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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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.
-------
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
-------
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) .
-------
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.
-------
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.
-------
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
-------
S
S
X
o
EH
B
a
4J
to
3
E
to
4J
O •
3 CO
"811
rH 3
O
C IH
•H ft
id 0)
I5
MH
MH 0
O
C
c o
0 -H
•rl 4-1
4J -H
n) u
i a
01 E
•rl 0
Oi o
o>
M rH
i id
OJ O
01
ft
U
id
4-1
S
>1
M
jS
u
0
V4
ft
A
g
to
0)
o
a
id
4->
to
A
3
w
4->
to
0)
EH
4-1
rH t)
n) 0)
CO 4-1
0) C id
to -rl S rH
D VH 3 3
1 g -H i
13 § TJ C
W fc W (14
•O
0)
4-1
01 c id
tO -rl rH
D H 3
'O c W
g 3 0
to
Ol 4J
e o
•rl 3
-p 'O
c id o
•rl i-l ,4
VH 3 ft
id E
§ in o)
3 0 to
i-H
rH Id
id co
o
•H e
C 3
rH
id
o
-H
c
a
0
EH
to
4J
c
01
E
^4
•^
D*
0)
os
4-1
D
to
4->
O
3
0
H
ft
01
4-1
O
3
•0
O
01
01
•p
id
n
4-1
c
o>
u
o
o
c
-rl
rH
e
5
c
•rl
rH
E
>-^
ft
id
4-1
&
»-
os _ os s
OS OS Z OS z O
rH
0)
5
os os o
OS OS Z OS Z rH
0)
m
s
os os os os os o
rH
0)
m
a
0
rH
os os os os os o>
s
o
rH
os os os os os o)
m
• • -rl • Id IH • W • • • *-*
to M • c in o • ™ • * i
4-1 3 • O 1 • O • •!
•rl Id 1 C • -H fl 01 -rl rH •
frj tn«— 01 fl E: *-* E -P Id 1*^
£^^C»C«— fcjli— 1°^ rH «—
& ~ id to -ri -- id 3 6
•iH ^^ ^~ O d) O • -H fi *~** ^ O
inlO«in^cyj>i I w
O«- OO Or~rHiH*-'O- —
vOCOl Ol-r4 idO^>C
0) •OWC4-14J 'CHH 'IdtO
3^4-1 -rHd>OID Id^rH-rl
CO'-ftlOtO-rH-HC/>.p4-l'-ld4->
O .rirato-OiH— oid on
rH'lHOI30)-r| 3 T) • -rt ID
UOOOOH4J-T3 OOlft
D-'DftDHOidftid^ftft
i< PQ CJ Q W b
OS OS Z OS z
OS OS Z Z Z
z z § z z
co en en os co
: : : : i
4-1 • •
C • •
•rl • •
O >1 •
ft 4J >i
-H 4-1
&> rH .rH
C -r| rH
^ -rl A -H
0 (H 4J 3 A
rH O rH rH Id
8>n 01 0 4-*
C5 S cn co
r-
8
VD
OS
«
OS
OS
CO
(U
4J
id
4J
in
rH
id
o
•H
01
>,
si
ft
r-
os
OS Z
OS OS
OS OS
OS OS
os os
o •
01 •
ft 4J
to c
-H
SH O
O ft
>1 C71
4J C
•rl -H
0] rH
C! -rl
01 O
a m
00 i Vi
01 1C 4J 0
01 4-1 -rl
01 01 i-H 01
rH -rl C
ft 01 pJ3 -rl
H ID S -rl
O i-i E Tl
ft O Id -H
(d M 4-> rH *
> ft to k, O
o <~ IN rn ^T
OS
OS
OS
OS
Z
os
z
01
01
01
c
0)
>
•H
to
0
rH
ft
m
OS
OS
OS
os
os
0}
u
•rl
4J
to
•H
V4
01
o
id
rl
id
Si
o
c
0
•rl
01
0
rH
10
Q
J
c
•H
13
Id
0)
4-1
•rl
I
CO
11
-------
8
M
X
a o
OiM-l
10 C
rH O>
to e
"H5
(0 rH
d) in
1.5
0) 'o
8B
dl <1)
M
. 0
o &
•rH Vj
4J 4J
(0 C
H 0)
1
0)
s
of*
CN
CM
f^ p^
OOOOOOOOOOOOOOOOGOOOCO t
rorororrirorororororopo •
i-Hi-Hr-HrHr-lr-Hr-Hr-lr-Hr-lrH (
g 4-1 <0
fc 8 Ul •
Ul Ul
rH 0) 0) C
(0 Al rH O
1 O
Q <0 -rH TJ
O.4J -O O
(0 C $ W
4-> Ul (U
X (!) rH £
W rH 03 53
d U
(U "H 4J
•8 ell
-------
^
3
£
3
B
•8
M *
0. M
•SB
U -n
(0 O
fa °*
0)
U-l -C Ul
O 4-* V
O O ID
•H 4J
4-> U W
(04-> J5
4-> a> io CA
in >M a
•rH 14-1 (0 4J
J l2j JJ
d) ->H m
VJ rH Q
•o
l-l rH in
0 -rj 4->
5 U
C 0)
O T3 Ul 10
(0 -H 0
•H fa -rH
vrt rri
*3 O
t-i U
O C Cd
IW O
1
e ° ^
(04-) 0)
U ID r-l
rH C "TO
Ou o t-1
SIM
as C
•rH
rH
ID C
k^
•O O
U rH
10 rH
*o o
C '1 1
4J
0 4->
H iH
0) U
^s
(5 ^^
r^ 13
4J
(0
1 ro "*-* s in
Tj £ 'O C O
c 9 8 o *-i
S Cu Oj fa di
4J in
0) c ro 4-1
(0 -rH rH O
C 3 O rJ
Qj pfj p^ p^
"to
0)
W 4->
c ro
•H kt
1 \ 1 J
c ro c
•rH rH 0)
M 3 O
ro £ c
£ C O
4J
rH C
rH TO -rH
8%
111
O 'O
g
i-H
rH
*
0)
rH
^Q
S
Ul
•rH
5
o
T
rH
•*=
jj
4J
•rH
C
•rH
S
Ul
•rH
rH
ro
S
i—l (M
f^ £
ro ro
vc vo
rH rH
O C
in u
Sio u
»
ro aj v-i
vj cL ro
Single-Dose 0
One Avian S
Subacute Diet
rH (M
4J
1
T3 ro
•rH
O 4j"
di O
•0 3
-j 0
o
o in
o ro
Wl -rH
0) «-J
It ^^
+«* "r"!
4-> "b
a 1
§Q)
U
ro
4J in
U rH
O 0)
p, jQ
E ro
3 rH
(Q
49 P
r^
"•^
"o"
rH
ro
vo
rH
•0
? ^
OQ
o
S CD ^J
O -P -P
M-t 'O W 03 (D
JM C D ? ?
4) *D O 'D 6
4J rH ffi rM C
g^^Si
0) 0) ^ 4)
S
s
o
•o
Ul
r-H,
rH
ro
U
O
roducti*
Ou
^
rH
ro
rH
2
Q
| 1
cs"
T3
X 0)
C •*-"
JQ Ul
•rH
4-1 rH
•iH
ro ui
XI O
•H
.s -g
W tt
0)
x; r-
•jj
rH
A
oo
vo
•
•
9
1
•88
S, S
>,ro
••H
o c
•H O
Secondary Tox
ing Study
CO
13
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
2.Required Labeling
With the present data gaps, this Standard does not require changes
in the current physical/chemical hazard labeling.
23
-------
JH
05
g
U
EH
B
Q
to
&
O
n)
D
4J
01
4J
u
•O
O
ft
i
£>
g
01
01
o
c
id
-p
to
1
| 1
01
-P
rH
id
to
H 3
E &H
9 o
h
i-H
id
o
•H
C!
x:
1
•o
0)
4-1
id
rH
3
£
O
•d
01
4-1
id
rH
3
2
O
01
4J
O
•d
o
^|
ft
01
01
3
-P
rH
id
to
E
•H
C?
i-H
id
o
•rl
C
o
EH
01
4J
C
0)
01
VI
•rl
3
1
4-1
t!
Q
01
4-i
O
'd
o
ft
to
-p
o
3
-d
o
ft
to
01
4-1
id
4J
c
0)
o
0
o
c
•H
>H
g
rt
Cn
VD 4-1
•rl id 1 C * •<-(
^ *!-i *n LI *n j
u ~ C • C «- J
C7! ^^ Id fO -rl
d o s VD c o iw
•rl " «- P 01 O
IH 1 0 • in -^ C
o «- o o o
1O C 4) 0) -rl
4) • 0 CO C 4-1 4J
M n -ri >^ o c: id
3 >O 4J -H 01 O
01 T- a » "> -H -H
0 -H 01 0] T) MH
rH • )H 01 3 01 --H
O O O O O to 4J
01 0) co o 01 tr> IH
•rl CO 0) H -rl C 01
Q — Q ft Q H U
at m u a
•
•
^
"
*"*
1
vD
^
lr-
•
o
01
01
-rl
id
fyj
z
05
«
o^
05
"0
0
5
s
B
rH
o
, \
4^
rH
id
c
id
Product
w
.
0)
0)
t
4-1
•rl
to
3
ft
'
to
o
id
T3
id
^
o
rH
0)
ID
s
o
rH
01
n
*
rH
01
CQ
[J
o
rH
01
n
s
o
rH
Oj
n
. co
. vo
i-H *
(Q fl
O VD
•H *-
s
01 •
-^ XI 0
1 CO
T- T3 ^
VO C
• id to
m 01
ID rH -rl
(Sec. 1
Physica
propert
PL,
P£ C£ Q* OH PH
D^PH^lXrSrSr^HPHrSrS
{£o«%zzz&zo«fl*c£p«
£& OH fti Pi PH PH
PH P^ OH PH Pi Pi Pi PH Pi PS
COCOCOtfCQKMpStfK
: : : : : 2 fe, : :
4J . . W JJ ft 4-1 iJ
-rl . . 4J 4-> -H 01
a>l * Id 01 h O 01
4J >, S O ft 01
-H 4J X. rH IH
CJlrH-HrH Id >ltjlft
C -rl rH O O 4-1 C
M -H ja -H C -rl -rl -rl iH
OM4->3J3H)tOtOrHO
rHOHrHn)4J>iC!-fHa
S!d41O4-lO^01Old
OSO)COOCHQ(0>
r-iNn^inor-cocno
Di PH Pi Pi Pi Pi
U PH Pi Pi Pi Pi
K K A 05 « K
Pi Pi
3i Pi Pi ^ 2 Pi
Pi Pi
:::§::
: : :tj : s
. : : « i
• >i • d 4J
-H " 0) (0
1 . ij tj
•rl « 0) 10
A >1 to 01 JH
Id 4J O 01 O
4J -H C
CO rH CP 01 C
•H C > O
4) jQ -rl -H -H
O> Id N to 01
Id g -rl O 0
O id -ri ft to
•r- ,
O
c
ft
rt
C
•d
C
id
•d
01
4-1
4J
•rl
CQ
II
co
•b
•d
to
•rl
3
ST
S
P-t
4J
a
ii
05
z
•h
SEND
' Required
w ii
w
j m
24
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
------- |