PA/737/R-80/001
vvEPA
             Uniteu
             Environmental Protection
             Agency
             Pesticides
            Office of
            Pesticides and Toxic Substances
            Washington DC 20460
September 1980
3-(alpha-acetonylfurfuryl)
    - 4-hydroxycoumarin)
                               •  R
           Fumarin

Pesticide Registration
Standard

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                   REGISTRATION STANDARD


PRODUCTS CONTAINING FUMARIN AND THE SODIUM SALT OF_ FUMARIN

      Richard S. Bright, Project Manager (SPRD)
      Juanita Wills, Section Head  (SPRD)

      Lachman Bhatia, Biologist (RD-IRB)
      William J. Boodee, Residue Chemist (HED-RCB)
      Douglas Chambers, Vertebrate Biologist (BFSD-ASIB)
      William Dykstra, Pharmacologist (HED-Tox B)
      Samuel F. Howard, Environmental Chemist  (HED-EFB)
      Krystyna Locke, Pharmacologist (HED-Tox B)
      Daniel Peacock, Biologist (RD-IRB)
                      September 1930


         Office of Pesticides and Toxic Substances
              Environmental Protection Agency
                   401 'M' Street, S.W.
                   Washington, DC  20460

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                          TABLE OP CONTENTS


Chapter 1  - 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 FIPRA 3(c)(l)(D) 	    5
    Obtaining Data to fill "Data Gaps";  PIPRA 3(c)(2)(B)  	    6
    Amendments to the Standard  	    7

Chapter 2 - Regulatory Position
    Regulatory Decision	    8
    Criteria for Registration Under the  Standard   	    8
       1.   Product Composition  	    8
       2.   Label ing  	    9
       3.   Data Gaps  	    9
              Product Chemistry  	   11
              Toxicology  	   12
              Ecological Effects  	   13
       4-   Additional Labeling Requirements  	   14
       5-   Efficacy Data Requirements  	   15

Chapter 3 - Product Chemistry
    Introduction  	   17
    Chemistry Profile  	   17
    Topical Discussion  	   18
         1.  Pumarin
             Chemical Identity  	*	   18
             Manufacturing Process 	   19
             Percentages of Components in Pumarin Products  ....   19
             Product Analytical Methods  and Data  	   20
             Physical/Chemical Properties  	   20
         2.  Sodium Salt of Pumarin  	   21
             Chemical Identity  	   21
             Manufacturing Process  	   21
             Percentages of Components in Sodium Salt of
               Pumarin  	   21
             Product Analytical Methods  and Data  	   21
             Physical/Chemical Properties  	   22
    Disciplinary Review  	   22
       Generic Data Gaps  	   22
       Required Labeling  	   23

Chapter 4 - Environmental Pate
       Use Profile  	   25
       Exposure Profile  	   27
       Topical Discussion  	   28
    Disciplinary Review  	   29
       Generic Data Gaps  	   29
       Required Labeling  	   29

Chapter 5  - Residue Chemistry  	   30

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Chapter 6 - Toxicology
    Toxicology Profile  	  31
    Topical Discussions  	  33
    Acute Effects  	  33
       Acute Oral Toxicity  	  33
       Acute Dermal Toxicity  	  33
       Acute Inhalation Toxicity  	  34
       Primary Eye Irritation  	  34
       Primary Dermal Irritation  	  34
       Dermal Sensitization  	  34
    Subchronic Toxicity  	  35
       Subchronic Oral Toxicity  	  35
       Subchronic Dermal Toxicity 	  35
       Subchronic Inhalation Toxicity  	  35
    Teratology  	  35
    Mutagenicity	  35
    Disciplinary Review  	  36
       Generic Data Gaps  	  36
       Required Labeling  	  37
       Bibliography  	  39

Chapter 7 - Ecological Effects
    Ecological Effects Profile  	  40
    Topical Discussions  	  40
       Birds  	  41
       Wild Animals  	  41
       Pish  	  41
       Aquatic Invertebrates  	  42
    Disciplinary Review  	  42
       Ecological Effects Hazard Assessment 	  42
       Generic Data Gaps	  43
       Required Labeling  	  43

Chapter 8 - Regulatory Rationale
    Regulatory Decision  	  44
    Product Composition  	  44
    Rationale for Labeling Requirements  	  44
    Rationale for Data Requirements  	  44
    Product Chemistry  	  44
    Environmental Pate  	  45
    Toxicology  	  45
    Ecological Effects  	  45
    Rationale for Efficacy Data Requirements  	  46
Bibliography
    Guide to the Use of this Bibliography  	  47
    Citations Considered to be Part of the Data Base
     Supporting Registration off This Standard  	  49
    Citations Examined and Judged to be Inappropriate
     for Use in Developing This Standard  	  50
    Standard Reference Material  	  51
                           ii

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                                   CHAPTER 1

                                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 Ftequirements 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
sutmarizes 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 o£ 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]."  Tb 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 suhmitted comply with
         the requirements of this Pet;
     (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

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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 product1 approach was often inefficient and sometimes resulted
in inconsistent or incomplete regulatory judgments.
Second, over the years, as a result of inevitable and continuing advancesin
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 EF& issued new requirements for registration in 1975 (40 CFR
162)  and proposed new guidelines for hazard testing in 1978 (43 PR 29686, July
10, 1978 and 43 FR 37336, August 22, 1978), many products that had already been
registered for years were being sold and used without the same assurances of
human and environmental safety as was being required for new products.  Because
of this inconsistency, Cbngress 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)].

Facing the enormous job of re-reviewing and call ing-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 documents
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, composition,
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 sane 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

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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.


Requirement _to Re-register Under the Standard

FIFRA Section 3(g) , as amended in 1978, directs EPA to re-register all
currently registered products as expaditiously 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,  1973, and 43 FR 37336, August 22, 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 sane 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

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r
               (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
           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  clor-ely 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 bo 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 163.81-1 (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 hunan
           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 hunan 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.

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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,
         U3DA 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
         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.)

Ai applicant for re-registration of an already registered product under this
Standard, or for registration of a new product inder 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
arespecific 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
fron 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 (C) (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

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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)

Seme 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 have 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".

FIFRA Section 3 (c) (2) (B) , added to FIFRA by the Cbngress 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 specific" data,  in seme 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 nutiber of currently registered products will
attempt to state definitively the "product specific" data gaps on a 'product by
product1 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-register ing 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) .

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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.
This "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 frcm
the Agency.  When all the present "data gaps" have been filled and the
submitted data have been reviewed, the Agency will revise the Registration
Standard.  Thereafter, when the Agency determines that the internally
maintained addenda have significantly altered the conditions for registration
under the Standard, the document will be updated and re-issued for publication.

While the Registration Standard discusses only the uses and hazards of products
containing the designated active ingredient(s) , the Agency is also concerned
with the potential hazards of seme inert ingredients and impurities.
Independent of the development of any one Standard, the Agency has initiated
the evaluation of seme inert pesticide ingredients.  Where the Agency has
identified inert ingredients of concern in a specific product to which the
Standard applies, these ingredients will be pointed out in the Guidance Package.

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                           CHAPTER 2

                       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 ingredients 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 Fumarin * and  its Sodium Salt available to the
Agency's reviewers as of August, 1979.

REGULATORY DECISION

The Agency has reviewed the data available to it on Fumarin  and
the Sodium Salt of Fumarin.   As will  be indicated in the
Topical Discussions which follow, scientific data on Fumarin
products are almost entirely  absent.  Based on the uses of this
rodenticide, however, the Agency believes that none of the risk
criteria found in Section 162.11 (a) of Title 40 of the U.S.  Code
of Federal Regulations would  be met or exceeded for Fumarin.
Fumarin products currently registered, therefore, may be  re-
registered subject to conditions imposed for filling the  data
gaps and the label modifications which have been identified.
When these data requirements  are filled, the Agency will
reassess the registration status of Fumarin products.

 CRITERIA FOR REGISTRATION UNDER THE  STANDARD

     1. Product Composition

        In order to be covered under  this Standard, technical
        Fumarin, Fumarin Sodium Salt, and their diluted
        products must comply  with the following standards.   All
        products must contain Fumarin (3- (alpha-acetonyl-
        f ur f uryl) -4-hyd roxycoumar in)   or its Sodium Salt as an
        active ingredient (a.i.).  The Agency expects technical
        Fumarin to be 98% a.i.  Should an applicant desire to
        register any products that depart from those covered by
        this standard, that applicant should contact the  Agency
        for specific directions on how to register those


         -ft-
*  Fumarin" is a registered trade name of Amchem Products,
Inc.  Its use in this document does not constitute endorsement
or recommendation for use by this Agency.  Since there  is no
acceptable common name for this compound, the trade name will be
used in this document for convenience.

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products.  The acute  toxicology  testing  on  technical  Fumarin and
technical Fumarin Sodium Salt must demonstrate into which
Toxicity Categories  (I through III)  the  products  fall for the
following acute effects:

             Acute Oral Toxicity;
             Acute Dermal  Toxicity;
             Acute Inhalation Toxicity;
             Primary  Eye Irritation;  and
             Primary  Dermal  Irritation.

    2.  Labeling

         Labels for currently registered manufacturing-use
         Fumarin products must include the  following:

         The intended end-use of products formulated  from
         technical and concentrated  products  determine  which
         data the applicants for (re) reg istration of  the
         manufacturing-use product are required  to submit or
         cite.  All technical and concentrated products must
         therefore carry one of the  following  statements on the
         label :

            (1)   For Formulation Into End-Use Rodenticide
                  Products Intended  Only for  Domestic,  Non-Food
                  Use;

            (2)   For Formulation Into End-Use Rodenticide
                  Products Intended  Only for  Non-Domestic, Non-
                  Food Use;

            (3)   For Formulation Into End-Use Rodenticide
                  Products Intended  Only for  Non-Domestic, Non-
                  Food Use excluding  dumps; or

            (4)   For Formulation Into End-Use Rodenticide
                  Products Intended  Only for  Domestic or Non-
                  Domestic, Non-Food  Use.

     3.   Data Gaps

         Additional testing  is a condition  for the reregis-
         tration of all currently registered  Fumarin  and Fumarin
         Sodium Salt products.  Under Section 3 (c) (2)(B) (i i)  of
         FIFRA, as amended, current  registrants of Fumarin and
         Fumarin Sodium Salt products must  agree  to develop the
         required data within 90 days of being notified of these
         standards in order  to remain eligible for rereg is-
         tration.  Anyone wishing to  register  new Fumarin and
         Fumarin Sodium Salt products or anyone  wishing to
         receive Federal registrations for  products which are
         currently registered in one  or  more  of  the states at
         the time these standards are published,  must agree to
         provide the required testing or to share in  the cost of
         developing the data as a condition of registration
         under 3(c)(7) and 3(c)(l)(D).   In  addition,  registrants

-------
of new products must offer compensation for all
applicable data used to set the standards listed  below
which were submitted to the Agency after December  31,
1969, as provided  in Section 3{c)  (1)(D) of  FIFRA.

The data needed to support the reregi stra tion of
formulations of Fumarin and its Sodium Salt are
tabulated according to discipline in the Tables which
follow.

These requirements are based on a review of the limited
scientific data available on Fumarin and the use
pattern and methods of formulations of Fumarin
products.  Most of the product chemistry data decribed
in 43 FR, No. 132, Part 163.61-2 are required by  the
Agency to characterize Fumarin and its Sodium Salt  and
to determine its environmental and health hazards.
Environmental Fate data are not being required because
of the use pattern of Fumarin and its Sodium Salt,  the
limited poundage that is available and the  small  chance
of residues being  found in soil or water.   The Agency
is requiring a label modification, however, to reduce
any potential hazard.  Toxicology data are  being
required, in most cases, for Technical Fumarin and  the
0.5% Fumarin concentrate only because currently
registered formulations of Fumarin are substantially
similar in composition and are formulated with natural
ingredients as inerts.  In addition, while  the Agency
expects some exposure, such exposure is likely to  be
low in most cases.

Ecological Effects data are not required so long  as the
registrant modifies labels to require use with bait
boxes and only in or around buildings and other
structures and in transport vehicles (truck, planes,
and ships) .  Available studies, although inadequate,
suggest that Fumarin is at least highly toxic to  wild
mammals.  Avian hazard can result from direct ingestion
of baits and through secondary poisoning.   Hazard  to
aquatic organisms and wildlife is expected  to be
minimal, however, because of the low volume of use  and
method of application.  Thus, registrants may satisfy
data requirements by modifying labels.  Should
registrants not wish to use required labeling, or
should other significant uses be proposed,  the
Ecological Effects data discussed in Chapter 7 may  be
required unless a logical argument can be made which
shows minimal expectation of exposure, and  consequent-
ly, risk.  Registrants who seek use in dumps on their
labeling must specifically address non-target effects
by either submitting data or demonstrating  to the
Agency that use patterns are such as to preclude
unreasonable exposure.  In addition, these  studies  may
be required to support the continued registration  of
these products if total yearly production of Fumarin
and its Sodium Salt reach 25,000 pounds.
                    10

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4.   Additional Label ing Requirements

    Much of the data needed to complete all the labeling
    requirements (40 CFR 152.10) and risk assessment
    requirements (Section 162.11)  for Fumarin products do
    not now exist.  However, until the data are submitted
    to complete this registration standard, the Agency
    will require registrants to update their labels
    according to current requirements.  These require-
    ments are found in Section 162.10, Subpart H  (Label
    Development)  of the Registration Guidelines (currently
    being drafted by the Agency) , and in the format labels
    which are being supplied to the registrants.

    Oral, dermal, and inhalation exposure may occur because
    of the type formulations (dust and liquid)  of Fumarin
    products and the location and duration of placement of
    the baits.  A review of Fumarin's methods of  formula-
    tion and use patterns indicates that commercial
    applicators and formulators as well as other  persons in
    contact with Fumarin products in and around homes and
    buildings, especially children, domestic animals, and
    wildlife, could be exposed  if use directions  are not
    followed explicitly.  Thus, label modifications are
    required to reduce any hazards associated with Fumarin
    products and to provide the reader with labels that are
    more likely to be understood and followed.

    Basically, the required labeling changes include
    clarifying the sites, pests, and methods of
    application; revising out-of-date precautionary and
    storage/disposal statements; and placing label text in
    a clear, readable format.

    Labels must include the following precautionary
    statements :

      a.  Tamper proof bait boxes are required for
          both Fumarin solid and Sodium Salt of Fumarin
          liquid end-use baits which are used for outdoor
          and agricultural uses.  For other uses, excluding
          dumps, tamper proof bait boxes are required or
          baits must be placed  in areas inaccessible to
          children, pets, and non-target wildlife.  Labels
          must sta te :

            1)  For outdoor agricultural premises prepared
                baits must be placed in tamper proof bait
                boxes .

            2)  For other uses, excluding dumps,  prepared
                baits must be placed in tamper proof bait
                boxes, or in areas inaccessible to
                children, pets, and non-target wildlife.

            3)  Baits and dead  animals are to be  picked up
                and disposed of properly, with care to
                          14

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                prevent baits and dead animals  from getting
                into soil and/or water,  including  sewage.

      b.  The term, "around", for labeling purposes means
          within five  (5) feet of exterior surfaces of
          buildings, and not in fields adjacent  to
          buildings.

      c.  Avoid contamination of food and feedstuffs.   Do
          not place baits in contact with food or  feedstuff
          or on food handling surfaces.

      d.  Note to physicians.

          If swallowed by humans, domestic animals, or
          pets, this material may reduce the clotting
          ability of the blood and cause bleeding.  In
          such cases,  intravenous and oral administration
          of vitamin K, combined with transfusion
          of fresh blood or fresh frozen plasma may be
          indicated as in the case of hemorrhage caused by
          overdoses of bishyd roxycoumar in .

      e.  Formula tors , commercial applicators, and mixers
          must wear protective clothing, including long
          sleeves and  impermeable hand gloves and  face
          masks when mixing and handling Fumarin
          products.  Remove clothing and wash after
          handling.

    f.    For Manufacturing Use products, including
          Technical and Concentrates, 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.

    The registrants of products containing Fumarin or its
    Sodium Salt must follow the appropriate labeling format
    provided by the Registration Division in the Guidance
    Package .

5.   Efficacy Data Requirements

    Because  the efficacy of products containing Fumarin and
    its Sodium  Salt is  formulation  specific,  the Agency is
    not including these data as part of the standard.
    However, as part of each application for  registration
    or re-reg istration, the  registrant must submit or
    reference acceptable laboratory efficacy data
    supporting  his/her  product.

    The following table summarizes  the required laboratory
    efficacy tests that need to be  submitted  or referenced
    for each type of product:
                           15

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                                Numerical Designation jo^f Test*
       Description o_E Products      1 .201 I .202 1 .203 T72J3T

       Technical & Concentrates                    X     X
       Formulated into Registered
       Products

II     Concentrates Diluted  into        X     X
       End Use Liquid Baits

III    Concentrates Diluted  into                   X     X
       End Use Dry Baits

IV     Concentrates Diluted  into                   XX
       Registered Baits

V      Ready-to-Use End Use  Dry                    XX
       Baits

       *The Registration Division will provide  the registrants
       with a copy of the protocols applicable  to their
       products and with a list of laboratories which do  this
       type of testing.  The types of testing required  for
       efficacy are contained  in EPA's Standard Test Methods
       for Anticoagulants, Revision 9, February 17, 1978.
       They are:

       1.201  Standard Norway  rat anticoagulant liquid  bait
              efficacy laboratory test method.

       1.202  Standard house mouse anticoagulant  liquid bait
              efficacy laboratory test method.

       1.203  Standard Norway  rat anticoagulant dry bait
              efficacy laboratory test method.

       1.204  Standard house mouse anticoagulant  dry bait
              efficacy laboratory test method.
                               16

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                        CHAPTER  3

                      PRODUCT CHEMISTRY

INTRODUCTION

FIPRA 3(c)(2)(A) requires the Agency to establish guidelines foi
registering pesticides in the United States.  The Agency
requires registrants to provide  quantitative data on all
added ingredients, active and inert, which are equal to or
greater than 0.1$ 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, and upper limits only for some unintentional
ingredients.  Subpart D (43 PR,   No. 132, 29696, July 10,
1978) 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.
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 and storage
stability).   The Agency uses these data to characterize each
pesticide and to determine its environmental and health hazards.

CHEMISTRY PROFILE
       •p
Pumarin , 3-(alpha-acetonylfurfuryl)-4-hydroxycoumarin, is a
rodenticide which contains a minimum of 98$ of the active
ingredient in its technical form.

Technical Pumarin is an amorphous cream-colored powder with a
very slight characteristic odor.  It is stable at ambient
temperature.   Technical Fumarin is very slightly soluble in
water and soluble in ethanol, methanol, isopropanol and
acetone.  The melting point range is from 121-123 C.

Technical Pumarin is a "manufacturing-use product" and is not
registered for end uses in technical concentrations.
                             17

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Amchem Products,  Inc.  a subsidiary of Union Carbide Agricultural
Products Company, Inc., is the sole manufacturer of Technical
Pumarin.  End-use products are formulated as both Fumarin solid
baits and Sodium Salt of Pumarin.  All products contain Fumarin
as the active ingredient, with no multiple active ingredient
products registered.  End-use formulations are registered both
for household and agricultural and industrial site uses for the
control of rats and mice.

There are no data available on the composition and percentages
of inerts in the 50$ and 10$ Pumarin concentrates.  In addition,
no physical/chemical properties for these formulations were
reported.

TOPICAL DISCUSSION

In accordance with each of the Topical Discussions listed below
is the number of the section in the  'Proposed Guidelines for
Registering Pesticides' of July 10, 1978 (43 PR, NO. 132, Part
163-61-2), which explains the minimum data that the Agency
requires in order to adequately assess a pesticide's Product
Chemistry.

 Data Gaps                                     Guidelines Section

Chemical Identity                                     163.61-3
Manufacturing Process                                 163-61-4
Percentages of Components in Pesticide Products       163-61-6
Product Analytical Methods and Data                   163.61-7
Physical/Chemical Properties                          163-61-8

1. Fumarin

Chemical Identity

Pumarin is the trade name for 3-(alpha-Acetonylfurfuryl)-4-
hydroxycoumarin.  Other trade names that include the identical
chemical compound as Pumarin are Coumafuryl, Coumarfuryl,
Poumarin, Krumkil, Lurat, Ratafin and Rat-A-Vay.

The technical chemical characterization for Fumarin follows:

Chemical Name:       3-(alpha-Acetonylfurfuryl)-4-hydroxycoumarin or
                     4-Hydroxy-3-[3-oxo-1 -(2-furyl)butyl] coumarin
Molecular Weight:    298.28
Chemical Formula:    C,,-jH,,0,-
Type:                Rodenticide
Shaughnessey #:      086001
C.A.S. #:            11.7-52-2
                            18

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Structural Formula:
                          OH
Manufacturing Process

The manufacturing process for Pumarin as employed "by Amchem
Products, Inc., was not reported.  This constitutes a data gap.
However, a British patent [Spiess et  al . 1955, 0500626] was
granted covering a general processTorThe production of 3-
substituted-4-hydroxycoumarins •   This process could be used to
show a methodology for producing Pumarin; but there is no
certainty that this process is used by the manufacturer.

In this process, furfurylidene acetone, 4-hydroxycoumarin and
trisodium orthophosphate in water are refluxed together for 4
hours.  Upon cooling, the reaction mass is washed with water and
dissolved in benzene.  The benzene solution is filtered and
purified by means of a diluted solution of alkali.  Purification
takes place by repeatedly dissolving the precipitate in alkali
and precipitating with acid.  The yield of this process is about
77$.  No indication of the degree of purity is reported.

Percentages of Components _in Fumarin Products

a.  Technical Pumarin:

Technical Pumarin contains 3-(alpha-Acetonylfurfuryl)-4-
hydroxycoumarin at 98$ minimum concentration and inert
ingredients at 2%,  The confidential statement of formulas for
the various Pumarin concentrates and ready to use products
contain the technical Pumarin at the percentages indicated plus
various inert ingredients.  The  identity of inert ingredients in
these products will not be discussed but are contained in a
"Confidential Statement of Formulas".  However, the Agency gave
full consideration to this information in developing the
Registration Standard.  The inert ingredients for Pumarin 50$
and 10$ concentrates were not included in the confidential
statement of formulas.  This constitutes a. data gap.

b.  Fumarin Solid Concentrates
a.  50$
b.  10$
c.  0.5$
                a.i.
                a.i.
                a.i.
                            19

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c.  Fumarin Solid Ready To Use

          0.5$  a.i.
          0.025$ a.i.

Product Analytical Methods and Data.

A method for the analysis of Technical Fumarin [Segal,  1958,
00001200] has been submitted.   In this procedure,  a sample is
extracted with ethylene dichloride.  After extraction,  decanting
and centrifuging, a portion of the clear liquid is mixed with \%
NaOH solution.  The alkali solution is decanted and the optical
density is measured at 305 millimicrons using a Beckman Model DU
Spectrophotometer.  The reading is compared with a  reading for a
standard amount of Fumarin, and the amount present in the sample
is calculated.  While  no validation data is offered, the method
is regarded as adequate for the purpose of quantification.  No
means of positive identification is reported.

No infrared, ultraviolet or mass spectral data were
submitted.  No methods were reported for the analysis of the
impurities in the technical material.  This lack of analytical
methods for impurities constitutes a data gap in the information
needed to support this standard.

Physical/Chemical Properties.

The physical/chemical  properties of Fumarin technical material
[Amchem, no date, 00001199] are depicted as follows:
    Color:
cream-colored
    Odor:     very slight characteristic odor depending on the
             purity of the technical material

    Melting Point:   121-123°C (pure 123-124°C)
    Solubility:

        water:
        ethanol:
        methanol:
        isopropanol:
        acetone:
        benzene:
        Monochlorobenzene:
        Toluene:
        Ethylene dichloride:
        Chloroform:
        Carbon tetrachloride:
very slightly soluble
soluble
soluble
soluble
soluble
7-25 grams/100 grams solvent
5-43 grams/100 grams solvent
4-02 grams/100 grams solvent
15-4 grams/100 grams solvent
26.7 grams/100 grams solvent _ __ _
0.69 grams/100 grams solvent @ 26 C
                                                 26°C
                                                 26°C
                                                 26°C
                                                 26°C
                                                 26°
    Stability:    completely stable at ambient temperature.
                 Fumarin forms water-soluble salts with
                 inorganic and organic bases.
                            20

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    Physical State;  amorphous powder

                Data were not submitted on the octanol/water
                partition coefficient, vapor pressure, pH,
                flammability corrosion characteris-
                tics.  This missing information consti-
                tutes a data gap which will be addressed under
                the section, "Generic Data Gaps."

                No physical/chemical properties data were
                submitted for any Fumarin formulation types.
                This constitutes a data gap for each type of
                formulation:  Technical Fumarin and Fumarin
                Solid Concentrates; and Fumarin Solid
                Ready to Use.

2. Sodium Salt _of Fumarin (for Liquid Use)

The Sodium Salt of Fumarin has been registered in formulations
of solid concentrate for dilution in aqueous solutions.  The
active ingredients range from 0.14 percent to 1.20 percent in
the formulations.

      a.  1.20$  a.i.
      b.  0.50$  a.i.
      c.  0.14$  a.i.

Chemical Identity

Data are not available on the chemical identity of the Sodium
Salt of Fumarin.  This constitutes a data gap.

Manufacturing Process

Data are not available on the manufacturing process of the
Sodium Salt of Fumarin.   This constitutes a data gap.

Percentages of Components in Sodium Salt of Fumarin

Data are not available on the percentages of components in the
Sodium Salt of Fumarin.   This constitutes a data gap.

Product Analytical Methods and Data

An analytical method for the determination of Sodium Salt of
Fumarin in a technical material and formulation was submitted
[Segal 1958, 00001200].   This analytical method is practically
the same as the one for Fumarin with the following exception.
Formulations containing Fumarin are extracted with ethylene
dichloride; however, this extraction method is not applicable to
the Sodium Salt of Fumarin because of the formation of emulsions
of sodium hydroxide and ethylene dichloride.  Consequently, the
Sodium Salt of Fumarin is extracted from the sample with dry
                            21

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acetone.   The acetone is decanted,  removed under vacuum,  and the
residue taken up with \% sodium hydroxide.  The absorption at
305 millimicrons is read on a Beckman Model D.U. Spectro-
photometer and correlated with a standard curve to determine the
Sodium Salt of Fumarin content.  This procedure was checked and
found to give recoveries of 99-7$ and 99-8$.   The sensitivity of
the method is ca 1  mg of Fumarin/100 ml of \% sodium hydroxide
solution.

No methods were submitted for the quantification and identi-
fication of possible impurities in the technical material and
formulations.  This constitutes a data gap.

Physical/Chemical Properties

Except for an analytical method for the determination of the
Sodium Salt of Fumarin,  no other data pertaining to the Sodium
Salt were submitted.  Accordingly,  none of the requirements
stated in the Proposed Registration Guidelines of July 10, 1978
(43 FR, No. 132, Part 163-61-8) are satisfied and this
deficiency constitutes a gap in the data base.

In addition, other registration requirements, i.e.,
identification of the compound, discussion of the manufacturing
process,  identification of impurities, discussion of inert
ingredients, methodology for the analysis of the compound and
its impurities, are also not satisfied.  Consequently, for the
(re)registration of the Sodium Salt of Fumarin, all of the
above data (except the analytical method) are needed.

DISCIPLINARY REVIEW

Generic Data Gaps
Required Labeling

1.Generic Data Gaps

Assuming that the Sodium Salt of Fumarin's properties are
different from Fumarin because of its more polar nature and
coupled with the lack of any chemical data on this compound, all
data requirements that are pertinent to its use are required.
The data for Fumarin and Fumarin Sodium Salt as technical
chemicals, concentrates (manufacturing use products) and end-use
formulated products are required.

The data requirements identified in Table 1 are gaps in the
product chemistry data base needed to adequately support a
Registration Standard for Fumarin.   Following each data
requirement is listed the type formulation of Fumarin on which
the Agency needs data.  This data is described in the Proposed
Registration Guidelines of July 10, 1978 ( 43 Fr, No. 132, Part
163-61).
                            22

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2.Required Labeling

With the present data gaps, this Standard does not require changes
in the current physical/chemical hazard labeling.
                            23

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                             CHAPTER  4

                       ENVIRONMENTAL  FATE
USE PROFILE

This  registration  standard  covers  Federally  registered  uses of
Fumarin,  3- (al pha-Ace tonyl furf ur yl) -4-hydroxycoumar in ,  and  its
Sodium Salt.  The  Environmental Protection Agency (EPA)  has
registered  these products as  single  active ingredients  in
different concentrations and  formulations.   The  registrations
are grouped into five different label  types  for  both  Fumarin and
the Sodium  Salt of  Fumarin.   This  section describes current
label use directions; changes in these directions have  been
dictated  in Chapter  II.

 Type   Description £f Products      Percentages

    I    Technical  and Concentrates  98%, 50°o,
         Formulated  into Registered
         Products

    II   Concentrates Diluted into   1.2-i, D.53,
         End Use Liquid Baits

    III  Concentrates Diluted into   3.51
         End Use Dry  Baits

    IV   Concentrates Diluted into   3.51
         Registered  Baits

    V    R3ady-to-Use, End  Use Dry   3.0251;
         Baits (meal, pellet, or
         block)
Fumarin, a minor use pesticide  that has a  total yearly
production of less than 5,300 pounds active  ingredient  (Kline,
1976), is an anticoagulant rodenticide, used as a dry bait  in
and around buildings and other  structures  and  in transport
vehicles (trucks, planes, and ships) for the control of  Norway
and Roof Rats anJ House Mice  (commensal rodents).   The  Sodium
Salt formulations are  intended  for use  in  liquid baits  for  the
control of the same rats and mice, in the  areas noted above.
Most of the older labeling simply instructs  th-2 user to  place
baits in areas where rats and mice "feed,  water or  travel".  A
few labels also specify trie use of Fumarin products  in  dumps.
The baits are to be placed in locations not accessible  to
children, pets, livestock, or nontarget wildlife or  be  placed in
tamper proof bait boxes.

Fumarin and its Sodium Salt are not mixed  with other pesticides,
although their baits may be used in conjunction with other
rodenticides in a control program.
                             25

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The methods of application for products containing Fumarin or
its Sodium Salt are summarized below:

Type I.    Technical (98%) and Concentrates (50%,10%)  Formulated
           into Registered Products

These products are to be used only to formulate other registered
products and, therefore, do riot have application directions.

Type II.   Concentrated.2%, 0.5%, 0.14%)  Diluted into End Use
           Liquid Baits

These products, which all contain the Sodium Salt of Fumarin,
are to be diluted with water to prepare a  liquid bait containing
D.0125% active ingredient.  The label specifies that the baits
are to be applied in the following manner  for control of
commensal rats and mice:

     a)  For rats, up to 1 quart of bait solution is
         placed in shallow containers,  chick founts,
         or special dispensers, where rats feed, water
         or travel.  Bait is maintained at these
         locations for a minimum of 10 days.

     b)  For mice, up to 1 pint of bait solution is
         placed in shallow containers, chick founts,
         or special dispensers, set at 3 to 12 feet
         intervals where nice feed, water  or travel.
         Bait is maintained at these locations for a
         minimum of 15 days.


Type III.  Concentrates  (0.5%) Diluted into End Use Dry
           Baits

Those products are to be diluted  (one part concentrate to 13
parts bait, by weight) with materials sucii as corn meal, rolled
oats, meat, and fish to  prepare an essentially dry bait
containing 0.025% active  ingredient.  The  label specifies that
baits are to b_> applied  in the following manner for commensal
rats and mice:

     a)  For ruts, 4 to  15 oz of bait is placed in
         dry, shallow containers at locations where
         r-ats feed, water or travel.  Bait is main-
         tained at these locations for a minimum of
         10 days.

     b)  For in ice, 0.25  to 0.5 oz of bait is placed
         in dry, shallow containers at internals of
         3 to 12 feet where mice feed, w-tar or tra/el.
         Bait is maintained at these locations for a
         minimum of 15 days.
                             26

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Type IV.   Concentrates  (0.5%)  Diluted  into  Registered
           Baits

This product is to be  used  only to  formulate other  registered
rodenticide baits.  This  type  of  product  will  not bear  end-use
application directions.

Type V.  Ready-to-'Jse,  End  Use Dry  Baits  (0.25"s)

These products, which  are formulated as ready-to-use  granular
meal, pellets, or block,  are  to  be  used without dilution  (ready-
to-use) according to the  generalized method  of application.
Directions for Type III Fumnrin  products,  apply.

EXPOSURE PROFILE

Products of Fumarin and tne Sodium  Salt of Fumarin  are  available
for use by commercial  applicators and by  homeowners in  the  form
of dust and liquid concentrates  as  well as end-use  dry
formulations.  The dust concentrate is diluted into end-use  dry
baits by mixing with materials such as oats,  corn meal, meat or
fish, and is placed in shallow containers  for  a minimum of  ten
days for the control of rats.   Liquid concentrates  are mixed
with water and then placed  in  the same aianner.  There is  a
potential for dermal contact during preparation and placement of
the end-use baits, particularly  in  the case  of untrained  or
inexperienced users.   Due to tne  extremely low potential  for
vaporization of either Fumarin or its Sodium Salt,  and the
coarse nature of the vehicle used for tlie dust co.icencr.it*--,
iiiiidla tion exposure is unlikely.  Since the  concentrates  are
mixed with edible substances and  remain in place for  several
days, there is a potential  for  ingestion  of  tne end-use baits
by cnildren and domestic  animals, especially  if use directions
are not followed explicitly.

Technical Fumarin
FumeU'in Sol id Concentrate
Sodium Salt of Fumarin Solid Concentrate
Fumarin Solid Ready to Use
      Technical Fumarin:   For persons involved  in  the
      handling, storage,  and shipment of Technical Fun arin,
      there is little likelihood of oral exposure.  There
      is a possibility of botn dermal and inhalation expo-
      sure, howev/er, because this product is  in the form
      of a powder.

      Fumarin Solid Concentrate and Sodium Salt of Fumarin
      Solid Concentrate;   For persons preparing baits by
      mixing the concentrate with an edible substance, there is
      a potential for dermal exposure because of contact with
      the active ingredient.  There is also potential for
      exposure through ingestion of the baits, particularly by
                             27

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      children and domestic animals.  Because the bait remains
      in place from 3  to 15 Jays,  such ingsstion could be
      repea ted.

      The potential for ingestion  also applies to wildlife which
      have access to the bait areas, especially birds, small
      mani;nals, related rodents, or other animals which may
      frequent the treatment areas.   Direct ingestion may occur
      as a result of contamination of the food web.   Predators
      nay eat exposed  wildlife or  the target animals.

      Furnarin Solid Ready _to Use;    For persons handling the
      ready-to-use Fumarin products, there is little chance
      of exposure by ingestion or  inhalation.  Dermal exposure
      is possible, but is expected to be less likely than during
      mixing and subsequent placement of the concentrates.  There
      is a potential for ingestion of the baits by children and
      domestic animals, especially if use directions are not
      followed explicitly.

      Tha potential for ingestion  applies as well to wildlife
      which have access to the bait areas, especially birds,
      small mammals, related rodents, or other animals which
      frequent treatment areas.  Direct ingestion may occur
      as a result of contamination of the food web.   Predators
      and domestic animals may be  exposed by eating  the target
      animal or exposed non-target wildlife (see Ecological
      Effects Chapter), especially if use directions are not
      followed explicitly.

TOPICAL DISCUSSION

Data usually required  for the manufacturing-use chemical
consists of hydrolysis and activated sludge metabolism studies
as specified in Sections 163.52-7(b) and 153.62-3(g),
respectively (43 FR, 29595).  Data usually required  for products
intended for domestic  outdoor applications are:  hydrolysis,
aerobic soil metabolism, field soil  dissipation and  absorption,
as specified in Section 153.52-5(1).  These data, however, do
not generally apply to all classes of products.  Use patterns of
codenticido products practically eliminate ths kinds of
potential hazards associated with  insecticide, herbicides, or
fungicide products use patterns.

Tumarin and its Sodium Salt are rodenticides wnicii are used to
control rats and mice  in and around  domestic dwellings, medical
facilities, agricultural premises, ships, public transport
vehicles, -waste dumps, and commercial, industrial and public
premises.  Because of the low application rates (0.0021 oz.
a.i./qt water, 1 pt/bait station and 0.004 oz. a.i./15 oz. solid
bait, with bait stations every 10  feet) for domestic uses, the
Agency does not expect that Fumarin residues will be in soil or
water or will remain in the vapor  state for any measurable
period of time such that an assessment of potential re-entry
hazard is necessary.  Consequently, no data are required on the
Environmental Fate of Fumarin or its Sodium Salt.
                              28

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DISCIPLINARY RCVIEW

Generic Da La Gaps
Required Labeling

Generic Da ta Gaps

Because of the use pattern of Fumarin  and  its  Sodium  Salt,  chc
limited poundage thac id available and  the  small  chance  of
residues be in 3 found  in soil or water,  Environmental  Fate data
are not needed to support the registration  of  products  of
Fumarin and ics Sodium Salt.

Requi red Label ing

All technical and concentrated Fu:narin  products must  carry  the
following warning on  the label under the "Hazards  to
Wildlife" section:

    Do not discharge  into lakes,  streams,  ponds,  or  public  water
    unless in accordance with an  NPDES  permit.  For  guidance,
    contact your Rsgional Office  of  the EPA.

Because of the potential for ingcstion  of baits by children and
domestic Animals, registrants are required  to  modify  labels to
require that baits be placed in inaccessible areas or be placed
in tamper proof bait  boxes as discussed in  Chapter 2.
                             29

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                            CHAPTER  5

                      RESIDUE CHEMISTRY

Fumarin and its Sodium Salt are used cas  rodenticides  for  the
control of various species of rats and mice.   These products
hava no food or faed use.  Thus, there ara no  residue  chemistry
data requirements for Fumarin and the Sodium Salt  of  Fumarin.
As a deterrant to its use around food and feed,  label
directions must include in the precautionary section  the
statement; "avoid contamination of food  and feedstuffs  and  food
handling surfaces."
                             30

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                          CHAPTER 6

                         TOXICOLOGY
TOXICOLOGY PROFILE

Scientifically sound data on  the  toxicity of  Pumarin  and  its
formulated products are not currently available.  A review of
Fumarin's uses suggests, however, that exposure may occur.  It
it likely that oral, dermal,  and  inhalation exposure  could
occur because of Fumarin's use  in and around  homes, buildings,
and farm buildings, however,  repeated significant exposure is
unlikely except for commercial  applicators who use Fumarin
routinely, especially in formulating baits from concentrates
(see Environmental Fate discussion)  .  Exposure to commercial
formulators and applicators could be greatly  reduced  if
protective clothing including gloves, long sleeves, and  face
masks are worn when handling  Fumarin products.

The Agency's Proposed Guidelines  (43 FR  163.81-.83) describe
the toxicity data requirements  needed by the  Agency to determine
the toxicity of pesticides to humans.  Ordinarily separate
studies are required for each end-use formulation.  The  Agency
has determined that currently registered formulations of  Fumarin
are substantially similar in  composition, differing only  in form
of the active ingredient - acid or  sodium salt - and  formulated
with natural ingredients as inerts.  Therefore, in most cases,
toxicity data will be required  for  technical  Fumarin  and  the
0.5% Fumarin concentrate only.  Because of the great  sensitivity
of the eye to foreign substances, irritation  testing  will be
required on technical Fumarin and some representative formulated
products to ascertain effects on  formulators  exposed  to  the
active ingredient and the dusts of  the inert  foodstuffs.  The
specific guidelines requirements  are listed under the individual
topical discussions that follow.

    Technical Fumarin

    Inadequate data were available  to assess  technical
    Fumarin's  acute toxicology and irritation potential.
    Testing is required for acute oral , acute dermal  and
    acute inhalation toxicity, primary eye irritation,
    primary dermal irritation and dermal sensitization.
    Additional testing is required  with the 98% technical
    Fumarin only.  Because inert  ingredients  are foodstuffs,
    testing is not required on 50 or 10 percent formulations.
    Toxicology tests from the 98% formulation will be
    representative and require only a 2 or 10 fold factor for
    extrapolation.

    Data were not available to  support an assessment  of
    technical Fumarin's subchronic  toxicity.  Pest control
    operators who normally handle Fumarin and farmers who use it
    for rodent control in and around farm houses and barns are
    among the persons who may be  repeatedly exposed to this
                             31

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pesticide.  The Agency, therefore, requires subchronic
testing data so that the effects on mammals can be used to
help assess the effects on humans in a similar manner.  The
test required is a 21-day subchronic dermal toxicity study.
Subchronic inhalation testing will not be required because
of extremely low potential for vaporization of Fumarin and
Sodium Salt of Fumarin, coarse nature of the vehicle used
for the dust concentrate, and because inhaled particles will
be swallowed rather than cross lung alveolar space.  Data
were not available to support an assessment of any
teratogenic potential of technical Fumarin.  Testing is
required.

Fumarin Solid Concentrate
Fumarin Solid Ready _to Use

Data were not available to assess the acute toxicity and
irritation potential of these types of formulations.
Testing is required for acute oral, acute dermal and acute
inhalation toxicity, primary eye, primary dermal irritation,
and sensitization for the five Fumarin Solid Concentrates
(0.5% concentrate) .  Primary eye irritation is required for
the Fumarin Solid Ready to Use.  Information from subchronic
tests on the technical Fumarin will be adequate to assess
potential effects to formulators.  Subchronic testing is not
required on these formulations because the exposure is
expected to be mainly acute.  Also, since both of the above
formulations consist of active ingredient without chemical
inerts , the results of acute tests with the. solid
concentrate (0.5% a.i.) will apply for the Solid Ready-to-
Use products with 0.025% a.i.  Primary eye irritation tests
are not required if the pH is less than 3 or greater
than 12.

Fumarin Sodium Salt Sol id Concentrate

The Sodium Salt of Fumarin is not stable after ingestion
because it dissociates rapidly in the stomach to Fumarin and
sodium.  Therefore, a separate set of toxicology feeding
studies for Sodium Salt of Fumarin is not required.  This
applies to both technical material and formulations.

To assess the potential hazard from dermal or inhalation
routes of exposure, an assumption cannot be made since the
rate of dissociation of the sodium from the Fumarin under
neutral pH is not known.

For formulators, inhalation of grain dust particles
impregnated with the Sodium Salt of Fumarin will result
primarily in oral exposure as the particles are swallowed
rather than inspired.  Little if any Sodium Salt of Fumarin
is expected to reach alveolar space.  Therefore, inhalation
studies are also exempted.

The irajor anticipated exposure mode for the formulator would
be dermal exposure.  Because neither the dissociation
                      32

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    constant nor dermal toxicity studies on the Sodium Salt form
    exists, acute dermal toxicity studies or a dermal uptake
    kinetics study on the Sodium Salt form is required.
    However, if a salt dissociation study is performed to show
    that under pH conditions comparable to skin epidermis the
    Sodium Salt readily dissociates, the above tests will be
    waived and the effects will be assessed using the toxicology
    studies on Technical Fumarin.

In accordance with each of the data requirements  (Data Gaps)
listed below is the number of the sections in the "Proposed
Guidelines" of August 22, 1978 (43 PR Part 163).  The
assessment of the toxic properties of the pesticides will be
made by implementation of the minimum data requirements of the
specified sections, unless otherwise stated under each section.
Where no section number is listed, a minimum requirement has not
been set for such information.
     Data Gaps                       Guidelines Section(s)

Acute Effects                        163.81-1, -2, and -3
Local Irritation                     163.81-4 and -5
Sensitization                        163.81-6
Subchronic Effects                   163.82-2,
Teratology                           163.83-3
Mutagenicity                         163.84-1, -2, -3, and -4

TOPICAL DISCUSSIONS

(Acute Effects)
Acute Oral Toxicity  (163 .81-1)

    An acute oral toxicity study of technical Pumarin was
    conducted on rats resulting in an estimated LD50 of 0.4
    gm/kg  (Repole and Gee, 1954, 00001190).  This study is
    insufficient to meet data requirements because of an
    improper testing protocol of using one animal per dose level
    by sex.
    Technical Fumarin
    Fumarin s"olid Concentrate
    Sodium Salt of Fumarin Solid Concentrate
    Fumarin Solid Ready _to Use

    There are no data available for the assessment.  Testing is
    required on the 98% technical and 0.5% concentrate.

Acute Dermal Toxicity  (163 .81-2)

    Technical Fumarin
    Fumarin Solid Concentrate
    Sodium Salt of Fumarin Solid Concentrate
    Fumarin SolicTReady to Use
                             33

-------
    There are no data available for assessment.   Testing  will
    be required on the 98% technical and 0.5% concentrate.
    Acute dermal toxicity studies on the Sodium  Salt concentrate
    will also be required unless a salt dissociation study shows
    that the sodium salt form readily dissociates under  pH
    conditions comparable to skin epidermis.

Acute Inhalation Toxicity (163 .81-3)

    Technical Fumarin
    Fumarin Sol id Concentrate
    Sodium~Salt of Fumarin Sol id Concentratg
    Fumarin SolicTReady _to Use

    There are no data available for assessment.   Testing  will
    be required on the 98% technical and 0.5% concentrate.

Primary Eye Irritation (163 .81-4)

    Technical Fumarin
    Fumarin Solid Concentrate
    Sodium~Salt jxf Fumarin Solid Concentrate
    Fumarin Sol id Ready _to Use

    No data exist for assessment.  Testing will  be required on
    the 98% technical and 0.5% concentrate.   Representative
    end use products containing 0.025% shall be  tested.   If the
    results of these tests indicate little or no irritation, no
    further studies are needed.  If serious problems arise, all
    formualtions must be tested to assure proper labeling and
    safety to consumers and formulators.  These  tests are not
    required for products whose pH is less than  3 or greater
    than 12.

        Dermal Irritation (163 .81-5)

    Technical Fumarin
    Fumarin Solid Concentrate
    Sodium~Salt of Fumarin Solid Concentrate
    Fumarin Solid Ready to Use
    There are no data available for assessment.  Testing will
    be required on the 98% technical and the 0.5% concentrate.

Dermal Sensitization (163 .81-6)

     Technical Fumarin
     Fumarin Solid Concentrate
     Sodium Salt of Fumarin Concentrate
     Fumarin Solid~Ready  to Use

     There are no data available for assessment.  Testing will
     be required on the 98% technical and 0.5% concentrate.
                             34

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Subchronic Dermal Toxicity  (163 .82-2)

    Technical Fumarin

    There are no data available for assessing subchronic
    dermal toxicity of any  Fumarin products.  Testing will be
    required on the 98% technical since this is expected to be
    the principal route of  exposure for formulators and users of
    concentrates.

gubchronic Oral Toxicity (163 .82-1)
£[ubchronic Inhalation ToxTcity  (163 .82-4 )

    Technical Fumarin

    There are no data available for assessment.  Testing will
    not be required of the  low expected exposure from this
    route, considering both low volatility and type of
    formulations .

Teratology (163 .83-3)

    There are no data available for assessing the teratogenic
    potential of Fumarin.    Anticoagulants have been associated
    with multiple congenital abnormalities in humans.  Since
    exposure to females is  possible,  testing of the 98%
    technical in two mammalian species is required.

Mutagenicity (163 .84-1 ,-2 ,-3 and -4)

    Mutagenicity studies are required for Fumarin because
    Fumarin is approved for general use.  Generally,
    mutagenicity data requirements cannot be waived on the
    grounds of minimal exposure resulting from protective
    clothing because mutagenic  effects may result from a range
    of exposure levels, subacute to chronic, and protective
    clothing is generally  efficacious in reducing acute
    exposures.

    The following studies  represent only the minimum
    requirements for data  on the potential heritable effects of
    Fumar in.

         1.   A mammalian in vitro  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 mammlian _in vitro  cytogenetics test.  If this
             test  suggest  a positive  result,  a dominant lethal
             or heritable  translocation test may be required.
                             35

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

Although the  Agency's mutagenic  testing  requirements are not
final, the standards for these tests should be  based on
principles set forth herein  (43  FR,  No.  163,  Tuesday, 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 .

DISCIPLINARY  REVIEW

Generic Data  Gaps
Required Labeling

Generic p_aj^a  Gaps

The following are gaps  (data  requirements)  in the
toxicology data base needed  to adequately  support a
Registration  Standard for Fumarin  and  its  Sodium
Salt.  Listed after each gap  is  the  section  in  the
Proposed Guidelines of August 22,  1978 (43 FR,  Part
163) that describes the type of  data required.   Under
the heading,  Data Requirments, is  listed  the  type of
Fumarin formulations for whTc~h data  are  required.
Applicants must agree to provide or  cite  the  required data
and adhere to the noted label requirements for  prote'ctive
clothing as discussed in the  Required  Labeling  Section of
thi s chapter.

 Category JDf  Test     Data Requirement     Guidel ine No .

 Acute Oral           An acute oral  toxi-          163.81-1
                      city test  on the
                      rat is  required  for
                      the 98% technical  and
                      the 0.5% concentrate.

 Acute Dermal         An acute dermal  toxi-        163.81-2
                      city study,  preferably
                      on the  rabbit, is  re-
                      quired  for the 98%
                      technical, and the  0.5%
                      concentrate  and  the
                      Sodium  Salt  concentrate.
                          36

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 Acute  Inhalation
 Primary Eye
 Irritation
 Primary Dermal
 Irritation
             An acute  inhalation          163.81-3
             test  is required  for
             the 98% technical  and
             the 0.5%  concentrate.

             A primary eye  irrita-        163.81-4
             tion  test on  the  rabbit
             is required for the 98%
             technical, the 0.5%
             concentrate, and  for
             representative end-use
             products  containing 0.025%.

             A primary dermal  irri-       153.81-5
             tation test, preferably
             on the rabbit, is  required
             for the 98% technical and
             the 0.5%  concentrate.
 Dermal
 Sensi ti zation
 Subchronic Dermal
 Teratology
 Mutagenic ity
Required Labeling
            A dermal sensiti zation      163.31-6
            test, preferably on  the
            guinea pig, is required
            for the 98% technical
            and the 0.5% concentrate.

            A 21-day subchronic  dermal  163.82-1
            toxicity test in the rabbit
            for the 98% technical.

            Testing is required on the  163.83-3
            98% technical Fumarin in
            two mammalian species.

            Testing is required  on the  163.84-1, -2,
            98% technical Fumarin.       -3, -4
Labels must be changed to require persons  (formulators,
commercial applicators, and mixers)  who handle technical
Fumarin and concentrates to wear protective clothing
includ ing
following
long sleeves, gloves, and face masks,
The
precautionary statements should be included:
1.  Wear protective clothing including long sleeves,
    impermeable hand gloves, and face masks when
    mixing and handling Fumarin products.  Remove clothing
    and wash after handling.
    Avoid contamination of food
    place baits in contact with
    food handling surfaces.
                      and feedstuffs.  Do not
                      food and feedstuffs or on
                          37

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3.   Each label  is required  to  have  a  section  entitled,  NOTE
    TO PHYSICIAN, because of possible ingestion of the  bait,
    especially  by children  and domestic  animals.   This
    section shall have the  following  instructions:

       If swallowed by humans, domestic  animals or pets,
       this material may reduce the clotting  ability of the
       blood and cause bleeding.   In  such cases,  intravenous
       and oral administration of vitamin K,  combined
       with transfusion of  fresh  blood or fresh frozen
       plasma may be indicated as in  the case of hemorrhage
       caused by overdose of bishydroxycoumarin .

 4.   Each label must include a first  aid statement in the
     precautionary labeling section:

       If swallowed, call physician immediately.
                         38

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                      BIBLIOGRAPHY
Kusano, T. 1969.  Studies on the improved effectiveness
    of anticoagulative rodenticides on rodents:   I.
    Synergistic toxic action between coumarin or  indandione
    derivatives and thallium salts on mice.   Journal of
    the Faculty of Agriculture, Tattori University
    5:15-52.

Repole, J., and Gee, A.H. 1954.  Toxicological testing of
    coumarin derivative on rodents and other animals.  A
    report of Foster D. Snell, Inc., August 3, 1954.
    (Unpublished .)
                         39

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                            CHAPTER 7

                       ECOLOGICAL EFFECTS
ECOLOGICAL EFFECTS PROFILE

Subpart E, Hazard Evaluation:  Wildlife and Aquatic  Organisms,
of the Proposed Guidelines issued on July 10, 1973,  describes
the fish and wildlife data requirements needed by  the Agency to
assess the hazards of pesticides to nontarget organisms and to
provide for adequate precautionary labeling.

In general, scientifically sound data on the toxicity of
Fumarin  to non-target organisms is almost entirely  absent.
Available studies by Msndenhall and Pank, 1979 (GS-0304-001)
and Pank and Hirata, 1976  (00332467) show that Fumarin can
cause secondary poisoning  in carnivores such as mongooses whan
                     rates but does not
                     to raptors such as
                   appear to
                   barn owls
result in
  (see Topical
fed to rats at field
secondary poisonings
Discussions below) .

TOPICAL DISCUSSIONS

Corresponding to each of the Topical Discussions listed  below  is
the number of the sections in the Proposed Guidelines of July
10, 1978 (43 CFR Part 132)  which explains the data  the Agency
would generally require to  adequately assess Fumarin's hazard  to
the environment.
Data Gaps

Birds
Wild Mammals
Fish
Aquatic inverte-
brates
Guidelines Sections

153.70-1, .70-4, .71-1, and .71-2
153.73-1, .70-4, .71-3 and  .70-l(e)
153.73-1, .70-4, and .72-1
153.70-1, .73-4, and .72-2
These data will not be required to support usa patterns oo/ered
by this Standard so long as the registrant modifies labels  to
require use with tamper proof bait boxes and only  in or around
buildings for outdoor and agricultural premises.   For other
registered uses, not including dumps, labels i.iust  be modified  to
require that baits be placed in tamper proof bait  boxes, or  in
areas inaccessible to children, pets, and non-target wildlife.
Should other significant uses be proposed or should registrants
not wish to use required labeling, these studies May be required
unless a logical argument can be made which shows  minimal
expectation of exposure and consequently, risk.  Also, such
studies may be needed if the total volume of use increases
substantially.
                             40

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Birds

The minimum data normally required  to  establish  hazard  to  birds
is a single-dose oral  LDr0 on one avian  species,  either  a
waterfowl  (preferably  mallard)  or an upland game  bird
(preferably bobwhite or other nativa quail, or ring-necked
pheasants) - the species shall  be the  same as one of two species
selected  for the avian dietary  LCc,,; a subacute dietary  LC,-a
on two avian species,  one waterfowl and one upland game biro
(barn owl) .  No acceptable studies  were  available to meet  these
requirements.

One study was available on the  secondary  toxicity of Fumarin
to birds.  Mendenhall  and Pank, 1979,  (550304-001) fed 0.0251;
Fumarin  (containing a  total of  73.63 mg)  mixed with oat groats
to rats.  The rats were then ingested by  a barn owl, which
survived.  Although this study  did  not include a  sufficient
number of test animals, it suggests that  secondary poisoning may
not necessarily occur  in barn owls  feeding on Fumarin  treated
rats at  field rates.

Wild Animals

The minimum data normally required  to  establish  the toxicicy to
wild mammals are a primary dietary  LC,-,, on carnivores
(preferably a mustelid or small canid); and a secondary  toxicity
feeding  study on carnivores (preferably a mustelid or  small
canid) .

No acceptable primary  study was available to meet the  require-
ment.  One study was available  on the secondary  toxicity of
Fumarin  to rfild mammals.  Pank  and  Hirata, 1976  (33302467)
mixed technical Fumarin with oat groats,  and fed  this
formulation to rats.   One mongoose  which  ingested 3 rats for a
total dosage up to 31.2 rag, survived.  Mongooses  which  ingested
6 rats (which were fed a total  dosage of  47.8 mg)  and 7  rats
(which were fed a total dosage  of 56.3 rag) did not survive.
This suggests that Fumarin can  cause secondary poisoning to
carnivores such as mongooses when it is  fed to rats at field
rates.   It is inadequate for concluding  the toxicity Lo mammals
due to an insufficient number of test animals (soe Toxicology,
Chapter  5).

Although no acute or subacute oral, dermal or dietary data ^re
available on rats or wild mammals,  this  information suggests
that Fumarin is at least highly toxic  to  wild mammals.

Fj.sh

The minimum data normally required  to  establish  toxicity of
Fumarin  to freshwater  fish is a 95-hr  LC^,, test on a coldwater
species  (preferably rainbow trout)  and a  warmwater species
(preferably bluegill).  No acceptable  fish studies are
available to meet these requirements.
                             41

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Aquatic I nvertebrat.es

The minimum data normally required to  establish  toxicity of
Fumarin to aquatic invertebrates is an acute  LC,-™ either for
43-hr on first instar daphnids, or for 95-hr  on  early  instar
amphipods, stoneflies or mayflies.  No acceptable aquatic
invertebrate studies were available to meet this requirement.

DISCIPLINARY REVIEW

Ecological Effects Hazard Assessment
Generic Data Gaps
Required Labeling

Ecological S f f ects H_a^z££d_ Assessment

    Formulated Products Containing Fumarin

The hazard to aquatic organisms and wildlife  from Fumarin
products is expected to be minimal because of the low  volume  of
use and method of application.  It is common  practice  for major
exterminators to rotate rodenticides to  reduce bait  shyness and
chance for tolerance buildup by target rodents.  The less than
5,000 pounds of Fumarin active ingredient produced annually are
not only of low volume usage, but are applied only in  spot
locations.

Despite the absence of data, it is possible to logically pursue
the expected exposure and hence significance  of  risks  to
wildlife and fish.  Aquatic exposure is  unlikely given the  use
patterns, and low total use of the compound.   Sodium salts,
while more soluble, are not expected to  cause  significant risks
even when used as liquids because of the use  pattern,  location
relative to water, and quantities.

It is expected that if there is a spill of the 0.3021  ounces  of
the Sodium Salt of Fumarin every ten feet and  the leaching  of
0.304 ounces of Fumarin from solid bait  every 10 faet,  neither
ground water or bodies of water would  be burdened because of  the
small amount of material going into the ground.  In  addition,
application directions do not pro/ide  for applying Fumarin or
its Sodium Salt to bodies of water.  On  the contrary,  outside
application of Fumarin is to be placed immediately around
buildings (within 5 feet) .

Avian hazard can result from two sources, direct ingestion of
baits or liquids and througn secondary poisoning by  consumption
of poisoned rodents.  Non-target mammals are  also susceptable to
such poisons.  Exposure to the first type of  risk can  be reduced
by making the bait, when used for outdoor and agricultural
purposes, less accessible to non-target species  through use of
appropriate bait boxes (for both liquids and  solids)  and
placement.   For other uses, not including dumps, risk  can be
reduced by use of bait boxes or by placing baits in  areas
inaccessible to children, pets, and non-target wildlife.  To
                             42

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reduce tha hazard of secondary poisoning, label changes could
require proper disposal of dead animals.

If registrants want to use these products in dumps, or
any place not immediately around buildings, Ecological
Effects data will be needed to fully assess the hazard of
Fumarin and its Sodium Salt to fish and wildlife.

Generic Data Gaps
Technical Fumarin and Its Sodium Salt

Ordinarily six basic and one conditional study would be required
to provide a toxicological profile on fish, birds, and aquatic
invertebrates.  This profile enables the Agency to write
precautionary labeling and assess environmental hazards for all
products covered by this Standard.  Since Fumarin is a minor use
pesticide, these studies will not be required.  Should yearly
production of Fumarin and its Sodium Salt reach 25,000 pounds,
the studies discussed abo/e may be required to support the
continued registration of these pesticide products.

Formulated Products containing Fumarin and its Sodium Salt

Usually data supplied on technical material is sufficient to
support formulated products.

These data will not ba required to support use patterns covered
by this Standard so long as the registrant modifies labels to
require use with tamper proof bait boxes and only in or around
build ings. Should other significantly different uses be proposed
or should registrants not wish to use required labeling, these
studies may be required unless a logical argument can be made
which shows minimal expectation of exposure and consequently,
risk .

Required Labeling

    Manufacturing Use

    Do not discharge into lakes, screams, ponds or public
    waters unless in accordance with an NPDES permit.  For
    guidance, contact your Regional Office of the EPA.

    Formulated Products:

    Bait Placements:   For outdoor and agricultural premises,
    liquid and solid baits are to be placed in tamper proof bait
    boxes.  For other uses, excluding dumps, baits must be
    placed in tamper proof bait boxes or in areas inaccessible
    to children and non-target birds and mammals.  These
    bait boxes should be placed at 8 to 12 feet intervals
    and/or at sites where rodents congregate.  For exterior
    building placement, bait is to be stationed around
    (within 5 feat of building outer walls) exterior
    surfaces only, and not in fields adjacent to buildings.
                             43

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                            CHAPTER 3

                      REGULATORY RATIONALE
A.  REGULATORY DECISION

    Tna Agency has determined that products of Fumarin  and
    the Sodium Salt of Fumarin can be Federally registered for
    United States sale and distribution.  Data are not
    available which would indicate that Fumarin or its Sodium
    Salt meet any of the risk criteria for unreasonable adverse
    effects as listed in 40 CFR 162.11(a)  [Criteria for Issuance
    of Notice of Intent to Deny Registration, Cancel Regis-
    tration, or to Hold a Hearing].  To be covered under this
    standard, applicants must agree to submit or cite the data
    and adhere to labeling requirements listed in Chapter II of
    this document.  In some cases, registrants have a choice
    between submission of data or modification of labels as
    discussed in the individual Chapters.   Labels also must
    conform to the general sample labels distributed by the
    Registration Division.

B.  PRODUCT COMPOSITION

    The Agency will consider for registration products
    which contain any percentage of Fumarin or its Sodium Salt
    as an active ingredient (a.i.) .  The Agency expects most
    technical material to be 93% a.i.  Should an applicant
    desire to register products that depart greatly from those
    currently registered, that applicant should contact the
    Agency for specific directions on how to register those
    products .

C.  RATIONALE FOR LABELING REQUIREMENTS

    Since most of the data needed to assess the hazard of
    Fumarin products does not now exist, the Agency's immediate
    efforts at risk reduction center on updating the product
    labeling to clarify the sites, pests,  and methods of
    application; revising out-of-date precautionary and
    storage/disposal statements; and placing label text in a
    clear, readable format.  Guch labeling modifications are
    being required in order to reduce any hazards associated
    with Fumarin products.

D.  RATIONALE FOR DATA REQUIREMENTS

    1.  Product Chemistry

         The Federal Insecticide, Fungicide, and Rodenticide Act
         Section 3(c)(2)(A) requires tha Agency to establish
         guidelines for registering pesticides in  the United
         States, including general chemistry requirements  (EPA,
                              44

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     1973a) .   The Agency requires data and information
     specifically on the manufacturing and formulation
     processes, analytical methods,  and on the formation of
     manufacturing impurities and other product ingredients
     in order to establish the composition of products
     proposed for registration.  Data on the physical and
     chemical properties also are required of all formu-
     lations.  The Agency uses these data to characterize
     each pesticide and to help determine the environmental
     and health hazards of the pesticide.

2.   Environmental Fate

     Environmental Fate data are not needed because usage
     of Fumarin and its Sodium Salt  are not broadcast.
     Instead, usage is localized and is only in spot
     locations.  Baits are protected from rain or snow,  and
     are therefore not expected to affect any crops or
     ground  water.

3.   Toxicology

     Data on the toxicity of Fumarin and its formulated
     products ara not currently a/ailable.  A review of
     Fumarin's uses suggest, however, that some exposure can
     occur on an acute or subchronic basis because of its
     uses in  and around homes, buildings, and farm buildings,
     although it is generally expected to be low.   Data,
     therefore, are needed by the Agency to determine the
     toxicity of Fumarin to humans.    Ordinarily,  separate
     studies  would be required for each end-use
     formulation.  The Agency has determined, however, that
     because  currently registered end-use formulations of
     Fumarin  are substantially similar in composition, in
     most instances,  toxicity data will be required for
     technical Fumarin and the 0.5%  Fumarin Concentrate
     only.  Da~ta generated from these formulations will  be
     used to  extrapolate to the toxicity of the other
     formulated products.  The exception to toxicity
     extrapolation is in the assessment of eye irritation
     potential where  testing will be required for  the
     technical Fumarin,  the 0.5% Fumarin concentrate, and
     representative end-use products.  Normally, testing
     would be required on all formulations, but because  of
     the similarities of these end-use formulations, testing
     will be  only required on some typical  products.

 4.   Ecological Effects

     In general, scientific data on  the toxicity of Fumarin
     to non-target organisms are entirely absent or
     inadequate.  Two available studies  Pank and  Hirata,
     1976, (00002457)  and Mendenhall  and Pank,  1979
     (GS0034-001)  show that Fumarin  can cause secondary
     poisoning  in carnivores when fed to rats at field
     rates.   Ths Agency has determined,  however, that fish
                         45

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         and wildlife studies are not required because of the
         use pattern of these pesticides, the relative low
         volume of use of these pesticides and the small chance
         of residues being found in water or soil.  The Agency,
         therefore, is instead requiring labeling changes for
         products covered by this standard to reduce and/or
         eliminate hazard to fish and wildlife.  Registrants
         desiring to use this pesticide in dumps or in areas not
         in or around buildings may be required to submit
         the data.
E.  RATIONALE FOR EFFICACY DATA REQUIREMENTS

    The Agency is not including thesa data as part of the
    Standard because the data must be formulation specific.

    Tha Agency's current policy is to require efficacy data to
    support public health uses.  A public health use exits
    whenever the continued presence of the target pest organisms
    may pose a threat to human health, either by direct action
    or througli transmittal of disease.  Such uses include
    commensal rat and mouse products.  Tnarefore, data would bo
    required to support the uses contained in this Standard.

    Tha effectiveness of products containing Fumariri and its
    Sodium Salt covered by this Standard depends upon .nany
    factors.  (Palmateer, 1974, 35001803; in press, G).  These
    factors include impurities in the technical; contamination
    of the product with other pesticides during manufacture and
    storage; type, quality, hardness, and particle size of
    inerts added to the technical and concentrates; and the test
    procedures.  The efficacy of pro-ducts with the saraa percan-
    tage of active ingredient can vary dramatically since
    efficacy is a function of bait acceptance.  For these
    reasons, standardized laboratory testing on each specific
    formula is required.

    For guidance on testing products, registrants are referred
    to Subpart G of the Guidelines, tha Agency's Manual of Tesc
    Methods (EPA, 1977) .
                              46

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                   Guide  to Use of Tais Bibliography

Content of Bibliography.  This bibliography contains citations of all
the studies reviewed by CPA in arriving at the positions and conclusions
statad elsewhere in this  standard.  Tae bibliography is divided  into
3 sections: (1) citations that contributed information useful to the review
oC the chemcal and considered to be part o£ 'die data base supporting
registrations under the standard, (2)  citations exnmincd and judgad to be
inappropriate for use in  developing the standard, and  (3) standard
reference material.  PrLnary sources for studies in this bibliography have
been the body of data submitted to SPA 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  publishad materials, this corresponds closely to
an article.  In the case  of unpublished materials submitted to the
agency, the Agency has sought to identify documents at a level parallel to
a published arcicle from  within the typically larger volunes 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  re^ie.-;, and
can be described witn 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.  Tne entries in tihis bibliography are sorted
by author, date of document, and title.  Each entry bears, to the left of
cii2 citation proper, on eight-digit numeric identifier.  Tais number is
unique to the citations,  and should be called the "tester Record
Identifier", or "I1RID'1.   It is not related to the six-digit "Accession
Number" which has been used to identify volunes of submitted data; see
paragraph 1(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 ^Iso to be used whenever a
specific reference is needed.

Form of the Entry.  In addition to the Master Racord Identifier  (MRIO) ,
each entry consists of a  bibliographic citation containing standard
elements followed, in the case of materials submitted  to EP'\, by a
description of the earliest known submission.  The bibliographic
conventions used reflect  the standards for die American National Standards
Institute (ANSI), expanded to provide for certain special needs.  Sane
explanatory notes of specific elements follow:

  a. Author .   Whene/ar the Agency could confidently identify one,
     the Agency has chosen to show a personal author.  When no indiviJual
     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.   Mian the date appears as four digits witii  no
     question marks, the  Agency took it directly from  the docunent.  When a
     four-digit date is followed by a question mark, the bibliographer
     daduced the date from evidence in the doeunsnt.  When the date
     appears as  (19??) , tne Agency was unable to determine or estimate the
     date of the docunent.
                                    47

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c. Title.  Hi is is die third element in the citation.  In some cases it
   has bean necessary for tna Ajency bibliographers to create or enhance
   a docu.ienc title.  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 Number.  The next element, immediately
             following the word 'under1, is the registration number,
             experimental permit number, petition nunber, or other
             administrative number associated with the earliest known
             submission.

        (3)  Submitter.  Tna third element is the submitter, following
             the phrase 'submitted by'.  Vfoen authorship is defaulted to
             the submitter, this element is omitted.

        (4)  Volume Identification.  The final element in the trailing
             parenthesis identifies the CPA accession number of the
             volune in .vhich the original submission ofo the study
             appears.  The six-digit accession number follows the symbol
             'CDL1, 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 123156, the first
             study would ba 123-155-A; the second, 123455-3; the 25th,
             123455-Z; and the 27th 123455-AA.
                                 48

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                  OFFICE OF PESTICIDE  PROGRAMS
               REGISTRATION STANDARD BIBLIOGRAPHY

   Citations Considered to be Pact of  the  Data  Base  Supporting
                Registrations Under the Standard


00001199    Am chain  (197?) Technical Service Data Sheet:
               Technical Fumarin Specifications.   (Unpublished
               study received Nov. 3,  1974 under 70-199;
               submitted by Rigo Co.,  Inc. Buckner,  Ky.;
               CDL:10333D-5-A)

03331200    Segal, H.S. (1953) Determination of Sodium Fumarin
               Content in Fumasol A Formulation.   Method  dated
               Aug., 1953.   (Unpublished study  received Nov.  3,
               1974 under 70-199; prepared by Amchem  Products,
               Inc., submitted  by Rigo Co., Inc., Buckner, Ky.
               CDL:100339-5-B)
                                49

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            Citations Examined and Judged  to  be  Inappropriate For
                       Use  in Developing  tne  Sr_andard

G533334-010 Kline, C.H.  (1975) Professional Markets  for
               Pesticides and Fcrcilizers,  Charles H.  Kline 5.
               Co., Farifield, MJ, 254-5.

35031747    Kusano, T. (19G9) Studies  on  ths  improved  eTfocciva
               ness of anticoagulative  rodanticides  on rodents:
               I Synergistic  toxic  iction  betwjjn coumarin
               or  indandione  dor i y..t ti /es and  thallium  salts on
               mice.  Journal of  che  Faculty  of  Agriculture,
               Tattori University  5 (2):15-52.

GS3334-331  Mcnd^nhjll,  V.M.; P..nk,  L.F.  (1979)  Secondary
               Poisoning of Owls by  Anticoagulant Rodenticides
               Unpublished  study  recei/ed  on  unknown date;
               prepared  by  U.S.  Fish  and Wildlife Ser/ice,
               Patuxent  Wildlifo  Research  Center. Maryland.

35331333    Palmataer, S.D.  (1974) Laboratory testing  of albino
               rats with Anticoagulant  rodinticides.  Pages 53-
               72, In Proceedings--Vortebratc Pesc Conference.
               Mo. 3

G33334-D32  Palmateer, S.D.  (in  press)  Method for Analysis of
               Rat Acceptance Data generated  in  Anticoagulant
               Bait Bioassays. j_n Tecnnical Publication XXX.
               American  Society  for  Testing and  Materials.
               Philadelpnia.

33332457    Pank,  L.F.;  Hirata,  D.N.  (1975) Primary  ..nd
               Secondary Toxicity of  Anticoagulant Rodenticides :
               dob Completion Rjport:   Work Unit DF-133.7.
               (Unpublished study received on unknown  date
               under unknown  jdnin.  no.; prepared by U.S. Fisn
               and Wildlife Damage Researcn Station, submitted
               by  Velsicol  Chemical  Corp.,  Cnicago,  111.;
               CDL:230307-B)

GS334-333   Peacock, D.B. and S.D. Palmatjer. 1J79.   Comparison
               of  EPA Animal  Biology  Laboratory  and  Company
               Laboratory Efficacy Data for Federally  Registered
               Rat and Mouse  Baits,  in  Technical Publication
               533.  Anerican Society for  Testing and  Materials.
               Philadelphia.  11-19  pp.

            Peacock, D.B. and S.D. Palmateer  (in press)
               Comparison of  CPA and Company  Laboratory Efficacy
               Data for  Federally Registered  Rat and Mouse
               Toxicants. j_n Technical  Publication XXX.
               American  Society  for  Testing and  Materials.
               Ph i 1 a d 31 p'n i a .
                                50

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D0001190
Repolu, J.; Gee, A.H.  (1054) Report to American
   Chemical Paint Corn pa ay on Toxicolog ical  Testing
               of Coumarin Derivative
               Animals.   (Unpublished
               1954, under 264-EX-36;
               Snoll,
               Amchem
               A)
          In::. , submitted
          Products, Inc . ,
on Rodents and Other
study received Aug. 25,
prepared by Foster D.
by Arachsn Product, In:j.,
Ambler, PA.;  CDL:123234-7-
05000G26    Spiess, P.; Spiess, W., inventors;  C.F.  Spiess  and
               Sohn, assignee  (1955) Process of producing 3-
               substi tuad-4-!iydroxycounar ins .   British  patent
               specification 734,142.  Jul 27.  3 p.  Cl.  2(3),
               C3A12.
                                51

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                  OFFICE OF PESTICIDE PROGRAMS
               REGISTRATION STANDARD BIBLIOGRAPHY

                   StandarJ Reference Material
Farm Chemical Handbook.   (1979) Mb is tor Publishing.  Willoughby.
   Ohio .

The Federal Insecticide,  Fungicide, and Rodenticide  Act,  as
   amended in 1973, 7ta U.S. Coda, Chapter  135,  61 Statute 1G3.
   73 Statute 19J.

U.S. Environmental Protection Agency  (1977); Manual  of
   Biological Testing Methods of Pesticides and  Devices,  Vol.
   1. Washington, D.C.

U.S. Environmental Protection Agency  (1973a);  Proposed
   Guidelines for Registering Pesticides  in the  United  States.
   Federal Register,  43  (132) 23595.

U.S. Environmental Protection Agency  (1973b);  Proposed
   Guidelines for Registering Pesticides  in cae  United  Scates;
   Hazard Evaluation:  Humans and  Domestic  Animals.   Federal
   Register, 43  (163) 37335.

U.S. Environmental Protection Agency  (1930). Regulations  for  the
   Enforcement of the Federal Insecticide,  Fungicide, and
   Rodenticide Act, Title 40, Ciiapter 1,  Part  152.

U.S.  Environmental Protection Agency (in press)  Proposed
   Guidelines for Registering Pesticides  in the  United  States.
   Subparts G (Product Performance) and H (Label  Development).

U.S. Environmental Protection Agency Standard  Test Methods for
   Anticoagulants, Revision 119, February  17, 1973.
                                     *U S GOVERNMENT PRINTING OFFICE: 1980 341-085/3944
                               52

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