to dogs and
    swine in their feed.  The ID™ for dogs was 2300 mg of formulation/kg
    which is equivalent to 12.6 mg of active ingredient/kg.  The LDcg for the
                                    -44-

-------
    swine was 3**00 mg of formulation/kg which is equivalent to 18 mg of
    a.i./kg.  This study does not meet Agency requirements for an acute oral
    toxicity test because too few animals were used in the experiments.  Taken
    alone, therefore, the results cannot be considered conclusive.  However,
    the data in this study support the results obtained  (Ives, 1962, 0004024)
    with the technical material.  The difference between the dog LD^g
    determination (3.7 mg/kg) from the technical material and the dog ID™
    determination from the .532 granular formulation is most likely due K5 the
    route of administration.  LD.-Q values are generally higher when
    substances,*are administered ?n feed than when they are introduced directly
    into the animals' stomachs by gavage.  Based on extrapolations from
    data on the technical chemical, formulations of 4-aminopyridine are
    assigned to the following Toxicity Categories for acute oral toxicity:'

         o Formulations containing 25% or more
           4-aminopyridine—Toxicity Category I
         o Formulations containing 2.5% to 242
           active ingredient—Toxicity Category II
         o Formulations containing less than 2.5%
           active ingredient—Toxicity Category III

Acute Dermal.. Toxicity (163.81-2)


Technical:  The minimum data requirement for testing the acute dermal
   toxicity (LDco) of 4-aminopyridine is one test on the technical
   formulation, preferably using the albino rabbit.  The acute dermal LDcn of
   4-aminopyridine hydrochloride is 327 mg/kg (S.D. = 54.3 mg/kg) for male
   rabbits (Ives, 1962,  00004024).  Animals exhibited signs of ataxia,
   hyperpnea,  salivation and tremors.  No gross pathlogical changes were noted
   in any tissues or organs examined.  Although data on female rabbits were not
   submitted,  the Agency considers the available data sufficient to assess
   the acute dermal toxicity of technical 4-aminopyridine.  Based on this
   study, technical 4-aminopyridine is assigned to Toxicity Category II for
   dermal effects.

Formulations:   No data specific to 4-aminopyridine formulations were
   available for assessing acute dermal toxicity.  Based on extrapolation from
   data available on the technical chemical, formulations of 4-aminopyridine
   are assigned to the following Toxicity Categories for acute dermal toxicity:

         o Formulations containig 65% or more
           4-aminopyridine — Toxicity Category
           II.
         o Formulations containing 6.5% to 64$ —
           Toxicity Category III.
         o Formulations containing less than 6.5%
           active ingredient-Toxicity Category IV.
                                      -45-

-------
Acute Inhalation Toxicity 063.81—3.)

A determination of the acute inhalation toxicity is required to support the
registration of a manufacturing use product and a formulated product if:

     1)  The product is a gas:
     2)  Tne product produces a respirable vapor; or
     3)  20 percent or more of the aerodynamic equivalent of the product is
         composed of particulates not larger than 10 microns in diameter.

Neither 4-aminopyridine manufacturing use products nor ready-to-use bait
formulations meet any of the conditions listed above.  Therefore,  no inhalation
testing of these products is necessary.  Dusts, however, meet condition 3.
In order to develop proper labeling dust formulations must be tested for acute
inhalation toxicity.  The minimum data requirement is one test, using the
albino rat, of a 50% a.i. dust.

Acute. Delayed Neurotoxicity (.163.8.1-7)

Acute delayed neurotoxicity data are required if the active ingredient,
or any of its metabolites, degradation products, or impurities cause esterase
depression or are structurally related to a substance that induces delayed
neurotoxicity.  4-Aminopyridine does not cause esterase depression nor is it
structurally related to a substance that is known to induce delayed
neurotoxicity.  Therefore no testing is required for the technical formulation
or any of its registered products.

Primary Eye Irritation (163.81-4)

The minimum data requirement for evaluating 4-aminopyridine eye irritation '
potential is one test on the technical chemical, preferably on the albino
rabbit.

Technical:  One study (Ives, 1962, 00004024) on primary eye irritation was
'    reviewed.  In the study, 10 mg of 4-aminopyridine hydrochlorids were
    instilled into the eyes of albino rabbits.  At 1 hour, iritis and
    conjunctival irritation were noted; these irritations disappeared by day
    7.  Although less 4-aminopyridine than the amount recommended by the.
    Proposed Guidelines (U.S. Environmental Protection Agency, 1978) was
    instilled into the rabbits' eyes, the Agency considers the data adequate to
    assign technical 4-aminopyridine to Toxicity Category III for primary eye
    irritation.

Formulations:  No data specific to formulations were available.  Based on
    extrapolation from data available on the technical chemical,  all 4-amino-
    pyridine formulations are assigned to Toxicity Category III.
                                       -46-

-------
Primary Dermal Irritation (,163.31-5)

The minimum data requirement for evaluating the dermal irritation potential of
4-aminopyridine is one test on the technical formulation, preferably on the
albino rabbit.

Technical:  Ives (1962, 00004024) observed rabbits after 5.0 mg of 4-
    aminopyridine hydrochloride were applied to abraded and intact skin.  He
    observed no signs of irritation, either at 24 hours or 72 hours.  Although
    less 4-aminopyridine than the amount recommended by the Proposed Guidelines
    was applied, the Agency considers the data adequate to assign technical 4-
    aminopyridine to Toxicity Category IV for primary dermal irritation.

Formulations:  Phillips Petroleum Co. (no date, 00004137) submitted a study
'in which granular 4-aminopyridine (amount unspecified) was applied to the
    clipped skin of rabbits on 10 consecutive days.  Each application remained
    in place for 18 hours but no signs of irritation were observed.  Because
    the amount of 4-aminopyridine applied to the skin was not specified, this
    study cannot be considered adequate for assessing the primary irritation
    potential of 4-aminopyridine formulations.  However, it does support data
    available on the technical chemical.  Therefore, based on this study and
    the data on the technical chemical, 4-aminopyridine is assigned to Toxicity
    Category IV for primary dermal irritation.

Subchronic Oral. Toxicity (1,63.82r1)

The minimum data requirement for assessing the subchronic oral toxicity of 4-
aminopyridine is one test in each of two mammalian species,  a rodent and a
nonrodent, on the technical chemical.

Technical:  No subchronic oral tests on 4-aminopyridine were available.  In
    one 90-day study, (Kohn et al., 1968, 00004026) rats were given dietary
    levels of 3, 30, and 300 ppm 4-aminopyridine hydrochloride (calculated as
    free base).  No gross or microscopic pathologic findings of significance
    were noted.  In the group given 300 ppm, all surviving animals were
    hyperirritable to noise and touch throughout the test.  No other abnormal
    behavioral reactions occurred.  Blood and urine analyses of rats given the
    high dose showed no significant changes.  Female rats given 300 ppm showed
    elevated brain weight (p<0.05); male rats showed elevated liver weight
    (p<0.05) when given the same dose.   This study is an adequate subchronic
    oral test in rats.

    A subchronic study was also conducted on dogs (Cervenka and Vega, 1968,
    00004027).  The study was informative,  although it was conducted for 90
    days instead of the desired 180 days.  4-aminopyridine hydrochloride was
    given in the diet at 0.1, 1.0,  and 2.0-3.25 mg/kg/day (corresponding to
    200,  2,000 or 4,000 - 6,500 ppm, calculated in terms of the free base).   At
    the highest dose, dogs exhibited salivation and muscular weakness but
    developed no abnormal lesions.  No dose-related trends occurred in mean
    organ weights,  but male and female dogs given the two highest doses showed
                                     -47-

-------
    decreased brain weights.  Blood and urine values were comparable in treated
    and control animals.

    In summary, rats and dogs in the 90 day studies showed no significant
    pathologic changes in any organ or tissue.  In both rats and dogs brain
    weight was affected, but examination of the brain revealed no abnormalities.

Formulations:  No significant subchronic oral toxicity effects were observed
    in tests of the technical chemical.  Therefore, none should result from
    exposure to 4-aminopyridine formulations.  No subchronic oral toxicity
    testing specific to ready-to-use baits or dusts is required.

Dermal Sensitization (163.8.1-6)
Subchronic 21-Day Dermal Toxicity (163.82-2)
Subchronic 90-Day Dermal Toxicity (153.52-3.)

Dermal sensitization data and subchronic dermal toxicity data are required if
repeated skin contact with a pesticide is expected under conditions of use.
Applicators who handle 4-aminopyridine manufacturing-use products, or any dust
or pretreated bait product which falls into Toxicity Category I or II for
dermal toxicity, will be required to wear protective clothing,  including
gloves, thereby greatly reducing the potential for repeated skin contact.
Applicators who handle pretreated baits which fall into Category III or IV for
dermal toxicity will not be required to wear gloves, since they are unlikely to
be exposed to the active ingredient in sufficient quantities for dermal
sensitization or subchronic toxicity problems to develop.  Because of the lack
of significant dermal exposure, no subchronic dermal toxicity or dermal
sensitization testing is required for 4-aminopyridine.

Subchronic Inhalation Toxicity Q63.32r4)

Data from a subchronic inhalation toxicity study are required to support the
registration of each manufacturing-use product and formulated product which
has been identified as toxic from the results of acute inhalation testing and
whose use may result in repeated inhalation exposure.  Because of the nature of
4-aminopyridine manufacturing-use products and ready-to-use baits, no
inhalation exposure to these products is expected.  Short term inhalation
exposure to dusts may occur if applicators do not wear respirators.  However,
based on available information on the use pattern of 4-aminopyridine dust
products, significant repeated inhalation exposure to dusts is not expected
to occur even if respirators are not worn.  Therefore, subchronic inhalation
toxicity testing is not required.
                                       -48-

-------
Subchronic Heurotoxicity  (163.32-5)

Data  from a  subchronic  neurotoxicity  evaluation  are  required  to support  the
registration of  each manufacturing-use  product and formulated product
containing an  active ingredient  which induced neuropathy  or delayed
neurotoxicity  in acute  tests.  A subchronic neurotoxicity study is not required
for 4-aminopyridine because  no neuropathy  or delayed neurotoxicity was observed
in acute tests.   In addition, significant  repeated exposure to 4-aminopyridine
is not  expected  to occur.

Chronic Fe.eding  (.163.3.3-1.)
Qncogenicity -yfr3«83riO''
Reproduction  (1 6.3.. 133-4 J
Metabolism (163'. S5-11

Chronic feeding, oncogenicity, metabolism, and multi-generation reproductive
studies are usually required if  use of  a pesticide is  likely  to result in
repeated human exposure over a significant portion of the human life span  or if
a use requires a tolerance or an exemption from  a tolerance.

Although significant prolonged exposure to handlers  and applicators of 4-
aminopyridine  is unlikely, the fact that 4-aminoypridine  has  a tolerance of
•0.1.ppm for  both corn and sunflowers  would normally  indicate  that long-term
studies are necessary.  However, the  Agency believes that residue levels in
crops resulting  from either  translocation  of 4-aminopyridine  to food crops or
from  the direct  application  of 4-aminopyridine to growing crops will be  lower
than  the tolerances set (see Residue  Chemistry Chapter -  Residues in corn
and sunflowers).  Therefore, because  dietary intake  of 4-aminopyridine is
expected to be negligible and because prolonged  human  exposure is unlikely,  the
long-term studies listed above are not  required  for  4-aminopyridine.

Teratology (163.83-3)

Teratogenic studies on  the technical  chemical, using two  mammalian studies,
are required if  the pesticide's  use requires a tolerance  or an exemption from a
tolerance or if  its use may  result in exposure to human females.  No
significant dietary or chronic exposure to 4-aminopyridine is expected (see
Residue Chemistry .Chapter and above discussion on long-term studies).  In
addition, no significant  (including short-term)  dermal exposure is expected
to result from the application of pretreated baits (see Dermal Sensitization
Topical Discussion).  However, if applicators of 4-aminopyridine dusts do  not
wear  protective  clothing, including long sleeves, gloves,  and respirators,
short-term inhalation exposure and dermal exposure to  dusts will occur.
Therefore, unless applicators of dust formulations are required, by the  label,
to wear protective clothing  including respirators, the teratogenic potential of
4-aminopyridine  must be determined.
                                        -49-

-------
Mutagenicity

Mutagenicity testing will be required for 4-aiiinopyridine unless applicators of
dust formulations are required by the label to wear protective clothing
including respirators (see above discussion on teratology).

The following studies represent the minimum requirements for data on the
potential heritable effects of a 4-aminopyridine.

1.  A mammalian in-vitr.o point mutation test.

2.  A sensitive sub-mammalian point mutation test. (Bacteria, fungi, insect.)

3.  A primary DNA damage test (i.e. sister chromatid exchange or unscheduled
    DNA synthesis).

4.  A mammalian in-vitro cytogenetics test.  If this test suggests a positive
    result, a dominant lethal or heritable translocation test may be required.

After results from these test systems and other toxicology disciplines have
been considered, additional testing may be required to further characterize or
quantify the the potential genetic risks.

Although the Agency's mutagenic testing requirements are not final, the
standards for these tests should be based on the principles set forth therein
(43 FR 37336 August 22,  1978).  Protocols and choices of test systems should
be accompanied by'a scientific rationale.  Substitutions of test systems for
those listed above will be considered after discussion with the Agency.

The requirements should be considered an interim guide and not final Agency
policy.  However,  the Agency does consider the above testing scheme to be a
reasonable minimum requirement.

Pharmacological. Effects

In Vivo Effects:  4-Aminopyridine produced prolonged increases in the
blood pressure of cats (Fastier, 1958, 05004214).  The cats' blood pressure was
increased an average of 50 mm Hg following administration of 1 mg/kg of 4-
aminopyridine intravenously.  It remained elevated by 20 mm Hg up to 30 minutes
after 4-aminopyridine adminstration.  Barbituate hypnosis in mice was
antagonized 302 by 5 mg/kg of 4-aminopyridine (Vohra et al. 1969, 05003184).
These effects indicate involvement of the autonomic nervous system.

In the rat brain and spinal cord, 4-aminopyridine stimulated release of
norepinephrine but not 5-hydroxytryptamine or dopamine (Anden annd Leander,
1979, 05003729).  4-aminopyridine did not stimulate norepinephrine by
electrical stimulation.   This suggests an effect on the electrical
conductivity of the nerve membrane.

In Vitro Effects:   In isolated skeletal and smooth muscle preparations,
                                     -50-

-------
 4-aminopyridine increases  twitch  tension  and  reverses  the  nondepolarizing
 neuromuscular  blockade.   Inhibition of membrane potassium  conductance by
 4-aminopyridine prolongs  the  presynaptic  spike,  allowing an  increase  in
 acetylcholine  release at  the  presynaptic  membrane.   The mechanism of  action of
 4-aminopyridine at  the neuromuscular junction is calcium-dependent, and  it
 probably acts  by affecting calcium  permeability of  the presynaptic membrane.

 Dose-dependent positive inotropic responses (contractions) were  produced by
 4-aminopyridine in  guinea  pig ileum (Moritoki et al.,  1978,  05003154) and
 canine tracheal muscle (Kann.an and  Daniel,  1978,  05005155).   The positive
 inotropic effect of 4-aminopyridine was reduced when treated with a combination
 of phenoxybenzamine (an alpha blocker)  and propranolol (a  beta blocker)
 (Leander et  al.,  1970, 05003158).   When phentolamine,  another alpha-blocker,
 was used instead of phenoxybenzamine,  no  reduction  in  the  effect of 4-amino-
 pyridine was observed.  This  suggests that 4-aminopyridine does  not have an
 agonistic effect on alpha-receptors.

 In superfused  guinea pig  ileum, 4-aminopyridine decreased  contractile responses
 stimulated by  carbachol by more than 50£  (Fastier,  1958, 05004214).
 Contractile  responses  were increased in the presence of choline  or by
 anticholinesterase  agents  such as physostigmine (Al Haboubi  et al., 1978,
 05005379) and  neostigmine  (Al Haboubi et  al.,  1978, 05006379).   Atropine,  a
 cholinergic  antagonist (Kannan and  Daniel, 1978,  05003155, Al Haboubi, 1978,
 05005379,  Moritoki  et  al.,  1978,  05003154) antagonized the contractile
 response to  4-aminopyridine.   Because initiation  and potentiation  of
 contractile  responses  were blocked  by atropine  and  tetrodotoxin  and increased
 by cholinesterase inhibitors,  it  is  suggested that  the effect of 4-amino-
 pyridine is  the result of  indirect  cholinergic  action.  The  action  of 4-amino-
 pyridine appears to be Ca   -  dependent  (Al Haboubi  et  al., 1978,
 05006379).   4-aminopyridine potentiated by eight  times the tension  of muscle
 twitch evoked  by phrenic nerve stimulation in the presence of tubocurarine
 (Bowman  et al.,  1977,  05003160).  In  the  presence of 4-aminopyridine,   extremely
 high doses of  curare were  required  to abolish twitches.  These data indirectly
 support  the conclusion that the mechanism of action of 4-aminopyridine is on
 the presynaptic membrane.

 In summary,  4-aminopyridine selectively blocks membrane potassium  conductance
 in both  nerve  and muscle.   Inhibition of membrane potassium  conductance
 prolongs the presynaptic action potential, resulting in an increase in the
 amount of neurotransmitter released  at  the presynaptic membrane.  The mechanism
 of 4-aminopyridine  is  calcium-dependent,  probably acting by  increasing the
 influx of  calcium ions during  the nerve terminal  action potential.

 Clinical Effects

 4-aminopyridine  increases  transmitter release from the nerve terminals,
 probably by increasing calciun permeability of-the nerve terminal membrane.
 4-aminopyridine  has  been shown to restore neuromuscular transmission in
myasthenia gravis,  Eaton-Lambert syndrome, and pancuronium-linconycin
 neuromuscular blockage in man.
                                       -51-

-------
In six patients with myasthenia gravis, intravenous adminstration of 10 to 20 mg
of 4-aminopyridine caused a marked improvement in clinical status (Lundh et
al., 1979, 05003494).  Similar improvements were reported for two Eaton-Lambert
syndrome patients (Lundh et al., 1977,Q05004217, Agoston et al., 1978,
05003173).  Electrophysiological examination before and after intravenous
injection of 4-aminopyridine revealed  some improvement in all eight patients
discussed above.  Results suggest that 4-aminopyridine may be a valuable drug
in the treatment of myasthenia gravis  and myasthenic syndrome, sometimes
associated with Eaton-Lambert syndrome.

Clinical Side Effects

In six adult patients with myasthenia  gravis, intravenous administration of 10-
20 mg of 4-aminopyridine produced perioral paraesthesia within seconds (Lundh
et al., 1979, 05003494).  The paraesthesia disappeared within a few minutes of
4-aminopyridine administration.

In a clinical study of 57 surgical patients, no signs of central nervous system
stimulation were observed after single intravenous doses of 0.15, 0.35, or 0.50
mg/kg of 4-aminopyridine (Miller et al.,  1979, 05004966).  After a single
intravenous administration of 10 to 20 mg,  four of six patients experienced a
temporary sensation of unsteadiness during walking, lasting 0.5-2 hours
(Lundh et al., 1979, 05003494).  However, no objective signs of disturbed gait,
posture, or coordination were observed.

Miller et al. (1979, 05004966), Lundh  et al. (1977, 05004217), and Lundh et al.
(1979, 05003494) reported no significant changes in blood pressure or heart  .  '
rate after administration of 4-aminopyridine.  Agoston et al. 1978,  (05003178)
reported a slight decrease in heart rate but no changes in blood pressure in an
Eaton-Lambert syndrome patient given up to 120 mg/day of 4-aminopyridine for
120 days (Lundh et al., 1977, 05004217).   No changes in routine blood tests of
liver or kidney function were observed in this patient.

These studies demonstrate that intravenous adminstration of single doses of 4-
aminopyridine at 0.5 mg/kg or repeated dosing of up to 120 mg/day for 20 days
produced no adverse effects in hunans.
                                          -52-

-------
DISCIPLINARY REVIEW
Toxicology Profile
Toxicology Hazard Assessment
Data Caps
Required Labeling


Toxicology Profile

Technical 4-amir.opyridine

The very low acute oral LDcQ in both laboratory rats (28.7 mg/kg) and dogs
(3.7 mg/kg) indicate a hign acute oral toxicity in humans.  The acute dermal
toxicity in male rabbits (LDt-g = 327 mg/kg) suggests a moderate dermal
toxicity in humans.  Technical 4-aminopyridine is expected LO produce only
mild, short-term eye irritation in humans, based on studies conducted with
rabbits.  Mild eye irritation lasting less than 7 days was noted when this
compound was instilled into rabbit eyes.  Technical 4-aminopyridine is not
expected to cause skin irritation in humans.  No sign of skin irritation was
noted when 4-aminopyridine was applied to intact and abraded rabbit skin.

Adequate subchronic 90-day oral toxicity data were available for technical 4-
aminopyridine.  No significant pathologic changes in any organ or tissue and no
compound-related effects in blood or urine in rats and dogs were noted.
However, at high doses (2.0-3.25 mg/kg/day) brain weight in dogs was affected,
although examination of the brain revealed no abnormalities.  The no-observable-
effect level (NOEL) was 3 ppm in rats and 200 ppm (.1 mg/kg/day) in dogs.

4-aminopyridine. Formulations

Very little data specific to any of the formulations of 4-aminopyridine were
available. Based on extrapolation fron data available on the technical
compound, formulations of 4-aminopyridine are assigned LO the following
Toxicity Categories:

Actus Oral Toxicity:           o Formulations containing 25% or more
                                 4-aminopyridine—Toxicity Category I
                               o Formulations containing 2.5% to 24%
                                 active ingredient—Toxicity Category II
                               o Formulations containing less than 2.57=
                                 active ingredient—Toxicity Category III

Acute Dermal Toxicity:         o Formulations containing 65% or more
                                 4-aminopyridine—Toxicity Category II
                               o Formulations containing 6.5% to 64%
                                 active ingredient—Toxicity Category III
                               o Formulations containing less than 6.5%
                                 active ingredient—Toxicity Category IV
                                       -53-

-------
Primary Eye Irritation:           Ail formulations—Toxicity Category III

Primary Dermal Irritation:        All formulations—Toxicity Category IV

No data were available for assessing the acute inhalation toxicity to humans of
4-.aminopyridine dust formulations.


                               Hazard Assessment
4-Amir.opyridine Formulations

The  'Exposure Profile' which appears in the Environmental Fate Chapter
indicates that there is little chance of oral exposure to 4-aminopyridine
formulations, except through accidental ingestion.  Dietary exposure from
residues in corn and sunflowers is expected to be insignificant.  Accidental
ingestion of 4-aminopyridine can result in serious poisoning, and in some cases
death.  The severity of the poisoning is dependent upon the concentration of
active ingredient in the formulation swallowed.

No inhalation exposure to ready-to-use baits will occur, due to the nature of
these formulations.  Inhalation of dusts may occur, however, if applicators do
not wear respirators.  No inhalation toxicity hazard assessment can be made for
4-aminopyridine dusts because of the lack of data.  Similarly, the potential
for teratogenic or mutagenic effects resulting from inhalation exposure cannot
be determined because of a lack of data.

Because the applicator will be required to wear gloves, there should be no
hazards resulting from dermal exposure to any 4-aminopyridine dust or
pretreated bait product which falls into Toxicity Category I or II for dermal
toxicity.  Applicators who handle pretreated baits which fall into Category IV
will not be required to wear gloves and may be exposed on a short-term basis to
very small amounts of 4-aminopyridine.  The hazard is slight, however, since
such products have very low dermal toxicities.  Accidental occular exposure may
occur while handling dusts.  Eye exposure to either the 5Q% or the 25* dust
formulation is expected to produce only mild, short-term eye irritation.
Since chronic exposure to 4-aminopyridine for either the applicator or the
.public will not occur, no oncogenic reproductive or general chronic effects are
expected to result from use of 4-aminopyridine products.
                                         -54-

-------
                              Data Gaps


The following are gaps in the Toxicology data base needed to adequately support
a Registration Standard for 4-aminopyridine.  Listed after each gap, is the
section in the proposed Guidelines (U.S. Environmental Protection Agency, 1978)
which describes that type of study and when it is required.

Technical 4-aminopyridine                               Guideline Section

No data requirements

4-aminopyridine Dusts

Acute inhalation toxicity study                                163.81-3

Registrants of dust formulations must agree to provide or cite the following
studies, OR_ to adhere to label requirements for protective clothing discussed
in the Required Labeling Section of this chapter.
                                                                          i
Teratogenicity (2 species)                                     163.83-3

Mutagenicity                                                   163.84-1,2,3,4


Required Labeling

Each 4-aminopyridine product must bear label statements appropriate to the
Toxicity Categories assigned to that product for each acute effect (Refer to
{162.10 of 40 CFR, 1978) with the following exception:  Labels on all 4-
aminopyridine dust products, regardless of the Toxicity Categories assigned,
must require applicators to wear protective clothing including long sleeves,
gloves,  and respirators.

To help prevent accidental oral ingestion, dust product labels must also bear
the requirement, "Bait materials resembling hunan food must be altered in form
by crushing, balling, or pelleting so that they are not readily recognizable as
hunan food.
                                                                  \
Despite precautions, accidental oral ingestion may still occur.  Consequently,
the following statement of emergency treatment must be.included on the label of
all 4-aminopyridine manufacturing-use, and formulated products:

IF SWALLOWED:  If the patient is unconscious, maintain breathing and heart beat
(CPR: cardiopulmonary resuscitation).  Contact your local Poison Control
Center,  hospital or physician immediately.

If patient is conscious, induce vomiting with syrup of ipecac (if not available
stimulate the back of the throat with finger).  Never give anything by mouth to
an unconscious person!  Contact your local Poison Control Center, hospital or
physician irnnedlately.
                                        -55-

-------
                             Toxicology Bibliography
 Agos ton ,  3.;  V.'esrd-sn ,  T.  von;  Westra,  P.;  Broekert,
                                                                   1>7
0-5006373



05003729


05003160


00004027
05004214
00004024
05003155
00004026
05003153
05004217
05003494
    Effects of 4-aminopyridine  in  Eaton  Lambert  syncroine.   British
    Journal of Anaethesie  50(4):333-335.
Al-!h>boubi, H.A.; Bovraan,  W.C.;  Houston,  J. ;  Savage,  A.G.  1973.
    Effects of 4-aminopyridine  on  the  isolated
    parasympathetically-innervated oesophagus of che.domestic fowl
    chick.  Journal of  Pharmacy  and  Pharmacology 30(3):517-513.
Anaen, M.E.; Leander, S. 1979.   Effects  of  4-aminopyridine  on the
    turnover of mor.oamines in the  central nervous  system of the
    rat.  Journal of Neural Transmission  44(i/2):1-12.
Eownan, W.C.;  Khan, H.H.;  Savage,  A.O. 1977.  Sane antagonists of
    cantrol-ane sodium on the isolated  diaphragm  muscle  of the rat.
    Journal of Pharmacy and Pharmacology  29(10):516-625.
Corvenka, H.;  Vega, 3.M. 1963.   Ninety-Day Subacute Oral Toxicity
    of Canpounc 1361 (4-Aminopyridine)—Beagle Dogs:  Project  Number
    777.  (Unpublished  study received  Dec 30, 1963 under IF'iOlj.;
    prepared by Lifestream Laborstories,  Inc., submitted by Phillips
    Petroleum  Co., Bartlesville, Okla.; CDL:091 /56-G)
Fastier, F.N.; McDowall, M.A. 1953.  A comparison of the
    pharmacological properties of  the  three isorneric
    aminopyriaines.  Australian  Journal of Experimental Biology
    jo:365-371.
Ives, M. 1962.   Report  to Phillips Petroleum  Company: Toxicity
    Studies on Compound 1361 Hydrochloride.   (Unpublished study
    received Dec 30, 1963 under  1F1013; prepared by Industrial Bio-
    Test Laboratories,  Inc., submitted by Phillips Petroleum  Co.,
    Bartlesville, Okla.; CDL:C91756-3)
Kannan, M.S.;  Daniel, E.E.  1973.   Formation of gap junctions  by
    treatment  in vitro  with potassium conductance blockors.
    Journal of Cell Biology 73(2):333-343.
Kohn, F.E.; Cervenka, H.; Kay, D.L.; Vega, 5.H.   1563.  90-Day Sub-
    acute Oral Toxicity of Canpounc  1361  (4-Amir.opyridine): Albino
    Rats: Project lium'oer 333.   (Unpublished study received  Dec 30,
    1963 under  1F101j;  preparec by Lifestrean Laboratories, Inc.,
    submitted  by Phillips Petroleum Co.,  Bartlesville, Okla.; CDL:
    091756-F)
Lzander, S.; Arner, A.; Johansson, 3.  1977.   Effects of
    4-ejfiinopyridine on mechanical activity ana r.oracrenaline
    release in the rat  portal vein in  vitro .  European Journal of
     Pharmacology 46(4):351-361.
Lundh, H.; Nilsson, 0.; Rosen, I.  1977.  4-Aminopyridine—a new
    arug tested in the treatment of Eaton-Lambert syndrome.
    Journal of Neurology,  ','eurosurgery, and Psychiatry
    40(10:1109-1112.
Lundh, H.; 'liisson, 0.; Rosen, I.  1979.  Effects of
    4-anir.opyridine in myasthenia gravis.  Journal of Neurology,
    Meurosurgery,  and Psychiatry 42(2):171-175.
                                        -56-

-------
05004305


05003154


OUOC41J7



05005134
Millar, R.D.; Booij, L.H.D.J.; Agoston, S.; Crul,  J.F.  1979.
    4--Aminopyridine potentiates neostigmine and pyridostigmine  in
    win. .  Anesthesiology 50 (5): 416-420.
,-ioritoki,  H.; Takei, M.; ."Jakarnoto, N.; Ishida, Y.  1973.   Actions
    of arninopyridines on guinea-pig ilaurn.  Archives
    Internationales de PharmacodynaT.ie et de Therapie  252(1):28-41.
Phillips Petroleum Conpany no date.   Percutaneous  Tests on  Rabbits
    with Grain Containing 1361, 4-Aminopyridine as the Hydrochlo-
    riae.    (Unpublished study received Oct 5,  1966 under  unknown
    admin, no.; CDL:103074-A)
Vohra, M.M.; Pradhan,  3.N.;  Jain, P.C.; Chatterjee, 3.K.; Anand,
    i*. 1365.  Synthesis and structure-activity relationships  of
    sane atninopyridir.es, imidszopyridines, and triazolopyriaines.
    Journal of Medicinal Chemistry 3(5):295-504.
                                         -57-

-------
                   Standard  References

Tiii3 40 -Prot»ct,ior; of the  Environment  40 CFR,  1370,.   Cods of
    Federal Regulations.  Chapter i -Environmental  Protection
    Agency.  Washington, D.C.:  U.S. Government  Printing Office.

U.o. Environmental Projection Agency 197G.   Proposed  Guidelines  for
    for registering P-asticidas in the United States.   Haajrc
    Evaluation:  Human and Domestic i\r.irr.als.   43 Feder-al Register,
    (153) 5/336. (August 22,  1973)
                               -58-

-------
                           VII. Residue Chemistry

Topical Discussions

the Proposed Guidelines for residue chemistry have not been published.
Accordingly there are no citations for guidelines corresponding to the types of
residue chemistry data normally required to support individual registrations.
In general, however, the Agency must have sufficient data for each proposed
product to be assured that the residues of the parent chemical and its
metabolites have been quantitatively and qualitatively identified.

Plant. Metabolism of 4-aminopyridine:

Data are required to examine the metabolism of 4-aminopyridine in the crop to
which it is applied.  The available information on this topic is summarized by
crop.

    Corn:  The amount of information available on the metabolism of 4-
    aminopyridine in plants is limited.  There is one report in the published
    literature (Starr and Cunningham 1975,  05003202) regarding the
    degradation of 4-aminopyridine in corn.  Young corn plants were exposed to
    10 ppm of 4-aminopyridine in nutrient solution for^ days.  TLC-
    autoradiography of the acetone extracts showed no   C-radioactivity
    other than parent compound in roots or  shoots.  A study (Starr and
    Cunningham 1966, 0004039) of the absorption of 4-aminopyridine from soil or
    nutrient solution bjf^variously aged corn plants demonstrated that older
    plants absorb less   C-4-aminopyjjidine  than younger plants.  2-month old
    corn plants absorbed much less   C-radioactivity from soil at 10 ppm than
    from nutrient solution.  Corn plants at three months showed that detectable
    radioactivity in an ear of corn and in  the uppermost 2 feet of stalk
    resulted fron exposure to nutrient solution at 5 ppm.  The first tbjjee 12-
    inch sections of the stalk contained 1.4,  0.074,  and 0.004 ppm of   C-
    equivalent to 4-aminopyridine respectively.  Nutrient solution exposure is
    much greater than exposure under field  conditions.  Therefore, residues of
    4-aminopyridine in corn under field treatments are expected to be
    considerably lower.

    In  summary,  the only residue of 4-aminopyridine found in corn plants was
    the compound itself.   No metabolites of 4-aminopyridine were detected.  No
     C-radioactivity was detected in corn  grain after nutrient solution
    exposure.   Based upon this information,  the low application rate,  and the
    field residue data discussed below, residues of 4-aminopyridine are not
    expected in  corn grain under normal use conditions.

    Sunflowers:   There are no available reports of the metabolism of 4-
    aminopyridine in sunflower plants.   Cunningham (1975, 00004088) studied the
    absorption of 4-aminopyridine by sunflower plants from soil treated at an
    exaggerated  rate of 20 applications.  The  concentration in the soil was
    0.02 ppm.   However, during the 8 weeks  of  growth,  there was no observable
    difference between treated and control  plants in  the amount of   C-
                                           -59-

-------
    radioactivity in sunflower leaves, stems and stalks, and flower plus
    leaves.  This information indicates that residues of 4-aminopyridine or its
    metabolites would not be expected in sunflower plants under field
    conditions.

    Other. Plants:  The metabolism and degradation of 4-aminopyridine in
    sorghum plants were reported by Starr and Cunningham (1975, 05003202).
    Acetone extracts of young sorghum plants exposed to 5 ppm 4-AP in nutrient
    solution fgr one week followed by one week without exposure, contained 3
    distinct   C- containing degradation products.  The th^e degradation
    products contained from 0.5? to 4.4? of the recovered   C [recovery
    ravage 83? to 95?].  The degradates were not identified or characterized
    other than by reportednRF values in a specific TLC procedure.  More than
    90? of the recovered   C was in the parent compound, as shown by TLC-
    autoradiographic procedures.  When more mature plants were tested, only low
    levels of unidentified   C-radioactivity were reported in sorghum seeds
    and heads, following nutrient solution exposure at 5 ppm.  This stu^y
    suggests that some 4-aminopyridine plant metabolism occurs, since   C-
    radioactivity was less easily recovered from older plants than from younger
    plants.

Animal Metabolism:

Data on animal metabolism are required if residues are found in animal food or
feed items.  Sullivan (1970, 00004030), reported that in vitro beef and chicken
liver honogenates showed no observable degradation of "^aminopyridine during 24
hours of incubation.  Although this study would not fulfill an animal
metabolism data requirement, additional data are not needed since residues of
4-aminopyridine are not expected in animal food and feed items (see above).

Analytical Methods:

Because 4-aminopyridine is used on crops, an analytical method for detecting 4-
aminopyridine residues in treated crops is required.  The method must be valid
and specific for 4-aminopyridine, without interference from other pesticides
which may be applied to these crops.

Several methods for the extraction, cleanup, and estimation of 4-aminopyridine
concentrations have been reported.  One method (Peterson, 1971, 05003193) was
considered to be inadequate due to lack of information regarding the
fortification samples.  However, further development and modification of-
Peterson's method were reported by Sullivan (1970, 00004030) and Phillips
Petroleum Company (no date,  00004016).  These improvements make this method
valid for the extraction, cleanup, and estimation of residues of 4-
aminopyridine in treated corn.  The method is as follows:

Fresh whole corn plant is chopped up into small particles and air dried to
constant weight.  An aliquot is blended with acetonitrile containing 3%
ammonium hydroxide.  After filtration, the acetonitrile solution is shaken just
to dryness.  The residue is transferred to a separatory funnel which is shaken
                                       -60-

-------
 vigorously for 5 minutes with n-butyl  acetate and 0.1  N HC1,  and the phases are
 allowed to separate.   The aqueous phase is transferred to another separatory
 funnel,  and is shaken again with n-butyl.acetate.   The phases are allowed to
 separate and both n-butyl acetate phases are discarded.  The aqueous phase is
 transfered to a third separatory funnel.  It is  adjusted to pH 11 with 10$
 sodium hydroxide and  n-butyl acetate is added.   The phases are allowed to
 separate and the aqueous phase is discarded.  The organic phase is passed
 through anhydrous sodium sulfate with  additional n-butyl acetate.  The solvent
 is  reduced just to dryness and the residue is quantitatively transferred to a
 graduated centrifuge  tube with redistilled acetone. 'The acetone solution is
 reduced to 1 ml or less  for gas chronatography under the following conditions:

          Colunn                        — Chromosorb 103
          Temperature   '               '  — 228 C
          Helium carrier  flow           — 15 at  40 psi = about 100 ml/min
          Sensitivity                    — 1  x 30
          Inlet                         — 250°C
          Transfer                  .    ~ 250°C
          Furnace                       — 900 C
          Detector                      — Nitrogen conductivity detector

 The minimum level detectable by this procedure is  10 nanograms or 0.1  ppm for
 100 gram samples (fresh  weight).   The recovery of  4-aminopyridine from 4
 control  samples  fortified at 0.1  ppm ranged  from 70? to 80 %,  while at 0.4 ppm
 the recovery in  one control sample was  86%'(Sullivan,  1970, 00004030).

 The analytical method described above was  used to  report the  residues  of
 4-aminopyridine  in field treated  samples of  corn.   It  was  also the  method
 published in the Pesticide Analytical Manual, Vol.  II,  for the determination  of
 4-aminopyridine  residues in corn.  The method has  been  subjected  to thorough
 analytical research for  accuracy and sensitivity in EPA laboratories.

 The same method  is considered  adequate  for residues of  4-aminopyridine  in
 sunflower  seeds  although a high degree  of scatter  of recovery values has  been
 reported  (Copeland, 1972,  00004050).  Attempts to  modify the method  to  improve
 the recovery from sunflower  seeds were reported  by Peterson (1974,  00004048;
 1975, 05003192).   Due to the high  content of oil and cellulose material,  the
 modifications  were thought to  be  necessary to allow the extraction  of 4-
 aminopyridine  fron sunflower seeds.  These modifications are  described  below:

 Seeds and  plant  tissues  are ground to 30 mesh and  extracted with  n-butyl
 acetate  and  sodium hydroxide.   The 4-aminopyridine  is partitioned from  n-
 butyl acetate  into water  under  acidic conditions and is  cleaned up  by passing
 through a weakly  acidic  cation  exchange resin (Amberlite IRC-50)  using
 hydrochloric  acid  as  regeneration  solvent.   The  residue  is. repartitioned
 between n-butyl acetate  and water containing either  sodium hydroxide or
 hydrochloric  acid.  The  residue is analyzed  on GLC  using flame  ionization
 detection or electrolytic conductivity detector.   ,The GLC  column material is 3/°
 Carbowax 20M and 0.1% potassium hydroxide on Chromosorb 750.. The lower limit
of  detector linearity  is  10 nanograms.  Recovery is reported at 50$ to 70%.
                                        -61-

-------
In addition to the gas liquid chronatographic detection system, procedures for
TLC identity confirmation and semiquantitative estimation of 4-aminopyridine
residues are reported by Sullivan (1970,  00004007; 1970, 00004030), Starr
(no date, 00004126), Schafer and Starr (1969, 00004011), and Phillips Petroleum
Company (no date, 00004029).

Residue Data —- Crops:

Data on 4-aminopyridine concentrations in treated crops are required to assure
that residues are below tolerance values under actual field conditions.  Field
residue data are expected to reflect the residues resulting from the registered
uses in regard to dosage rates, modes of application, numbers and timing of
treatments, formulations used and geographical areas.

    Field Corn:   One valid study (Sullivan, 1970, 00004030) reported traces of
    4-aminopyridine in field corn receiving up to 5 applications of a 1 pound
    per acre treatment.  Traces of 4-aminopyridine in whole corn plants were
    reported to be less than the minimum detectable residue, 0.1 ppm.  There
    were no differences between the control samples and treated samples.

    Sweet Corn:   A report of uncertain validity (Peterson, 1974, 00004100),
    showed corrected residues of 4-aminopyridine at 0.03 ppm maximum in ears of
    sweet corn.   The accuracy of this information cannot be determined because
    the analytical method was not adequately described.

    Sunflowers:   There is one report of residue data for 4-aminopyridine in
    sunflowers receiving both label rates and exaggerated dosages, (USDI, no
    date, 1015-002-01).  At label rates of up to 5 applications, there were no
    detectable differences between control and treated values.  All residue
    values were less than 0.01 ppm.  At exaggerated rates totaling 12.6 pounds
    of bait per acre in 13 treatments, treated seed samples showed 0.05 ppm of
    4-aminopyridine while control samples showed 0.008 ppm.

    Estimated Residues in Corn and Sunflowers:  In addition to residue data for
    corn and sunflowers, a variety of calculations or estimates have been made
    of the residues of 4-aminopyridine that would be expected based on
    application of active ingredient at the rates indicated on product labels.
    These calculations are based upon the characteristics of the formulated
    product and use pattern.  The formulated product is applied as a
    heterogenous mixture of 1% (by weight) treated bait particles and 99% (by
    weight) untreated bait particles.  The treated bait particles contain 3%,
    by weight, active ingredient.  The bait formulation applied contains 0.03%,
    by weight, 4-aminopyridine.  At one pound of bait per acre, per treatment,
    the amount of active ingredient 4-aminopyridine applied to the crop is
    0.0003 Ibs per acre.

    One report (Phillips Petroleum Company, no date, 00003993) stated that the
    yield of corn and fodder is 40,000 pounds per acre.  Based on this
    assumption and three applications of 0.0003 pounds active ingredient per
    acre, the maximum concentration of 4-aminopyridine in corn and grain would
                                          -62-

-------
    be  0.0225 ppm if all the applied 4-aminopyridine were absorbed and
    translocated.  However, testimony presented  (Phillips Petroleum Company, no
    date, 00004017) contended that 80% to 9555 of the bait granules reach the
    ground.  Assuming that  103 of the particles lodged in the plant during
    three applications, the average residue in corn grains and fodder would be
    0.0023 ppm.

    Another report (Phillips Petroleum Company, no date, 00004022) estimated
    from particle weight and plant yield per acre that the concentration of 4-
    aminopyridine in a corn plant would be 6.6 x 10~  g/g of corn plant if
    one active treated particle lodged in one corn plant weighing 2.5 pounds.

    Similar estimates were made for sunflower seed, based upon yield of seed
    and plants per acre.  Assuming 3 and 4 applications, residues in sunflower
    plants would be 0.0225 ppm in good sunflower crops (40,000 pounds of plants
    per acre) and 0.052 ppm in poor crops (23,000 pounds per acre) (Avitrol, no
    data, 00004049).

A study (Swindle, 1973, 00004039) was conducted to observe the actual number
of bait granules lodging in sunflower seed heads or other portions of the
plant.  Calculations based on the maximum observed number of granules per acre,
estimated the residues of 4-aminopyridine in sunflower seeds to be 0.01V ppm,
assuming complete adsorbtion and translocation.

This information, together with plant metabolism data, the estimates of
residues, and the actual residue data, provide sufficient information on
residues of 4-aminopyridine in corn and sunflower seeds.  Based upon these
data, residues of 4-aminopyridine at method sensitivity (0.1 ppm) are not
expected in either corn or sunflowers.

Residue Data ~ Processed, Commodities:

Data on residues in processed commodities are required if residues are found in
the raw agricultural commodity.  There are no data available for residues of 4--
aminopyridine in processed ccmmodities.  However, since residues of 4-amino-
pyridine do not occur in the raw agricultural commodities (corn, corn fodder
and forage, and sunflower seeds), residues of 4-aminopyridine should not occur
in processed commodities derived from these raw agricultural products.
Therefore, residue data on processed commodities are not required.

Residue Data -- Meat, Milk, Poultry,, and Eggs

Data on residues in meat, milk, poultry,  and eggs are required if residues are
found in animal food or feed items.  Based upon residue data on agricultural
commodities,  significant residues of 4-aminopyridine are not expected to occur
in animal food or feed items.   Residues of 4-aminopyridine would not be
expected in meat, milk, poultry or eggs from animals consuming feed or food
items treated with 4-aminopyridine according to label directions.  Therefore,
data on residues in meat, milk, poultry and eggs are not required to support
currently registered uses of 4-aminopyridine.
                                         -63-

-------
DISCIPLINARY REVIEW
Residue Chemistry Profile
Tolerance Reassessment
Data Gaps
Required Labeling


Residue Chemistry, Profile

At the sensitivity of the method no residues of 4-aminopyridine are likely to
be found in corn grain, corn fodder and forage, sweet corn (including popcorn)
or sunflower seeds when products are used according to label directions.  In
addition, calculation of maximum possible residues in these commodities based
on the low dosage rates indicates that residues should not result from the
label maximums of five applications per year for sunflowers and four
applications per year for corn.  Since no residues of 4-aminopyridine at method
sensitivity are expected in the raw agricultural products, no data are needed
for processed commodities or for meat, milk, poultry or eggs.

Available plant metabolism data indicate that sane metabolism occurs, with
three metabolites isolated (but not identified or characterized) in sorghum
plants.  No metabolites were found in corn.  4-aminopyridine is absorbed and
translocated in corn plants from nutrient solution, but less so from soil.
Based on this absorption, translocation and metabolism information, plant
uptake of 4-aminopyridine is not expected to be significant in. corn and
sunflowers.

There were no available studies of animal metabolism of 4-aminopyridine.  When
4-aminopyridine was studied in vitro in beef and chicken liver homogenate
systems, there was no observable metabolism.  These data would not fulfill an
animal metabolism data requirement, but additional data are not needed because
4-aminopyridine residues are not expected in animal food and feed items.

Tolerance Reassessment

The Theoretical Maximum Residue Contribution (TMRC) for 4-aminopyridine in corn
(all types) and sunflower is 0.0033 mg/day for a diet of 1.5 kg.  This amount
is 4.233 of the Acceptable Daily Intake which is 0.0015 mg/kg/day.  In the
reassessment of this tolerance, calculations were based upon the level of
detection, as were the original tolerances.  The Agency does not expect
the Average Daily Intake to result in any unsafe levels of 4-aminopyridine
in the human diet.

Data Gaps

There are no residue chemistry data requirements for non-food uses of 4-amino-
pyridine, nor are there any generic residue chemistry data gaps resulting from
food uses of 4-aminopyridine at present.  The registration/tolerance data
requirements for the food uses on corn and sunflowers have been satisfied.
Uses of 4-aminopyridine on raw agricultural commodities other than corn and
                                        -64-

-------
sunflowers would require a validated analytical method, residue data and plant
metabolism data.  If residues of 4-aminopyridine were to be found in raw
agricultural commodities other than corn and sunflowers, data on residues of 4-
aminopyridine in meat, poultry and eggs would be required, including
identification of the animal metabolites of 4-aminopyridine.
Required Labeling


Labeling of 4-aminopyridine products must bear a warning or restriction
against use, storage, or disposal of a 4-aminopyridine formulation in a manner
likely to result in contamination of human food items. The bait formulations
intended for use on corn and sunflowers should be limited to a maximum of five
applications per crop season for sunflowers and four applications per crop
season for corn.  The specific labeling restrictions for the pretreated bait
formulations necessary to prevent contamination of human or animal foods are:

    For all products

    Do not use where food (grain or meat) might become contaminated.

    Do not contaminate water, food or feed by storage or disposal.

    For pretreated baits

    Do not feed to livestock or poultry.

    Do not mix with grain for livestock or poultry feed.

    For products intended for use in cattle, feed lots

    Keep treated bait off the ground, out of reach of cattle.
                                        -65-

-------
                            Bibliography
00004049   Avitrol Corporation (no date) Toxicology: Mathematical Approach:
               Consumer Safety from Pesticidal Residues.  (Unpublished study
               received Apr 30, 1974 under 4F1498; CDL:094836-W)
00004050   Copeland, G.L. (1972) Interim Report: Development and Evaluation of
               Methodology to Determine Residues of 4-aminopyridine in Sun-
               flower Seeds.  Method dated Jul 14, 1972.  (Unpublished study
               received Apr 30, 1974 under 4F1498; prepared by Hazleton Labora-
               tories, submitted by Avitrol Corp., Tulsa, Okla.; CDL:094836-X)
00004088   Cunningham, D.J. (1975) Translocation of 14C-4-aminopyridine in
               Sunflowers and Wheat Growing in Treated Soils: (Report of Study
               No. 37, Work Unit DF-102.2).  (Unpublished study received Apr
               28, 1975 under 11649-15; prepared by U.S. Fish and Wildlife
               Service, Denver Wildlife Research Center, submitted by Avitrol
               Corp., Tulsa, Okla.; CDL:225254-E)
           Food and Drug Administration (1978) Pesticide analytical manual.
               Volume II.  Methods for individual residues.  U.S. Department
               of Health, Education and Welfare:   Washington, D.C.
05003203   Glover, W.E. (1978) Potentiation of vasoconstrictor responses by
               3- and 4-aminopyridine.  British Journal of Pharmacology
               63(4):577-585.
05003193   Peterson, J.E. (1971) A microanalytical method for 4-aminopyridine
               in corn plant tissues.  Bulletin of Environmental Contamination
               and Toxicology 6(1):72-80.
05003192   Peterson, J.E. (1975) A microanalytical method for 4-aminopyridine
               in sunflower seeds and plants.  Bulletin of Environmental
               Contamination and Toxicology 13(6):641-645.
00004048   Peterson, J.E. (1974) Gas Chromatographic Method for 4-aminopyri-
               dine in Sunflower Plants and/or Seeds.   Method dated Apr 24,
               1974.  (Unpublished study received Apr 30, 1974 under 4F1498;
               submitted by Avitrol Corp.,  Tulsa, Okla.; CDL:094336-U)
00004100   Peterson, J.E. (1974) Sweet Corn—4-AP Residue Analyses.  (Unpub-
               lished study received Mar 18, 1975 under 11649-12; prepared by
               U.S. Fish and Wildlife Service, Denver Wildlife Research
               Center, Section of Chemical  Research and Analytical Services,
               submitted by Avitrol Corp.,  Tulsa, Okla.; CDL:094799-1)
00004016   Phillips Petroleum Company (1971) Applicability of Proposed GLC
               Analytical Method for 4-aminopyridine Residues in Corn Grain.
               Summary of study 093322-B.   (Unpublished study received on un-
               known date under IF 1013; CDL:093322-A)
00004029   Phillips Petroleum Company (no date) Methodology:  [4-aminopyridine].
               Includes two undated methods.  (Unpublished study received Jan
               3, 1973 under 1F1013; CDL:091757-B)
00003993   Phillips Petroleum Company Cno  date) Residue Data: 4-aminopyridine
               (Avitrol 200; DRC-1327).  (Unpublished study received Apr 22,
               1969 under 224-EX-3; CDL: 122747-G)
                                        -66-

-------
00004017   Phillips Petroleum Company (no date) Calculations for Amount of
               Residue Likely to Migrate to Corn Plant as a Consequence of
               Lodging of Bait on Plant during Application.  (Unpublished study
               including letters dated Mar 24, 1971 and Mar 25, 1971 from
               R.N. Smith to Merrill Schnitzer, received June 25, 1971 under
               1F1013; prepared in cooperation with U.S. Fish and Wildlife
               Service, Div. of Wildlife Research; CDL:093322-B)
00004022   Phillips Petroleum Company (no date) Residue Data: Estimate of
               Possible Contamination of Com Plant as a Consequence of Lodging
               of an Active Bait Particle in the Plant.  (Unpublished study
               received Jan 8, 1973 under 1F1013; CDL:091755-D)
00004011   Schafer, E.W.; Starr, R.I. (1969) The Use of Thin-Layer Chromato-
               graphy as a Confirmatory Method for the Analysis of 4-amir.o-
               pyridine: Progress Report—September 29, 1969.  (Unpublished
               study received Oct 20, 1969 under 224-EX-3; prepared by U.S.
               Fish and Wildlife Service, Denver Wildlife Research Center,
               submitted by Phillips Petroleum Co., Bartlesville, Okla.; CDL:
               122744-R)
05003440   Starr, R.I.; Cunningham, D.J. (1974) Phytotoxicity,  absorption,
               and translocation of 4-aminopyridine in corn and sorghum
               growing in treated nutrient cultures and soils.   Journal of
               Agricultural and Food Chemistry 22(3):409-413.
00004039   Starr, R.I.; Cunningham, D.J. (1966) Translocation and Degradation
               of 4-aminopyridine in Corn Plants.  (Unpublished study received
               Jan 3,  1973 under 1F1013; prepared by.U.S.  Fish  and Wildlife
               Service, Denver Wildlife Research Center,  submitted by Phillips
               Petroleum Co.,  Bartlesville, Okla.; CDL:091757-T)
05003202   Starr^R.!.; Cunningham, D.J. (1975) Degradation of 4-aminopyridine
               -  C in corn and sorghum plants.  Journal of Agricultural and
               Food Chemistry 23(2):279-281.
00004126   Starr, B. (no date) Thin-Layer Chromatography—Avitrol.  (Unpublish-
               ed study received Apr 15, 1969 under 224-EX-3; prepared by U.S.
               Fish and Wildlife Service, Denver Research Center, submitted by
               Phillips Petroleum Co.,  Bartlesville,  Okla.; CDL:122745-J)
00004030   Sullivan, J.B. (1970) Final Report: Evaluation of 4-aminopyridine,
               Evaluation of the Sponsor's Analytical  Method,  and Analysis of
               Field Samples.   Includes method dated May 27, 1970.  (Unpublish-
               ed study received Jan 3,  1973 under 1F1013; prepared by Hazleton
               Laboratories, Inc.,  submitted by Phillips Petroleum Co.,
               Bartlesville, Okla.; CDL.-091757-C)
00004007   Sullivan, J.B. (1970) Progress Report: Evaluation of 4-aminopyri-
               dine.  Includes method entitled:  Thin-layer Chromatography
               (Betagram 0).  (Unpublished study received on unknown date under
               224-EX-3; prepared by Hazleton Laboratories, Inc.,  submitted by
               Phillips Petroleum Co.,  Bartlesville, Okla.; CDL:122744-N)
00004039   Swindle,  K. (1973)  Results of Particle Entrapment Experiment.  (Un-
               published study received Apr 24,  1975 under 11649-15; prepared
               in cooperation  with U.S.  Fish and Wildlife  Service and U.S.
               Environmental Protection Agency,  submitted  by Avitrol Corp.,
               Tulsa,  Okla.; CDL:225254-F)
1015-002   U.S. Department of the Interior,  Analysis of 4-aminopyridine
    -01        residues on Sunflower  seeds  and plants.
                                       -67-

-------
                  VIII.  regulatory  ria cion^ie


   DC -
  -_. v. c;
  ysc:;   an   cemca   proper t  -3
             or reregistration  of  all  4-aminopyr idino
mcr.ufactur ing-use  and  formulated  products  so  that  the  Agency car.
characterize  each  pesticide.   Because  4-aminopyridine  is  a  minor
use  pesticide with an  annual  production  of less  than  350  pounds,
the  following ecological  effects  and environmental  fate  studies
arc-  not  required:
     o acute  toxicity  studies  on  coldwater fish
       and  aquatic  invertebrates
     o a hydrolysis  study
     o an activated  sludge seudy
Studies  or  the fate  of  4-aminopyridine in  soil are  not  r=quired
because, based on  available information  on the use  patterns of  4-
AP end-use  products, n-aminopyr idi.ne residues  in soil  are noc
expected to reach  significant  levels.  Certain chronic
toxicology  studies  are  not required because of ehe  following:
     1 )  The use pattern is not  expected  to result  in repeated
         exposure over  a significant portion of one  human  life
         span.
     2)  Although 4-aminopyr idine  has a tolerance of 0. 1ppm  for
         both corn  and  sunflowers, human  dietary  intake  from
         consumption  of  these  crops is  expected to  be negligible.
In order to develop  proper labeling, acute inhalation  toxicity
data are required  for  the registration or  rer egistr ation  of all
dust products.  Because of the  possibility of shore-term
exposure, teratology and rr.utagen ici ty  da^a will  be  required if
applicators of dust  products  are  not required, by  the-  label,  to
wc^r protective clothing, including long sleeves,  gloves,  and
respirators.

Products t_o b£ Covered  Under This Standard

M a r. u f s c t u r i n g -U s e  Pr oducts
Having considered  all  the available information  on  4 -
.•iminopyridine manufacturing-use products,  the Agency has
ceterr.iined  that manufacturing-use U-crninopyricin.c  does  noc,  caus?
unreasonable adverse effects with proper- label directions  and
precautions.  Therefore, the  Agency will accept  for r egistration
or r eregistr-a t ion manufacturing-use products with  sny  percentage
of M-arninopyr idine so  long as  inert ingredients  greater than
1.0",, by weight of tha  total product, consist of food  or
feed stuffs  only.

Fort.-iulateG  Products
Th i s 3t :.;nc arc covers only 'ready-to-use  bait' and  'dust'  type
formulations whose inert ingr rCiiints consist only  of food or
ftecstuffs.   Products containing  o-chor iner-Ls ingredients  coulc
have- significantly different properties,  ana products  in  forms
cizli^r than  Gusts or ready-to-use  bair.s would have  significantly
cifferc-n^ application methods not consicered by  data available
on the currently registered pr<">aucts.  Additional cata
po-rtjin ing  c.o x,.-..- produce chemistry,  environmental  fate,


                             -68-

-------
 toxicology,  residue  chemistry  and  ecological  effects  of  n-2u
 formulation  types  2nd  thtir  appliestion  methods  may  be needle
 to  support the  registration  of  such  products.

 available data  are  insufficient to adequately determine  the
 hazards  to humans  and  wildlife  from  pretreated bait  or dust
 products with uses  other  than  those-  currently registered,
 including use of re-ady-to-use  baits  on additional  crops.
 Because  such uses  could re-suit  in  increased exposure  and  in
 higher 4-AP  residue  levels in  soil  and crops,  additional
 en v iror.mental fate,  residue  chemistry and  toxicology  data  would
 be  required  GO  support such  uses.   Specifically, additional
 residue  chemistry  data would be  required to establish  tolerances
 for crops other than corn or sunflowers.   The  available  residue
 chemistry data  s>-e  sufficient  to'establish tolerances  onlyfor
 corn  and sunflowers.   4-arninopyridine ready-to use baits may be
 applied  at a rate  of up to .0144 ounces  active ingredient  per
 acre  or.  trie  treated  portion  of  a field a maximum of  four times
 per year for corn  and  a maximum  of  five  times  per  year for
 sunflowers without exceeding the established  tolerances.

 Hazards  _to Wildlife

 Manufacturing-Use Products
 To  prevent unauthorized disposal of  4-aminopyridine,  all
 manufacturing-use 4-aminopyridine  products must carry  the
 following warning on the  label:
      Do  not  discharge  into lakes,  streams, ponds,  or  public
      waters  unless in  accordance with an NPDE3 permit.   For
      guidance contact  your regional  office of  EPA.

.For  mulcted Products
 Although currencly registered 4-aminopyridine  ready-to-jse baits
 an-d dust products are  potentially hazardous to wildlife, the
 Agency considers these products suitable for  registration
 because  regulatory actions will help prevent  nontarg^t wildlife
 exposure and unnecessary  target bird mortality.  To reduce -
 the potential for unreasonable  adverse effects on  wildlife,
 all 4-aminopyridine  products will  be classified as restricted
 use pesticides  for use only by  certified applicators or
 persons  undar their  direcc supervision.  In addition,
 formulated products will  be restricted to the  following
 percentages  of  active  ingredient and dilution  ratios.  Reacy-to-
 use bait formulations -nust not  exceed i.0,i 4-aminopyridine per
 treated  granule diluted to .Oj/i 4-aniinopyr idin e per total
 product when registered for use in agricultural crops.
 Heady-to-use baits must not exceed 0.5/j  4-a:ninopyr idine when
 registered to control house sparrows, cowbirds, blackbirds, or
 pigeons  in che  area of nesting  and roosting sites, or  1.0,-j 4-
 aminopyricine when registered to control starlings in cattle
 feedlots, or crows near nesting and  costing  sites. Dust
 formulations must not exceed 50* 4-aminopyridine when registered
 to control starlings in cattle  feedlots, or- 25,'i 4-aminopyr idin 3
 when registered to control Herring Gulls near nesting and
 roosting sit^-s  and at sanitary  landfills. Dilution of bait
 before application should be no less than the  following:


                                -69-

-------
     o  1 part treated bait to j parts untreated bait  for
        pretreatea baits used to control pigeons at  nesting
        and roosting sites, and for pretreati-c bait  and dusc
        formulations used  in cattle feedlots.
     o  1 part treated bait to 10 parts untreated bait for dust
        formulations used  to.control Herring Gulls at  sanitary
        landfills and at nesting and roosting sites.
Thi ^-aminopyridine concentrations and trie .-dilution ratios noted
for the various formulations, reflect the maximum concentrations
of active ingredient and  the minimum dilution ratios  of
currently registered products.  Available ecological  effects
cata indicate that unnecessary target bird mortality, as well as
an increased hazard to nontarget wildlife would result if
products cor.tair.ea higher percentages of ^-aminopyridine or if
dilution ratios were lowered.

The following label statements', in addition to the  restrictions
discussed, above, will help reduce exposure to nontarget birds:
     For pretreated baits applieci to agricultural crops:
        o Dtfore application in'your area, consult endangered
         spe-cies personnel of the U.3. Fish and Wilalife Service
         to ensure that endangered ana rare biru species are
         not likely to be adversely affected by use of this
         product.
        o Do not allow bait to remain in unprotectec places after
         control measures are completed.
        o Confine treatment to areas 50 feet in from field edge.
     For products used at sanitary landfills, cattle
     feedlots and nesting and roosting structures:
        o This product must not be applied where nontarget
         bird species feed.
        o Careful observation of bird habits must therefore be
         made to establish proper feeding locations and to
         determine that no nontarget bird species are feeding
         on prebait.

Label directions to "Pick up and dispose- of dead birds by
burial" on all dust products and on reacy-to-use bait products
containing greater than 3.0,3 H-aminopyridine per treated granule,
should reduce the potential for secondary poisoning of predatory
wildlife. The label directions."Do not contaminate water by
cleaning of equipment or disposal of wastes11 snould help
eliminate fish anc aquatic organism exposure to significant
quantities of ^-arninopyr idine .

 Hazards _to Humans and Domestic Animals

 R-; :.icy--to !Js.e Bsit and Dust Products
All '•i-aminopyridine products will be classified as restricted
•JS-. p.-sticic^s and will be handled only by licensed applicators
wno can be expected to comply with label precautions,  ana with
directions to -./ear protective clothing.   This should greatly
r:;ouc;j th.-:- potential  for accidental exposure to 4-AF formulated
products.

In addition,  tne following warnings will be included,  where
                            -70-

-------
priato,  on product  labels  to  r-duce  the risks f>-o:n
culcir routes of  exposure:
For ^cciGcnccl or^i  exposure  to  all  products:
   o Do rot us~;  '.;har£  food  (gr^in  or  ;nea:;)  might brcorii.v
     con tain ino'ced.
For ciccidantul oral  exposure  to  dust  products:
   o Gait materials  rss-iinbling human  food  muse  be
     altered in  form by  crushing,  balling,  or pelleting
     so that they are  nou  readily  recogr. izsble  as food.
For domestic anitnsl  =xposurr  to  pricreatrd bait produce:
   o Keep bait off  the ground out  of  r=ach of
     -^ •- 4- *- ^ ~
     C 3 t -., i.': .
   o Do no- feed  to  livestock or poultry.
   o Do rot mix  with grain  for livestock or poultry.
For domestic animal  exposure  to  ousts products:
   o Keep iWciy from  livestock, poultry ana pc-ts.
                       -71-

-------
APPENDIX A:  CHEMICAL DATA SHEET



Chemical Abstracts Chemical Names:

    4-Aminopyridine

Other Chemical Names:

    gamma-am inopyridine
    p-aminopyridine
    4-pyridinamine
    4-pyridylamine

Structural Formula:
Molecular Formula:                    ....

    C^HrNp free base                                          ' '

    CcH~N2Cl hydrochloride salt

Molecular Weight:  94.11'free base             '               '
                   130.58 hydrochloride salt

Chemical Abstracts (CAS) Registry Number:'

    504-24-5

Approved Common Name:  There is no approved common name at this time.


Other Common Names, Trade Names,  or Codes:

    Avitrol 200      •         •-                    .              '
    Phillips 1861
    4-AP
    WLN: T6NJ DZ
                                         -72-

-------
              APPENDIX B:  SUMMARY OF LABEL INGREDIENT STATEMENTS
Three companies, Avitrol, Huge and Woodbury,  are the producers of the 26
registered end-use products now on the market.  Nine of these products display
the complete ingredient statement of the labels:
                                           i
    1.  Huge Company:  EPA Registration Number 2270-256

              4-aminopyridine           0.05  %
              Mixed grains*            99.931
              HC1                       0.019

        "Mixture of 1/3 cracked corn, 1/3 whole wheat, and 1/3 milo.

    2.  Avitrol Corporation:   EPA Registration Number 11649-2

              4-aminopyridine           1.0   %                .      .....
              Pelletized feed          98.62
              HC1                       0.38

    3.  Avitrol Corporation:   EPA Registration Number 11649-3

              4-aminopyridine           0.5   %
              Sorghum                  99.31
              HC1                       0.19

    4.  Avitrol Corporation:   EPA Registration Number 11649-4

              4-aminopyridine           0.5   %
              Mixed grains             99.31
              HC1                      0.19

    5.  Avitrol Corporation:   EPA Registration Number 11649-5

              4-aminopyridine           0.5   %
              Corn                     98.62
              HC1                       0.38

    6.  Avitrol Corporation:   EPA Registration Number 11649-6

              4-aminopyridine           0.5   %
              Corn Chops               99.31
              HC1                       0.19

    7.  Avitrol Corporation:   EPA Registration Number 11649-7

              4-aminopyridine           0.5   %
              Corn                     99.31
              HC1                       0.19

    8.  Avitrol Corporation:   EPA Registration Number 11649-3

              4-aminopyridine           1.0   %
              Corn                     98.62


                                  -73-

-------
          HC1                       0.53

9.  Avitrol Corporation:   EPA. Registration Number  11649-9

          4-aminopyridine            0.8   %
          Corn chops               79.1
          Peanut butter            19.8
          HC1                       0.3
                            -74-

-------
                   Guide  to Use of  This Bibliography

Content of Bibliography.  This bibliography contains citations of  all
che studies reviewed by EPA in arriving at the positions and conclusions
stated elsewhere in this  standard.  The bibliography is divided  into
5 sections: (1) citations that contributed information useful to the review
of the chemical and considered to be part of the data base supporting
registrations under the standard, (2) citations examined and judged to  be
inappropriate for use in  developing the standard, and (3) standard
reference material.  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, and the published technical
literature.

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. The Agency has sought to identify documents at a level
parallel to a published article from within the typically larger volur.es 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.

Identification of Entries.  The entries in this bibliography are sorted
by author, date of document,  and title.  Each entry bears,  to the  left of
the citation proper, an eight-digit numeric identifier.  Tnis number is
unique to the citations, and should be called the "Master Record
Identifier", or "MRID".  It is not related to the six-digit "Accession
Number" which has been used to identify volumes of submitted data; 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.  Tnis is also to be used whenever  a
specific reference is needed.

Form of the Entry.  In addition to the Master Record Identifier  (MRID),
each entry consists of a bibliographic citation containing standard
elements followed, in the case of materials submitted to EPA, by a-
description of the earliest known submission.  The bibliographic
conventions used reflect the standards for the American National Standards
institute (ANSI),  expanded to provide for certain special needs.   Some
explanatory notes of specific elements follow:

  a. Author .   Whenever the Agency could confidently identify one,
     tne 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 known submitter as author.

  b. Document Date.   When the aate appears as four digits with no
     question  marks,  tne 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.
                                        75

-------
c. Ti tie.  Tnis is the third element in the citaitnn.  In some cases it
   has been necessary for tha Agency bibliographers to create or enhance
   .£ document oitie.  Any such editorial insertions are contained
   between square brackets.

d. Trailing Parenthesis.  For studies submitted to us in the past, the
   trailing parenthesis include (in addition to any self-explanatory
   text) the following elements describing the earliest known submission.

        (1)  Submission Date.  Immediately following the word
             'received' appears the date of the earliest known
             submission.

        (2)  Administrative ?Jumber.  The next element, immediately
             following the word 'under', is the registration number,
             experimental permit nunber, 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.  The final element in the trailing
             parenthesis identifies the EPA accession number of the
             volume in which the original submission ofo 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-M.
                                    76

-------
MRID

05006131
OOCC4101
00004073
OOOu'1035
05003407
0000402/
0000405G




05010341


00004033
GoG015-004
                       REGISTRATION STANDARD 3I3LICGRAPHZ     . ,
          Citations Considered  to b=  Part  of  the'D^ta  Ease  Supporting
                         Registrations  Under- the  Standard
Biisr, J.E.  (1943 )'Alkyl Poiysulfides and 4-Aminopyridine and
    Related  Compounds  [Doctoral.Dissertation].  Philadelphia, Pa:
    University of Pennsylvania.  (Twenty-oneiunpaged figures)
Bess or, J.F.  (1963) Compilation of Information on the : Chronic
    Toxicity  of 4-Aminopyridine to Pneasant, Quail and Starlings.
    (Unpublished study received.Mar 2, .1973 under 11649-12|.prepared
    by U.S.  Fish and Wildlife Service,.Denver Wildlife Research
    Center,  submitted by Avitrol Corp., Tulsa, Okla.-; CDL: 120117-A)
Oesser, J.F.; Cummings, J.L. (1.975) Avitrol FC Corn Chops-99 Baits
    for Protecting Sunflowers from Blackbirds in North Dakota,
    Minnesota, and South Dakota: (Report of Study No. 59, Work Unit
    DF-102.5).   (Unpublished -study received Nov 11, 1375 under
    11549-15; prepared by U.S. Fish and Wildlife Service, Denver
    Wildlife  Resesrch Center, submitted by Avitrol Corp., Tulsa,
    dels.; CDl:223451-I)
Besser, J.F.; Cummings, J.L. (1975) • Avitrol FC Corn, Chops-35 3aits
    for Protecting Sunflowers from Blackbirds'.in liorth Dakota,
    Minnesota, and South Dakota: (Report of Study Mb. 59, Work Unit
    DF-102.3).   (Unpublished-study including draft, received Apr 23,
    1975 under 11649-15; prepared by U.S. Fish and Wildlife Service,
    Denver Wildlife Research, Center,  submitted by Avitrol Corp.,
    Tulsa,'Okla.; CEL:225254-A)                   . '    '
Setts, P.M.;  Giddings,  C.W.; Fleeker,  J.R. (1975) Degradation of
    4-sminopyridine in soil.  .Journal of•Agricultural and Food
    Chemistry 24 (3): 571-574.     "••••'..
Cervenka, H.; Vega, 3.M. (1953) Ninety-Day Subacute'Oral Toxicity
    of Compound 1861 (4-Aminopyridine)—Beagle Dogs:  Project Number
    777.   (Unpublished study received Dec 30,  T958 under 1F1013;
    prepared by Lifestream Laboratories, Inc., submitted by Phillips
    Petroleum Co.,  Bartlesville, Okla.; CDL:C91755-G)
Copeland, G.L. (1372) Interim Report:  Development and Evaluation of
    Methodology to Determine Residues of 4-Aminopyridine in Sun-
    flower Seeds.  Method dated Jul 14, 1972.   (Unpublished study
    received Apr 30, 1974 under 4F1433; prepared by Uazieton Labora-
    tories, submitted by Avitrol Corp., Tulsa, Okla.; CDL:094336-X)
Craig, J.C.,  Jr.; Pearson, D.E. (1953) NMR proof of the structure
    of 4-iminoquinolines and pyridines.  Journal of Heterocyclic
    Chemistry 5(5):531-637.
Cunningham, D.J.  (1975) Transiocation of 14C-4-Aminopyridine in
    Sunflowers and Wheac Growing in Treated Soils: (Report of Study
    No. 37, Work Unit DF-102.2).  (Unpublished study received Apr
    23, 1975 under 11549-15; prepared'by U.S.  Fish end Wildlife
    Service, Denver Wildlife Research Center,  submitted by Avitrol
    Corp., Tulsa, Okla.; CDL:225254-E)
 Fink, R.; Reno,  F.E^ (1975) Eight-day dietary LC— - Mallard duck.
    (Unpublished study received February 9, 1330 under 11549-12;
    prepared by Hazleton Laboratories  America, Inc.,  submitted by
    Avitrol Corp.,  Tulsa,  Okia.)
                                         77

-------
00004025
05003195


00004048



00004100
00004325   Ivts, M.  (1952) Report to Phillips Petroleum Canpany:-Acute  A jl
               To::ieity Studies on Compound 1351 Admixed on Grain.  (Jnpub-
               lished study rece-ivcd Dae 50, 195G under 1F1013;  prepared by
               Industrial Bio-Test Laboratories, Inc., submitted by Phillips
               Petroleum Co., Bartlesvilie,' Okla.; CDL;091756-C)
00004024   Ives, M.  (1252) Report to Phillips Petroleum Company: Toxicity
               Studies on Compound 1851 liydrochloriue.  (Unpublished study
               received Dec 50,. 1953 under IF1015; prepared by Industrial Bio-
               Tcst  Laboratories, Inc., submitted by Phillips Petroleum Co.,
               Bartlesvilie, Okla.; CDL:091756-3)
           Kohn, F.E.; Cervenka, H.; Kay, D.L.; Vega, S.M. (1963) 90-Day Sub:-
               acute Oral Toxicity of Compound 1351  (4-Aminopyridine): Albino
               fiats: Project Number 33C.  (Unpublished study received Dec 30,
               1968 under 1F1013; prepared by Lifsstream Laboratories, Inc.,
               submitted by Phillips Petrol-urn Co.,  Bartlesvilie, Okla.; CDL:
               091756-F)
           Peterson, J.E. (1971) A microanalytical method for 4-aminopyriUine
               in corn plant tissues.  Bulletin of Environmental Contamination
               and Toxicology 6(1):72~30.
           Peterson, J.E. (1974) Gas Chronatographic Method for  4-Aminopyri-
               dine  in Sunflower Plants and/or Seeds.  Method dated Apr 24,
               1974.  (Unpublished study received Apr 50,  1974 under 4F149G;
               submitted by Avitrol Corp., Tulsa, Okla.; CDL:Q943j5-U)
           Peterson, J.E. (1974) Sweet Corn—4-AP Rc-sidue Analyses.  (Unpub-
               lished study received Mar 18, 1975 untie*- 11649-12; prepared by
               U.S. Fish and Wildlife Service, Denver Wildlife Research
               Center, Section of Chemical Research  and .Analytical Services,
               submitted by Avitrol Corp., Tulsa, Okla.; CDL:094?99-D
05003192   Peterson, J.E. (1975) A microanalytical method for 4-aminopyridine
               in sunflower seeds and plants.   Bulletin of Environmental
               Contamination and Toxicology 13.(6):641-645.
00004019   Phillips Petroleum Canpany (ho date)  .[Identity,  Physical and
               Chemical Properties, and Formulations of Avitroi].  (Unpublished
               study received Jul 15, 1970 under IF 1013; CDL:093322-D)
00004017   Phillips Petroleum Company (no date) Calculations for Amount of Resi-
               dua Likely to Migrate to Corn Plant ~.s a Consequence of Lodging
               of Bait on Plant during Application,  (unpublished study includ-
               ing letters dated Mar 24, 1971  and Mar 25,  .1971 from R.N. Smith
               to Merrill Schnitzer, received  Jun 25, 1971 under 1F1015; pre-
               pared in cooperation with U.S.  Fish and Wildlife Service, Div.
               of Wildlife Research; CDL:093322-3)
00004029   Phillips Petroleum Canpany (no date) Methodology:  [4-Aminopyrioine].
               Includes two undated methods.  (Unpublished study received Jan
               5, 1975 under 1F1013; CDL:091757-B)
00004137   Phillips' Petroleum Company (no date) Percutaneous Tests on Rabbits
               with Grain Containing 1351, 4-Aminopyridine as the Hydrochlo-
               rlae.  (Unpubiishsa study received Get 5,  1955 unaer unsown
               :jcm in. no.; C DL: 103 07 4 -A)
00004022   Phillips Petroleum Company (no date) Residue Data: Estimate of Pos-
               sible Contamination of Corn Plant as a Consequence of Lodging of
               ;:n Active Bait Particle in the  Plant.  (Unpublished study re-
               ceived Jan 3,  1973 under IF 1013; CDL:091755-0)
0000j935   Phillips Petroleum Company (no date) Residue Data: 4-Aminopyridine
               (Avitrol 200;  DRC-1527).  (Unpublished study  received Apr 22,
               1953 under 224-EX-3;  CDL.122747-G)
                                        78

-------
30004112    Phillips  Petroleum  Company (no  date)  Technical  Data  Sheet:  Phillips
         •   •-   Avitrol  200  (1C51).   (Unpublished study received 1363 und:ir  un-
               :
-------
00004126   Starr, B. (no date) Thin-Lay?-;-.1" Chraiiatogrsphy—Avitrol.
               (Unpublished study received Apr 15, 1939" under 224-EX-3;
              prepared by U.S.  Fish end Wildlife Service, Denver- Research
              Center, submitted by  Phillips Petroleum Co., oartiesvilie,
              Okla.; CDL:122745-J)
00004037   Starr, R.I.; Cunningham, D.J. (no date) Phytotoxicity.  (Unpublished
               study received Jan 3, 1975 under 1F1013; prepared by U.S. Fish
               and Wildlife Service-, Denver Wildlife Research Center, submitted
               by Phillips Petroleun Co., Bartlesville, Okla.; CDL.-091757-R)
00004039   Starr", R.I.; Cunningham, D.J. (1956) Translocation and Degradation
               of 4-Aminopyridine in-Corn Plants.  (Unpublished study received
               Jan 3, 1973 under 1F1013; prepared by U.S. Fish and Wildlife
               Service, Denver Wildlife Research Center, submitted by Phillips
               Petroleum Co., Bartlesville, Okla..; CDL:091757-T)
00004001   Starr, R.I.; Cunningham, D.J. (1970) Translocation bnd Degradation
               of 4-Aminopyridine in Corn Plants—Its Movement and Degradation
               in Soil Systems: [Third Periodic -Report, Avitroi Concentrate!.
               (Unpublished study received Apr 24, 1970 under 224-SX-3; pre-
               pared by U.S. Fish and Wildlife Service, Denver Wile-life Re-
               search Center, submitted by Phillips Petroleum Co., Sartles-
               ville, Okla.; CDL:1227^4-H)
05003440   Starr, R.I.; Cunningham, D.J. (1974) Phytotoxicity, absorption,
               and trar.slocation of 4-amir.opyriciir.e in corn and sorgaur,
               growing in treated nutrient cultures and soils.  Journal of
               Agricultural and Food Chemistry 22(3);; 409-413.
05003202   Starr, R.I.; Cunningham, D.J. (1975) Degradation of
               4-aminopyridine-14C in corn and sorghum plants.  Journal of
               Agricultural and Food Chemistry 23(2):279-231.
05003135   Starr, R.I.; Cunningham, D.J. (1975) Leaching and degradation of
               4-aminopyridir.e-14C in several soil systems.  Archives of
               Environmental Contamination and Toxicology 3d): 72-33.
00004030   Sullivan, J.3. (1970) Final Report: Evaluation of 4-Arninopyridine,
               Evaluation of the Sponsor's Analytical Method, and Analysis of
               Field Samples.  Includes method dated May 27, 1970.  (Unpublish-
               ed study received Jan 3, 1973 under 1F1013; prepared by Hazleton
               Laboratories, Inc., submitted by Phillips Petroleum Co.,
               Sartlesvilla, Okla.; CDL:091757^C)
00004007   Sullivan, J.3. (1970) Progress Report: Evaluation of 4-Aminopyri-
               dine.  Includes method entitled: Thin-layer chrrmatography
               (Eetagram 0).  (Unpublished study received on unknown date under
               224-ZX-3; prepared by Hazleton Laboratories, Inc., submitted by
               Phillips Petroleum Co.,  Bartlesville, Okla.; CDL:122744-N)
00004033   Swindle,  1C. (1973) Results of Particle Entrapnent Experiment.  (Un-
               published study received Apr 24, 1975 untie- 11643-13; prepared
               in cooperation with U.S. Fish and Wildlife Service and U.S.
               Environmental Protection Agency, submitted by Avitrol Corp.,
               Tulsa, Okl3.; CDL:225254-F)
iO 1500201  U.S.  Department of the Interior (no date) Analysis of 4-Aminopyri-
               dine residues on sunflower seeds and plants.  Unpublished
               document
                                         80

-------
                           OFFICE CF PESTICIDE PROGRAMS
                        REGISTRATION STANDARD 3I3LICGRAPHY
            Examined  and Judged to be Citations inappropriate for Us-:-
                           in Developing the Standard
 HRID

 05003173


 05006379



 05003729


 05014933



 05003181
;ITATION
00004065


00003964


00004257


000040:34


00004107


00003975



00004131


00004043


00004033


00004063
    Agoston,  S.;  Weerden,  T.  van; Westra,  P.;  3roek-:-rt,  A.  (1973)
        Effects of  4-aminopyridine  in  Eaton  Lambert  Syndrome.   British
        Journal of  Anaethesia 50(4):503-335.
    Al-Haboubi, H.A.;  Bownan,  V.C.;  Houston,  J.;  Savage, A.O.  (1973)
        Effects of  4-aminopyridine  on  the  isolated
        parasyrnpathetically-innervated oesophagus of the domestic  foul
        chick.  Journal-of Pharmacy and  Pharmacology 30(3):517-513.
    Anden,  M.E.;  Leander,  S.  (1979)  Effects  of 4-aninopyridine  on  ens
        turnover  of rr.onoamines in the  contra!  nervous  system of the
        rat.  Journal  of Neural  Transmission 44(1/2):1-12.
    Anden,  M.E.;  Leander,  S.  (1979)  Turnover of noradrenaline,
        dopamine  ana 5-hydroxytryptsr,ine in  the CMS  under the influence
        of  4-aninopyridine.   Acta Physiologies Scandinavica
        105(1):45-45.
    Aue, D.H.; Webb, ii.M.;  Bowers,  M.T.; Liotta,  C.L.; Alexander,
        C.J.; Hopkins, H.P.,  Jr.  (1976) A  quantitative comparison  of
        gas-  and  solution-phase  basicities of  substituted pyridinas
        [letter].   Journal  of  the American Chemical  Society
        90(3):354-355.
    Avitrol Corporation (no date) Durability of Avitrol 200, 4-Amino-
        pyridine  Hydrochloride on Grain.   (Unpublished study received
        Get  17, 1973 under  11649-1; CEL:'Q11002-0)
    Avitrol Corporation (no cate) Introduction ana Surrmar-y: L^O  Document-
      ed Reports on Bird Species and Baits].   (Unpublished study
      received Apr 10, 1975 under  11549-10; CDL:115276-A)
    Avitrol Corporation (no date) Pesticidal Safety: [4-Aminopyridine].
        (Unpublished  study received Feb 15,  1973 under  11649-12; CDL:
        003234-E)
    Avitrol Corporation (no date) Pigeon Control with  1351 on a  Dewey,
         Oklahoma,  School Building.  (Unpublished study receiver Oct
         I/, 1572 under 11649-1; CDL:011002-3)
    Avitrol Corporation (no date) Technical Data Sheet: Avitrol.   (Unpub-
         lished study received Sep 23, 1972 uncbr 11549-EX-5;  CDL:
         22225C-A)
   Avitrol Corporation (no date) The Name, Chemical Identity and Compo-
       sition of the  Pesticide Chemical:  L4-Aminopyriaine].  (Unpub-
       lished study received Apr 5, 1973 under 11649-14; CDL:
       223313-A)
   Avitrol Corporation (no aate) Toxicity Data Summary: 4-Aminopyridine
         (Compound 1361;  DRC-1327).  (Unpublished study received Stp
      '   23, 1972 under 11649-EX-5; CDL:222250-D)
   Avitrol Corporation (no date) Toxicology: Mathematical Approach:
       Consumer Safety from Pistioidal Residues.   (Unpublished study
       received Apr JO,  19(4 under 4F1493; CDL:094335-W)
   Avitrol Corporation (1961) Control of Feral Pigeons with Chemical
       1351: Weber  Farm,  Dewey, Oklahoma,  1961.  (Unpublished  study
       received 'Oct 17,  1973 under  11549-1;  CDL:011002-C)
   Avitrol  Corporation (1963) Gull  Tests in Florida, 1953.   (Unpub-
               tudy received Oct 17, IS^.-uncsr 11649-1; CDL:01 1002-L)
                                          81

-------
           Avitroi Corporation (1955) The Control of Gulls with Avitroi 200 on
               and Near the Metropolitan Oakland international Air-port.  (Un-
               published study received Apr 10, 1975 under 11649-10; CDL:
                ^•1 " '-"-7 ••* T-» \
                IjcT/o-F)
           Avitroi Corporation (19i'0) Residue Data.  (Unpublished study re-
               ceived Jul 20, 1972 under 5G1297; CDL:094671-O)
           Avitroi Corporation (1972) Reasonable Ground [sic] in Support of
               the Petition: [4-Aminopyridinej.  (Unpublished study received
               Apr 11, 1973 under 11549-EX-3; CDL:095015-D)
           Avitroi Corporation (1973) Avitroi Survey: Bird Damage in Pecans.
               (Unpublished study received Hay 3, 1973 under 116U9-3; CDL:
               220239-B)
           A-/itrol Corporation (197-0 Introduction:  [4-Aminopyridine].  (Un-
               published study received Mar 10, 1975 under 11649-12; C'DL:
               094799-A)
           Avitroi Corporation (1974) [Avitroi on Sparrows and Pi-
               geons].  (Unpublished study received Apr 10, 1975 under 11649-7;
               CDL:119797-E)
           Avitroi Corporation (1974) Avitroi: Summary Test Results—Gulls.
               Summary of studies 115276-D and 115276-F.   (Unpublished study
               received Apr 10,  1975 under 11649-10; CBL:115275-C)
           Avitroi Corporation (1974) Avitroi: Summary Test Results—Pigeons.
               (Unpublished study received Apr 10,  1975 under 11649-6; CDL;
               113303-E)
           Avitroi Corporation (1974) Avitroi: Summary Test Results—Pigeons.
               (Unpublished study received Apr 10,  1975 under 11649-7; CDL:
               119797-C)
           Avitroi Corporation (1974) Avitroi: Summary Test Results—Sparrows.*
               (Unpublished study received Apr 10,  1975 under 11649-6; CDL:
               119303-C)
           Avitroi Corporation (1974) Avitroi: Summary Test Results—Star-
               lings, Blackbirds  in Feedlots.  (Unpublished study received  Apr
               10, 1975 under 11649-11;  CEL:115277-C)
           Avitroi Corporation (1974) Summary and Comments—Avitroi Test Re-
               sults—1974.  Summary of studies Q34799-D through 094739-H.
               (Unpublished study including letter  dated Feb 23, 1975 from  R.M.
               Smith to Kelly Swindel, received Mar 13, 1975 under 11649-12;
               CDL:094799-3)"
           Avitroi Corporation (1975) Avitroi Documentary Report—Structural.
               (Unpublished study received Apr 10,  1975 under 11549-7; CDL:
               119793-A)
00303363   Avitroi Corporation (1975) Avitroi FC Corn Chops—93 Baits for
               Protecting Sweet  Corn from Blackbirds in Ulster County, New
               York.  (Unpublished study including  letter datea Sep 12, 1975
               from J.E. Forbes  to Kelly Swindle, received Feb 1o, 1976 under
               11649-12; prepared in cooperation with U.S. Fish and Wildlife
               Service; CDL:224248-A)
00004127   Avitroi Corporation (1375) Avitroi: Summary Test Results—Star-
               lings, Blackbirds  in Feedlots.  (Unpublished study received  Apr
               10, 1Q75 under 11643-5; prepared in  cooperation uith Ag Past
               Control, Inc., Loyal Pest Control and American Fertilizer, Inc.;
               CDL:119311-C)
00004037   Avitroi Corporation (1975) Crop Economics.  (Unpublished study re-
               ceived Apr 28, 1975 under 11549-15;  CDL:225254-D)
000039 i^5



00004134

00004074


00004052


00004094


00004091


00003955


00003977


00004090


00003970


00003959
00004095
00004093
                                        82

-------
05003152
05019579
00004092
05005423
00004070
00004072
00004063
00004057
00004053
05010065


05003161
Babiak, 3.; T-sta, A.C.  (1976)  Fluorescence  lifetime  study  of
     c.minopyridin-is.   Journal  of Physical  Chemistry
     ' '• .-~\ / 1 -7 N . 1 *"> 'i O  1 ^ r *~
     •j-J (11  ;: looJ-1 jv. J.
Bacon,  R.G.R.; Hamilton, 3.D.  (19/4)  Metal ions  and complexes in
     organic reactions_  Part  XVIII__  Structural  variations  in the
     production of polycyclic  heterocyelic systems by
     iron(II/-promote-d  cyclisatior.s  of nitro-substituted  precursors.
     Journal of the Chemical Society,  Parkin  Transsections 1
     16:1370-1975.
Bailay, T.D.; McCill,  C.IC., ir.ventors;  Reiily Tar anc Chemical
     Corp., assignee  (1979) Process  for  substituting and
     dequaternizing pyridylethyl quaternary sales of pyridina and
     bipyridirs bases.  if.S. patent  4,15S,093.  Jun 12".   10  p. Int.
     C1.-.2? C 07D  213/05; U.S. Cl. 542/455.
Barber, E.H.  (1974) Report of the Results Obtained in Pigeon Con-
     trol  at ths Port  of  Mew Orleans.  (Unpublished study received
     Apr 10, 1975  under 11549-7;  prepared  by  Barber Laboratories,
     submitted by  Avitrol Corp.,  Tulsa,  Okla.;  CDL:119797--F)
Batts, B.D.; Spinner,  E. (1969)  Vibration-spectral unc structural
     comparison of the  4-aminopyridir.s cation  :;ith the
     4-hydroxypyriciinium  ion and 4-pyridone.   The .protio  parent
     ions, M- and  C-deuteratsd,  and  M-methylatid  ions. Ravelant
     j'MR spectral  studies.  Australian Journal  of Chemistry
     22(12):2595-25IO.
Baumgardner, R.K. (1952) Chemical Control of House Sparrows  in
     Sunflower Fields.  (Unpublished study received Get 17,  1973
     under 11549-1; prepared by  Oklahoma State  Univ.,  Research Foun-
     dation, Bird  Management Project,  submitted by Avitrol Corp.,
     Tulsa, Okla.; CEL:G11002-W)
Baumgartner, F.M. (1962) Annual  Report  to Phillips Petroleum Com-*
     pany July, 1951-June, 1952:  Bird  Management  Tests.   (Unpublished
     study received Oct 17,  1973  under 11649-1; prepared  by Oklahona
     Stste Univ.,   Dept. of Zoology,  submitted  by  Avitrol  Corp.,
     Tulsa, Okla.; CDL:011002-Y)
Baumgartner, F.M. (1952) Bird Management  Project Progress Report
     for September, 1952.  (Unpublished  study r-aceiv-cd Oct 17,  1973
    under 11649-1; prepared by  Oklahoma Staue  Univ.,   Research Foun-
    dation, submitted by Avitrol Corp., Tul K. , Okla.; CDL:011002-U)
Baumgartner, F.M. (1952) Report  on House  Sparrow Management  at
     Southern Great Plains Ficad  Station,  Woodward, Oklahoma,  August
     15-17, 1952.   (Unpublished  study  received  Oct  17,   1973 under
     11549-1; prepared by Oklahoma State Univ., Research  Foundation,
    submitted by Avitrol Corp.,  Tulsa, Okla.; CDL:011002-T)
Baumgartner, F.M. (1952) Report  bo Phillips  Petroleum Company:
    Bird Management Tests,  January—February,  1952.   (Unpublished
    study  received Oct 17,  1973  under 11549-1; prspared 'by Oklahoma
    Stats Univ.,  Research Foundation, submitted  by Avitrol Corp.,
    Tulsa, Okla.; C DL:011002-V)
Benoist, J.M.; Ls-m-ignan, M.;  Lechat, P.  (1959)  Study of the
    action of 4-aminopyrid.ine on the  isolated vas  deferens of the
    guinea-pig.   Pharmacology 2(3):151-160.
Beresford, R. ; Bills,  G.N.3.;  Fastier, F.M.   (1977) Site  of th:;
    stimulant  action on muscle of such bases ;>s  guanidini. jp.d
    4-iminopyridine.   Hev/ Zealand Medical Journal  36(399)':443.
                                        83

-------
00004021    Bessor,  J.F.  (1970) A  Discussion of the  Problem of  Blackbird  Damage
               to  Field  Corn.  (Unpublished study received Jan  2,  1972 uncier
               1F1012; prepared by  U.S.  Fish  ;-;nd" Wildlife Service,  Denver
               Wildlife  Research  Center,  submitted  by  Phillips  Petrol-:urn Co.,
               Bartlesville, Okla.; CDL:091757-E)
00004042    Besser,  J.F.  (1972) '4-Aminopyridine Baits for Protecting Sunflowers
               from Blackbirds in Tennessee:  (Report of Stuoy  Ho.  47,  Work  Unit
               DF-102.2).   (Unpublished  study received Apr 20,  197'! under
               4F1498; prepared by  U.S.  Fish  and Wildlife Service,  Denver Wild-
               life Research Center, submitted by Avitrol Corp., Tulsa,  Okla.;
               CDL:094326-L)
00004032    Besser,  J.F.  (1575) Relationship of Bird Pressure to the Effective-
               ness of Avitrol-,(R) FC Corn Chops-99 for Protecting  Cropfields
               from Blackbirds.  Summary of studies 222451-3, 22_>451-I,  222451-
               J,-223451-K, 225255-A, 225255-J through 225255-L.   (Unpublished
               study received Mov 11, 1Q75 under 11543-15; prepared by U.S.
               Fish and 'Wildlife Service, Denver Wildlife Research  Center,  sub-
               mitted by Avitrol Corp.,  Tulso, Okla.;  CDL;225255-3)
05017365    Besser,  J.F.  (1975) 4-Aminopyridine for protecting crops  from
               birds—a currant review.   Pages 11-15,  In Proceedings of  the
               Vertebrate Pest Conference.  Vol. 7.  Sacramento, Calif.:
               California Vertebrate Pest Technical Committee.
000040C5    Besser,  J.F.; Cunningham, D.J. (19/4) 1974  Test Results.   (Un-
               published study received  Apr 23, 1375 under 11545-15; prepared
               by  U.S. Fish and Wildlife  Service, Denver Wildlife Research  Cen-
               ter, submitted by Avitrol  Corp., Tulsa, Okla.; CDL:225254-B)
00003995    Besser,  J.F.; Mott, D.F. (1970) Field Work  with 4-Aminopyridine  in
               Idaho Cornfields.  (Unpublished study received Dec 13,  1970
               unaer'224-EX-3; prepared by U.S. Fisn and Wildlife Service,
               Denver Wildlife Research  Center, submitted by Phillips  Petro-
               leum Co.,  Bartlesville, Okla.; CDL:122744-B)
05003953    Bogaert, P.P.  van; Snyders, D.J.  (1973) Dose-dependent effects of
               4-aminopyridine on the electrical activity of cardiac Purkinje
               fibres [abstract no. 21].  Pfluegers Archiv.  European  Journal
               of  Physiology 272:12.
05004213    Booij,  L.H.D.J.; Miller, R.D.; Crul, J.F. (1973) ileostigmine  and
               4-aminopyridine antagonism of lincomycir.-pancuronium
               neurotnuscular blockade in  man.  Anesthesia and Analgesia,
               Current Researches 57(2):216-221.
05004232   Bounan, W.C.;  Harvey,  A.L.; Marshall, I.C.   (1377) The actions of
               aminopyricines on. aviar. muscle.  ilaunyr.-Schmiedeberg's  Archives
               of Pharmacology 227(1):99-103.
05002160   Down an,  W.C.;  Khan,  11.H.; Savage,  A.O. (1977) Some antagonists of
               dantrolene sodium on the  isolated diaphragm muscle of the rat.
               Journal of Pharmacy and Pharmacology 29(10):516-525.
05020247   Bowman, W.C.;  Rodger,  I.W.; Savage, A.O. (1979) Effect of
               4-arninopyridine on muscle contractility in the cat.   British
               Journal of Pharmacology 65(2):465-467.
05003949   Brown, K.L.;  Chernoff,  D.;  Keljo,  D.J.;  Kullen,  R.G.  (1972)
               Coenzyme B 12  model studies..  Equilibria ana kinetics  of axial
               ligation  of methylaquocobaloxime by primary amines ana
               4-subssituted pyridin.es.   Journal of the American Cnemical
               Society 94(19):6697-6704.
05003159   Burley,  E.S.;  Jacobs,  R.S.  (1977) The effects of 4--aninopyridine
               on r.iuromuscular transmission in frog sartorius muscle.
               Federation Proceedings 25(2):975.
                                        84

-------
05015251   Hurley, E.S.; Jacobs, R.S.  (1973) Effect of  4-aniinopyridir.e  (4AP)
               on  extracellular nerve  terminal  action potentials  (iJTAP)  on
               frog sartorius muscle-sciatic nerve preparation  [abstract  no.
               523].  Pharmacologist 21(j):244.
050031/7   Chao, H.; Sci'iempp, E. (1977) An X-ray and MQR study  of
               4-sninopyridine and related aromatic amines.  Acta
               Crystallographica, Section 3 333(5):1557-1564.
05003556   Christen, D.; Horbury, D.;  Lister, D.G.; Palmi;-ri, P.  (1975)
               Microwave spectra and structure  of  the an ine  group in
               3-aminopyridine and 4-aminopyridine: ab  initio molecular
               orbital  calculations of the structure of the  ar.ine group  in  the
               aminopyridines.  Journal of the  Chemical Society,  Faraday
               Transactions 71:433-446.
05003176   Colton, J.S.; Schauf, C.L.; Colton,  C.A. (1975) Effects of the
               aminopyridines and sparteine on  Myxicola axons and the lobster
               neuromuscuiar junction.  Biophysical Journal, Supplement
               1 "  1 :1 '"I *•>
                \ '~\ * I -A,-\ .'
00003336   Coon, R.A.  (1971) Avitrol Program: Ohio-Micnigan,  1970.   (Unpub-
               lished  study received Apr  19,  1971 under 224-EX-3;  prepared by
               U.S. Fish and Wildlife Service, Div. of Wildlife Services,
               Ohio Office, submitted by  Phillips Petroleum Co., Bartlssvilie,
               Okla.;  CDL:122743^3)
05019632   Coon, R.A:-(1974) Corn losses  from birds reduced with repellent.
               Science in  Agriculture 21(4):13.
00004030   Cumrnings, J.L.; Besser, J.F.;  Mott,.D.F. (1973) 4-Aminopyridine
               Baits for Reducing Blackbirds Damage to Ripening Grain Sorghum
               in Oklahoma: (Report of Study No. 53A, Work Unit DF-102.3).
               (Unpublished study received Mov 11, 1975 under  11549-1:?;  pre-
               pared by U.S. Fish and Wildlife Service, Denver Wildlife  Re-
               search  Center, submitted bv Avitrol Corp., Tulsa, Okla.;  CDL:
               223451-J)
05003164   Cumper, C.W.N.; Singleton, A.  (1963) The ultraviolet spectra  of
               aniline, 2-, 3-, and 4-aminopyridines and of sane of  their
               derivatives in n-hexane 1,4-dioxan, ethanol, and water
               solutions.  Journal of the Chemical Society, Section  3
               6:649-651.
00004113   Custom Cii-imical Specialties' (1353) Avitrol Field Tests.   (Unpub-
               lished  study received 1968 under unknown admin, no. ;  prepared in
               cooperation with Drown 3: Bryant, Inc. and Soilserv, I-nc., sub-
               mitted  by Phillips Petroleum Co., Bartlesvillo, OUla.; CDL:
               221959-C)
00003995   De Grazio,  J.W.; Sesser, J.F.; Cunningham., D.J. (19^9) Project DF-
               102: Bird Damage Control Research.  (Unpublished stuay received
               Dec 13, 1970 under 224-EX-3; prepared by U.S. Fish and Wildlife
               Service, Denver Wildlife Research Center, Section of  Birds in
               cooperation with Sand Lake National 'Wildlife Refuge,  submitted
               by Phillips Petroleum Co., Bartlesville, Okla.; CDL:122744-A)
0301543,'   Do Grvizio,  J..W.; Besser, J.F.; De Cino, T.J. ; Guarino, J.L.;
               Starr,   R.i. (1971) Use of  4-arninopyridint. to protect  ripening
               corn .from blackbirds.  Journal of Wildlife I-ian^g&rntnt
               35(3):555-559.
05013435   De Grazio,  J.W.; Besser, J.F.; DeCino, T.J.; Guarino, J.L.;
               Schafer, E.W., Jr. (1972)  Protecting ripening corn from
               blackbirds by broadcasting 4-aninopyldin; baits.  Journal of
               Wildlife Management 36(4):1316-1320.
                                         85

-------
•JU0039/'3    De  Grazio,  J.V/.;  5^-sser,  J.F.;  DeCino,  T.J.;  Gu^rir.o,  J.L.;
               Schaftr,  I.]-!.,  Jr.  (1972)  Protecting ripening corn from  black-
               birds by  broadcasting 4-ATiinopyridir.e baits.   Journal of Wild-
               life i-Lnagement 33(4): 131 5-1320.   (Also In unpublished submis-
               sion received Jun 21,  1977 under  11649-12; submitted by  Avitrol
               Corp.,  Tulsa,  Okla.;  CDL:2j0555-3)
00004114    De  Grazio,  J.W.;  Besser,  J.F.;  Guarino,  J.L.;  West,  R.R. (1957)
               Annual  Progress Report:  Wildlife  Research  Work Unit: Denver
               Wildlife  Research Center:  Calendar  Year 1967:  Work Unit  F-4.1:
               Control of  Blackbird  Damage to Corn in South  Dakota.  (Unpub-
               lished  study  received  Apr  23,  1955  under 224-CX-j; prepared  by
               U.S. Fish and  Wildlife Service, Denver Wildlife  Research Cen-
               ter, Section  of Birds.in cooperation with  Sand Lcke National
               Wildlife  Refuge and South  Dakota  Dspt. of  Game,  Fish and Parks,
               submitted by  Phillips  Petroleum Co.,  Bartlesville, Okla.;  CDL:
               122745-A)
00004123    Do  Grazio,  J.W.;  Besser,  J.F.;  Guarino,  J.L.;  West,  R.R. (1959)
               Annual  Progress  Report:  Denver Wildlife Research Center:  Calen-
               dar Year  1968:  Project DF-102:  Bird Damage Control Re-search:
               Work Unit DF-102.3.   (Unpublished study received Jan 9,  196cj un-
               der 224-EX-3;  prepared by  U.S.  Fish  and Wildlife S?rvic.»,  Den-
               ver 'Wildlife  Research  Center,  Section of Birds in  cooperation
               with Sand Lake  National  Wildlife  Refuge and South  Dakota Dept.
               of Game, Fish  and Parks, submitted  by Phillips Petroleum Co.,
               Bartl3sville, Okla.; CEL:122745-IO
00004002    De  Grazio,  J.W.;  Besser,  J.F.;  West,  R.R. (1959)  Annual Progress
               Report: Denver  Wildlife  Research  Center, Calendar  Year 1969:
               DF-102.3-9.   (Unpublished  study received Jan  20,  1970 under  224-
               iX-3; prepared .by U.S. Fish and Wildlife Service,  Denver Wild-
               life Research  Center,  Section  of  Birds in  cooperation with Sand
               Lake National  Wildlife Refuge,  submitted by Phillips Petroleum
               Co., Bartlesvills, Okla.; CDL:122/44-1)
U0004116    De  Grazio,  J.W.; Schafer,  E.W.,  Jr.;  Besser, J.F.  (1957) Baiting
               Experiments.   (Unpublished  study received  May  22,  1967 under
               224-EX-3; prepared by  U.S.  Fish and  Wildlife  Service, Denver
               Wildlife Research Center, submitted  by Phillips  Petroleum Co.,
               Bartlesville, Okla.; CDL: 12274-5--C)
            De  Grazio,  J.W.; Stone,  C.P. (1971) South Dakota  Field Tests:
               Avitrol FC Corn Chips.   (Unpublished  study received i!ov  19,  1971
               under 224--EX-3; prepared by U.S.  Fish and  Wildlife Service,
               Denver  Wildlife Research Center,  submitted by  Phillips Petrol.:-uin
               Co., Bartlesville, Okla.; CDL:12274B-B)
            De  Grazio,  J.W.; Stone, C.P. (1972) Project DF-102:  Bird D-v^ge
               Control Research: Second Periodic Report—Avitrol.   (Unpublished
               study received  Mar 27, 1972 under 224-EX-3; prepared by  U.S.
               Fish and Wildlife Service,  Denver- Wildlife Research Center in
               cooperation with Sand Lake  National  'Wildlife  Refuge, submitted
               by Phillips Petroleum Co.,  Bartlesville, Olcla.;  CDL: 122PI3-3)
05019575   Del Bone, J.E.-(1979) An ab  initio molecular- orbital study of 2
               anc 4-monosubstitut-od pyridines.  Journal  of the American
               Chemical Society 10 I (21 ):6'I34-61C9.
05004634    Desiderl, P.G.;  H«inler, D.; Leprl, L.  (1973)  Differential
               voitammstry at  solid electrodes: determination of  the
               amir.opyriaines.  Journal of Eltctroanaiyticai  Chemistry  anc
               Interfacial Electrochemistry 37(2):2/5-232.
00003939
00003931
                                         86

-------
05004219   De Silva, A.J.C.; Lee, C.  (19/3)  IL'iirrciusculsr  and  cardiovascular
               depression produced -by prolonged  exposure, to  Polymyxi-r.  3.
               Canadian Anaesthetists' Society Journal 25(4): J03-506.
UOOO'IG95   Doibeer, R.A.; Ingrain, C.R. (13/5)  1974 Test.of 4-Arninopyridine
               (Avitrol) Efficacy in Pr-eventing  Bird  Damage  to Sweet Corn in
               Ohio: Progress  Report: January  1,  1974-December J1,  1974: Work
               Unit P-F-jj-11.   (Unpublished study received  Mar  13,  1975 und^r
               11549-12; prepared by U.S. Fish and Wildlife  Service, Patuxent
               Wildlife Research Center, Section of An IT, 31 Depredations Control
               Studies, Ohio Field Station,  submitted by Avitroi Corp., Tulsa,
               Okla.; CDL:094799-H)
00003372   Dolbeer, R.A.; Ingram, C.R.; Seubert, J.L.; Stickisy, A.R., Jr.;
               Mitchell, R.T.  (1975) 4-Aminopyridine  effectiveness  in  sweet
               corn related to blackbird population density.   Journal  of Wild-
               life Management 40(3):554-570.  (Also?Ir.?unpubiish£d submission
               rscoived Jun 21,  1977 under  11549-12;  submitted by Avitrol
               Corp., Tulsa, Okla.; CDL:230665-A)
GOOQ4034   Dolbeer, R.A.; Stickiey, A.R., Jr.; Ingram, .C.R.  (1974) Efficacy of
               4-Aminopyridine in Protecting Sunflowers from Blackbirds in
               'Ohio: Progress  Report: January  1,  1973—December 31,  1973, Work
               Unit P-F-33.1C.   (Unpublished study received  Jul 22,  1974 under
               11:549-15; prepared by U.S. Fish and Wildlife  Service, Patuxent .
               Wildlife Research Center, Section of Animal Depredations Control
               Studies, submitted by Avitrol Corp., Tulsa, Okla.; CDL:226529-A)
05020241   Din-ant, H.I.1.; Lee, C.; Katz, R.L. (1979) 4-Arninopyridine reversal
               of ganglion block [abstract].  Anaesthesiology  5K3):263.
03007043   Fairchild, E.J., ed.  (1977) .Agricultural Chemicals  and Pesticides:
               A Subfile of the NIOSH Registry of Toxic Effects of Chemical
               Substances.  Cincinnati, Ohio:  National Institute for
               Occupational Safety and Health. (Pagination includes 46 pages
               numbered i-xlvi; available from: NTIS, Springfield, VA: PB-274
               743)
05004214   Fastier, P.M.; ;
-------
05017026



05004525


05013373


05005337
 Garrison,  M.V. ;  Mott,  D.F.;  Guellette,  M.R.;  Holquin,  G.  (1979)  n
     tabletac  corn  bjit to deliver  uniform  cosage  of 4-aniinopyr'idini
     to red-winged  blackbirds.   Journal  of  Wildlife  Management
0500320J


05020055


05003493



05019577



05010T35


00004259
00004143
05004470
05013331
Gillespie,  J.I.  (1977)  Voltage-dependent  blockage of the ds-laysd
   • potassium current in  skeletal muscle  by  4-aminopyridine.
    Journal of .Physiology 2/3 (2): 64-55.
Gillespie,  J.I.; Hutter,  O.F.  (1975)  The  actions  of
    4-aninopyridine  on  the delayed  potassium current in  skeijtal
    muscle  fibres.   Journal of  Physiology (London) 252(2):70-71.
Girault, G. ; Coustal, 3.;.'Rumpf, P.  (1972) Contribution  i 1' etude
    de derives 'amines de  quelques hetcrocycles azotes.
    II. — Preparations,  absorption dans  1' ultraviolet c
-------
 0004043
00004031
00004073
00004146
00004044
00004115
00004033
000059J7
00004145
Guarir.o,  J.L.  (1974)  4-Aminopyridine  for  Protecting  Sunflowers from
    Blackbirds  in  Steele  County,  North  Dakota:  (Report  of stjdy
    ;io. 45, Work Unit  DF-1G2.3). .  (Unpublished  study including un-
    dated  letter from  J.L.  Guarino  and  C.P.  3tone  to Lancov^nEr ,  r~~
    ceived Apr  30,  1974 under  4F149G; prepared  by  U.S.  Fish  and
    Wildlife Service,  Denver Wildlife Research-Center ,  submitted by
    Avitrol Corp.,  Tulsa, Okla.; CDL:09433&-M)
Guarino,  J.L. ;  Royali, W.C., Jr.; Cumndngs,  J.L.  (19i75) 4-Amino-
    pyridine Baits  for Reducing Blackbird  Damage to  Ripening Grain
    Sorghum in  Kansas: (Report of Study Ho.  533, '.fork Unit DF-
    102.3).   (Unpublished study received  Mov 11,  1975 under  11549-
    15; prepared by U.S. Fish  and Wildlife Service,  Denver Wildlife
    Research Center, submitted by Avitrol  Corp., Tulsa,  Okla.; CDL:
                     -1C)
Guarino, J.L. ; Stone, C.P. ; Royall, W.C.; 3ray, O.E.  (1973)  DF-
     102.3-45 — 4-/iminopyridine  for  Protecting Sunflowers  fran Black-
     birds in  Steele Co., ilorth Dakota.   (Unpublishad  study received
     i-iov  11, 1975 under  11649-15; prepared by U.S. Fish and Wildl.'.f-:;
     Service,  Denver Wildlife Research Center, submitted  by Avitroi
     Corp., Tulsa, Okla.; CDL:223451-B)
Hanson,  R. (1970) Field Test Project on  4-Amino-pyridine (DRC-1327,
     Avitrol 200).   (Unpublished study received Jun  16, 1972  under
     unlcnov.Ti admin, no.; prepared by U.S. Fish and Wildlife Service,
     Div. of Wildlife Services, submitted by Avitrol Corp., Tulsa,
     OUla.; CCL:210151-H)
Hanson,  R.M.  (1959) Field Test Project on 4-Amino-pyridine (ORC
     1327, Avitrol 200).  (Unpublished study received  Apr 30,  1974
     under 4F1498; prepared by  U.S. Fish  and Wildlife  Service,
     Div. of Wildlife Services, submitted by Avitrol Corp., Tulsa,
     Okla.; CEL:09U835-M)
Hanson,  R.V.  (1963) Field Test Project on 4-Amino-pyridine (DRC
     1327, Avitrol 200), Season 1967.  (Unpublished study  received
    Apr  23, 1953 under 224-EX-3; prepared by U.S. Fish and Wild-
     life Service, Div. of Wildlife Services in cooperation with Den-
     ver  Wildlife Research Center and North Dakota Game and Fish
     Dcpt., submitted by Phillips Petroleum Co., Bar tlesviile, Okla.;
    GEL: 1227 45-3)
Hanson,  R.V.  (1969) Field Test Project on 4-A:nir.opvridine (DRC
     1327).  (Unpublished study received Jan 3, 1973 under 1F1013;
    prepared  by U.S. Fish and  Wildlife S-rvice, Denver Wildlife
     Research  Center in cooperation with North Dakota  Gar;ic and Fish
    Dspt., submitted by Phillips P2trolaum Co., Bartlesville, Okla.;
    CDL:C-91757-J)
Hanson,  R.V.  (1970) Field Test Project on 4-Amino-pyridine (DRC-
     1327, Avitrol 200).  (Unpublished study received  Apr  19,  1271
    under 224-EX-3; prepared by U.S. Fish and Wildlife Service,
    Div. of Wildlife Services, North Dakota Office, submitted by
    Phillips  Petroleum Co., Bartlasville , Okla.; CDL: 122743-H)
Hanson, R.V.  (1970) Field Test Project on 4-Asnino-pyridins (DRC-
     1327, Avitrol 200).  (Unpublished study including supplement da-
    ta, received Jun 16, 1972 under unknown admin, no.;  prepared by
    U.S. Fish and Wildlife Service, Div. of Wildlife Servicss, •
    submitted by Avitrol Corp., Tulsa, Okla.; CDL:210151-G)
                                         89

-------
00004045   Hanson, R.V.  (1970) Supplemental Test.   (Unpublished  study
               received Apr 30,  1974 under 4F1493; prepared, by U.S.  Fish  ana
               Wildlife Services, Div. of Wildlife Services, submitted by
               Avitrol Corp., Tulsa, Okla.; CDL:0943^5-P)
00003938   Hanson, R.V.  (1971) Worth Dakota Field Tests: First Periodic  Report
               —Avicrol Concentrate.  (Unpublished study  received Mov  13,
               1371 under- 224-EX-3; prspared by U.S. Fish,  and Wild!if-3 Ser-
               vice, Div. of Wildlife Services, North Dakota Office,  Submitted
               by Phillips Petroleum Co., Bartlesvills', Okia.; CDL: 122743-A)
00004034   Hanson, R.V.; Pfeifer, W.K. (1953) Field Test Project on  4-Amino-
               pyridine  (DKC 1327): North Dakota, 1958.  (Unpublished study
               received Jan 3, 1972 under 1F1013; prepared  by U.S. Fish  ana
               Wildlife Service, Denver Wildlife Research  Center in  coopera-
               tion wiih North Dakota Game and Fish Dept.,  submitted  by
               Phillips Petroleum Co., Bartlesville, Okla.;  CDL:091757-X)
00004144   Hanson, R.V. ; Pfeifer, W.K. (1969) Field Test Project on  4-;\mino-
               pyridine  (DRC 1527, Avitrol 200).  (Unpublisheo stuay  receivea
               Jun 16, 1972 under unknown, admin, no.; prepared by U.S. Fish
               zno. Wildlife Service, Div. of Wildlife Services,  submitted by
               Avitrol Corp., Tulsa, Okie.; CDL:'210151--F)
00004123   Hanson, R.V.;  Pfeifer, W.K. (1959) Field Test Project on  4-Amino-
               pyridina (DRC 1327, Avitrol 200).  (Unpublished study  received
               Apr 15, 1959 under 224-£X-3; prepared by U.S. Fish and Wild-
               life Service, Div. of 'Wildlife Services in  cooperation with Den-
               ver Wildlife Research Center, and North Dakota Game and Fish
               Dept., submitted  by Phillips Petroleum Co.,  Bartlesville,  Okla.;
               CDL: 122745^3)
05020243   Hara, Y.;  Kitamura,. K.; Kuriyama, H. (1930) Actions-of
               4-arainopyridine on vascular smooth muscle tissues of the
               guinea-pig.  British Journal of Pharmacology 63(1):99-106.
050044(72   Harris, M.G.;  Stewart, R. (1977) Amino group acidity  in
               aminopyridines and aminopyrimidines-.  Canadian Journal of
               Chemistry 55(21):3300-3306.
050143C3   Harvey, A.L.;  Marshall, I.G.  (1977) A comparison of the effects of
               aminopyridines on isolated chicken anc rat  skeletal muscle
               preparations.  Comparative Biochemistry ana  Physiology, Part C
               53 (2): 151-165.
05003204   Marvsy, A.L.;  Marshall, I.G.  (1977) The facilitatory  actions of
               aminopyridines and tetraethylammoniurn on neuranuscular
               transmission and muscle contractility in avian muscle.
               i.'aunyn-Schrnieceberg's Archives of Pharrtiacoiogy 299(1):53-60.
00033330   Held, L.J. (1963) A Report of the Animal Control  Program,  Fiscal
               Year 1363.  (Unpublished study received Aug  13, 1953 under' 224-
               £X-1;  prepared by U.S. Fish and Wildlife Service,  3r-nch of
               Predator and Rodent Control in cooperation with the Illinois
               Pork Council, submitted by Phillips Petroleum Co., Bartlesville,
               Ckla.; CDL: 122741^)
05011233   Hermann, G. (1970) Chernische Prqdukte gegcn Schaeden  durch Vo^el
               und Saeugetiere.  [Chcmic-il products for the  prevention of
               injury from birds and mammals.]  Pages 534-59f, In Chernie  der
               Pfianzcnschutz- und Schaidlinssb&kaaapfungsrniutel.  Eoitea by
               R. Wegler.  Ife,v York:  Springer.
                                          90

-------
05C050S?
05003306   Hcuser, J.E.  (1977) Synaptic vesicle  exocytosis revealed  in
               quick-frozen  frog neuromuscular junctions  treated  with
               4-aainopyridine and given a single  electrical  shock.  Pages
               215-233,  In Society for Ueu'-osoier.ce Symposi-j.   '/ol.  2:
               Approaches to the Cell Biology of Neurons.  Bethesda, Md.:
               Society for Neuroscience.
00003367   Hext, D.D." (1965) Experimental Gull Control  Utilizing  Avitrol 200
               au Oakland International Airport.   (Unpublished  study received
               Apr 10, .1975  under  11649-10; submitted by  Avitrol  Corp., Tulsa,
               Gkl.i.; CCL:H5276-D)
00004075   Hicicnan, G.L.  (1353) Blackbird—Corn  Damage  Briefing for  S'.ii Idaho
               and SE Oregon.  (Unpublished study  received Jun  C,  I372 under
               11549-EX-1; prepared by U.S. Fish anc Wildlife Service, Civ.
               of Wildlife Services, submitted by  Avitrol Corp.,  Tulsa,
               Ckla.; CCL:223341-F)
           Horn, A.3.; Lambert, J.J.; Marshall,  I.G. (1973) A comparison of
               the fccilitatory actions of 4-aminopyricinc methiodids and
               4-arninopyridine on neuromuscular  transmission.   British Journal
               of Pharmacology 55(1):53-62.
           Horn, R. (1973) Propagating calcium spikes in  an axon
               of Aplysia.  Journal of Physiology  231:513-534.
           Hotchandani,  3.; Testa, A.C. (1973) Phosphorescence  emission and
               polarization of aninopyridincs.   Journal of Chemical  Physics
               53(2):595-600.
           Hoylc, W.C. (1973) The high-precision thermometric and coulometric
               assay of  primary standard 4-aminopyridine.  Dissertation
               Abstracts International B 34(7):3133.
           Hue, B.; Pelhate, H.; Callec, J.J.; Chanelet, J. (1975)
               Modifications par la 4-aminopyridine de  1'activite synaptiqus
               a'u nivcsu du dernier ganglion abdominal  de la Blatte
               (Periplansta americana)  [Modifications  induced  by the
               s'ynaptic  activity of 4-aminopyridine at  the level  of  the last
               abdominal ganglion of the cockroach (Periplaneta americana)]
               Ccmptes Rendus dss Seances de la Societe de Eiologie  et de 3es
            '   Filiales  169 (4):375-o33.
           Hue, 3.; Pelhate,. H.; Callec, J.J.; Chanelet, J. (1375) Effeis
               d'un convulsivant, la 4-aninopyridin:v, sur la transmission
               synaptique au niveau du dernier ganglion abdominal de lj blatte
               (Periplaneta americana)   [Effects of a  convulsant,
               4-ci:iinopyridine, on the synaptic transmission at the  level of
               the cockroach's last abdominal ganglion  (Periplaneta
               americana)] [abstract].  Journal de Physiologic  (Paris)

05006313 ..Hue, B. ;• Pelhste, H.;  Callec, 'J.J.; Chanelet, J. (1275) Synaptic
               transmission' in the sixth ganglion of the cockroach: action of
               4-aminopyridine.  Journal of Experimental Biology
               65 (5 ):517-5 27.
05005035   Hue, B.;. Pelhate, M. ;  Callec, J.J.; Chanelet, J. (1977) Effets
             •  pro- et postsynaptiques de la 4-aninopyridine.    [Presynaptic
               and postsynaptic effects of 4-cminopyridine] [abstract].
               Journal de Physiologic (Paris)  ,72(3):95.
05004235   Hue, 3.; Pelhate, M.;  Callec, J.J.; Chdnsl-t, J. (1373)
               Postsynaptic effects of 4-aminopyridine  in the  sixth abdominal
               ganglion of the cockroach.   European Journal, of Pharmacology
               49(3):327-329.
05003353



05004235

05003205


05006299


05011386
                                         91

-------
05006033   iluo, 3.; Prlhate, M.; Chjnelet, J.  (197j) Effets ce la
               4-aiiinopyridine  (;l-AP)-sur 1'sctivite cie  la .fibre nf-
               grant-; i3oi_:s ci'insect*  (Peripl^ngtn sirericuna)
               Journal da Physiologic  (Paris)  5Y(5):54T>.

00004140   Hyatt, ii.1V. (1955) Starling Control Using Avitrol 200 Concentrate
               Sugar Mixture.   (Unpublished study received Aug 24,  1966 under
               224-EX-4; submitted by Phillips Petroleum Co., Bartlesvilie,
               Okia.; CDL:122749<:)
00004139   Hyatt, H.if. (1966) Starling'Control Using Avitroi 200 Concentrate
               Sugar Mixture.   (Unpublished study received Aug 24,  1966 under
               224-EX--4; submitted by Phillips Petroleum Co., Cartlesvill-,
               Okla.; CDL:122749-3)
00004143   Hyden, S. (1963) Bird Management Process: LDG-123-53P.   (Unpub-
               lished study received Jul  17, 1963 under unknown admin, no.;
               prepared by Nepers Chemical Co., submitted by Fnillips Petro-
               leum Co., Bartlesville, 01«la.; CDL: 103063-A)
05003139   llles, P.; Thesleff, S. (1973) 4-Aminopyridine and evoked
               transmitter release from motor nerve endings.  British Journal
               of Pharmacology  54(4):623-629.
03007430   Jackson, W.B., ed.  (1976) Proceedings of the 7th Bird Control
               Seminar; Mov 9-11, 1976, Bowling Green State University,
               Bowling Green, Ohio.  Bowling Green, Ohio:  Environmental
               Studies Canter,  Bowling Green State University.  (Available
               from; NTIS, .Springfield, VA: .P3-277 755; six unnumbered pages
               preceding text)         •
05010056   Jacobs, R.S.; Burley, E.S. (197.3) Nerve terminal facilitatory
               action of 4-aminopyridine: an analysis of the rising phase of
               the endplate potential.  Neuropharmacology 17(7):439-444.
05014230   Jan, Y.M.; Jan, L.Y.; Dennis, M.J.  (1977) Two mutations of
               synaptic transmission in Drosophila.  Proceedings of the
               Royal Society of London, Series 3 193:37-103.
05005174   Jankowska, E.; Lundberg, A.; Rudomin, P.; Sykova, E. (1977)
               Effects of 4-aninopyridine on transmission in excitatory and'
               inhibitory synapses in the spinal cord.  Brain-Research
               136(2).-367-292.                                 .    -
050031/5   Johns, A.; Golko, D.S.; Lauzon, P.A.; Paton, D.M. (1976) The
               potentiating effects of 4-aminopyridine on adrensrgic
               transmission in  the rabbit vas daferens.  European Journal of
               Pharmacology 33(1):71-73.
05005155   Xannon, M.S.; Daniel, E.E. (1973) Formation of gap junctions by
               treatment in vitro with potassium conductance blockers.
               Journal of Cell  Biology 73(2):533-343.
05003492   Kcnyon, J.L.; Gibbons, W.R. 01979) 4-aminopyridine and the early
               outward current of sheep cardiac purkinje fibers.  Journal of
               General Physiology 73(2):139-157.
05011403   Khalaf, M.; Rimpler, M. (1979) Photometrlsche Bestirnmung von
               Aminen mittels
               5-Isothiocyanato-l, 3-dioxo-2-p-tolyl-2, 3-cihydro-1!!-benzyde! iso.
               chinolin_  [Spectrophotonetric determination of anines ;(Vith
               j-isothiocpn^to-l, 3-cioxo-2-p-toiyl-2,5-cihydro-1H-binzydo! iso
               quinoline ]  Fresenius Zeitschrift fuer • Analytische Cheinie
               294 (4): 235.
0500322?   Kh--n, A.R.; Edman, K.A.P. (1979) Effects of 4-sminopyridine on the
               c-xcit^tion-contraction coupling in frog and rat skeletal
               muscle.  Acta Physiologic.; Scandinavici 105(4): 443 -452.
                                         92

-------
050035J1    Ximurn,  X.;  Takaoka,  H.;  Nagai,  R.  (1977)  Luminescence of
                amir.opyridines  and  related molecules.   Bulletin of the Chcaiicii
                Society  of  Japan  50(5):13^3-1344.
Oj30J170    Xirpo'-:.-r,  !-i.; Xirpek^r,  3.M.;  Prat,  J.C.  (1976) Effect of
                4--aninopyridine (4 AP) on  release  of  norepinephrine CJE) from
                the  perfused  cat  spleen  by nerve stimulation (N3) and
                potass iurn(X).   Pharmacologist  18 (2): 203.
0500^166    Xirpekar,  M. ; Xirpekar,  3.M.;  Prat,  J.C.  (19(7) Effect of
                4-aminopyridine on release1..of  noradrenaline from the perfused
                cat  spleen  by nerve  stimulation.  Journal of Physiology
           !    'V • *^ / i \ — i «-y  f~ »-v O  •
                £«;(_>)::> l7-3^0.
05003159    Xirpekar,  M.; Xirpekar,  S.M.;  Prat,  J.C.  (1377) Effects of
                guanethidine  (G)  on  norepinephrine CJE)  rslib.se from the
                cat  spleen.   Federation  Proceedings i;5(o):i27.
0500:167    Xirpekar,  M.; Kirpekar,  S.M.;  Prat,  J.C.  (1975) Reversal of
                guanethidins  blockade of sympathetic  nerve terminals by
                tetrsethylamnonium and 4-aminopyrldine.   British Journal of
                Pharmacology  62(1):75-7o.
050149^1    Kirscn,  G.E.; Oxford, G.3.;  Yeh, J.Z.;  Narahashi,  T. (1979)
                i-ioduiation  of aminopyridine  block  of  potassium channels by
                membrane potential,  H+,  ano  Cs+  [abstract no.  T-AM-09].
                Biophysical Journal  25(2):137.
05003IT!    Kishore, N.; Agraual, P.; Gupta, R.C.  (1974)  MMR study of soiici
                4-amino  pyridine.  Indian 'Journal-  of Physics^qCi 1): 1007-1010.
00004105    Knit tie, C.E.;  Guarino,  J.L.;  Ouellette, M.R..;' Bray, O.E.;  .
                Cunmir.gs, J:L.  (1974) 4-Aminopyridine  for Protecting Ripening
                Sweet  Corn  from Blackbirds in Wisconsin:  (Report of Study No.
                51, Work Unit DF-102.3).   (Unpublished study including undated
                letter from D.  Bowden to Joseph  L.  Guarino,  received Mar 1£,
                1975 under  11649-12; prepared  by U.S.  Fish and Wildlife Service,
                Denver- Wildlife Research Center, submitted by  Avitrol Corp.,
                Tulsa, Okla.; CCL:226530-E)...
05003172-    Xoch, W.F.; Hoyle, W.C.; Diehl,  H.  (1975)  A high-precision
                titration of  4-aminopyridine:  a  value  for ohe  faraday.   Talanta
                22(9):717-727.
05003173    Xoch, v.'.?.; Poe,  D.P.; Dishl, II. (1975) Location of ^id-points in
                high-precision coulomb/try.   Talanta 22(7):609-611.
00004110    Xoh.n, F.E. (1963) Report to  Phillips Petroleum Cotapany:  Four-.v'eek
                3ubacut3 Oral Toxicity of Compound  1361 Hydrochloride—Albino
                Rats.  (Unpublished  study received Jan 2,  1965 under-  224-12;
                prepared by industrial'Bio-Test  Laboratories,  Inc.,  submitted by
                Phillips Petroleum Co.,- Bartlesviile,  Okla.; CDL:223344-E)
05014344    Xi-;iatkouski,  J.3.;  Zurawski, 3.  (1967) On  the eiectrophiiic
                substitutions in rnonoaminosubstituted  pyridines and
                pyrirnidines.  Acta Physica Polonica XXXII (6): 393-902.
00004133   Larson, 3. (1966) Starling.Control Using Avitrol 200 Concentrate
                and Sugar Mixture.   (Unpublished study received Aug 24,  1966  un-
               der 224-EX-4; prepared by Paramount P.ast  Control,  Inc.,  submit-
               ted by Phillips Petroleum Co.,  Bartlc-sville, Okla.; CDL:
                122749-A)
0500jV55   Le.:ind-;r, S.;  Arner,  A.;  Johansson,  3.  (1977)  Effects of
                4-aminopyridine on mechanical activity and  noradr-enaline
                release in the rat portal vsin in vitro.   European  Journal of
                Pharmacology 46 (4):351-361.
                                        93

-------
05003653   Lechat,  P.; Deysson, G.;  Lemeignan, M.;  Adolphe,  M.  (1953)
               Toxieit- aigu~ compiree de quolques  uiiino.pyridiiris  in vivo
               (Souris) ei in vitro  (cultures ceilulair.;s).   [Comparison of
               ths  acute toxicity  of some ;::nir.opyriJin~:5  in  vivo  (in mice) in a
               in vitro (cell cultures)]  Annales Phariiu^ceutiques  Francaises
               25 (5): 3^-343.
05003157   Lee, C.; de Silva, A.J.C.; Xatz, R.L. (1973) Antagonism of
               polymyxin 3-induceu neur muscular and cardiovascular depression
               by 4-cminopyridine  in the anesthetized cat.   Anesthesiology
               43 (4):256-259.
00003979   Lse, J.O. (1963) Starling Control: Bait  Acceptance Tests, Winter
               1952-63.  (Unpublished stuay received on unknown date under 224-
               EX-1; prepared by U.S. Fish and Wildlife Service, Branch of
               Predator and Rodent Control, submitted by  Phillips  Petroleum
               Co., Bartlasvilla, Okia.; CDL:122741-3)
05007913   Lemaignan, M. (197D Abord pharmacologique de  1'etude du mecsnisme
               ds 1'action convulsivanto do l'smino-4 pyridine.
               [Pharaacological approach to the study of  the convuls&nt action
               mechanism of 4-aninopyridine]  Therapio XXVI(5):927-340.
05010734   Lemeignan, H. (1972) Analysis of the action of  4-anino  pyridin:- on
               the  cat lunbsr spinal cord.  1.   Modification of the afferent
               vollay,  the monosynsptic discharge anplitude  and the
               polysynaptic evoked responses.  Meuropharmacoiogy
               11(4):551-55G.
05010054   Lemeignan, H. (1973) Analysis of the effects of 4-amino pyridine
               on the lumbar spinal  cord of the cat II—Modifications of
               certain spinal inhibitory phenomena, post-tetanic potentiation
               and  dorsal root potentials.  Neuropharmacology 12(7):641-651.
05012334   Lemeignan, M.; Auclair, M.C.; Rodallec,  A.; Lechat, P.  (1975)
               Analyse electrophysiologique des effets de  l'anino-4 pyridine
               sur  le lambeau ventriculaire isole de coeur de Cobaya.
               [Electrophysiological analysis of the effects of
               4-cminopyridine on guinea pig myoc^rdial ventricular isolated
               strips]  Archives Internationales de Pharmacodynamia et de
               Tnerspie 215(1):165-175.
05012335   Le Meignan,  M.;  Chanelet, J.; Sa^de, -J.E. (1959) Etuda  de 1'Action
               d'un convulsivunt special (la 4-aminopyridine) sur  les nerfs d=
               vertebres.  [Action'of a special convulsant,  M-aninopyridine,
               on vertebrate nerves]  Conptes Renaus des Seances de la
               Societe de Biologie et de Ses Filialas l53(2):353-365.
05012256   Lemeignan, M.;  Lechst,  P. (1957) Sur I1action anticurare des
               arainopyridir.es.  [On  the anticurare actions-of the
               aminopyridines]  Cnnptss Rendus Hebdonadcires des Stances de
               I'Acjdcrnia des Sciences, Serie D 254(1): 169-172.
05013095   Lemaignin, M.; Molgo,  J.; Lechat,  P. (1977) Donn^-es sur Ic-
               mecanisme do 1'action facilitatrice  de l'snino-4-pyridine au
               niveau de la jonction neuranusculaire.  [Data on the mechanism
               of the facilitatory effect of 4-arninopyridine in a
               neuronuscular junction]   Journal de  Pharmscologie
               3(4):523-529.
OjQ03543   Lav-Tov, A.; Erulkar,  3.D.;  R,ah=;niinoff,  R. (1977) The role of
               calcium in augmented transmitter release due to potassium
               channel blockade.   Israel Journal of Medical Sciences
               13(5):537-53c.
                                         94

-------
OQ004026   Life-stream Laboratories,  Incorporated  (1363)  Dot^mir.ation  of the
               Maximum Tolerated Dose of Compound  186'I--Mongrel  Dogs.   (Unpub-
               lished study received Dec 30,  1363  under  1F1013;  submitted by
               Phillips Petrolyum Co., Bartlssvillj, 3ki.ii.; CDL:G91736-1)
013010063   Llinas, R.; Walton, K.; Bohr, V.  (1973) The action of 3-  and
               4-aminopyridine- on synaptic  transmission  in  the squid giant
               synapse [abstract!.   Biological Bulletin  149(2):435.
05003155   Llinas, R.; WE1ton, K.; Bohr, V.  (1975) Synoptic transmission in
               squid giant synapse after potassium conductance blockage  with
               external 3- and 4-arninopyridine.  Biophysical Journal
               l6(1):33-36.
05016210   Lugovkin, B.P.; ZmLyanitskaya,  E.T.; ICargalov,  A.A.;
               Gabdulkhaevu, A.F. (1974) Gpredelenie ai'fa-aminopiridina,
               gamma-aminopiridina i yl'fa-amir.okhinoiina v vozdukhe
               kolorimetricheskim i  spektrofotanctricheslcim metodom.
               [Determination of alpha-pyridinamir.e, garnma-pyriainamine,  and
               alpha-quinolinamine in the atmosphere by  colorimetric and
               spectrophotanetric methods]   flauehnys Raboty Institutov
               Okhrany Truda Vsesoyuznogo Tsentrai'nogo  Sovota
               Professional'nykh Soyuzov.   [Scientific Vibrks of  the  Institutes
               of Labor Protection of th-2 Ail-Union Cantrsl Council  of Trade-
               Unions.! 36:61-65.
03003433   Lundh, H. (1973) Effects  of 4-aminopyridine on neuromuscular
               transmission.  Drain  Research 153(2):307-313.
05014934   Lundh, H. (1979).Effects  of 4-aminopyridine on statistical
               paraneters of transmitter release at the  neuromuscular
               junction.  Acta Pharmacologies st Toxicologies 44(5):343-346.
05004216   Lundh, H.; Leander, S.;  Thssleff, S.  (1977) totagonism of the
               paralysis produced by botulinum toxin in  the rat:  the effects
               of tstraethylammonium, guanidine and 4-aminopyridin-i.   Journal
               of the neurological Sciences  32(1):29-42.
05004217   Lundh, H.; Nilsson, 0.;  Rosen, I.  (1977) 4-Aminopyridine— a new
               drug tested in ths treatment  of Eaton-Lambert syndrome.
               Journal of Neurology, ifeurosurgery, and Psychiatry
               40(11):1109-1112.
050034^4   Lundh, H.; Nilsson, 0.;  Rosen, I.  (1979) Effects of
               H-.iTiinopyricine in rnyasthenia gravis.  Journal of Neurology,
               Meurosurgery, and Psychiatry  42(2):171-175.
05003542   Lundh, H.; Thssleff, 3.  "(1977) The mode of action of
               4-arninopyridin-D and guanidine on transmitter relc-as^  froin motor-
               nerve terminals.  European Journal of Pharmacology
               42(4):411-412.
05012199   ;-iue-.ani, T.; Shiba, Y.;  Muneokd,  Y.; Kanno, Y. (I379) Effects  of
               Zn2+,  U022+ ond 4-sminopyridine on twitch contraction and
               action potential in the mouse skeletal muscles.   Hiroshima
               Journal of Medical Sciences 23(1):43-43.
05003105   Haitian, J.C.; Walker, K.-C.; Westlake, V/.E. (196j) An  improved
               colori;netric method for  determining enaosulfan (Hiiodan)
               residues in Vi-:get-ablys and beef fut.  Journal of  Agricultural
               und Fcou Chemistry 11(5):416-41G.
05004215   iiandri.-k, 1C.; Golenhofen,  K.  (19/7) Analysis of
               4-aminopyridir.s-ir.duced automatic activity in the  gi^nt axon of
               the squid.  Pfluegers Ar-chiv.  European Journal of Physiology
               -  • - - ~
                                         95

-------
 05003459


 00004055



 1)0004050
00004057
00004054
00004052
00004147
05005555
G30015-005



05004419


05006035
0500345G
 Kandrek,  K.;  Larrcei,  E.  (V37J) Influence of 4-.;:niropyridino, TEA
     v^r.o Cs  on the  potassium kinetics of the squid giunt exor..
     Pfluegers Archiv.   European Journal of Pnysioiogy 577:41.
 Marquardt,  R.E.  (no date)  Control of Sparrows and Dlackbircs -at tn:
     Jenkins  Rice Mill,  Anahuac, Texas.   (Unpublished study received
     Get 17,  19f5 under1  11649-1; prepared by Phillips Petroleum
     Co.,  submitted by Avitroi  Corp.,  Tulsa, Gkla.;  CDL:011002-D)
 Harqusrdt,  R.E.  (1952) Use of  Chemical  1861 for Control of Black-
     birds in  Ricefields  in Chambers  County, Texas.   (Unpublished
     study received Get  17,  1973 under 11649-1;  prepared by Phillips
     Petroleum Co.,  submitted by Avitroi Corp.,  Tulsa,  Gkla.; CDL:
     011002-I)
 Marqu^rdt,  R.E.  (1952) Use of  1351 for  Bird Control at Psntcx Stor-
     age,  Anariilo,  Texas.   (Unpublished study received Get 17,  '975
     under 11549-1;  prepared by Phillips Petroleum Co.,  submitted by
     Avitrol  Corp.,  Tulsa,  Okla.;  CDL:011002-E)
 i-iarquirdt,  R.E.; Cantrel,  K.E.  (1953) Bird Control  Tests with Chsn-
     icai  1351 at the Martin Farm,  independence;,  Kansas,  1952-195j.
     (Unpublished study received Oct  17, 1973 under  11543-1;  prepared
     by  Phillips  Petroi&urn  Co.,  submitted by Avitrol Corp.,  Tulsa,
     Okla.; CDL:011002-M)
 Harquardt, R.E.; Cantrel,  K.E.  (1}53) Herring Gull  Tests in  Mew
     Hanpshire, 1952-1963.   (Unpublished study received Oct 17,  1975
     unaer 11549-1;  prepared by Phillips Petroleum Co.,  submitted by
     Avitrol Corp.,  Tulsa,  Okla.;  CDL:011002-iO
 Matlock,  R.S.; Oswalt, R.H.  (1955?) Report of Sunflower  Research in
     Oklahoma.  (Unpublished study received Jun  16,  1972  under  un-
     known adrnin. no.; prepared  by Oklahoma State Univ.,  Dept.  of A-
     gronany,  submitted by  Avitrol Corp.,  Tulsa,  Okla.; CDL:210151-I)
 Hatsubara, H.; Obara, Y. (19i;3) Pyridine,  diazine,  triuzine
     oyobi triazole-ksi zassozai narabi  ni  kanrenkagobutsu  no hina
     ni  taisuru hatsumosei  ni tsiute_  [On  the blinding activities
     of  pyridines, diazines,  triazines,  triazole  and their
     related compounds on baby  chicks  (Studies on the biological
     activity  of heterocyclic compounds,  Part 1II)_J   Nippon  Mogei
     K.3gal
-------
05004356
oooo'; 093
05012005
05003368
05005034
0500j242


05003495



05020237



05003154


05015032
Miller, R.D.; Eooij, L.H.D.J.; Agoston, S.; Crul,  J.F.  (1979)
    4-A:ninopyridins potentiates neostigmir..,- and pyridostigmir.e  in
    tnr.n.  Anesthesiology 50 (5): 415-420.
Miller-, R.D.; Dennissen, P.A.P.; Van Der  Pol, F.;  Agoston,  3.;
    Booij, L.Ii.D.J.; Crul, J.F. (1973) Potsntiation of  neostigrnine
    and pyridostigmine by  4-aninopyridine in  the  rat.   Journal  of
    Pharmacy and Pharmacology jO(11):699-702.
Mitchell, I\.T.; Linihan, J.T.; Ingram, C.R.;  Meanley, D.; Martin,
    P.3.  (1975) 1974 Test  of 4-Aminopyridine  (Avitrol)  Efficacy in
    Preventing 3ird Damage to Sweet Corn  in Maryland: Progress  Re-
    port: January 1-December 31, 1974: Work Unit  P-F-11-33.13.   (Un-
    published study received Mar 13, 1975 under 11649-12; prepared
    by U.3. Fish and Wildlife Service, Patuxent Wildlife  Research
    Center, Section of Animal Degradations Control Studies,  submit-
    ted by Avitrol Corp.,  Tulsa, Okla.; CDL.-094799-0)
Mitsov, V.; Uzunov, P. (1972) Otnocno  tokcichnostta na
    s'edinenieto VMI-10-3.  [Toxicity of  the  compound VMI-10-3]
    Exsperirrientsina Meditsina i Morfologiya.  [Experimental
    Medicine and Morphology.]•XI(3):162-165.
Miyajirna, G.; Sss=ki, Y.;  Suzuki, M.. (1972) Carbon-13 nuclear-
    magnetic resonance spectroscopy.  VI.  Studies on carbon-13
    magnetic resonance spectra in aromatic and heteroaromstic
    systems.  (2).  On the chonical shifts of substituted pyridine
    derivatives.  Chemical and Pharmaceutical Bulletin
    20(3):429-437.
Molgo, J. (1973) Voltage-clamp analysis of the sodium and
    potassium currents in  skeletal muscle  fibres  treated with
    4-aminopyridine.  Experishtia 34(10):1275-1277.
Molgo, J.; Lemeignan, M.;  Lechat,  P. (1975) Modifications de la
    liberation du transmetteur a la jonction  reurotnusculaire de
    grenouille sous I1action de l'amino-4 pyridine [Changes in  the
    transmitter release at the neuromuscular  junction of the frog
    induced by the action of 4-aminopyridine]  Canptes  Rendus
    Hebdomadaires des Seances de I'Academie des Sciences, Serie D
    231(21):1637-1639.
Molgo, J.; Lemeignan, M.; Lechat,  P. (1977) Effects of
    4-amir.opyridine at the frog neuromuscular junction.  Journal of
    Pharmacology and Experimental Therapeutics 203(3):653-663.
Molgo, J.; Lemeignan, M.; Lechat,  P. (1979) Analysis of the action
    of 4-aminopyridine during repetitive  stimulation at the
    neuromuscular junction.  European Journal of  Fnarmacology
    53(3):307-311.
Molgo, J.; Lundh, il.; Taesleff, S.  (1930)  Potency of
    3,4-diaminopyridine and 4-aminopyridine on mammalian
    r.euromuscular transmission and the effect of  pH changes.
    European Journal of Pharmacology 61(1):25~34.
Moritoki, H.; Taksi, M.; Nakamoto,  U.; Ishida, Y.   (1973) Actions
    of aminopyridines on guinea-pig ileum.  Archives
    Internationales de Phurmacodynamis at  de Therapie 232(1);23~41.
Morrison, D.J.;  Johnson,  A.L.3. (1975) Zinc chloride effectively
    controls Fomes annosus stump infection.  Bi-monthly Rosearch
    Motes, Canadian Forestry Service 31('T):5-6.
                                         97

-------
00004077   Mott, D.F.; Besscr. J.F.  (1970?) Project DF-102: Bird Damage Con-
               trol Research: DF-102.3-20.  (Unpublished study r-ceivod
               Jun 3,  1972 under 11649-EX-.1; prepared by U.S. Fish <_nci Wild-
               life Service, Denver Wildlife Research Ccnte", submitted by
               Avitrol Corp., Tulsa, Okia.; CDL:223541-G)
00004103   Mott, D.F.; Besser, J.F.; W-st, R.R.; Da Grazio, J.W. (1972?) Bird
               Damage to Peanuts and Methods for Alleviating the- Problem.  Dy
               U.S. Fish and Wildlife Service, Denver Wildlife Research
               Center.   Washington, D.C.: Dept. of the Interior.  (Proceed-
               ings, 5th Vertebrate- Pest Control Conference, Mar 7-9, 1972,
               Fresno, Calif.; also in unpublished submission received Feb 15,
               1973 under 11549-12; submitted by Avitrol Corp., Tulsa, Okla.;
               CDL:008284-B)
00004102   Mott, D.F.; Guarino, J.L. (1972) Investigation of Blackbirds and
               the Damage Thuy Cause during the Peanut Damage Season in South-
               eentrai Oklahoma, 1972: (Technical Report Mo. 5, Work Unit DF-
               102.3).  (Unpublished study received Ftb 15, 1973 under 11649-
               12; prepared by U.S. Fish and Wildlife Service, Denver Wildlife
               Research Center, submitted by Avitrol Corp., Tulsa, Okla.; CDL:
               0032G4-A)
00004096   Mo-t, D.F.; Royall, W.C., Jr. (1975) 4-Aminopyridine for Protecting
               Ripening Sweet Corn from Blackbirds in Idaho: (Report of Study
               lio. 52, Work Uni^ CF-I02.3).  (Unpublished study including sta-
               tistical review, received Mar 18, 1975 under 11649-12; prepared
               by U.S. Fish snd Wildlife Service, Denver Wildlife Research
               Center, submitted by Avitrol Corp., Tulsa,  Okla.; CDL:094799-D)
05015253   Msrahashi, T. (1979) Cellular neuropharmacological study of drug
               action [abstract no. 11.04031.   Toxicology Research Projects
               Directory.   Section 1 4(11):50.
05006421   Nelson, H.A.; Decker,  R.A.; Osheim,  D.L. (1976) Case report:
               poisoning in zoo animals with 4-aminopyridino.  Veterinary
               Toxicology 13(3):125-126.
00004000   Nelson, J.tf. (no date) Field Tests of Avitrol in Virginia.  (Unpub-
               lished study received Dec 18, 1970 under 224-EX-3; prepared by
               Virginia Dept. of Agriculture,  State Bird Control, submitted by
               Phillips Petroleum Co., Bartlesville, Okla.; CDL:122744-G)
00004051   Mewsom, J.D.; Wilson,  R.C. (1973) An Assessment of Crow Control
               Techniques in Pecan Orchards in Louisiana:  Projecc Number LW-56-
               WU.  (Unpublished study including project no. LW-57-iVU,  received
               Hay 3,  1973 under  11643-8; prepared by Louisiana State Univ.
               sjnd Agricultural and Mechanical College in cooperation with
               U.S. Fish and Wildlife Service,  submitted by Avitroi Corp.,
               Tulsa,  Okla.; CDL:220239-A)
00003971   Kewson, J.D.; Wilson,  R.C.; Murray,  M. (19/3) An Assesanent of Crow
               Control Techniques in Pecan Orchards in Louisiana: Project
               Number: LW-56-WU.   (Unpublished study received Jui 26, 1973
               unaer 11649-3;  prepar-.3d by Louisiana State Univ., submitted by
               Avitrol Corp.,  Tulsa, Okla.; CDL:227059-A)
05004420   Nicholson,  C.;  Ten Bruggencate, G.;  Sentkowitsch, R. (1976) Large
               potassium signals  and slow potentials evoked during
               a;:iir.opyridine or barium super-fusion in cat cerebellum.  Brain
               Research 113(3):606-610.
00004071   North, C.A. (no date)  Evaluation of Selected Chemicals as Bird
               Management Agents.  (Unpublished study received Oct 17,  1973
               under 11649-1;  prepared by Oklahoma State Univ., submitted by
               Avitrol Corp.,  Tulsa, Okla.; CDL:011002-X)

                                          98

-------
05009411
0500j183
05005197
00004255
00004111
05003194
00004141
0000410J




05005425


05013564
IJorth, C.A.  (1962)  Suamary of  Fie-la  Studies,  July,  1952—August;,
     1962 to  Phillips  P:;troleu:n Company:  Bird  Mana^rnenu Testa.   (Ur.--
     published study received Get  17,  1975  under  11649-1; prepared
     by Oklahoma State Univ., submitted by  Avitroi Corp., Tuisa,
     Ckia.j CDL:011002-Z)
Dscik, J.; Chojnacka, G.  (1957) Wspolzal^znosc miadzy
     wspolczynnikatii RM-> w chronatografii adsorpcyjnej  i
     pociziaiowc-j.  II.  Wspolczynniki RM-. nitroanilin  i
     aminopirydyn.   [Correlation of RH-, values in adsorption  and
     partition chromatography.   II.   RM-.  coefficients of
     nitroanilines and aninopyridine-sj.   Chemia Analityczna
     (Warsaw).  [Analytical Chemistry.]  12(6):1213-1213.
Padhye, M.R.; Bhujle, V.V.  (1953) Vibrational and electronic
     spectra  of 2-,  3- ana 4-aminopyridines and deuterated
     analogues.  Indian Journal of Pur-; and Applied  Physics
     5(2):104.
Padhye, M.R.; Ohujls, V.V. (1959) Fluorescence, phosphor-sscance
     anc selective fluor=sc£nce polarization spectra of
     arninopyridinss  [litter].   Current Science 33(9):215.
Palazzolo, R.J. (1952) Report  to Phillips  Petroleum Company:
     Special  Acute Toxicity Study on  Compound  1351 Hydroehlorids.
     (Unpublished study received Dec  30,  1963  under  1F1013; prepared
     by industrial Bio-Test Laboratories, Inc., submitted by  Phillips
     Petroleum Co.,  Bartlesville, Okla.;  CDL:091736-D)
Palazzolo, R.J. (1963) Report  to Phillips  Petroleum Company:  Toxic-
     ity to Salt Water Life of  Compound 1361 Hydrochloride.  (Unpub-
     lished study received Jan  2, 1953 under 224-12; prepared by  In-
     dustrial Bio-Test Laboratories,  Inc.,  submitted by Phillips  Pe-
     troleum  Co., Bartlesville,  Okla.; CDL:229344--F)
Part, H.C.;  Terakawa, S.; Daumgoid,  J.;  Tasaki, I.; Gainer,  H.
     (1973) Protein  release from the  internal  surface of the  squid
     giant axon membrane during excitation  end potassium
     depolarization.   Biochimica et Biophysica Acta 513(1):132-140.
Paramount Pest Control Service (1955) Resume  of Avitroi  Bird  Man-
     agement  Process for Halas  Brothers Building Service  Performed
    City of  Oakland,  California.  (Unpublished study including let-
     ter dated Sep 15, 1965 from E.W. Bushing  to Phillips Petrol-jura
     Co. and  letter  dated Sep 20, 1965 fron H.W. Hilcs  to Phillips
     Petroleum Co.,  received Jun 27,  1957 under 224-EX-6;  submitted
    by Phillips Petroleum Co.,   Bartlesville,  Okla.; CDL:122751-A)
Parrnenter, R.E. (1957) Final Report: Investigations of the Usabili-
     ty of Avitroi 200-D29 as a  Pigeon Repellent.  (Unpublished study
     including preliminary report, received Jan 2, 1963 under  224-12;
     prepared by Abilene Pest Control Service, Inc., submitted by
     Pnillips Petroleum Co.,  Bartlesville,  Okla.; CDL:229344-D)
Paul, 3.;  Rao, D.-V.R. (1969) Cadmium  (II)  complexes with
     2-aminopyridine,  4-aminopyridine and 4-amino.jntipyrine.
     Journal of the  Institute of Chemists XLI(5):177-131.
P'.'ihat;?, M.; liue,  3.; Chanol3t, J.  (1;72)  Effets da la •
     4-amiro-pyridine sur le systems nerv^ux d'un insects:  la  blatt-s
     (Per ipljneta >mfericora L).   (Poriplarcta amcricanr.  L_ )
                                        99

-------
03012594   Pelhate, M.;

05006033
05005032
      •>7
050042
05015003
00004125
00004119
00004010
OOGOUOOo
                              B. ;  Chans let,  J.  (1974)  Modifications,  par la
                              nr. ,  d-;3  caractsristiquvis electriques c:- i'axoni
               geant  isola d'un  inseote,  la Elatta  (Pariplgnrtn
               arncricar.a L±   -[Modification by 4- aminopyridins of the
               electrical characteristics of the  isolated  giant axon of the
               cockroach (Peri planet a americans L_)_  j   Comptes  Rendus des
               Seances do 1=  3oci:;te  de Biologic  et de Sc-s Filiaies
               155(1 ): 27-34.
           Peihate, M. ; Dichon,  Y.  (1974) 5jL:ctive Inhibition of Pot ass ram
               Current in the Giant Axon  of the Cockroach  J.  Physiol. 242 pgs.
               90-91.05005033   Peihate,  M.; Hue, 3.;  Pichon,  Y. ; Chanel:-t, J.
           Peihate, M.; Hue,  3.;  Pichon,  Y. ; Chsnelet,  J.
               4-2nino-pyridine  sur ia manbr'ane ds 1'axone isola  d'ins^ctc-
               [ Action of 4-sninopyridine on tivs membrana  of  the  isolated
               insect axon]   Comptes  Hindus Hebdomad air ss  c-as' Seances de
               I'Academie d-cS Sciences, Serie  D 27S(22):2807-2G09.
           Pelhste, H. ; Mony, L. ; Mue, B.;  Chaislst,  J.  (1975) Action de ij
               4-;^ninopyridine  (4-AP) sur les  courtnts  ioniques membr-anairss ;
               cas de 1'axone geant isolo ds la blatte
               amsricana)   [Action of 4-sminopyridine  (4-AP) on the
               inernbranate ionic currents; cass of the isolated giant  axon of
               tine cockroach (Pariplanrta americana)    Journal de
               Physiologic (Paris) 71(2): 'J5o\
           Papose, J.S. ; Lisman, J.E. (1973) Voltage-sensitivf potassium
               channels in Limulus ventral pho^oreceptors .  Journal of General
               Physiology 71 (1 ): 101-120.
           Parlkov, I.G. ; Chaplinov, P.E. ; Polkovnichenko, P.T. (1974)
               Spektrofotonetricheskoe izuchenie 4-aminopidina v
               vodno-solavykh rastvorakh.  [Spectrophotometric investigation
               of 4-aminopyridine in watsr-salt solutions].  Zhurnal
               Fizicheskoi Khimii.  [Journal of Physical Chemistry.]
               43 (4): 1005-1006.
           Peterson, J. (no date) Microanalytical Method Development  for
               Avitrol. (Unpublished study received Apr 15, 1959 under 224-EX-3
               prepared by U.S.  Fish and Wildlife Service, Denver Ros r.rch
               Carter  submitted by Phillips Petroleum Co., BartL-zsville, Gkij.;
               GEL: 1227 45 -I)
           Peterson, J.E. (1969) Development of Analytical Mathod for 4-A:uino-
               pyridine: Fourth Periodic Report — July 5, 1959.  Includes method
               dated Jul 1,  1959.  (Unpublished study received Jui 24, 1959 un-
               der 224-EX-3;  prepared by U.S. Fish and  Wildlife Service, Denver
               Research Center,  submitted by Phillips Pc-troleum Co.,  Qartl-s-
               vilie,  Okla.;  CDL:122745-B)
           Peterson, J.E. (1969) Microanalytical Method for 4-Aminopyridinc-.
               Method  dated Sep 19, 1969.  (Unpublished study received Get 20,
               1959 under 224-EX-j; prepared by U.S. Fish -and Wildlife Ser-
               vice, Denver Wildlife Research Center, 'submitted by Phillips
               Petroleum Co.,  Bartlasville, Okla. ; CDL: 122M4--Q)
           Poterson, J.E. (1959) Microanalytical Mothod for 4-.Vainopyridine in
               Corn Plcint Tissue.  Hechod dated Dec 22, 1v59.  (Unpublished
               study received Jan 20, 1970 und^r 224-EX-3; prepared by U.S.
               Fish and Wildlife Service, Denver Research Center, submitted by
               Phillips Petroleum Co.,  Bartlesville, Okla.; CDL: 122744-L)
                                         100

-------
05000001


00004033


00014578


00004013
00004021


00002935


00004121



00004117



00004135


00003991



00004023



00003990
 Petrowitz,  U.J.;  Psssusla,  G.;  W^re-,  G.  (19o5)  !Jc-ter
    Du /nnschichtchrorriatographi ? heterocyclisohsr
    SticUstoff-Vvrbindungc-n c-;-.r Pyridin-  und  Chinolir-Rcihe.
    LThin-.layar  ahroiv.atogr^phy  of heterocyciic r.i'trog\n  compounds
    of the  pyridine  and  phiroline group].   Chsmiker-Zeitung
    ' • f I 1 > . 7 1O
    G 7 U ;. i - I £.
 Pfi.nningsr, K.;  Akert, 1C.;  Moo*-,  H.  and 3anc-i, C.  (19f2)  Tru
    Fine Structure of Freeze Fractured  Presynaptic  Msmbrijr.3.  J.
    Meurocytol pgs.  129-149.
 Phillips Pawroliun Company  (r.o  date) Composition  jurd  For.nul::tion:
    [Avitrol].   (Unpublished study received Jen 3,  1973  under
    IF1013; CDL:031757-3)
 Phillips Petr-oleun Company  (no  date) Compound 1361  Hydrochlorids.
    (unpublished  study raceivs'd on unknown  -daw under 1F1013; CDL:
    093522-D)
 Phillips Petroleum Company  (no  date) Formula:  Avitrol FC Corn Chops
    1-10 Concentrate.   (Unpublished  study received  Jul  13,  1970
    under  1F1013; CDL:093322-C) .
 Phillips Petroleum Company  (no  date  Laboratory Evaluation  of  4-Mino-
    pyridinc Toxicity and Bait  Formulations.   (Unpublished study
    received Jan  3,  1973 under  1F1013;  prepared in  cooperation with
    U.S. Fish =nd Wildlife  Service,  Denver  Wildlife Rist-ireh
    Center; CDL:091757-F)
 Phillips Petroleum Company  (r.o  dats) Rsasonable Grounds  in Support
    of the  Petition: [Avitrol].  (Unpublished  study received Jul 13,
    1970 under 1F1013; CDL:093322-G)
 Phillips Pstroieum Company  (no  date) Residue  Data:  [4-Amino-z
    pyridine (Unpublished study received Jul  17,  1970 under 224-EX-
    3~; CDL: 122743-D)
 Phillips Petrols-urn Company  (no  date) Residue  Data:  Estimate of Possi-
    ble Contamination of Corn Plant  as  a Consequence  of  Lodging  of
    an Active Bait Particle in  the Plant.   (Unpublished  study re-
    ceived  Jun 6, 1969 under-224-EX-3;  CDL:122745-E)
 Phillips Petroleum Company  (no  date) Results of a Laboratory Tost to
    Determine the Rate of Degradation of 4-Atninopyridine in Soil:
    Good-67-ojR.  (Unpublished  study received  Hay TJ, 1965 undar
    224--EX-3; CDL:122746-D)
 Phillips Petroleum Company  (no  date) Technical Data Sheet: Phillips
    Avitrol 200  (I860.  (Unpublished study received  Jan 17, 1953
    under ur.knov.n admin, no.; CDL: 10J072-A)
 Phillips Petroleum Company  (no  date) Toxicity  Data  Summary: 4-/Vnino-
    pyridins (Compound 1261; DRC-1327): (Active Component—Avitrol
    200 Bird Management).   (Unpublished study  received Apr- 22, 19o9
    under 224-EX-3; CDL: 122747-^)
 Phillips Petroleum Company  (no  date) Toxicology: Consumer  Safety
    from Pesticidal Residues.   Summary  of studies 09 1 i'55-3
    through 091755-J.  (Unpublished study received  Dec 30, 1963
    under IF 1013; CEL:091756-A)
 Phillips Petroleum Company  (no  date) 4-Amino pyridine Data Sheet:
    Properties of U-Aminopyridine  (Compound 1351;  DRC-b2,7).  (Un-
    published stucy received Apr 22,  1959 under 224--EX-3; CDL:
    122747-A)
Phillips Petroleum Company  (no  date)  4-Aminopyridine Data Sheet:
    Properties of 4-Aminopyridine  (Compound 1361;  DRC-1327).
    (Unpublished study received Jul 17, 1970 under 224-EX-3;
    CDL:122743-2)
                                         101

-------
00004122   Phillips Petroleum Company  (1953) Ohio Field Evaluation of Aviiroi
               200 Used to Discourage  Blackbird Depredation,  to Field Corn.
               (Unpublished study including suimary report, received Apr 15,'
               195} under 224-EX-3; CDL:122745-F)
OOOC4130   Phillips Petroleum Company  (19-38) Periodic Report for Avitroi FC
               Corn Chops Concentrate.   (Unpublished study received Sep 33,
               1963 under 224-EX-3; CDL: 1227450).
00004129   Phillips Petroleum Company  (1953) Toxicity Studies or. Avitrol 200:
               (Compound 1361).  (Unpublished study received Jan 5, 1959 under
               224--EX-3; prepared in. cooperation with Lifestream Laboratories,
               Inc.; CDL:122,745-L)
00002992   Phillips Petroleum Company  (1959) Effectiveness Data: 4-Aminopyri-
               dinfc (Avitrol 200).  (Unpublished study received Apr 22, 1969
               under 224-EX-3; CBL:122747-F)
00004120   Phillips Petroleum Company  (1969) Field Test Project on 4-Amino-
               pyridimo (DRC-1327).  (Unpublished study received Apr 24, 1970
               under 224-EX-3; prepared  in cooperation with U.S. Fish 
-------
05017364
0030405.;
00004059
00004014



0000401j



05005503


05003196


05020246



05015593
05011' .591
05014332
05014J3
 Ray, .V.C.;  u-jnulinas,  3.II.;  R:;agor,  J.C.  (1973)  Applications  of
    high  performance  liquid  ehromatogrjphy to veterinary
    toxicology.   Pages 135-134,  in  American  Association  of
    Veterinary Laboratory  Diagnosticians,  21st Annual  Proceedings.
    Madison, Wis.:  American Association of  Veterinary* Laboratory
    Diagnosticians.
 R-.nr.c-rt,  A.J. (no date) Field Tests  on Starlings with  1561  at Beard
    town, Illinois.   (Unpublished study Deceived Get  17,  13/3 under
    11543-1; prepared  bv Pnillips Petroleum  Co,,  submitted by
    Avitrol Corp., Tuls-1,  Okla.;• CDL:011002-A)
 Reinert,  A.J. (1963) Field Tests on  Starlings with  1351  near
    Columbus, Ohio.   (Unpublished study received Oct  17,  13T3 under
  •  11649-1; prepared  by Phillips Petroleum  Co.  in  cooperation with
    U.S.  Fish and Wildlife Service,  submitted by Avitrol Corp.,
    Tulsa, Okla.; CEL:011002-H)
 Rein-art,  A.J. (1963) Crow  Control Tests with Avitrol 200 at Fulton,
    Arkansas.  (Unpublished  study received Jul 17,  1370  under
    224-EX-2; submitted by Phillips  Petroleum Co.,  Eartlesville,
    Okia.; CDL:122742~D)
 Reinert,  A.J.; Cantrel, K.E. (1965)  Crow Control Tests with Avitrol
    200 at Leonard Bend, Texas.   (Unpublished study received  on  Jul
    17, 1970 under 224-EX-2; submitted by  Phillips  Petroleum  Co.,
    Bartlesville, Okla.; CDL:122742-3)
 Reinert,  A.L., inventor; Phillips Petroleum  Co.,  assignee (1365)
    Bird  control and bird management compositions.  U.S.  patent
    3,193,455.  Jul 6.  5 p. Cl.  167-46.     :
 Ross,  W.N.; Stuart, A.E. (1978) Voltage sensitive calcium channels
    in the presynaptic terminals of  a decrementally conducting
    photoracsptor.  Journal of Physiology  274:173-191.
 Rubin, A.; Dhahir, P.H.; Crabtree, R.E.; Henry,  D.P. (1379) The
    disposition of
    1 -3-(diinethylamino)-(m-dioxan-5-yl)methylpyridine  in' man.
    Drug  Metabolism and Disposition  7(3):149-154.
Suade, M:E.; Chsnelet, J.; Lonchampt, P. (1971)  Action
    f jcilitatric= de microinjections de 4-aminopyricine-  sur Iss
    Ectivites medullairss re-flexes de la gr-:.-nouille  [Facilitating
    action of microinjections of 4-aninopyridine on spinal  reflex
    activity in the frog]  Cornptes Rencus  de.? Seances  de ia
    Societe de Biologic ec de Ses Filial&s 155(11):2069-2077.
Ssade, IJ.E.; Chanelet, J.; Lonchampt, P. (1971)  Differents  :nodes
    c'activation reflexe de  la rnene  preparation  rie  grenouillo
    spinale: ieur facilitation par la -l-aminopyridine  [Different
    modes of reflex activation of the same preparation of frog
    spinal: their facilitation by 4-arnir.opyridinej  Comptes Rendus
    des Seances de la  Societe de Biologie  et de  Ses Filiales
    155(5):1242-1249.
Sc.-ppaticci, K.A.; ladarola, M.J.; Dretchen,  K.L. (1973)  The
    interaction of potassium and calcium ion  channel biockers at
    the neuromuscular  junction [abstract no  1915].  Federation
    Proceedings 37(3):577.
Scjppatieci, K.A.; lacaroli, M.J.; Dretchen,  K.L. (137-)  The;
    interaction of potassium ana- calcium ion  channel blockers at
    the neuromuscular  junction [abstract no  1915].  Federation
    Proceedings 37(3):577.
                                         103

-------
0000^997
00004006
05003187


0501543G


05003!93




00004142
050054GO
00004003
05003133


05003200


05004220
 Schafer,  E.W.  (1372?)  Acute  Toxicity  of  4-Amiropyricine  to 40 Ani-
    mal Species.   (Unpublished  stucy  receivcc  Feb 15,  1373 -Jr.djr
     11545-12;  submitted  by Avitrol  Corp.,  Tulsa,  Okla.;  CDL:
    'OQ3234-D)
 Schafer,  E.W.,  Jr.  (1370) A  Summary of the Acute  ToxicUy,  Chronic
    Toxicity,  and  Secondary  Hazards of 4-A'ninopyridine (DRC-1j2/')  to
    Birds and  Mammals.   Summary of  studies 122744-D  and  122744-1.
     (Unpublished study received Dec'13,  1970 unaer 224-SX-3;  prc—
    pared by U.S.  Fish and Wildlife Service, Denver  Wildlife  Re-
    search Center,  submitted by Phillips  Petroleum Co.,  Bartles-

 Schafer,  E.W.,  Jr.; Brunton, R.B. (1370)  Secondary Hazard  Studies
    with  !l-Arfiinopyridins-Kili3d Blackbirds on  Avian  and  Mammalian
    Predators.   (Unpublished study  received Jan 20,  1970 under 224-
    EX-3;  prepared  by U.S. Fish .and Wildlife Service,  Denver
    Wildlife Research Center, submitted by Phillips  Petroleum Co.,
    Bartlesville, Okla.; CDL:122/44-M)
 Schafer,  E.W.,  Jr.; Brunton, R.3.;  Cunningham, D.J.  (1373)  A
    summary of the  acute toxicity of  4-aminopyridine to  birds and
    matrmals.   Toxicology and Applied  Pharmacology 26(4):5j2-532.
 Schafer,  E.W.,  Jr.; Marking, L.L. (1375) Long-term effects  of
    4-aminopyricina exposure to birds  and  fish.'  Journal of
    Wildlife Management  33(4):307-311.
 Schauf, C.L.;  Colton, C.A.; Colton,  J.S.;  Davis,.F.A.  (1275)
    Aminopyridir.es  and sparteine as inhibitors of membrane
    potassium  conductance: effects  on  Myxicola giant axons  and the
    lobster neuromuscular junction.  Journal of Pharmacology  and
    Experimental Therapeutics 197(2):414-425. .
 Scott, J.F.R.,  Jr.  (1364) Report of Crow Infestation at  Friendship
    International Airport, Baltimore,   Maryland.   (Unpublished study
    received on unknown date under  unknown  admin, no.; prepared by
    City of Baltimore, Dept. of Aviation,  Friendship International
    Airport; submitted by Phillips  Petroleum Co., Bartlasville,
    Ckla.; CDL:122733-A)
 See, W.R.; Folgering, M.; Schlaefke, M.E.  (1973) Central
    respiratory and cardiovascular  t-ffects of the ACh releaser
    4-uminopyridine (4-AP).  ?fluggers Archiv.  European Journal
    of Physiology 377:20.
 Seubart, J.L..; Mitchell,  R.T.;  Stickley,  A.R., Jr.; Francis,  W.J.;
    Dyer,  M.I.; Meanley,  B.;  Hardy,  J.W.   (1969) Project: P-F-33:
    Studies on Methods of Reducing Blackbird and Starling Popula-
    tions.  (Unpublished study  received Jan 20,' 1970 under-  224--EX-3;
    prepared by U.S. Fish and Wildlife Service, Patuxent Wildlife
    Research Center, submitted  by Phillips  Petroleum Co., Dartles-
    vills, Okla.; CDL: 122744-J>
 bhapovalov, A.I.; Shiriaev,  B.I. (1973) Modulation of transmission
    in different electronic junctions  by aminopyridini.
    Experientia 54(1):67-5G.
Simpson, L.L.  (1373) Pnarmacological studies on the  sube-lluiar
    site of action of boi;ulinum toxin  type A.  Journal of
    Pharmacology and Experimental Therapeutics 206(3):561-653.
 Singh, Y.N.; Marshall, I.G.;  Harvey, A.L.  (1973) Some effects of
    the aminoglycoside antibiotic amikacin on ncuromuscular and
               50(2):109-117.
                                        British Journal of .Anaesthesia
                                        104

-------
05003201


05003931

05013692
00004065
050052Q7
00004265
05003409   Skirboil, L.R.;  Baizer,  L.;  lacarola,  M.;  ScanacHjrt, F.G.j
               Morgenroth,  V.H.; Drstchsn,  K.L.  (1977) The  effects  of  calcium,
               mang^nG3_, lanthanum tetrsothylamrnonium and  -jrninopyridines  or
               the cyclic nucieotid-?  syst£;n in motor  r.ervt  terminals.
               Federation Proceedings  36 (3): 976.
00004035   Smith, R.M.  (1963) Summary:  Field  Evaluation  of  Avitrol  200 Used
               to Protect Large Areas  of-Field Corn from Blackbird  Depredation
               in Ohio  and  Michigan,  1963.   (Unpublished study received Jan 3,
               1973 undsr 1F1013;  prepared  by U.S. Bureau of  Sport  Fisheries
               2nd Wiidlif-3, submitted by Phillips Petroleum  Co., BsrtlisvilL*,
               Okla.; CDL:091737-H)
           Snyders, D.J.; Bogaert,  P.P. van (1978). Edification of  cardiac
               pace-maker current  by  4-aninopyridin2.  Archives
             •  Internationales de  Physiologie e-c,  as Biochimic- 36(1): 190-191.
           Sobek, V. (1970) On the pharmacology of 4-aninopyridina  compared
               with adrenaline.  Physiologia  Bohemoslovaca  19(5):417-419.
           Sobsk, V.; Lerneignan, M.;  Stretch en bergcr, G.; Benoist,  J.H. ;
               Gogue-1,  A.;  Lechat,  P.  (1963) Etude sur la diaphragrn-a isolj de
               rat de 1'antagonisme entre substances  curarisantes -it
               aminopyridines [Scudy  on isolated  rat  diaphragm in regard to
               the antagonism between  curarizir.g  agents  and aninopyr idines_!
               Archives Internationales de  Fnarraacodynarnic  et de Therapie
               171(2):356-368.
05003190   Spearman, S.A.;  Goldstein,  J.H.  (1977) NMR studi.es
               substituted  pyridine derivatives oriented, in iyotropic
               mesophases.  Journal of Molecular  Structure  36(2):243-251.
00004053   Stansbury, R.E.  (1962)  Test  with 1861  on Pigeons at the  University
               of Arkansas.  (Unpublished study received "Dot  17,  1973  under
               11649-1; prepared by Phillips  Petroleum Co., submitted  by
               Avitrol  Corp., Tulsa, Okla.; CDL:011002-G)
00004061   Stansbury, R.E.  (1962)  Use  of Chemical 1361 Hydrochlorice to
               Control  Crows Menacing  Air Traffic at  Standiford Fi^ld  Airport,
               Louisville,  Kentucky.   (Unpublished study received Oct  17,  1973
               under 11549-1; prepared  by Pnillips Petroleum  Co.  in cooperation
               with Louisville and Jefferson County Air  Board,  submitted by
               Avitrol  Corp., Tulsa, OUla.; CDL:011002-J)
           Stansbury, R.E.  (196j)  Demonstration of 1861  on  Gulls at Common-
               wealth Pier  in Boston,  Massachusetts.  (Unpublisned  study re-
               ceived Oct 17, 1973 under 11549-1; prepared  by Phillips Petro-
               leum Co., submitted by Avitrol Corp.,  Tulsa, Okla.;  QDL:
           Starr, R.i.  (1972) Hie  absorption, translocation,  and metabolism
               of 14C-4-aminopyridir.e  in corn -and sorgh'jm:  its movement  and
               de-gradation  in soil systems.  Dissertation Abstracts
               International 3 33(5):2443-2444.
           Star!^ R.I.  (1972) Too  absorption, 'cransloca^ion,  and metabolism of
                 C-4-oninopyridine in  corn  and sorghum:  Its movement -and
               degradation  in soil systems.  Dissertation Abstracts Interna-
               tional XXXIII(6/D):2443-2444.  (Also In unpublished  submission
               received Mar 18,  1975 under  11649-12;  submitted by Avitroi
               Corp., Tulsa, Gkla.; -CCL:0947?9-J)  .'
               011C02-M)
00004124   Starr, R.; Cunningham,  D.; Brunton, R. (1955?) Absorption and
               Translocation of 4-Aminopyridine by Corn  Plants.   (Unpublished
               study received Apr  15,  1969  under 224-EX-3; prepared by U.S.
               Fish and Wildlife- Service, Denver-Research Center, submitted by
               Phillips Pctrol;um Co.,  3jrtlosvill^, Okla.; CDL:122743-H)
                                         105

-------
05010703


05005461
U5000Q02
OOOC-H13    Scarr,  R.;  Cunningham,  D.;  Brunt on,  R.  (1969)  Absorption  and  Trans-
                location  of 4-Aminopyridine by Corn Plants:  Fourth Periodic  Re-
                port—July  5,  1965.   (Unpublished  study  received Jul  24,  1965
                under 224-EX-3; prepared  by U.S. Fish  and  Wildlife Service,  Den-
                ver  Research Center,  submitted by  Phillips Petroleum  Co.,  3ar-
                tlasville,  Olds.; CDL: 122745-A)
00004009    Starr,  R.I.  (1969) Absorption  .and  Translocation  of  4-/ininopyridine
                by  Corn Plants:   Progress  Report !!o. 3—September  29,  2963.
                (Unpublished study  received Get  20,  1969 under  224-EX-3;
                pv'spared  by U.S.  Fish  and  Wildlife  Service,  Denver Wildlife
                Researcn  Center,  submitted by  Phillips Petroleum Co.,  Bartols-
                villa, Old a.; CDL:   122744-P)
00004004    Starr,  R.I.;  Cu'T.inghan,  D.J.  (1969) Absorption,  Transioc::tion
                and  Metabolism of 4-Aminopyridine  by Corn  Plants:  Progress Re-
                port !!o.  4—December  23,  1969.   (Unpublished study received  Jan
                20,  1970  under 224-EX-3; prepared  by U.S.  Fish  and Wildlife
                Service,  Denver Wildlife  Research Center,  submitted by  Phil-
                lips Petroleum Co., Bartiesvill*, Okla.; CDL: 122,'44-X)
00004132    Starr,  R.I.;  Cunningham,  D.J.  (1972) Fate of 4-Aminopyridine  in
                Cor-n, Sorghum, and  Soil Systems: A  Summary of Research  Findings.
                (Unpublished study  received Apr  16,  1973 under  3G1320;  prepared
                by  U.S. Fish and Wildlife  Service,  Bureau  of Sport Fisheries ana
                Wildlife, submitted by Avitrol Corp., Tulsa,  Oklj.; CDL:G9354D~
                A)
            Stefanovic, D.; Gruetzmacher,  H.F.  (1974) The  ionisation  potential
                of  some substituted pyridines.  Organic  Mass  Spectronetry
                9(10):1052-1054.
            Steinberg, R.;  Nicholson, C.;  Bruggencate, G.;.Stoeckle,  H.
                (1977) Spreading cepression-liko Ca2-i-, K,  and
                potential transients  induced by sea anemone  toxine II and
                4-aninopyridine.  Pfluegers Archiv.  European Journal of
                Physiology  353:30.
00004097    Stickley, A.R.,  Jr.;  Ingram,'C.R.  (1975) 1974  Test  of  4-Aminopyri-
                dine (Avitrol) Efficacy in Preventing Bird D^nage  to  Sweet Corn
                in Mew York: Progress Report:  January 1, 1974-Decembar  31, 1974:
                Work Unit P-F-33-12.   (Unpublished  study received  !-kr  1C,  1975
                under 11649-12; prepared by U.S. Fish and  Wildlife Service,
                Patuxent Wildlife Research Center,   Section of Animal  Depreda-
                tions Control Studies, Ohio Field Station, submitted  by Avitroi
                Corp., Tulsa, Okla.; CDL:094799-F)
00003Q74    Stickley, A.R.,  Jr.; Mitchell, R.T.; Heath,  R.G. ; Ingrain, C.R.;
                Bradley, E.L.,  Jr.  (1972)  A method  for appraising  the bird
               repellency  of 4-Aminopyridine.  Journal  of Wildlife Management
               36(4):1313-1316.  (Also in unpublished submission  received Jun
               21,  1977 under 11549-12; submitted  by Avitrol Corp.,  Tulsa,
               Ckla.; CDL:230655-C)
OjOl5205   Stickley, A.R.,  Jr.; Mitchell, R.T.; Seubert,  J.L.;  Ingram, C.It.;
               Dyer, H.I.  (1976) Large-scale  evaluation of  blackbird
               frightening agent 4-arninopyridine in corn.   Journal of  Wildlife
               Management 40(1):126-131.
rait, P.; Akert, X.; Sandri ,
                                              Livingston, R.B. ana Moor, 11.
               (1972) Dynamic infrastructure of Presynaptic Membranes i>z lier-ve
               Terminals in the Spinal Cord of Rats:  Anesthetized and Unanes-
               thttized Preparations Compared.  Brain Researcn 543 pg.  11-26.
                                         106

-------
05U12255
050057-30
05005454   T
05004,222


Q500J72-3


00004041



05000003

05004224



00005394


00005935
00004C4G
00004133
00004047
05004255
Suoha, L.; Urner, Z.; 3uch~nek, H.  (1971) Dissociation constants
    of substitution derivatives of  pyridine.  -Sbornik Vysoke Skoiy
    Ch<::-;niekp-Technologicke v ?r.JZ3, Anaiy-icka Chernio.   [Scientific
    P£-p=rs of the Institute of Chemical Technology, Prague,
    Analytical Chemistry.! H7:105-116.
Tasaki, I. (1-373) Futher studies of periodic  miniature responses
    in squid giant axons.  Japanese Journal of Physiology
    23(1):30-103.
T>sta, A.C.; Weisstuch, A.; Hennessy, J.  (1969) Fluorescence and
    singlet energy transfer from aminopyrioines.   Pages
    353-377, in Molecular Luminescence, An International
    Conference; Aug 20-23, 1968, Loyola University, Chicago,
    Illinois.  Edited by E.C. Lim.  [Jew York:  W.A. Benjamin.
Thompson, S.H. (1977) Three pharmacologically distinct potassium
    channels in raolluscan neurones.  Journal  of Physiology
    255(2):465-433.
Tokunaga, A.; Sandri, C.; Akert, K. (19/9) Ultrastructural effects
    of 4-aniropyridine on the presynaptic membrane in the rat
    spinal cord.  Drain Research V3j(1): 1-3.
Trott, R.L. (1974) Introduction annd Surmary: [Avitrolj. Sumnary
    of studies 094335-3 through 094335-X. (Unpublished study
    received Apr 50, 1974 under 4F1498; submitted by Avitrol Corp., .
    Tulsa, Okld.; CDL:03;t33o-A)
Uehara, Y.; Burnstock, G. (1970) [J. Cell Biol.j "Demonstration of
    gap junctions between smooth muscle cells"  44: pg. 215-217.
Ulbricht, '.V.; Wagner, H.H. (1976) Block of potassium channels of
    the nodal membrane by 4-aminopyridine and its partial removal
    on depolarization.  Pfluegers Archiv.  European Journal of
    Physiology 367(1):77-37.
U.S. Fish and Wildlife Service.  (1963) [Avitrol 200].   (Un-
    published study received Apr 22, 1959 under 224--EX-3; submitted
    by Phillips Petroleum Co., Bartlesville,  Okla.; CDL: 12274.7-K)
U.S. Fish and Wildlife Service, Denver Research Laboratory (no date)
    Toxicity of Avitrol to Bluegill and Channel Catfish at Selected
    Water Qualities and" Temperatures: Table.  (Unpublished study
    received May 13, 1971 under 224-EX-5; prepared in cooperation
    with La Crosse Fish Control Laboratory,  submitted by Phillips
    Petroleum Co., Eartlesvilie, Ukla.; CDL:122/43-F)
U.S. Fish and Wildlife Service, Division of Wildlife Services'
    (1971) Field Test Project on 4-Amino-pyridine  (DRC-1327, Avitrol
    200).  (Unpublished study received Apr 30, 19/4 under 4F1493;
    submitted by Avitrol Corp., Tuisa, Okla.; CDL:094356-R)
U.3. Fish and Wildlife Service, Division of 'Wildlife Services
    (1972) Field Test Project on 4-A-nino-pyridine.  (Unpublished
    study received Mar 5, 1973 under 3G1297; submitted by Avitrol
    Corp"., Tulss, Okla.; CDL:094671-K)
U.S. Fish and Wildlife Service, Division of Wildlife Services
    (1972) Field Test Proj-ct on 4-Amino-pyridine  (DRC-1327, Avitrol
    200).  (Unpublished study received Apr 30, 1974 unacr 4FV493;
    submitted by Avitroi Corp., Tulsa, Okla.; CDL:094336-3)
Van. Til,  A.E.;  Johnson, D.C. (1977) A new calorimstric standard:
    4-aminopyridine.  Thermochimica Acta 20(2):177-193-
Vizi,  E.S.;  van Dijk,  J. ; Foldes, F.F. (1977) The effect of
    'i-aninopyridins on acetylcholine release.  Journal of Neural
    Transmission 41(4):255-274.
                                        107

-------
0:;0031>3;+    Vohru, H.M.;  Pradhsn,  3.U.;  Jain,  P.O.;  Chatterj^e,  S.ii.;  An .-JIG,
               !;. \1965) Synthesis  and  structure-Lctivity  relationships  of
               sane- aminopyriaines,  iniidazopyriclines,  and  triazoiopyridines.
               Journal of i'iodicinal  Chemistry 3(3):296-304.
03014044    Vorbrucggen,
05005494


00005334
00003953
05003012

00004104
000040J5
00004075
05005154


05006424



J5003749
                  inventor;  Schering A.G.,  assignee  (1575)  Meues
    Aminierungsverfahren .   [A new  amination  process].   German  (Fed.
    Hep.) offtnlcgungsschrift 25,17,/74.   Occ  23.   13  p.  Int.
    Cl~.-.2? C 07D 213/72, C  G7D 401/04.
Wagner, H.H.; Uibricht, IV.  (1575)  Voltage-dependent block of ;C
    channels by 4-aminopyridine.   Pfluegers  Arehiv.  European
    Journal of Physiology 252:31.
Wails, D.T.-097D Field Demonstration of  Avitrol 200  for Repelling
    Blackbirds in Minnesota Field  Corn: Thi^d  Periodic Report --
    Avitrol Concentrate.  (Unpublished study received  May 1o,  1971
    under 224-EX-3; prepared by U.S. Fish  and  Wildlife Service,  Den-
    ver Wildlife Research Center in cooperation with Minnesota,
    Dept. of Agriculture and Agricultural  Extension  Service, sub-
    mitted by Pnillips Petroleum Co., Bartlosviile,  Okla.; CDL:
    122743-S)
Ware, J.E. (197D Report on Avitrol Gull Repellency Test:  Si-iem,
    Massachusetts, 1971.  (Unpublished study received  Apr  10,  1975
    under 11549-10; prepared by U.S. Bureau  of Sport Fisheries and
    Wildlife, Div. of Wildlife Services, submitted by  Avitroi  Corp.,
    Tulsa, Okla.; CCL: 115275-E)
Weisstuch, A.;  Testa, A.C.  (1953) A fluorescence study  of
    aininopyridines.  Journal of Physical Chemistry  72(5): 1932-1937.
West,  R.R.; Besser, J.F.; De Grazio, J.F.  (1959) Project  DF-
    102:  Bird Damage Control Research: DF-102.3-10.  (Unpublished
    study received Feb 15,  1973 under 11549-12; prepared  by  U.S.
    Fish and Wildlife Service, Denver Wildlife Research Center in
    cooperation with Oklahoma Division of Wildlife Services  and
    Tishomingo National Wildlife Refuge, submitted by  Avitrol  Corp.,
    Tulsa, Okla.; CDL:003234^)
Winters,  R.O. (1959) Field Evaluation of Avitrol 200 Used  to Pro-
    tect Large Areas of Field Corn from Blackbird Depredations in
    Ohio, Michigan, and Indiana during Summer  1959.  (Unpublished
    study received Jan 3, 1973 under 1F1013; prepared  by  U.S.  Fish
    and Wildlife Service, submitted by Phillips Petroleum Co.,
    Bartlesville, Ckla.; CDL:091757-O)
Winters,  R.O. (197.2) Report on Field Trial Use of Avitrol 200  to
    Protect Sueet Corn.  (Unpublished study received Jun  8,  1072
    under 11549-EX-1; prepared by U.S. Fish  end Wildlife-  Service,
    Div.  of Wildlife Services,  submittea by Avitrol  Corp., Tulsa,
    Okla.; C DL: 22354 1-D)
Woods, W.T.; Urthaler, F.; Jarnes , T.i.'. (1973)  Chronotropic effects
    of tetraethylammor.ium and 4-aminopyridine  in canine sinus  node
    pacemaker cells.  Circulation.  Supplement II 57/53 (4): 45.
Woronecki, P.P.;  Dolbeer, R.A.; Ingram, C.R.;  Stickley, A.R.,  Jr.
    (1979) 4-Aminopyridine effectiveness reevt-.luated for  reducing
    blackbird damage to corn.  Journal of Wildlife Management
•    43(1);1G4-191.
Yarngisavva, T.;  Satoh, X.; Tsira, N. (19/3) Effects  of
    4-aminopyricine on the isolated, blood-perfused  sino-atrial
    rod;.-  preparation of the cog.  Japanese Journal of  Pharmacology
                  -JT
                   I .
                                         108

-------
0500j179   Yanagisawa; T.;  Satoh,  K.;  Taira,  N.  (1973) Excitation of
               autononiic  ncrv<:s  by 4-:aminopyridino in th^ isolated,
               blood-perfused  sino-atrial node preparation of t:K- dog.
               European Journal  of Pharmacology 49 (2):. 139-192.  •  '
0501957G   Yanagisav;s, T.;  Taira,  N.  (1973-) Positive inotropic efface of
               4-aminopyridine on  dog  ventricular muS'.':l3.
               iiaunyn-Schmiedeberg's Archives of Pharmacology 207 (j) :207-212.
00004103   YaLe-3, J.  (1967) Use  of Avitrol Process for Pigeon Control.  (Un-
               published  study rsceiv-id Jan 2, 195G undar 224-12; prep^r-ic by
               Redd P-ast  Control Co.,  submittsd  by Phillips Petroleum Co.,. .
               Bartlesvills, Okla.; CDL:229344-B)
0-j003130   Y-c-h, J.Z.; Oxford,  G.S.; Wu,  C.H.; Marahsshi,  T. (1975)
               Interactions of aninopyridines with potassium channc-is of squid
               axon insmbranes.  Biophysical Journal 16(1):77-31.
03004223   Yah, J.Z.; Oxford,  G.S. ; Wu,  C.H.; Narahashi,  T. (19'/6) Dynamics
               of aminopyridina  block  of potassium channels in squid axon
               rnembrarrj.  Journal  of General  Physiology 55(5):519-;3j5.
G500a3o2   Zangger, P. (1973)'Fictive  locomotion in curarized high spinal
               cats a-licited with  4-.aminopyridine and DOPA.  Experientia
               j4(7):904.
                                        109

-------
                          STANDARD REFERENCE MATERIAL

Chemical Abstracts Service  (1973)  Chemical Abstracts 8th collective index
         Vols. 66-75  (1967-1971),  American Chemical Society
Chemical Abstracts Service  (1977)  Chemical Abstracts 9th collective index
         Vols. 76-85  (1972-1976),  American Chemical Society
Food and Drug Administration  (1978)  Pesticide analytical manual. Vol. II.
         Methods for  individual  residues.  U.S. Department of Health, Education
         and Welfare:  Washington,  D.C.
Title 40 Protection of the  Environment  (40 CFR,  1978) Code of Federal
         Regulations.  Chapter I-  Environmental  Protection Agency.  Washington,
         D.C.:   U.S. Government Printing  Office.
U.S. Environmental Protection Agency (1976) Manual of chemical methods for
         pesticides and devices.  Washington, D.C.
U.S. Environmental Protection Agency (1978) Proposed Guidelines for Registering
         Pesticides in the  United  States.   Federal Register 43(132)  29696.
U.S. Environmental Protection Agency (1978) Proposed Guidelines for Registering
         Pesticides in the  United  States.   Hazard  Evaluation:  Human and
         Domestic Animalsjd.   Federal  Register  43(163) 37336.
                                             *U S GOVERNMENT PRINTING OFFICE: 1980 341-085/3947
                                            110

-------