United States Prevention, Pesticides EPA738-H-38-OO7
Environmental Protection And Toxic Substances July 1998
Agency (7508W) .
Reregistration
Eligibility Decision (RED)
Rodenticide Cluster
-------
-------
United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508W) ' -. '
EPA-738-F-38-004
July 1998
R.E.D. FACTS
Rodenticide Cluster
Pesticide
Reregistration
All pesticides'sold or distributed in the United States must be'
registered by EPA, based on scientific studies showing that they can be used
without posing unreasonable risks to people or the environment. Because of
advances in scientific knowledge, the law requires that pesticides which .
were first registered before November 1, 1984, be reregistered to ensure
that they meet today's more stringent standards.
In evaluating pesticides for reregistration, EPA obtains and reviews a
complete set of studies from pesticide producers, describing the human
health and environmental effects of each pesticide. The Agency develops
any mitigation measures or regulatory controls needed to effectively reduce
each pesticide's risks. EPA then "reregisters pesticides that can be used
without posing unreasonable risks to human health or the environment.
Use Profile
When a pesticide is eligible for reregistration, EPA explains the basis
for its decision in a Reregistration Eligibility Decision (RED) document. '
This fact sheet summarizes the information in the RED document for
reregistration case 2755, brodifacoum; case 2760, bromadiolone; case 2765,
bromethalin; case 2100, chlorophacinone; case 2205, diphacinone and its
sodium salt, and, case 2810, pival and its sodium salt
These chemicals are for the control of mammal pests, particularly
commensal rats and mice but also a variety of field rodents [note:
commensal rodents are Norway rat, roof rat, and house mouse.] Products
can be used in and around buildings, alleys, transport vehicles (trains, ships,,
aircraft) and related port terminals, or in sewers. A few diphacinone labels
allow applications hi wet or damp sites such as dumps, irrigation ditches,
along fences, and in gullies. Other products have limited uses.
Bromadiolone products can be applied only indoors in non-urban areas..
Diphacinone sodium salt liquid (i.e., drinking) bait can be applied only
indoors, and diphacinone and chlorophacinone tracking powders can only be
used indoors and in rodent burrows along the outside walls of buildings".
-------
Most rat and mouse products are formulated as pelletized baits. Some
products are sold in place packs (pellets contained in small plastic or paper
bags applied unopened) and others, especially those for use in sewers, as
paraffinized bait blocks. Current labels for rat and mouse baits used
outdoors require that baits be applied in protective bait stations or placed in
areas inaccessible to nontarget wildlife (e.g., in burrows).
Both chlorophacinone and diphacinone have section 3 and Special
Local Needs (SLNs) registrations for field uses. Each has one product for
hand-applied, underground baiting of pocket gophers. Chlorophacinone has
one product for underground baiting of moles. Diphacinone has one
product for field control of ground squirrels. Twenty states have one or
more SLNs for vole control, predominantly in dormant fruit orchards, and
nine states have SLNs for control of ground squirrels. Other SLNs target
various rat species (CA, FL), deer mice (CA), pocket gophers (CA), moles
(OR, WA), chipmunks (CA), muskrats (CA), woodrats (CA), jackrabbits
(CA, OR), and mongoose (HI).
Most products are 6.005% active ingredient or 0.01% active
ingredient food pellets; others include treated whole grains, paraffinized
food blocks, a chlorophacinone orchard spray for voles, meat bait for
mongoose, and treated artichoke bracts for voles in California artichoke
fields. Many of the orchard applications for voles include aerial
broadcasting of food bait.
Regulatory The Agency's predecessor, the U.S. Department of Agriculture
History (USDA), first regulated vertebrate control agents after Congress passed
FIFRA in 1947. Since then, additional rodenticides have been registered
including diphacinone which was registered in 1960 followed by the
registration of its sodium salt in 1962. Chlorophacinone and brodifacoum
were registered in 1971 and 1979, respectively, followed by bromadiolone in
1980 and bromethalin in 1984. This RED covers 243 of the currently
registered 406 products, including Section 3 and 24(c) used to control
vertebrate pests by baits and tracking powders. The decisions made in this
RED will affect many of the remaining 182 vertebrate controlled products,
which were the subject of past REDs as well as those subject to future
reregistration.
Human Health Toxicity
Assessment In studies using laboratory animals, brodifacoum, bromadiolone,
bromethalin, chlorophacinone, and diphacinone and its sodium salt generally
-------
have been show to be highly acutely toxic. All chemicals, with the
, . exception of bromethalin, are in categories I for oral, inhalation and dermal
t - exposure. Bromethalin is category II for dermal exposure.
Dietary Exposure ,
-j . ,
The Agency considers the uses of brodifacoum, bromadiolone,
bromethalin, chlorophacinone, and diphacinone and its sodium salt to be
nonfood. Based on current use patterns and exposure profiles, residues in
and on food and/or feed are not expected to occur. Therefore, a dietary
risk assessment is not required.
Occupational and Residential Exposure
EPA is concerned about the likelihood of risk of human exposure,
resulting from continued use of rodenticides in residential settings. The
number of human incidents reported has increased greatly in recent years
with the advent of a new reporting network. In 1988, more than 10,000
rodenticide incidents were reported in the American Association of Poison
Control Center's National Data Collection System. About 90% of these '
' cases involved children under six years of age. Nearly all of such exposure
incidents are classed as accidents. The human exposure incidents that are
. reported may represent less than half of those which actually occur. Well
<< over 80% of reported human rodenticide exposures involve anticoagulant
' compounds. . .
-->ป. -
The Agency has determined that there is potential exposure to
applicators and/or other handlers during typical use patterns associated with
these chemicals. Specifically, the Agency is concerned about potential
dermal and inhalation exposures to handlers during the loading and
application of these chemicals. Based on the use patterns and potential
exposures, major handler scenarios were identified such as (1) placing bait
packs; (2) loading bait boxes or bait stations with meal bait, grain bait, bait
' pellets, or other food-based bait from larger containers; (3) breaking
parafinized blocks into pieces and placing the pieces in bait stations; (4)
securing large paraffin blocks in bait stations used in sewers; (5) applying
. bait by hand; and (6) applying bait, e.g. pellets in broadcast treatments
using ground and (6) spray.
Human Risk Assessment
Rodenticides are acutely toxic to humans. Margins of Exposure
(MOEs), when bait is ingested,,are less than one. Generally, the Agency
{ '
*' ' '''.' ' . - . -."_.
. - 3 ' - .
-------
Environmental
Assessment
considers a MOE of 100 or above to be protective of the public's health.
The Agency, for example, has calculated the dose a 10 kg child receives
from a 43 gram packet (standard commercial package). The Agency's
calculation resulted in a MOE of 0.5.. Because of improved data collection,
it appears that the high number of human unintentional or accidental
exposures to rodenticides remain constant each year, or may be increasing.
From the number of exposures to children, it is clear that children under six
years-old are disproportionately more at risk to the continued use of these
products in and around the home. EPA is therefore concerned about the
risk from accidental exposures to these chemicals from residential users,
particularly children.
Environmental Fate
While generally the rodenticides are very similar in their
environmental fate characteristics, there are a few exceptions. The
rodenticides are generally stable to hydrolysis, except for diphacinone at pH
5 (which has a half-life of 44 days), moderately persistent to persistent to
aerobic soil degradation (half-lives of 26 to 178 days) and, except for
bromethalin can generally be considered to be immobile in the soil (Kds =
5.4 to 1000, and found in the upper soil layer of column leaching studies).
Generally the potential for these chemicals to reach ground water is
low. They probably reach surface waters through adsorption to eroding
soil, as opposed to dissolution in runoff water. Because of their generally
high adsorption coefficients and/or demonstrated lack of movement hi soil
leaching columns they would have a good probability of partitioning into the
suspended and bottom sediments instead of the water column after reaching
surface waters.
Based on the available data, little if any contamination of surface and
ground waters is expected for brodifacoum, bromadiolone, chlorophacinone
and diphacinone. These chemicals, although persistent, tend to be relatively
immobile in soil and fairly insoluble in water. Most are applied as a
pelleted bait in and around buildings and mostly in protective bait stations
when used outdoors. Because of the lack of leaching data, the
environmental fate of bromethalin is uncertain at this time. Leaching data is
beingjrequested for bromethalin in the RED.
Ecological Effects
Primary toxicity to mammals is very high for all five of these
products. Primary toxicity to birds is mostly high to very high for the
single-feeding compounds (brodifacoum, bromadiolone, bromethalin),but
-------
mostly moderate for the multiple-feeding compounds (diphacinone,
. cMorophacinbne). Toxicity to aquatic organisms ranges from moderate to
very high.
Available laboratory and/or field data indicate that rodents poisoned
with brodifacoum and bromadiolone baits can kill avian and mammalian
secondary consumers. Sufficient data also exists to indicate that 0.01 % a.i.
diphacinone bait is secondarily hazardous to birds and mammals and that
0.01 % a.i. chlorophacinone bait is hazardous to mammalian predators.
: ' 7
Ecological Effects Risk Assessment
The Agency believes that there is a high risk of secondary poisoning,
.'..'.' especially~to mammals, from the use of these rodenticides outdoors (i.e.,
"around" buildings) in rural and suburban areas. The available data
indicate that brodifacoum, bromadiolone, and 0.01 % a.i. chlorophacinone
and diphacinone baits may pose a secondary hazard to avian and/or
mammalian predators that feed on poisoned rodents. Brodifacoum and
bromadiolone likely pose the greatest secondary risks, because they are
more acutely toxic, especially to birds, more persistent in animal tissues,
and can be lethal in a single feeding. In contrast, chlorophacinone and
diphacinone tend to be less toxic to birds, less persistent hi the tissues of
primary consumers, and must be eaten over a period of several days to
cause mortality. Therefore, a predator feeding only once on a poisoned
carcass may not die if the the rodent was poisoned with diphacinone or
. chlorpphacinone, but is more likely to die if the rodent was poisoned with
brodifacoum or bromadiolone. Data is being requested in the RED for
bromethalin in order to determine secondary 'risks.
The Agency recently became aware of incident data which suggests
that there may5,be a potential incident problem specifically involving the
active ingredient brodifacoum. At this time the Agency is reviewing the
data; no final conclusions have been reached. Additionally, through the
"Notice of Availability" for this document, the Agency requests state
incident data for all rodenticides to better understand the extent of this
potential problem. After review, the Agency may impose additional
restrictions on the use of brodifacoum and/or other active ingredients.
Risk Mitigation To address the risks posed by the rodenticides bromadiolone,
bromethalin, brodifacoum, chlorophacinone, diphacinone and its sodium
salt, EPA has developed a two-phased approach to minimize exposure
particularly to infants and children.
-------
Additional Data
Required
During Phase I the Agency will require the products covered in the
rodenticide cluster to incorporate an indicator dye (to help identify whether
a child or pet has actually consumed the pesticide) and a bittering agent into
the formulations. The Agency is aware that all mitigation measures
required during Phase I may not be feasible within the 8-month time frame
usually accorded by the RED process to submit labeling changes. While
registrants will still be required to submit revised labeling within the 8-
month time frame, the Agency recognizes that the formulation changes
required by the add-on of the indicator dye and bittering agent may take
longer. The tuning for the incorporation of the dye and bittering agent in
rodenticide products will be an outcome of the initial stakeholder meeting.
In Phase II, EPA will form a stakeholder group that will include
representatives from industry, states, various poison control centers, rodent
control experts, the medical community and other interested parties to
develop additional means of significantly reducing exposures to children and
pets.
v
In addition to the mitigation measures discussed above, EPA is
requiring a number of label revisions to rodenticides used in and around the
home as well as requiring registrants, under the authority of FIFRA, section
3(c)(2)(B), to submit data from the American Association of Poison Control
Center. The data will be for the years 1999 through 2009. Restricted Use
classifications will also continue to be maintained.
EPA is requiring the following additional generic studies to confirm
its regulatory assessments and conclusions:
Brodifacoum
21-Day Dermal - rabbit/rat [82-2)
Estimation of Dermal Exposure at Outdoor Sites [231]
Estimation of Inhalation Exposure at Outdoor Sites [232]
Estimation of Dermal Exposure at Indoor Sites [233]
Estimation of Inhalation Exposure at Indoor Sites [234]
Bromadiolone
Leaching/Adsorption/Desorption [163-1]
Estimation of Dermal Exposure at Outdoor Sites [231]
Estimation of Inhalation Exposure at Outdoor Sites [232]
Estimation of Dermal Exposure at Indoor Sites [233]
Estimation of Inhalation Exposure at Indoor Sites [234]
-------
Bromethalin
_ General Metabolism [85-1] '
Leaching/Adsorption/Desorption [163-1]
Estimation of Dermal Exposure at Outdoor Sites [231]
Estimation of Inhalation Exposure at Outdoor Sites [232]
Estimation of Dermal Exposure at Indoor Sites [233]
.- ' Estimation of Dermal Exposure at Outdoor Sites [234]
Secondary Poisoning, Mammal [70-A-SS]*
Protocol
Secondary Poisoning, Bird [70-B-SS]*
Protocol , .
Whole Body Residue, Target Species [70-C-S]*
Protocol ,
*Studies are not required for "indoors and along the outside walls of
buildings", but are required for any other uses.
Chlorophacinone .
Avian Reproduction, Quail [71-4(a)]*
( Avian Reproduction Duck [71-4(b)J*
Estimation of Dermal Exposure at Outdoor Sites [231]
Estimation of Inhalation Exposure at Outdoor Sites [232]
Estimation of Dermal Exposure at Indoor Sites [233]
Estimation of DermaTExposure at Outdoor Sites [234]
Secondary Poisoning, Mammal [70-A-SS]**,
. Protocol
Secondary Poisoning, Bird [70-B-SS]**
Protocol
. , Whole Body Residue, Target Species [70-C-S]**
Protocol
*Required to support Product CAS 90023.
**Studies are not required for "indoors and along the outside walls of
buildings", but are required for any other uses.
Diphacinone, and Salt
General Metabolism[85-l]
-------
Hydrolysis [161-1]
Leaching/Adsorption/Desorption [163-1]
Estimation of Dermal Exposure at Outdoor Sites [231]
Estimation of Inhalation Exposure at Outdoor Sites [232]
Estimation of Dermal Exposure at Indoor Sites [233]
Estimation of Dermal Exposure at Outdoor Sites [234]
Secondary Poisoning, Mammal [70-A-SS]*
Protocol
Secondary Poisoning, Bird [70-B-SS]*
Protocol
Whole Body Residue, Target Species [70-C-S]*
Protocol
*Studies are not required for "indoors and along the outside walls of
buildings!', but are required for any other uses.
The Agency also is requiring product-specific data including product
chemistry and acute toxicity studies, revised Confidential Statements of
Formula (CSFs), and revised labeling .for reregistration.
Product Laboling All brodifacoum, bromadiolone, bromethalin, chiorophacinone and
ChariQGS diphacinone and its sodium salt end-use products must comply with EPA's
Reauired current pesticide product labeling requirements and with the following. For
a comprehensive list of labeling requirements, please see the Rodenticide
Cluster RED document.
Labeling Requirements:
1. Incorporate the word "POISON" (in Spanish and English), and skull
and cross bones icon on the labels.
2 The section on labels for pets must include a hazard to pet statement,
first aid treatment for pets, and a note to veterinarians.
3. To clarify that bait can be applied only as specified on the label the
following must be added: "Do not apply this product by any method not
specified on this label".
4. Specific information regarding use sites and use directions should be
included on SLN labels to help avoid inappropriate use of these products.
-------
5 Dust masks/respirators and water-proof gloves are required for
commercial handlers (Mixer/loader/applicator) when handling rodenticide
chemicals not already in place packs.
6 All products intended primarily for occupational use must contain the
following statement: "Do not contaminate water, food, feedstuffs, food or
feed handling equipment, or milk or meat handling equipment".
7. Products intended primarily for consumer use (OTC) must contain the
following stat: "Do riot apply this product in a- way that will contact any
person or pet. Keep people and pets out of the area during application.
8. All products must contain an environmental hazard statement stating:
"Do not apply directly to water or to areas where surface water is present or
to intertidal areas below the mean high-water mark. Do not contaminate
water when disposing of equipment, wash water, or rinsate".
9. All tracking powders must limit treatment areas to concealed,
inaccessible places such as spaces between floors and, walls. Powder may
not be applied along walls, in corners or in open floor areas of rooms in
which food or feed is handled or stored.
10 All rodenticide products labeled for field use, except those limited to
manual underground bailing for pocket gophers and moles, will be restricted
use. ' . ""'.,-
11. Where applications for the control of mice and rats in non-urban and
rural settings are not limited indoors and against the outside walls of
buildings, labels shall state to place baits:
"indoors and along the outside walls of buildings."
12. The second sentence: of the "Environmental Hazards "precautionary
labeling on all food bait products should read as follows: "Predatory and
scavenging mammals and birds might be poisoned if they feed upon animals
that have eaten the bait."
13. For chlorophaeinone orchard spray products, the statement should be
modified to read: ,
."Predatory and scavenging mammals and birds might be poisoned if they
feed upon animals that have been poisoned by this product.
-------
Regulatory
Conclusion
With the exception of pival and its sodium salt, the Agency has
concluded that the uses, as prescribed in the RED document, with additional
labeling requirements and a number of risk mitigation measures, will not
cause unreasonable risks to humans or the environment
The Agency has determined that all uses of brodifacoum, bromethalin,
and bromadiolone are eligible for reregistration.
The Agfency has determined that all uses of chlorophacinone and
diphacionone and its sodium salt are eligible for reregistration, with the
exception of certain field bait uses. The Agency has determined that field-
bait uses containing .005 % chlorophacinone and diphacionone and its
sodium salt are eligible for reregistration.
The Agency has determined that field-bait uses containing more than
.005 % chlorophacinone and diphacionone and its sodium salt are ineligible
for reregistration. Field tests have adequately demonstrated that products
with lower-concentrations of these active ingredients are sufficiently
efficacious for target pest species, and that the uses with higher
concentrations have the potential to cause unnecessary secondary poisonings
to avian and mammalian consumers.
For More
Information
The EPA has determined that all uses of pival and its sodium salts are
ineligible for reregistration. Pival and its sodium salt was suspended by the
Agency in December 1994 for failure of the registrant, Motomco,
Incorporated, to respond to the Agency's Data Call-in Notice (DCI) and
submit the required data to support the continued registration. In the future,
EPA may seek cancellation of the registration for pival and its sodium salt.
!
EPA is requesting public comments on the Reregistration Eligibility
Decision (RED) document for brodifacoum, bromadiolone, bromethalin,
chlorophacinone and diphacinone and its sodium salt, during a 60-day time
period, as announced in a Notice of Availability published in the Federal
Register. To obtain a copy of the RED document or to submit written
comments, please contact the Pesticide Docket, Public Response and
Program Resources Branch, Field Operations Division (7506C), Office of
Pesticide Programs (OPP), US EPA, Washington, DC 20460, telephone
703-305-5805.
Electronic copies of the RED and this fact sheet can be downloaded
from the Pesticide Special Review and Reregistration Information System at
10
-------
703-308-7224. They also are available on the Internet using ftp on
FTP.EPA.GOV, or using WWW (World Wide Web) on WWW.EPA.GOV.
Printed copies of the RED and fact sheet can be obtained from EPA's
National Center for Environmental Publications and Information
(EPA/NCEPI), PO Box 42419, Cincinnati, OH 45242-0419, telephone
513-489-8190, fax 513-489-8695.
Following the comment period, the Rodenticide Cluster RED
document also will be available from the National Technical Information ,,
Service (NTIS), 5285 Port Royal Road, Springfield, VA 22161, telephone
703-487-4650.
For more information about EPA's pesticide reregistration program,
the brodifacoum, bromadiolone, bromethaUn, chlorophacinone, and ,
diphacinone and its sodium salt RED, or reregistration of individual
products containing brodifacoum, bromadiolone, bromethalin,
chlorophacinone, and diphacinone, please contact the Special Review and
Reregistration Division (7508W), OPP, US EPA, Washington, DC 20460,
telephone 703-308-8000.
For information about the health effects of pesticides, or for assistance
in recognizing and managing pesticide poisoning symptoms, please contact
the National Pesticides Telecommunications Network (NPTN). Call toll-
free 1-800-858-7378, between 9:30 am and 7:30 pm Eastern Standard
Time, Monday through Friday.
11
-------
-------
, .
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
' ' '
WASHINGTON, D.C. 20460
OFHCEOF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
AU3 3 IS38
CERTIFIED MAIL
Dear Registrant:
I am pleased to announce that the Environmental Protection Agency has completed its
reregistration eligibility review and decisions on the rodenticide cluster pesticide case which
includes the active ingredients brodifacoum, bromodialone, bromethalin, chlorophacinone and
diphacinone and its sodium salt, and pival and its sodium salt. The enclosed Reregistration
Eligibility Decision (RED), which was approved on September-30, 1997, contains the
Agency's evaluation of the data base of these chemicals, its conclusions of the potential human
health and environmental risks of the current product uses, and its decisions and conditions
under which these uses and products will be eligible for reregistration. The RED includes the
data and labeling requirements for products for reregistration. It also includes requirements
for additional data (generic) on the active ingredients to confirm the risk assessments.
To assist you with a proper response, read the enclosed document entitled "Summary
of Instructions for Responding to the RED." This summary also refers to other enclosed
documents which include further instructions. You must follow all instructions and submit
complete and timely responses. The first set of required responses is due 90 days from the
receipt of this letter. The second set of required responses is due 8 months from the date
of this letter. Complete and timely responses will avoid the Agency taking the. enforcement
action of suspension against your products.
- Please note that the Food Quality Protection Act of 1996 (FQPA) became effective on
August 3, 1996, amending portions of both pesticide law (FIFRA) and the food and drug law
(FFDCA). This RED takes into account, to the extent currently possible, the new safety
standard set by FQPA for establishing and reassessing tolerances. However, it should be
noted that in continuing to make reregistration determinations during the early stages of FQPA
implementation, EPA recognizes that it will be necessary to make decisions relating to FQPA
before the implementation process is complete. In making these early case-by-case decisions,
EPA does not intend to set broad precedents for the application of FQPA. Rather, these early
determinations will be made on a case4>y-case basis and will not bind EPA as it proceeds with
further policy development and any rulemaking that may be required.
-------
If EPA determines, as a result of this later implementation process, that any of the
determinations described in this RED are no longer appropriate, the Agency will pursue
whatever action may be appropriate, including but not limited to reconsideration of any
portion of this RED.
If you have questions on the product specific data requirements or wish to meet with
the Agency, please contact the Product Reregistration representative Venus Eagle at (703)
308-8045. Address any questions on required generic data to the Special Review and
Reregistration Division representative Dennis Deziel at (703)308-8176.
Sincerely yours,
A. R^sgi, Director
Special Review and
Reregistration Division
Enclosures
-------
SUMMARY OF INSTRUCTIONS FOR RESPONDING TO .
THE REREGISTRATION ELIGIBILITY DECISION (RED)
1 DATA CALL-IN (PCD OR "90-DAY RESPONSE"-If generic data are required for
reregistration, a DCI letter will be enclosed describing such data. If product specific data
are required, another DCI letter will be enclosed listing such requirements. If both generic
and product specific data are required, a combined Generic and Product Specific letter will
be enclosed describing such data. Complete the two response forms provided with each DCI
letter (or four forms for the combined) by following the instructions provided. You must
submit the response forms for each product and for each DCI within 90 days of the date
of this letter (RED issuance date); otherwise, your product may be suspended.
2. TIME EXTENSIONS AND DATA WAIVER REOTJESTS-Nn time extension requests
, will be granted for the 90-day response. Time extension requests may be submitted only with
respect to actual data submissions. Requests for data waivers must be submitted as part of the
90-day response. Requests for time extensions should be submitted in the 90-day response,
but certainly no later than the 8-month response date. All data waiver and time extension
requests must be accompanied by a full justification. All waivers and time extensions must be
granted by EPA in order to go into effect
3. APPLICATION FOR REREGISTRATION OR "8-MONTH RESPONSE"-You must
submit the following items for each product within eight months of the date of this letter
(RED issuance date). --..-
a. Application for Reregistration (EPA Form 8570-1). Use only an original
application form. Mark it "Application for Reregistration." Send your Application for .
Reregistration (along with the other forms listed in b-e below) to the address listed in item 5.
b. Five copies of draft labeling which complies with the RED and current regulations
and requirements. Only make labeling changes which are required by.the RED and current
regulations (40 CFR 156.10) and policies. Submit any other amendments (such as formulation
changes, or labeling changes not related to reregistration) separately. You may delete uses
which the RED says are ineligible for reregistration. For further labeling guidance, refer to
the labeling section of the EPA publication "General Information on Applying for Registration
in the U.S., Second Edition, August 1992" (available from the National Technical Information
Service, publication #PB92-221811; telephone number 703-487-4650).
c. Generic or Product Specific Data. Submit all data in a format which complies
with PR Notice 86-5, and/or submit citations of data already submitted and give the EPA
identifier (MRID) numbers. Before citing these studies, you must make sure that they meet
the Agency's acceptance criteria (attached to the DCI)
d. Two copies of the Confidential Statement of Formula (CSF) for each basic and
each alternate formulation. The labeling and CSF which you submit for each product must
comply with P.R. Notice 91-2 by declaring the active ingredient as the nominal
.concentration. You have two options for submitting a CSF: (1) accept the standard certified
-------
limits (see-40 CFR ง158.175) or (2) provide certified limits that are supported by the analysis
of five batches. If you choose the second option, you must submit or cite the data for the five
batches along with a certification statement as described in 40 CFR ง158.175(e). A copy of
the CSF is enclosed; follow the instructions on its back.
e. Certification With Respect to Data Compensation Requirements. Complete and
sign EPA forms 8570-34 and 8570-35 for .each product. "
4. COMMENTS IN RESPONSE TO FEDERAL REGISTER NOTICE -Comments
pertaining to the content of the RED may be submitted to the address shown in the Federal
Register Notice which announces the availability of this RED.
5. WHERE TO SEND PRODUCT SPECIFIC PCI RESPONSES (90-DAY) AND
APPLICATIONS FOR REREGISTRATION (8-MONTH RESPONSES!
By U.S. Mafl:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
EPA, 401 M St. S.W.
Washington, D.C. 20460-0001
By express:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
Room 266A, Crystal Mall 2 .
1921 Jefferson Davis Hwy.
Arlington, VA 22202
6. EPA'S REVIEWSEPA will screen all submissions for completeness; those which are not
complete will be returned with a request for corrections. EPA will try to respond to data
waiver and time extension requests within 60 days. EPA will also try to respond to all 8-
. month submissions with a final reregistration determination within 14 months after the RED
has been issued.
-------
REREGISTRATION ELIGIBILITY DECISION
RODENTICIDE CLUSTER
LISTB
CASES 2100, 2205, 2755, 2760, 2765, 2810
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
SPECIAL REVIEW AND REREGISTRATION DIVISION
-------
-------
TABLE OF CONTENTS
RODENTICIDE CLUSTER REREGKTRATION ELIGIBILITY DECISION TEAM . . i
I. INTRODUCTION ........ 1
"**-.* . - 1
n. . CASE OVERVIEW . . . . : ,......._....;.... .2
A. Chemical Overview . - 2
B. Use Profile -........;.........; '/. .............. ....... 2
1. Brodifacoum Summary of Use Patterns and Formulations . . .... 3
2. Bromadiolone Summary of Use Patterns and Formulations ..... 4
3. Bromethalin Summary of Use Patterns and Formulations 4
4. CMorophacinone Summary of Use Patterns and Formulations ...5
5. Diphacinone Summary of Use Patterns and Formulations ...... 6
C. Estimated Usage of Pesticide . . . . . ...... . . ..... . . ......... 6
D. Data Requirements . . ... . . . 7
E. Regulatory History . . 7
SCIENCE ASSESSMENT , .... . .". /. .'.... ...... 9
A. Physical Chemistry Assessment . . '.9
B. Human Health Assessment . . 10
1. Toxicology Assessment . . 10
a. Acute Toxicity ......;.......... 10
(1) Brodifacoum Acute Toxicity .''..', 10
(2) Bromadiolone Acute, Toxicity '. . . , 13
(3) Bromethalin Acute Toxicity . . ... .-..;" . 14
(4) Chlorophacinone Acute Toxicity ............. 15
(5) Diphacinone and its sodium salt Acute Toxicity ..17
b. Subchronic Toxicity 21
(1) Brodifacoum Subchronic Toxicity 21
(2) Bromadiolone Subchronic Toxicity ........... 21
(3) Bromethalin Subchronic Toxicity 22
(4) Chlorophacinone Subchronic Toxicity . . 23
(5) Diphacinone and its sodium salt Subchronic Toxicity
'. .. 25
c. Chronic toxicity 27
d. Carcinogenicity ............................. 28
e. Developmental Toxicity . . . ... 28
(1) Brodifacoum Developmental Toxicity . 28
(2) Bromadiolone Developmental Toxicity ......... 30
(3) Bromethalin Developmental Toxicity .......... 30
(4) Chlorophacinone Developmental Toxicity ....... 31
(5) Diphacinone and its sodium salt Developmental
Toxicity 34
-------
f. Mutagenicity 35
g. Metabolism 35
(1) Brodifacoum Metabolism . 35
(2) Bromadiolone Metabolism . . . 38
(3) Bromethalin Metabolism . 39
(4) Diphacinone and its sodium salt Metabolism 39
(5) Chlorophacinone Metabolism 40
h. Other lexicological Considerations . 42
(1) Brodifacoum - Other Toxicological Considerations
. . 42
(2) Bromadiolone - Other Toxicological Considerations
42
(3) Bromethalin - Other Toxicological Considerations
....... 43
(4) Chlorophacinone - Other Toxicological Considerations
. . ... . . . 44
(5) Diphacinone and its sodium salt - Other Toxicological
Considerations 44
2. Exposure Assessment .46
a. Dietary Exposure 46
b. Occupational and Residential Exposure , 46
(1) Brodifacoum Occupational and Residential Exposure
Assessment 47
(2) Bromadiolone Occupational and Residential Exposure
Assessment .. v. 48
(3) Bromethalin Occupational and Residential Exposure
............. 49
(4) Chlorophacinone Occupational and Residential
Exposure ... 52
(5) Diphacinone and its sodium salt Occupational and
Residential Exposure 53
3. Risk Assessment . . . 54
a. Occupational and Residential 54
C. Environmental Assessment 56
1. Ecological Toxicity Data . . 56
a. Toxicity to Terrestrial Animals 57
(1) Birds, Acute and Subacute 57
(2) Birds, Chronic Toxicity . . . 61
(3) Mammals .61
b. Toxicity to Aquatic Animals 63
(1) Toxicity to Freshwater Fish 63
(2) Toxicity to Freshwater Invertebrates 65
c. Birds and Mammals, Secondary Toxicity Tests 67
d. Terrestrial Field and Simulated Field Testing ......... 68
e. Birds and Mammals, Secondary Toxicity Tests 69.
-------
2, Environmental Fate 70
a. Environmental Fate and Transport ... . . 70
(1) Brodifacoum Environmental Fate and Transport . 70
(2) Bromadiolone Environmental Fate and Transport
.'..'.... ......;.............. 71
(3) Bromethalm Environmental Fate and Transport .. 73
(4) Chlorophacinone Environmental Fate and Transport
. ... . , . . . . . 74
(5) Diphacinone and its sodium salt Environmental Fate
and Transport 76
3. Ecological Exposure and Risk Characterization ............ 78
a. Brodifacoum Ecological Exposure and Risk Characterization
;.,........,... 79
(1) Brodifacoum Exposure and Risk to Nontarget
Terrestrial Animals .-..,'.., 80
(2) Brodifacoum Exposure and Risk to Nontarget Aquatic
Animals 81
(3) Brodifacoum Exposure and Risk to Nontarget Plants
and Insects ... . . 81
(4) Brodifacoum Endangered Species Concerns ..... 81
b. Bromadiolone Ecological Exposure and Risk Characterization
-. - . . . 82
(1) Bromadiolone Exposure and Risk to Nontarget
Terrestrial Animals . . 82
(2) Bromadiolone Exposure and Risk to Nontarget
Aquatic Animals 83
(3) Bromadiolone Endangered Species Concerns .... 83
c. Bromethalin Ecological Exposure and Risk Characterization
. . . . ........ 83
(1) Bromethalin Exposure and Risk to Nontarget
Terrestrial Animals ..................... 83
(2) Bromethalin Exposure to Plants and Insects ....... 84
(3) Bromethalin Exposure and Risk to Nontarget Aquatic
Animals ........ ... . 84
(4) Bromethalin Endangered Species Concerns ..... 84
d. Chlorophacinone Ecological Exposure and Risk
Characterization '.;.... 85
(1) Chlorophacinone Exposure and Risk to Nontarget
Terrestrial Animals 85
(2) Chlorophacinone Exposure and Risk to Nontarget
Aquatic Animals ..:.. .......... 90
(3) Chlorophacinone Endangered Species Concerns . . 91
e. Diphacinone and its sodium salt Ecological Exposure and
Risk Characterization ............;........... 92
-------
(1) Diphacinone and its sodium salt Exposure and Risk to
Nontarget Terrestrial Animals 92
(2) Diphacinone and its sodium salt Exposure and Risk to
Nontarget Aquatic Animals 95
(3) Diphacinone and its sodium salt Endangered Species
Concerns . . . , 95
IV. RISK MANAGEMENT AND REREGISTRATTON DECISION ........... 97
A. Determination of Eligibility . 97
1. Eligibility Decision 98
2. Eligible and Ineligible Uses . . . 98
B. Regulatory Position 98
1. Summary of Risk Assessment Conclusions 98
a. Human Health Risk 98
(1) Dietary .........:...... s 98
(2) Residential and Occupational Risk 99
b. Risk to Household Pets ....,.' 101
c. Environmental Risk . . 101
(1) Environmental Fate 101
(2) Ecological Effects 101
2. Summary of Rodenticide Benefits . 102
3. Risk Mitigation Overview 103
a. Reducing Risk for Children and Household Pets 104
b. Incremental Risk Reduction 104
(1) Phase One: Short-Term Risk Mitigation Measures
, . . , . . . 105
(2) Phase Two: Long-Term Risk Reduction 107
c. Risk Mitigation Measures for Products Intended for
Occupational Use . 108
(1) Gloves 108
(2) Protective Eyewear and Inhalation Protection . . . 108
4. Endangered Species Statement . 109
V. ACTIONS REQUIRED OF REGISTRANTS 109
A. Manufacturing-Use Products 110
1. Additional Generic Data Requirements . 110
a. Brodifacoum 110
b. Bromadiolone 110
c. Bromethalin 110
d. Chlorophacinone 110
e. Diphacinone and its sodium salt Ill
2. Submission of Poison Control Centers Data Ill
B. End-Use Products ".'... . . 112
1. Formulation Changes - Indicator Dye and Bittering Agent .... 112
2. Stakeholder Meetings 112
-------
3. Tracking Powders Classified as Restricted Use ...... 112
4. Field Use Classified as Restricted Use . . 112
5. Field Uses of Chlorophacinone and Diphacinone and its sodium salts
...? ....... . v. . ...... .... .'. . . .. 112
6. Additional Product-Specific Data Requirements ........... 113
7. PPE/Engmeering Control Requirements for Pesticide Handlers
",- . '. ... .v.....\.. ........... us
a. Products Intended for Occupational Use ......:.... 113
(1) Formulation Specific PPE Requirements ...... 113
(2) Determining PPE Labeling Requirements for End-Use
Products 113
(3) Placement in Labeling -.". .... .114
b. Products Intended for Residential Use 114
8. Other End-Use Product Labeling Requirements ........... 114
a. All End-Use Products : 114
(1) Directions for Use 114
(2) First Aid (Statement of Practical Treatment) ... 116
(3) Note to Veterinarian .................... 116
(4) PR Notice 94-7 116
D. Existing Stocks 120
VI. APPENDICES ~. ..... ... . . ,..'.V. . . 121
APPENDIX A. Table of Use Patterns Subject to Reregistration ...... 122
APPENDIX B. Table of the Generic Data Requirements and Studies Used to
Make the Reregistration Decision . ... . . . . 141
APPENDIX C. Citations Considered to be Part of the Data Base Supporting
the Reregistration of the Rodenticide Cluster . 153
APPENDIX D. Generic Data Call-In ................. . . . . . 170
Attachment 1. Chemical Status Sheet . 189
Attachment 2. Generic DCI Response Forms Inserts (Form A) plus
Instructions 191
Attachment 3. Requirements Status and Registrants' Response Forms
Inserts (Form B) plus Instructions ...'....... 199
Attachment 4. List of Registrants) sent this DCI (Insert) 211
APPENDIX E. Product Specific Data Call-in 217
Attachment 1. Chemical Status Sheet . ................. 229
Attachment 2. Product Specific Data Call-in Response Forms (Form
A inserts) Plus Instructions ............... 230
Attachment 3. Product Specific Requirement Status and Registrant's
Response Forms (Form B inserts) and Instructions
-....'...-.. ... . . . ., .':-. ............. 237
a. Chlorphacinone ..'. 241
b. Diphacinone, and Salts 249
c. Brodifacoum 257
d. Bromadiplone ...........;.... 265
e. Bromethalin ...........:............ 273
-------
Attachment 4.
Attachment 5.
APPENDIX F.
EPA Batching of End-Use Products for Meeting Data
Requirements for Reregistration . 283
Cost Share, Data Compensation Forms, Confidential
Statement of Formula Form and Instructions ... 293
List of Available Related Documents 307
-------
Tables
Table 1 - Chemical Overview 2
Table 2 - Use Profile ....:.......,...... ... ....... ; ...'.'/.'.'.'. '.'/.'. ! ! 3
Table 3 - Regulatory History of Mammalian Toxicants Used as Baits and Tracking
Powders . . ............................. 8
Table 4 - Physical Chemistry Assessment ........... 9
Table 5 - Acute Toxicity Values of Technical Brodifacoum 10
Table 6 - Acute Toxicity Values of Brodifacoum Formulation Concentrate (0.25%) . . 12
Table 7 - Acute Toxicity Values for Bromadiolone . . . . . . 13
Table 8 - Acute Toxicity Values of Technical Bromethalin . 14
Table 9 - Acute Toxicity Values of Technical Chlorophacinone ; 15
Table 10 - Acute Toxicity Values of Technical Diphacinone 17
Table 11 - Dose Levels and Mortality in an Oral LDSO Study with Diphacinone 18
Table 12 - Dose Levels and Mortality in a Second Oral LDSO Study with Diphacinone
:... 19
Table 13 - Dose Levels and Mortality in a Dermal LDSO Study with Diphacinone ... .19
Table 14 - Prothrombin and Activated Partial Thromboplastin Times in a 21-Day
Subacute Dermal Study in Rabbits - Statistically Significant Findings 24
Table 15 - Prothrombin Time in Seconds in Rats Following a Single Dose of Diphacinone
....... - ...................:...-.-'. 26
Table 16 - Activated Partial Thromboplastin Time in Seconds in Rats Following a Single
Dose of Diphacinone . . . . . 27
Table 17 - Prothrombin Time in Seconds in Rats Following Repeated Doses of
Diphacinone 27
Table 18 - Activated Partial Thromboplastin Time in Seconds in Rats Following Repeated
Doses of Diphacinone . . 27
Table 19 - Prothrombin Time in the Preliminary Developmental Toxicity Range-Finding
Study in the Rabbit (Day 20)* . . . . ... .'." ..... . . . . . ....... 29
Table 20 - Prothrombin (PT) and Activated Partial Thromboplastin Times (APTT) in a
Preliminary Rat Developmental Toxicity Study . 32
Table 21 - Fetal and Litter Incidences of Treatment Related Effects in a Rat
Developmental Toxicity Study.... .32
Table 22 - Prothrombin (PT) and Activated Partial Thromboplastin Times (APTT) in a
Preliminary Rabbit Developmental Toxicity Study . 33
Table 23 - Kaolin Cephalin and Prothrombin Time in a Metabolism Study in Male Rats
...'.. "' ,. .... ... ............... 37
Table 24 - Percentage of radioactivity retained in the liver following single-dose
administration of 14C Brodifacoum . . . ........... 38
Table 25 - Mean blood concentration of chlorophacinone (in pg equivalents) following
oral administration of 1 mg chlorophacinone . . 40
Table 26 - Mean concentration of chlorophacinone (#g/g of organ) .... . . . ... . . . 41
Table 27 - Mean blood concentration of chlorophacinone (in jtg equivalents) following
three daily oral administrations of 1.43 mg chlorophacinone ..,:.- 41
Table 28 - Relative MOEs for the Chemicals in the Rodenticide Cluster and Zinc
Phosphide 47
Table 29 - Brodifacoum Avian Acute Oral Toxicity 57
-------
Table 30 - Brodifacoum Avian Subacute Dietary Toxicity . 57
Table 31 - Bromadiolone Avian Acute Oral Toxicity . . . 58
Table 32 - Bromadiolone Avian Subacute Dietary Toxicity ... 58
Table 33 -Bromethalin Avian Acute Oral Toxicity 59
Table 34 - Bromethalin Avian Subacute Dietary Toxicity 59
Table 35 - Chlorophacinone Avian Acute Oral Toxicity 59
Table 36 - Chlorophacinone Avian Subacute Dietary Toxicity ................. 60
Table 37 - Diphacinone and its sodium salt Avian Acute Oral Toxicity 60
Table 38 - Diphacinone and its sodium salt Avian Subacute Dietary Toxicity 61
Table 39 - Brodifacoum Mammalian Acute Oral Toxicity . . 61
Table 40 - Bromadiolone Mammalian Oral Toxicity 62
Table 41 - Bromethalin Mammalian Oral Toxicity . 62
Table 42 - Chlorophacinone Mammalian Oral Toxicity 63
Table 43 - Diphacinone and its sodium salt Mammalian Oral Toxicity 63
Table 44 - Brodifacoum Freshwater Fish Acute Toxicity '.....' 63
Table 45 - Bromadiolone Freshwater Fish Acute Toxicity 64
Table 46 - Bromethalin Freshwater Fish Acute Toxicity , , 64
Table 47 - Chlorophacinone Freshwater Fish Acute Toxicity 64
Table 48 - Diphacinone and its sodium salt Freshwater Fish Acute Toxicity 65
Table 49 - Brodifacoum Freshwater Invertebrate Acute Toxicity .............. 65
Table 50 - Bromadiolone Freshwater Invertebrate Acute Toxicity . 66
Table 51 - Bromethalin Freshwater Invertebrate Acute Toxicity 66
Table 52 - Chlorophacinone Freshwater Invertebrate Acute Toxicity 66
Table 53 - Diphacinone and its sodium salt Freshwater Invertebrate Acute Toxicity . . 67
Table 54 - Mammalian Secondary Toxicity . 67
Table 55 - Chlorophacinone Terrestrial and Simulated Field Tests 68
Table 56 - Diphacinone Avian and Mammalian Secondary Toxicity 69
Table 57 - Risk Presumptions for Terrestrial and Aquatic Organisms 79
Table 58 - USFWS 1993 Biological Opinion for Brodifacoum . 82
Table 59 - USFWS 1993 Biological Opinion for Bromadiolone 83
Table 60 - USFWS 1993 Biological Opinion for Bromethalin ... 85
Table 61 - EECs1 on Potential Avian and Mammalian Food Items After a Single Pesticide
Spray Application of 1 Ib a.i./A and a Chloriphacinone Orchard Spray of 0.2 Ib
a.i./A 86
Table 62 - Avian Acute RQs for a Single Ground Spray Application of Chlorophacinone
86
Table 63 - Avian (Granivore) Acute RQs (LDsos/day) for Chlorophacinone Food Baits
87
Table 64 - Avian (Granivore) Acute RQs For Chlorophacinone Food Baits 87
Table 65 - Aquatic FJECs and Acute RQs For Freshwater Organisms 90
Table 66 - USFWS 1993 Biological Opinion for Chlorophacinone .... 91
Table 67 - Acute Risk Presumptions for Birds 92
Table 68 - Avian (Granivore) Acute RQs (LD50s/day) 93
Table 69 - Avian (Granivore) Acute RQs For Diphacinone Food Baits 93
Table 70 - USFWS 1993 Biological Opinion for Diphacinone 96
Table 71 - Required Labeling Changes 117
-------
RODENTICIDE CLUSTER REREGlSTRAtlON ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biological and Economic Analysis Assessment
Frank Hernandez
William Gross
Economic Analysis Branch
Biological Analysis Branch
Environmental Fate and Effects Risk Assessment
Sharlene Matten
James Goodyear
William Erickson
Harry Craven . , .
Richard Mahler
Larry Liu/ ;
John Jordan
Health Effects Risk Assessment
Byron T. Backus ,
Thomas Campbell
John Redden
Whang Phang
John Leahy
Registration Support Risk Assessment
Daniel Peacock
Bill Jacobs
Risk Management '
Dennis Deziel ,
William Wooge
Registration Support Risk Assessment
Carol Glasgow
Debbie McCall
Science Analysis and Coordination Staff
Ecological Effects Branch
Ecological Effects Branch
Ecological Effects Branch .
Environmental Fate and Groundwater Branch
Environmental Fate and Groundwater Branch
Environmental Fate and Groundwater Branch
Toxicology Branch II '
Occupational and Residential Exposure Branch
Risk Characterization and Analysis Branch
Toxicology Branch II
Occupational and Residential Exposure Branch
Insecticide-Rodenticide Branch
Insecticide-Rodenticide Branch
Reregistration Branch I
Reregistration Branch I
Reregistration Support Branch
Registration Support Branch
-------
11
-------
GLOSSARY OF TERMS AND ABBREVIATIONS
x ' ' " -
ADI Acceptable Daily Intake. A now defunct term for reference dose (RfD).
AE Acid Equivalent . ,
a.i. , Active Ingredient . - -
ARC Anticipated Residue Contribution ""
CAS Chemical Abstracts Service .
CI Cation ,
CNS Central Nervous tSystem
CSF Confidential Statement of Formula
DFR Dislodgeable Foliar Residue
ORES Dietary Risk Evaluation System . ' ''
DWEL Drinking Water Equivalent Level (DWEL), The DWEL represents a medium specific (i.e.
drinking water) lifetime exposure at which adverse, non carcinogenic health effects" are not '
anticipated to occur. '
EEC Estimated Environmental Concentration. The estimated pesticide concentration in an
environment, such as a terrestrial ecosystem. -
ECSO Median Effective Concentration. The concentration at which 50% of an exposed test population
'is effected sublethally. , '
EP End-Use Product .
EPA U.S. Environmental Protection Agency
FAO/WHO Food and Agriculture Organization/World Health Organization
FDA Food and Drug Administration
FIFRA Federal .Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act . .,
FQPA Food .Quality Protection Act
FOB Functional Observation Battery
GLC Gas Liquid Chromatography
GM , Geometric Mean . ' -
GRAS Generally Recognized as Safe as Designated by FDA
HA Health Advisory (HA). The HA values are used as informal guidance to municipalities and other
organizations when emergency spills or contamination situations occur.
HOT Highest Dose Tested, ' . . ,
LC50 Median Lethal Concentration. A statistically derived concentration of a substance that can be
expected to cause, death in 50% of test animals. It is usually expressed as the weight of substance
per weight or volume of water, air or feed, e.g., mg/1, mg/kg or ppm.
LD50 Median Lethal Dose. A statistically derived single dose that can be expected to cause death in
50% of the test animals when administered by the route indicated (oral, dermal, inhalation). It is
expressed as a weight of substance per unit weight of animal, e.g., mg/kg.
' LD10 , Lethal Dose-low. Lowest Dose at which lethality occurs.
LEL Lowest Effect Level . ..
LOG Level of Concern ,
LOD Limit of Detection *
LOEL Lowest Observed Effect Level .
MATC Maximum Acceptable Toxicant Concentration
MCLG Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency to regulate
contaminants in drinking water under the Safe Drinking Water Act.
/ig/g ' Micrograms Per Gram .
mg/1 Milligrams Per Liter
MOE Margin of Exposure
MP Manufacturing-Use Product .
MPI Maximum Permissible Intake >
MRID Master Record Identification (number). EPA1 s system of recording and tracking studies
submitted.
Ill
-------
N/A
NOEC
NPDES
NOEL
NOAEL
OP
OPP
Pa
PADI
PAG
PAM
PCO
PHED
PHI
ppb
PPE
ppm
PRN
Q*,
RBC
RED
REI
RfD
RS
RUP
SLN
TC
TD
TEP
TGAI
TLC
TMRC
torr
WP
WPS
Not Applicable
No effect concentration
National Pollutant Discharge Elimination System
No Observed Effect Level
No Observed Adverse Effect Level
Organophosphate
Office of Pesticide Programs
Pascal, the pressure exerted by a force of one newton acting on an area of one square meter.
Provisional Acceptable Daily Intake
Pesticide Assessment Guideline
Pesticide Analytical Method
Pesticide Certified Operator
Pesticide Handler's Exposure Data
Preharvest Interval
Parts Per Billion
Personal Protective Equipment '
Parts Per Million .
Pesticide Registration Notice
The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
Red Blood Cell
Reregistration Eligibility Decision
Restricted Entry Interval
Reference Dose
Registration Standard
Restricted Use Pesticide
Special Local Need (Registrations Under Section 24 (c) of FIFRA)
Toxic Concentration. The concentration at which a substance produces a toxic effect.
Toxic Dose. The dose at which a substance produces a toxic effect.
Typical End-Use Product
Technical Grade Active Ingredient
Thin Layer Chromatography
Theoretical Maximum Residue Contribution "
A unit of pressure needed to support a column of mercury 1 mm high under standard conditions.
Micrograms per liter
Wettable Powder
Worker Protection Standard
IV
-------
ABSTRACT
The U. S. Environmental Protection Agency .(EPA) has completed its reregistration
eligibility decision of the pesticides brodifacoum, bromadiolone, chlorophacinone, diphacinone
and its sodium salt, bromethalin, and pival and its sodium salt. This decision includes a
cpmprehensive reassessment of the required target data and the use patterns of currently registered
products. These chemicals are rodenticides used in urban, suburban, and rural areas for the
control of commensal rodents. Chlorophacinone and diphacinone are also used in the field to
control a variety of vertebrate pests, mainly rodents but also jackrabbits (lagomorphs), moles
(insectivores), and mongoose (carnivores), With the exception of bromethalin, which is a
neurotoxin, the chemicals being reregistered in this decision document are anticoagulants. With
the exception of pival and its sodium salt, the Agency has concluded that the uses, as prescribed
in this document, with additional labeling requirements and a number of risk mitigation measures,
will not cause unreasonable risks to humans or the environment.
i * - " .
The Agency has determined that all uses of brodifacoum, bromethalin, and bromadiolone
are eligible for reregistration. .
The Agency has determined that all uses of chlorophacinone and diphacionone and its salt
are eligible for reregistration, with the exception of certain field bait uses. The Agency has
determined that field-bait uses containing .005% chlorophacinone and diphacionone and its salt
are eligible for reregistration.
The Agency has determined that field-bait uses 'containing more than .005%
chlorophacinone and diphacionone and its salt ar.e ineligible for reregistration. Field tests have
adequately demonstrated that products with lower-concentrations of these active ingredients are
. sufficiently efficacious for target pest species, and that the uses with higher concentrations have
the potential to cause unnecessary secondary poisonings to avian and mammalian consumers.
The EPA has determined that all uses of pival and its sodium salts are ineligible for
reregistration. Pival and its sodium salt was suspended by the Agency in December 1994 for
failure of the registrant, Motomco, Incorporated, to respond to the Agency's Data Call-in Notice
(DCI) and submit the required data to support the continued registration. In the future, EPA may
, seek cancellation of the registration for pival and its sodium salt.
ป . ' -
Rodenticides, when used as currently sold and marketed, are responsible for a number of
human incidents and accidental exposures each year. As with human exposures, EPA is concerned
about the increased risk posed to non-target domestic animals, as well as primary and secondary
risks to nontarget mammals and birds, from the use of rodenticides used. However, EPA also
. . ' . v ' ' - ' - -
-------
recognizes the important public health benefits of rodenticides. Specifically, the Agency
considered the benefits from rodent control relating to prevention of disease transmission,
property damage, and attacks on humans.
In order to address the risk concerns posed from the use of these products and still.
maintain the benefits afforded by their use, the Agency has developed a two-phased approach to
mitigatingjrisk. The first phase will put into place in short-term measures that will serve to
identify when an exposure has occurred, to lessen the amount of exposures, and monitor
exposures. The second phase will reduce exposures in,the long term. Ideally, the Agency would
have preferred to impose measures to immediately eliminate opportunities for exposures;
however, it recognizes that new technologies do not exist and must be developed to accomplish
this while still maintaining the efficacy of the product. The Agency has therefore developed this
phased approach to allow time for the development and testing of this new technology.
In addition, outside the scope of this RED process, the Agency is requiring similar risk
mitigation measures to the registrations of other rodenticide active ingredients such as zinc
phosphide, warfarin and salts, difethialone, vitamin D-3, and red squill and, if necessary,
registrations of new rodenticide active ingredients.
The Agency recently became aware of incident data which suggests that there may be a
potential incident problem specifically involving the active ingredient brodifacoum. At this time
the Agency is reviewingjthe data; no final conclusions have been reached. Additionally, through
the "Notice of Availability" for this document, the Agency requests state incident data on all
, rodenticides to better understand the extent of this potential problem. After review, the Agency
may impose additional restrictions on the use of brodifacoum.
Phase One: Short-Term Risk Mitigation Measures
I ' ,: 1 ' -1 !
(A) Indicator Dye and Bittering Agent
All registrants of rodenticides, other than those with products used exclusively at
agricultural sites, must incorporate an indicator dye into their formulations. The dye is intended
to help identify whether a child or household pet has actually consumed a rodenticide by dying
, their mouth and/or hands a bright color. EPA believes the dye will play an important role in
identifying when an exposure has occurred, thereby helping to determine if treatment is required.
Typically, it is very difficult for parents and guardians of children and pet owners to discern
whether an exposure or ingestion has actually occurred, which may lead to unnecessary treatment
at a medical facility as a precautionary measure. In turn, the Agency believes this measure will
also enable parents and guardians of children and pet owners to seek medical or veterinarian
attention sooner rather than later and avoid a serious medical episode. EPA recognizes that many
of the formulations currently contain a dye. All registrants may present data demonstrating that
the current dye meets the intent of this requirement. <
All registrants of rodenticides, other than those with products used exclusively at
agricultural sites, must incorporate a bittering agent into their formulations to make the bait less
palatable to humans. EPA believes that the bittering agent may cause some children to expel the
vi
-------
bait if placed in the mouth. The Agency is fully aware that children younger than one year old
do not have fully formed taste buds and may not be fully protected by this measure. However,
this measure should prevent some exposures to children older than one year of age. Likewise,
the EPA is also aware that this measure may not affect exposures to non-target household animals'.
(B) Improved Labeling Requirements
EPA is requiring a number- of label revisions to rodenticide registrations. These
requirements are set forth in Section V of this RED document and are in addition to those in PR
Notice 94-7 that have already been implemented.
Labels which currently allow placement of .rat and mouse baits "in and around buildings"
must be amended to "indoors and against the outside walls of buildings." Rat and mouse bait
placements will be allowed "around" buildings only if registrants demonstrate from secondary
toxicity testing that secondary risks to birds and mammals are likely to be minimal.
- - , . j -.-''ป'
(C) Annual Submission of American Association of Poison Control Centers (AAPCC)
Data
Under the authority of FIFRA section 3(c)(2)(B), the Agency is requiring registrants of
rodenticides subject to this RED document, to submit to the Agency annual American Association
of Poison Control Centers' (AAPCC) data. The Agency is requiring AAPCC data for the years
1999 through 2009. Registrants are encouraged to share the cost of generating data, whenever
appropriate. If needed, the Agency may ask registrants of rodenticides for additional annual
submission of AAPCC data. These data will enable the Agency to determine whether the
imposed risk mitigation measures are reducing incidents/exposures to humans, in particular
children. AAPCC data obtained by the Agency for 1995 and 1996 will serve as baseline data.
(D) Restricted Use Classification for Tracking Powders
EPA has determined that the use of these chemicals as tracking powders in and around
residences, schools, recreation areas, and other places that children may frequent, pose a
significant risk to children, household pets, and non-target animals. EPA believes that children
and pets can easily come in contact with rodenticides used as tracking powders simply based on
their use patterns and use locations. To protect children and non-target animals from exposure,
all products formulated as tracking powders must must remain classified and labeled as restricted
use because of acute toxicity and undue secondary risk to non-target species. Certified applicators
receive training on the importance of following label directions and overall application, and,'
therefore are more likely to apply the product correctly. Moreover, tracking powder products
must bear a strong precautionary statement and new restrictions limiting placement of powder to
locations not accessible to children, household pets, and non-target animals.
EPA is also concerned about the potential exposure (inhalation and dermal) to the certified
applicators of these types of product formulations. Due to the low inhalation LCSO value and the-
possibility of users inhaling or. ingesting powders during pouring and application, EPA is limiting
use of the powder formulations to .use by certified applicators, EPA is requiring protective
vu
-------
eyewear and dust/mist respirators for such users in addition to other personal protective
equipment.
(E) Restricted Use for Field Products
All products labeled for field uses, except for those limited to manual underground baiting,
must be reclassified and relabeled as restricted use because of acute toxicity and high potential for
primary and secondary risks to nontarget mammals and birds.
Phase Two: Long-Term Risk Reduction
The Agency believes that the required risk mitigation measures outlined in Phase One
should be followed by further exposure/risk reduction measures for rodenticides. EPA is also
aware that a safer technology, which is efficacious and equally effective to eliminate human and
household pet exposures may not currently exist. However, the Agency will require the
development of and movement into a new, safer rodenticide use technology. The EPA is
convinced that development of this technology can be achieved. Therefore, Phase Two of the
Agency's risk mitigation approach, is the requirement to move rodenticides into a safer use
technology. To achieve this end, within 120 days of the issuance of the REDs, the Agency will
form a Stakeholder group and hold a series of meetings to discuss means of significantly reducing
exposures to children and pets. The Stakeholder group will consist of members from industry,,
states, CDC, CPSC, AAPCC, rodent control experts, members of environmental groups, the
medical community, and the veterinary community.
The Agency will conclude the Stakeholder process within 9 months from the issuance of
the REDs. The Agency expects, at the conclusion of this process, to have a recommendation on
how to further mitigate risk to children and household pets and a implementation plan to achieve
significant risk reduction.
Risk Mitigation Measures for Products Intended for Occupational Use
The Agency has determined that all labels for occupational use products require
commercial handlers to wear gloves while handling these rodenticide chemicals not already
contained in place packs to reduce dermal exposure unless registrants submit data which indicate
there is no dermal exposure. The Agency has determined that occupational handlers (commercial
applicators) must wear protective eyewear, and a dust mask/mist respirator when handling non-
parafinized formulations of these chemicals such as meal or grain-based baits, unless these
formulations are contained in place packs or the registrants can determine via data that there is
no inhalation exposure. In addition, the Agency is requiring all occupational handlers who handle
powder formulations or any other non-parafinized formulation of chlorophacinone to wear a
dust/mist respirator and protective eyewear during open pouring and application unless registrants
submit data indicating there is no inhalation exposure.
VUL
-------
i. INTRODUCTION :
. In 1988, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)~was amended
to accelerate the reregistration of products witH active ingredients registered prior to November
1, 1984. The amended Act provides a schedule for the reregistration process to be completed in
nine years. There are five phases to the reregistration process. The first four phases of the process
focus on identification of data requirements to support the reregistration of an active ingredient
and the. generation and submission of data to fulfill the requirements. The fifth phase is a review
by the U.S. Environmental Protection Agency (referred to as "the Agency") of all data submitted
to support reregistration.
FIFRA Section 4(g)(2)(A) states that in Phase 5 "the Administrator shall determine
whether pesticides containing such active ingredient are eligible for reregistration" before calling
in data on products and either reregistering products or taking "other appropriate regulatory
action." Thus, reregistration involves a thorough review of the scientific data base underlying a
pesticide's registration. The purpose of the Agency's review is to reassess the potential hazards
arising from the currently registered uses of the pesticide; to determine the need for additional ,
data on health and environmental effects; and to determine whether the pesticide meets the "no
unreasonable adverse effects" criterion of FIFRA.
. On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) (Public Law 104-
170) was signed Into law. FQPA amends both the Federal Food, Drug, and Cosmetic Act
" (FFDCA), 21 U.S.C. 301 et seq, and the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA), 7 U.S.C. 136 et seq. The FQPA amendments went into effect immediately. Among
other things, FQPA amended the FFDCA by establishing a new safety standard for the
establishment of tolerances. The FQPA does not, however, amend any of the existing
reregistration deadlines set forth in Sec. 4 of FIFRA. Thus, EPA.is embarking on an intensive
process, including consultation with registrants, States, and other interested stakeholders, to make
decisions on the new policies and procedures that will be appropriate as a result of enactment of
FQPA. This process will include a more in-depth analysis of the new safety standard and how
it should be applied to both food and non-food pesticide applications. However, in light of the
statutory deadlines with respect to reregistration, the Agency will continue its ongoing
reregistration program while it continues to determine how best to implement FQPA.
This document presents the Agency's decision regarding the reregistration eligibility of
the registered uses of brodifacoum, bromadiolone, bromethalin, chlorophacinone, diphacinone
and its. sodium salt, and pival and its sodium salt, The document consists of six sections. Section
I is the.introduction. Section n describes these chemicals' uses, data- requirements and regulatory
history. Section m discusses the concerns regarding human health and environmental assessment
based on the data available to the Agency. Section IV presents the reregistration decision for
brodifacoum, bromadiolone, chlorophacinone, diphacinone and its sodium salt, bromethalin, and .
pival and its sodium salt. Section V discusses the reregistration requirements for brodifacoum,
bromadiolone, chlorophacinone, diphacinone and its sodium salt, and bromethalin. Finally,
Section VI contains the Appendices supporting this Reregistration Eligibility Decision. Additional
details concerning the Agency's review of applicable data are available on request.
-------
H. CASE OVERVIEW
A. Chemical Overview
Table 1 - Chemical Overview
Common/
Case Name
Brodifacoum
Bromadiolone
BromclhaJin
Chlorophacinone
Diptueinonc
Pival
Reiegtsteation
2755
2760
2765
2100
2205
2810
OPP
Chemical
Code :
112701
112001
112802
67707
67701
67703
Chemical Name i
3-[3-(4'-bromo[l ,1 'biphenyl]-4yl)-
1,2,3 ,4-tetrahydro-l -napthalenyl]-
4-hydroxy-2H-l-benzopyran-2-one
3-[3-(4'-Bromo[l , 1 '-biphenyl]-4-
yl)-3-hydroxy-l-phenylpropyl]-4-
hydroxy-2H-l-benzopyran-2-one
N-Methyl-2,4-dinitro-N(2,4,5-
tribromophenyl)-6(trifluoromethyl)
benzenamine
2-[(4-Chlorophenyl)phenyl acetylj-
IH-indene-l ,3-(2H)-dione
2-(diphenylacetyl)-l ,3-indanedione
2-(trimethyacetyl)-l ,3-indanedione
CAS
Registry #
56073-10-0
28772-56-7
63333-35-7
3691-35-8
82-66-6
83-26-1
Empirical
Formula
ซ*,
CmH^BiOt
Cl3H,Br3F3N3O
4
m
ซA'
C14HU03
Structural Formula
o6/
OH **y^ OH S~\ /=\
>YV**tO~w*
%cP^
Cl
H
ks/^ir 8>^
0
0"
MaJUSactuier
Zenicjt;
Bell Laboratories -
Lipha; -
Bell Laboratories
PM Resources.
Lipha
*
Bell laboratories;
HACCO, Inc.
Motoinco
B. Use Profile
The following table (Table 2) lists the sites, pests, formulations (as applied), and
application methods for rodenticides covered by this RED document. These chemicals are for the
control of mammal pests, particularly commensal rats and mice but also a variety of field rodents
[note: commensal rodents are Norway rat, roof rat, and house mouse].
-------
Table 2 - Use Profile
iCategory
Sites
Jn/ Around Buildings
Inside Transport/Cargo Vehicles
Sewers
Landfills
Terrestrial Nonfood
Forestry Plantings
Nurseries
Levees/Ditch banks
Orchards (dormant or nonbearing)
Small Grains
Small Fruits (dormant or
nonbearing)
Terrestrial food Crops (bait boxes)
Terrestrial Food Crops
Artichokes
Aquatic, Non-Food (bait boxes)
.Pests
Norway Rat
Roof Rat
House Mice
White-footed Mice
Meadow Mice/Voles
Ground Squirrels
Chipmunks
Jackrabbits
Cottontail Rabbits -
Pocket Gophers
Cotton Rats
Wood Rats
Rice Rats
Florida Water Rat
Muskrat
Polynesian Rat -
Moles
Mongoose
FORMULATIONS: (as applied)
Solid Baits
Liquid Sprays
Liquid Baits (salt)
Tracking Powders
APPHC ATION METHODS
Hand Placement
Hand Broadcast (field use)
Ground Broadcast (field use)
Aerial Broadcast' (field use)
Name of Rodenticid&
Pival
X
Plvat
X
X
X
Pival
X
X
Pivat
X
1
DiphaoJaoneor it&Sodfam Salt
X
X
. X ,
X
X
X
X
X
* X
X
X
'' x
X
Diphacinone or its; Sodium Salt
X
X
.X
X
X
X
'X
X
X
X.
X
X
X .
X ,
'- x
X .
- . ,. '
X
Diphacinone or its Sod'juw Salt
X
X
X
Diphacinone or its Sodium Salt
X
-' .x ' .'
.X
X
C^orophachione
X.
X
X
X
. > X
X
X
X
X
X
X
Chfarophaclnone
X
X
X
X
X
X
X
X -
X
- X
X
x .
X
CWoropftacittone
X
x ,.
X
Chlorophacinone. ;
X
X
X
,. X
Brodifacoum
X
X
X
. . ^
Brodifacoum :
X
X
X
Brodifacotim; ;
X
Brodifacoum :
X
,
Bromadiolonซ
X
X
X .
^
Bromadiolone
X
' , X
X
-;- .
-
Brflmadioloae
X
Bromadiolone
X
Bromethalua.
X
X
X '
Bromethalia
X
X
X
-
-
Bromefibalift
X
Bramethalia
X
1. Brodifacoum Summary of Use Patterns and Formulations
Brodifacoum (3-[3-(4-bromo[l,l-biphenyl]4-yl)-l,2,3,4-tetra-hydro-l-napthalenyl]4-
hydroxy-2H-l-benzophyran-2-one) is a rodent control agent for use against commensal rats and
mice only. It is an anticoagulant and is formulated as meal bait, paraffinized pellets, rat and
-------
mouse bait ready-to-use place packs, and paraffin blocks. All end-use products contain 0.005
percent active ingredient.
Brodifacoum is currently registered for the control of rats and mice in and around farm
structures, households and domestic dwellings, uncultivated agricultural and non-agricultural.
areas, inside transport vehicles, commercial transportation facilities, industrial areas, sewage
systems, aircraft, ships, boats, railway cars, and food processing, handling, and storage areas and
facilities. Application may be made as frequently as is necessary. Only general-use brodifacoum
products are currently registered. ,
Baits and bait packs are placed at 15 to 30 foot intervals for rats and 8 to 12 foot intervals
for mice. When bait blocks are used in sewage systems, wire is used to secure blocks above the
high water mark. The maximum rates of application are 16 ounces of product per 15 foot interval.
for controlling commensal rats and 2 ounces of bait per 8 to 12 foot interval for controlling house
mice. According to labels, all baits are to be placed out of the reach of children, pets, domestic
animals, and nontarget wildlife, or in tamper-resistant bait stations. Tamper-resistant bait stations
must be resistant to destruction by dogs and by children under 6 years of age, and must be used.
in a manner that prevents children from reaching into bait compartments and obtaining the bait.
If the bait can be shaken from stations when they are lifted, stations must be secured or otherwise
immobilized. Baits may be loaded into bait stations by hand (place packs, cakes, blocks, and.
slabs), or by using a scoop for loose baits (meal baits, grain baits) and pellets.
2. Bromadiolone Summary of Use Patterns and Formulations
Bromadiolone (3-(3-(4'-bromo-(l,l'-biphenyl)-4-yl)-3-hydroxy-l-phenylpropyl)-4-
hydroxy-2H-l-benzopyran-2-one) is a rodent control agent for rats and mice in and around
buildings, inside transport vehicles and sewers. It acts as an anticoagulant and is formulated as
meal bait, paraffinized pellets, rat and mouse bait ready-to-use place packs, and paraffin blocks,
(all formulations contain 0.005 percent a.i.).
Baits and bait packs are placed at 15 foot intervals for rats and 8 foot intervals for mice.
When bait blocks are used in sewage systems, wire is used to secure blocks above the high water
mark. The maximum rates of application are 16 oz per 15 ft interval for controlling commensal.
rats and 2 oz of bait per 8 ft interval for house mice. According to labels, all baits are to be
placed out of the reach of children, pets, domestic animals and nontarget wildlife, or in tamper-
resistant bait stations. Bait stations must be resistant to destruction by dogs and by children under
6 years of age, and must be used in a manner that prevents children from reaching into bait
compartments and obtaining bait. If the bait can be shaken from stations when they are lifted,
stations must be secured or otherwise immobilized.
3. Bromethalin Summary of Use Patterns and Formulations
Bromethalin (N-methyl-2,4-dinitro-N-(2,4,6-tribromophenyl)-6-(trifluoromethyl)
benzenamine) is a rodent control agent for use against roof rats, Norway rats, and house mice in
and around buildings and in transport vehicles. It is a single-dose poison that blocks nerve
transmissions. Bromethalin is formulated as paraffinized blocks, meal bait, "all-weather bait,"
bait pellets, bait cups, place packs, bait packs, rat pellets, mouse pellets, and "mouse poison bait
-------
stations." All products are 0.01 percent,a.i., with the exception of one, which is 0.005 percent
active ingredient. . .'..;, ,- . --
Bromethalin is currently registered for the control of commensal rats and mice in and
around sewers, homes, industrial and agricultural buildings, and similar man-made structures.
It may also be used in alleys located in urban areas, inside transport/cargo vehicles such as ships,
trains, and aircraft, and in and around related port or terminal buildings. Baits may be placed in
rodent burrows. Placement of bromethalin formulated as pellets or meal baits is prohibited in
sewers. Baits are not to be applied to water or areas where surface water is present, or where
mere is the possibility of contaminating food or surfaces that come in direct contact with food.
Applications may be made as frequently as"necessary. At this time the Agency is aware of only
general-use bromethalin products.
The maximum application rate is 8 ounces of bait per 15 foot interval for controlling
commensal rats and 3 ounces of bait per 8-foot interval for controlling house mice. Several labels
recommend baiting rodent burrows. When baiting rodent burrows, labels specify inserting bait
into the burrow far enough so only a person who knows the bait is there would be likely to see
it. . - . ' ' . ' . ' ':.'":'"'-'-
Bromethalin product labels specify, that baits are to be applied in locations out of the reach
of children, pets, domestic animals and non-target wildlife, or in tamper-resistant bait stations.
Bait stations must be resistant to destruction by dogs and by children under six years of age, and
must be used in a manner that prevents children from reaching into bait compartments and
obtaining bait. If bait can be shaken from stations when they are lifted, stations must be secured
or otherwise immobilized.
4. Chlorophacinone Summary of Use Patterns and Formulations
Chlorophacinone 2-[(p-chlorophenyl)phenylacetyl)] 1,3-indandione is a vertebrate control
agent used to control a variety of vertebrate pests, mainly rodents, but also jaekrabbits
(lagomorphs), and moles (insectivores). It is an anticoagulant and is formulated as tracking
powder, (0.2% a.i.) as loose-grain bait, paraffinized pellets, rat and mouse bait ready-to-use place
packs, and paraffin blocks. Baits are mostly formulated as 0.005 % active ingredient, but some
,0.01% active ingredient baits are registered: Chlorophacinone is currently registered for the
control of rodents in and around buildings, households and domestic dwellings, uncultivated
agricultural and non-agricultural areas, commercial transportation facilities; industrial areas, and
food processing; handling, and storage areas and facilities. Baits are applied as frequently as
needed only for commenal rats and mice; most field uses have a limited number of applications.
Both general use and restricted use Chlorophacinone products are currently registered.
For Chlorophacinone, as well as all the rodenticides discussed in this RED, baits and bait
packs are placed at 15 to 30 foot intervals for rats and 8 to 12 foot intervals for mice. The rate
of application is 16 ounces of bait per 15 foot interval for controlling commensal rats and 2
ounces of bait per 8 foot interval for controlling housemice. According to labels, all baits are to
-------
be placed out of the reach of children, pets, domestic animals and nontarget wildlife, or in tamper
resistant bait stations. Bait stations must be resistant to destruction by dogs and by children under
6 years of age, and must be used in a manner that prevents children from reaching into bait
compartments and obtaining bait. If bait can be shaken from stations when they are lifted, stations
must be secured or otherwise immobilized. Baits may be loaded into bait station by hand (place
packs, cakes, blocks, and slabs), or by using a scoop for loose baits (meal baits, grain baits) and.
pellets.
Twenty states currently have special local needs (SLNs) registrations for field uses of
Chlorophacinone. Most SLNs are for control of meadow and/or pine voles in orchards (17
states), mainly dormant fruit orchards, or for control of ground squirrels (8- states). Most
products are food baits (pellets or treated whole grains), but a spray concentrate exists for vole
control (4 states). Other SLNs include control of moles in Oregon and Washington; jackrabbits
in Oregon and California; and pocket gophers, ground squirrels, deer mice, chipmunks, muskrats,
woodrats, and commensal rats and mice in California.
5. Diphacinone Summary of Use Patterns and Formulations
Diphacinone and salt 2-(diphenylacetyl)-l,3-Indandione products are formulated
predominantly as 0.005% a.i. food baits (loose bait, feeder boxes, place packs, or paraffinized
bait blocks) for control of commensal rats (Norway rat, roof rat) and mice (house mouse). Food
baits also are registered for controlling ground squirrels and pocket gophers. One product is
registered as a tracking powder (0.2% a.i.) for control of rats and mice indoors and at burrows
located along the periphery of buildings. Because Diphacinone salt is highly soluble, it is also
used to prepare water baits for indoor control of rats and mice. Use sites for rat and mouse food
baits are predominantly in and around buildings and similar man-made structures. Some labels
include sewers or other wet or damp sites such as dumps, irrigation ditches, along fences, gullies,
and other such areas. Ground squirrels can be baited in bait stations placed in or near levee or
ditch banks, around farm .buildings, along fence lines, in orchards, in or near crops, and in
noncrop areas. Pocket gophers can be baited in underground burrow systems located in
rangeland, cropland, forest, and noncrop areas.
Twenty-three states currently have one or more special local needs (SLNs) registrations
, for field uses of Diphacinone. Most SLNs are for control of meadow and/or pine voles in
dormant or non-bearing orchards and tree plantations or for control of ground squirrels. Other
SLNs target meadow voles around perimeters of small grain crops in Washington and Idaho,
commensal rats, cotton rats, rice rats, and Florida water rats in noncrop areas adjacent to crop
fields in Florida, mongoose and commensal rats, including the Polynesian rat, in forests, offshore
islands, and other noncrop outdoor areas in Hawaii, and deer mice, jackrabbits, chipmunks,
muskrats, woodrats, voles, and commensal rats and mice in California.
C. Estimated Usage of Pesticide
The total annual usage of the rodenticides included in this RED is estimated to have been
about 250,000 Ibs. of active ingredient over the last few years [Note: usage data based on
proprietary information].
-------
Pest control operators (PCOs) use rodenticides primarily to control mice and rats in
residential, industrial and institutional buildings.:, The majority of PCOs use single dose
anticoagulants. Brodifacoum and bromadiolone-based products account for virtually all sales
of single dose anticoagulants. \ '
According to proprietary sources, approximately 60 percent of total rodenticides used by
PCOs are for the commercial (non-residential) segment of the market. Residential applications
account for approximately 40%. Local health departments contract PCOs, who primarily use
anticoagulant rodenticides like brodifacoum, bromadiolone, chlorophacinone and diphacinone.
Over the past few years, the single dose anticoagulant brodifacoum represented about 30
percent of total pounds of rodenticide active ingredient. Bromadiolone ranked second with about
20 percent of the rodenticide market. Multiple-dose anticoagulants chlorophacinone and
diphacinone, and the acute poison bromethalin accounted for another 20 percent market share.
D. Data Requirements
Appendix B includes all data requirements identified by the Agency for currently
registered uses needed to support reregistration.
E. Regulatory History
The Agency's predecessor, the U.S. Department of Agriculture (USDA), first regulated
vertebrate control agents after Congress passed FIFRA in 1947. During the initial year of
regulation, the USDA registered the four mammalian poisons: strychnine, strychnine sulfate, zinc
phosphide and red squill. Two of these chemicals are still registered 50 years later, but with
several restrictions. -
This Reregistration Eligibility Decision (RED) covers the neurotoxin bromethalin and five
anticoagulant active ingredients (brodifacoum, bromethalin, bromadiolone, chlorophacinone and
diphacinone and its sodium salt) applied as baits or tracking powders to control small mammals,
such as rodents. This RED covers 243 of the currently registered 406 products, including Section
3 and 24(c) used to control vertebrate pests by baits and tracking powders. However, decisions
, made in this RED may impact many of the remaining 182 vertebrate control products, which were
the subject of past REDs (e.g., warfarin arid its sodium salt, strychnine and strychnine sulfate),
or those that will be the subject of future reregistrations (e.g., difethialone, zinc phosphide,
cholecalciferol/Vitamin D-3).
The following table (Table 3) includes all active ingredients with use patterns similar to
those chemicals covered by this RED document and, those active ingredients (e.g., fumarin and
its sodium salt) that are no longer registered.
Table 3 includes the name of each active ingredient grouped under "Anticoagulant
Rodenticides" or "Other Rodenticides". Also, the table groups the anticoagulants by1 structural
similarity and indicates which groups are considered to be "multiple-dose" or "single-dose"
toxicants. Multiple-dose anticoagulants require repeated feedings over several days to Mil, but
, ' 7 .'"
-------
single-dose ones typically require only a single-day's feeding. Brodifacoum and bromadiolone
are considered "second-generation" anticoagulants because they are capable of killing rats that are
resistant to warfarin, the original "first generation" anticoagulant rodenticide, which was
registered in 1950.
Table 3 also lists the year of first registration and the current numbers of interstate (section
3 of FIFRA) and intrastate (section 24(c)) products.
Table 3 - Regulatory History of Mammalian Toxicants Used as Baits and Tracking Powders.
Tjhe names of active ingredients covered by this RED are bold.
Name of Active Ingredient/Type of Rodenticide
Year First
Registered
Number of Products
SecS
Sec24(c)
I, ANTICOAGULANT RQDBNTICIDES
A. Type I, 4-
hydroxycoumarin -
Multiple-Dose
B. Type I, 1,3
indandione -
Multiple-Dose
C. Type H, 1,3
indandione -
Multiple-Dose
D. Type n, 4-
hydroxycoumarin -
Single-Dose
1. Warfarin
2. Sodium Salt of Warfarin
3. Fumarin
4. Sodium Salt of Fumarin
1. Pival
2. Sodium Salt of Pival
3. Calcium Salt of Pival
4. PMP
5. Calcium Salt of PMP
1. Diphacinone
2. Sodium Salt of Diphacinone
3. Chlorophacinone
1 . Brodifacoum
2. Bromadiolone
3. Difethialone
1950
1954
1954
1958
1953
1954
1967
1962
1963 '
1960
1962
1971
1979
1980
1995
40
1
0
0
4
1
0
0
0
61
5
16
32
27-
6
0
0
0
0
0
0
0
0
0
40
0
43
0
0
0
U OTHER RODBNtrCIDES , ' '
A. Single-Dose
B. Multiple-Dose
1. Strychnine
2. Strychnine Sulfate
3. Red Squill (Scilliroside)
4. Zinc Phosphide
5. Bromoethalin
1. Cholecalciferol (Vitamin D-3)
1947
1947
1947
1947
1984
1984
39
0
0
40
19
4
6
0
0
20
o
1
-------
'I-
03
Cfl
0)
en
0)
U
1
OO
^
;P
i
i
S
"rt
1
3
t
Q
ง
Ghlorophacil
is
Bromethali
Bromadiolone
e
i
pa
|
1
"5
a
u
I
1
o
1
-
'ง'
in
t--
1
CN
^5
s.
a
f
1
""3$
ง
p
5
t-
VO
i;
s
00
1
1
>ง
o ;
^
JS
Cu
0
1
1
%
, Pale Yello
rs
White Crysti
S
1
1
U
:
1
o-
i
i
<3
13
s
u
o
fi
crocrystalline
Is.
r\
0
Powder at 25
-, Powdered Solid .
CO
1
o
1
nl
I
a-
o
1
Q
)t Reported
ฃ
s
1
Not Availab
Odorless
-
"S
.ซ
^
J
'
Q
U
0 ,
ง
~>
o
,r
o
o
OO
U
o
oo
o\
i
" S
R CM
"O '
ฃ
i
6
1
1
oo
1
.8
"ฃb
0
O
O
.S
00
S
o
-H
o\
SO
ป 1.5164g/ml
i.
i
' \ *' ' '
t
Q
-. f ' '
Q
"^oit-oo^ ^cs**
OX0oOov"^1~''~'O
a
rt .
r^ O (*
iisllllil
;,
' - !
Q
.','-
' - i 222
S* in tn c<-i
^3 CN ^^ O\
IS ^^ t*- ->o
B , . .
of = ' a> 1
ง > .2 " S
ง ซซ ^t O O CM' O O CM t^
ฐฐ CM o o , r- S en en CM
000-0000 VI CM 00
a;22 -.a . .
a ' ฎ ซ>
% -S =2 _
f 1
1 "1
'
<
' .
" ,
1
' &
o
.1
Q
1
1
1 .
i
Not Applicable/Very Low
Water Solubility
S
'O
S'
'*
X
I
o
i
ง
a
1.
ii
e?
00
S
II
1
CL,
'$
O ^
00 II
Vo?
*
II
O*
in
oo
:
Vi
ง
a
iBiiili
KSSBSSSSSBSSS
f
i
i Q
2 u
*" o
99%degradable)
p
S ''
ฃ
o
1
: i.
GO
vi
-------
B. Human Health Assessment
1. Toxicology Assessment
The lexicological data bases for, brodifacoum, bromadiolone, chlorophacinone,
diphacinone and its sodium salt, and bromethalin are adequate and will support reregistration
eligibility.
a. Acute Toxicity
(1) Brodifacoum Acute Toxicity
Results of the acute toxicity studies conducted with technical brodifacoum are summarized
below in Table 5:
Table 5 - Acute Toxicity Values of Technical Brodifacoum
Route
Oral
Dermal
Inhalation
Eye Irritation*
Skin Irritation*
Dermal
Sensitization*'b
Species
Rat
Rabbit
Rat
Rabbit
Rabbit
Guinea
Pig
Results
LD50 (M) = 0.418 mg/kg LD50 (F) = 0.561 mg/kg
LDSO (M) = 5.21 mg/kg LDSO (F) = 3.16 mg/kg
LCSO (M) = 4.86 Mg/L LC50 (F) = 3.05 /ig/L
Some minor eye irritation, clearing by day 7.
Unlikely to cause anything more than mild irritation; the high
toxicity (note the dermal LD50 values above) precludes necessity
for testing the technical for dermal irritation potential.
Non sensitizer
MRID
42687501
42232101
43110501
66938
None
None
Toxicity
Category
I
I
I
m
-
N/A
* Not required for TGAI, however, presented here for informational purposes.
b Conducted on the 0.25% Brodifacoum Formulation Concentrate; see below.
In an oral LD50 study in which technical brodifacoum (96.1%) was administered as a.
suspension in polyethylene glycol to 300 rats, there were no mortalities or signs of toxicity in.
males or females at 0.25 mg/kg, nor in males at 0.35 mg/kg (females were not tested at this dose
1 level). However", 5/5 males and 1/5 females died following dosage at 0.5 mg/kg, and 5/5 females
died following dosage at 0.75 mg/kg (males were not tested at this dose level). Signs of toxicity
at 0.5 and 0.75 mg/kg included pallor, bleeding from the nose and/or rectum and/or other sites.
Deaths occurred in the period from 3-8 days after dosing. Post mortem examination of those
animals that died or were sacrificed in extremis and/or showed signs of bleeding, revealed the
presence of free or clotted blood in the abdominal and/or thoracic cavity. Discoloration or pallor
of a number of organs was also observed. These findings are consistent with the known
anticoagulant activity of brodifacoum. The LD50 is calculated to be 0.418 mg/kg for males (95%
confidence interval between 0.35 and 0.5 mg/kg) and 0.561 mg/kg for females (95% confidence
interval 0.472-0.667 mg/kg). .These results place brodifacoum in Toxicity Category I (MRID
42687501) by the oral exposure route.
10
-------
In a dermal LD50 study with rabbits, brodifacoum technical (95.6%) was applied as a
suspension in corn oil (500 mg/kg), olive oil (10 rag/kg), or polyethylene glycol 600 (1 mg/kg),
with 24-hour occluded dermal exposure. At 500 mg/kg, all the males were euthanized in extremis
on days 5-6, and all females between days 5 and 8. At 10 mg/kg, 4/5 males were found dead or
were euthanized in extremis between days 7 and 11, and 5/5 females between days 6 and 8. The
animals that died or were euthanized showed signs of extreme toxicity consistent with
anticoagulant activity (pallor, bleeding/bruising, breathing abnormalities) immediately prior to
death. There were practically no signs of skin irritation on any of the animals. The dermal LD56
of brodifacoum technical was calculated to be 5.21 mg/kg (95% confidence interval 1.95-13.8
mg/kg) for males, and 3.16 mg/kg (95% a.i. l.OQ-10.00 mg/kg) for females. These results place
technical brodifacoum in toxicity category I (MRID 42232101) in terms of dermal toxicity
potential. . . -.
In an inhalation LC50 study in rats, groups of young adult Wistar-derived rats, 5/sex, were:
exposed (nose only) for 4 hours to aerosols of brodifacoum (96.1% a.i.) generated from an
acetone solution. The mean paniculate concentrations were 0.82, 1.88, or 4.96 jtg/L;
corresponding brodifacoum concentrations were 0.69, 1.72 or 4.40 /wg/L. The mass median
diameters were 0.80, 0.89 and 0.68 jon, and the geometric standard deviations were 3.09, 1.91
and 2.54, respectively. Animals were observed for 14 days after exposure. Mortalities
(accompanied by symptoms consistent with anticoagulant activity) occurred on days 4-6 in 3/5
males and 5/5 females exposed to the highest concentration (4.96 /tg/L). The inhalation LC50 for
males = 4.86 jKg/L (based on paniculate concentration)^ and for females = 3.05 pcg/L.
Brodifacoum technical (96.1%) is in toxicity category I (inhalation LCSO at or below 50 jttg/L)
based on the LC5o values in both sexes (MRID 43110501).
Jn an eye irritation study in rabbits, aliquots of 100 mg technical brodifacoum (92.5%)
were instilled in the conjunctiva! sac of the left eye in each of 9 New Zealand white rabbits.
Three of the rabbit eyes were irrigated for one minute with lukewarm tap water starting 30
seconds after instillation of the test material. In some of the rabbits, there was subsequent iritis
and/or slight redness of the conjunctivae with slight chemosis and discharge; with all irritation
clearing by day 7. Brodifacoum technical (92.5%) is in toxicity category III in terms of, eye
irritation-potential (MRID 00066938). However, it is noted that because of the high toxicity of
brodifacoum, absorption of any significant amount of the technical material by the ocular
exposure route might result in mortality (arid the animals in this study were followed for only 7
days after exposure). Technical brodifacoum is in toxicity category HI in terms of its ocular
irritation potential.
There are no dermal irritation studies on technical brodifacoum." Because of the relatively
high toxicity, dermal exposure to undiluted (or mixtures containing a relatively high percentage
of) technical brodifacoum would probably be fatal (the dermal LD50 of brodifacoum technical in
rabbits is given above as 5.21 mg/kg for males, and 3.16 mg/kg for females).
Because of the high toxicity of technical brodifacoum, end-use products (mostly containing
0.005% brodifacoum) are usually manufactured from a formulation containing 0.25%
brodifacoum. Results of the acute toxicity studies conducted with brodifacoum Formulation
Concentrate are summarized below in Table 6:
11
-------
Table 6 - Acute Toxicity Values of Brodifacoum Formulation Concentrate (0.25%)
Route
Oral
Dermal
Skin Irritation
Dermal Sensitization
Species
Rat
Rat?
Rabbit
Guinea
Pig
Results
LD50 (M) = 163 mg/kg
LD50 (F) = 152 mg/kg
LD50 (M) > 2000 mg/kg
LDJO (F) > 2000 mg/kg
Test material stained the skin pink at application site, but
no indication of an inflammatory response
Evaluation complicated by pink staining at the application
site, but no evidence of a sensitization response.,
Toxicity
Category
II
in
rv
N/A
MRID
44021701
44021702
44021703
44021704
"Study conducted with rats; however, rabbits may be a more sensitive species
' ," i * "
In an acute oral toxicity study (MRID No. 44021701), groups of fasted, young
Alpk:APfSD (Wistar-derived) rats, 5/sex were given a single oral dose of brodifacoum
Formulation Concentrate (active ingredient: brodifacoum: label declaration 0.25%; analytical
concentration 0.259%) in deionized water at doses of 50, 200, or 500 mg/kg (males), and doses
of 100, 150 or 200 mg/kg (females), and were subsequently observed for 14 days.
LD50 Males = 163 (95% C.I.: 97-275) mg/kg
Females = 152 (95% C.I.: 132-175jmg/kg
Combined = not reported
Brodifacoum Formulation Concentrate (0.25%) is in toxicity category II based on the oral
LD50 in both sexes.
Animals that died or subsequently showed symptoms were generally normal through day
4; symptoms (decreased activity, pallor, piloerection, stains around nose) in some animals were
observed only on the day of (or the day before) death. Some rats that were found dead had
showed no previous signs of toxicity. Mortalities occurred 4-7 days after dosing. Necropsy
findings in rats that died included pallor of the kidney, liver, lung, pancreas and spleen, and
clotted and/or free blood in the thymus and/or thoracic cavity, consistent with the anticoagulant
activity of brodifacoum. There were no consistent effects on body weight.
In an acute dermal toxicity study (MRID No. 44021702), a group of five male and two
groups each with five female young adult Alpk:APfSD (Wistar-derived) rats received a single 24-
hour occluded dermal exposure to 2000 mg/kg undiluted brodifacoum Formulation Concentrate
(active ingredient: brodifacoum: label declaration 0.25%; analytical concentration 0.259%). At
24 hours the application site was cleansed with cotton swabs. In order to prevent ingestion of any
residual material, rats were fitted with collars that were kept in place until day 4 for the males and
first group of females, and throughout the observation period for the second group of females.
The animals were observed for 14 days following removal of the occlusive dressings. 1/5 males
and 2/10 females died on days 7-9 with symptoms consistent with anticoagulant activity. One of
the dead females was reported to have chewed and partly removed the dressing.
Dermal LDSO Males > 2000 mg/kg
Females > 2000 mg/kg
Combined > 2000 mg/kg
12
-------
Brodifacoum Formulation Concentrate (0.25%) is in Toxicity Category, IE in terms of
dermal toxicity potential, based on the dermal LD50 values in both sexes. It is noted that this study
was conducted with rats as opposed to rabbits. Rats may be a less sensitive species than rabbits
which are generally used in dermal toxicity studies. ,
Among the survivors, one female showed bruising at the application site on days 10-15.
Necropsy findings (pallor of the brain, liver, lung, pancreas and/or spleen) for animals that were
euthanized in extremis were consistent with anticoagulant activity of brodifacoum. Survivors all
gained weight.
In a primary dermal irritation study (MRID No. 44021703), a group of six female young
adult rabbits (New Zealand white), weights ranging from 3940-4290 g, each received a!single 4-
hour occluded dermal exposure to 0.5 ml of undiluted brodifacoum formulation concentrate
(0.25% a.i.), with scoring for dermal irritation within the first hour after removal of the occlusive
wrap, and at 1, 2 and 3 days. There was slight edema in one rabbit, which occurred within one
hour following exposure. The test material stained the skin pink at the application sites thereby
preventing full assessment of erythema. However, subsequent histopathological examination of
application and unexposed skin sites showed no indications of an inflammatory response associated
with exposure to the test material.
Brodifacoum formulation concentrate (0.25%) is in Toxicity Category IV in terms of
dermal irritation potential, based on the lack of any significant irritation (slight edema observed
in only one animal within one hour following exposure, and lack of inflammatory response
observed in histopathological examination).
In a dermal: sensitization study (MRID 44021704) with brodifacoum Formulation
Concentrate (0.25% a.i.), administered at challenge undiluted and as 30% and 10% w/v
suspensions in deipnized water, young adult Crl:(HA)BR male guinea pigs were tested using the
method of Buehler. There were no indications of a sensitization reaction, although evaluation was
complicated by pink staining at the application sites. Skin samples were examined
histopathologically, with no indications of a significant inflammatory response. In this study,
brodifacoum Formulation Concentrate (0."25% a.i.) is not a dermal sensitizer.
(2) Bromadiolone Acute Toxicity
The acute toxicity data for bromadiolone are summarized in Table 7:
Table 7 - Acute Toxicity Values for Bromadiolone
Study
Oral LDso-rae
Dermal LD50-rabbit
Acute inhalation LCso-rat
Eye irritation-rabbit
- Dermal irritation-rabbit
Dermal sensitization
Results , , "
between 0.56 and 0.84 mg/kg
1.71mg/kg ' . "
0.43Aig/kg '
Irritation cleared by 4 days 7
Minimally irritating
Not a dermal sensitizer
Category
I
I
I
ffl
IV '
n/a
MRH>
41900001
42673701
4197690-
88113
88112
41847401
aThis study was conducted with a concentrate which provides an understanding of the acute oral toxicity of
bromadiolone.
13
-------
A number of acute toxicity studies have been conducted with bromadiolone in the technical
form or as a concentrate. The acute oral LD50 in rats was tested using a concentrate (2.5 gm/L)
and doses were between 0.56 and 0.84 mg/kg (Toxicity Category I, MRID 41900001). An
acceptable acute oral toxicity study with technical grade is currently unavailable, but the available
data indicate that bromadiolone is very toxic. Requiring another acute oral toxicity with the
technical grade may not add more information than what is currently available. The acute dermal
LDjo in rabbits was 1.71 mg/kg (Toxicity Category I, MRID No. 42673701. This study satisfies
Guideline 81-2 requirement). The LC50 for acute inhalation toxicity in rats is 0.43 /-ig/L (Toxicity
Category I, MRID No. 41976901. This study satisfies Guideline 81-3).
A primary eye irritation study in rabbits indicated that bromadiolone technical produced
no irritation in washed eyes. Conjunctivitis and iritis were seen in the unwashed eyes for 4 days.
No corneal opacity was seen in either the washed or unwashed eyes (Toxicity Category III, MRID
No. 00088113. This study satisfies the Guideline 81-4).
A primary dermal irritation study in rabbits showed that, after 24 hours of dermal
application, bromadiolone produced minimal irritation on the application site (Toxicity Category
IV; MRID No. 00088112. This study satisfies Guideline 81-5)
A dermal sensitization study in guinea pig showed that bromadiolone was not a dermal
sensitizer (MRID No. 41847401. This study satisfies Guideline 81-6).
(3) Bromethalin Acute Toxicity
Results of the acute toxicity studies conducted with technical bromethalin are summarized
below in Table 8:
Table 8 - Acute Toxicity Values of Technical Bromethalin
Route
Oral
Dermal
Inhalation
Eye Irritation*
Skin Irritation1
Dermal Sensitization1
Species
Rat
Rabbit
Rat
Rabbit
Rabbit
Guinea Pig
Results
LDSO (Males) = 10.7 mg/kg
LD50 (Females) = 9.1 mg/kg
LD50 = 2000 mg/kg
LCSO = 0.024 mg/L
Slight irritation
Not an irritant
Non sensitizer
Toxicity Category
I
II
I
m
IV
N/A
MRID
00026524
00026524
00026524
00026524
00026524
41653001
"Not required for TGAI, however, presented here for informational purpose
An acute delayed neurotoxicity study was conducted in the hen. White rock strain hen (30
animals) were initially dosed with bromethalin in PEG-400 at 9 mg/kg and redosed on day 3 with
15 mg/kg. Observation was for 24 days. Bromethalin did not produce acute delayed
neurotoxicity in the hen. (MRID 00101543).
14
-------
An acute neurotoxicity study was conducted in rats. Male and female Sprague-Dawley CD
rats were orally, gavaged with bromethalin in mineral oil at doses of 0, 0.8, 1.5 or 3 mg/kg. The
NOEL was greater than 3 mg/kg (HOT) and the LOEL was not determined in this study.
Although this study was classified as unacceptable, the study can be upgraded if the registrant can
provide the following data: the rationale of vehicle choice and volume used, the stability of test
material in mineral oil, the rationale for choice of testing time on dosing day, and body
temperature measurements. Body temperature is a measurement that should have been taken,
given the mechanism of action of bromethalin (uncoupler of oxidative phosphorylation) (MRID
42793101). Howeve'r^ a new study will not be required since adequate information is available
to determine an acute NOEL for bromethalin neurotoxicity.
(4) Chlorophacinone Acute Toxicity
Results of the acute toxicity studies conducted with technical chlorophacinone' are
summarized in Table 9: '. >
1 - -.-= ' ' ' - "
Table 9 - Acute Toxicity Values of Technical Chlorophacinone
Route
Oral
Dermal
Inhalation
Eye Irritation3
Skin Irritation"
Dermal
Sensitizationa'b
Species
Rat
Rabbit
Rat
Rabbit
Rabbit
Guinea Pig
Sesalts '
LD50 (M) = 3.15 mg/kg LDSO (F) = 10.95 mg/kg
combined = 6.26 mg/kg
LD50 (M) = 0.329 mg/kg .
LDSO (F) = not done ;
LC50 (M) = 7 Atg/L . ,
LC50(F)=12Mg/L :
No eye .irritation at 1, 24, 48, or 72 hours.
PIS = 0, but mortalities occurred (same study as
dermal LDJO assay)
Non sensitizer
ToxHiy '
Category
I
I
I
IV ,
IV
N/A
MRID-
41875301
41702801
41981102
41874001
41702801
41578601
a Not required for TGAI, however, presented here for informational purposes.
b 2/10 animals died .
In an oral LD50 study in which technical chlorophacinone (99.36% by potentiometry,
102% by UV spectrophotometry) was administered as a suspension in polyethylene glycol 300 to
Sprague-Dawley rats, there were mortalities at all dose levels in males (2.0 mg/kg: 4/10; 3.2
mg/kg: 6/10; 5.2 mg/kg: 4/10; 8.2 mg/kg: 8/10; 13.2 mg/kg: 10/10; 21 mg/kg: 9/10). There
were no mortalities in females receiving doses of 2.0 or 3.2 mg/kg, but mortalities occurred at
higher dose levels (5.2 mg/kg: 2/10; 8.2 mg/kg: 3/10; 13.2 mg/kg: 6/10; 21 mg/kg: 9/10)!
Deaths, with symptoms consistent with internal hemorrhage or other evidence of anticoagulant
activity, occurred on days, 4-13 after dosage. The acute oral LD50 for males was calculated as
3.15 mg/kg, with 95% confidence limits of 1.48-6.68 mg/kg. For females it was 10.95 mg/kg,
with 95% confidence limits of 6,46-18.57,mg/kg. The combined oral LD50 for both sexes was
calculated as 6:26 mg/kg (95% confidence limits of 3.96 to 9,89 mg/kg). These results place
technical chlorophacinone in Toxicity Category I (MRID 41875301) by the oral exposure route.
15
-------
In a dermal LD50 study with male New Zealand white rabbits chlorophacinone technical
(100%) was dissolved in acetone and spread onto 2.0 x 2.0 cm pads. Each pad was allowed to
dry before it was applied to a shaven dermal area on one of 10 male rabbits/dose level. Doses
applied were 0.25, 0.5 or 0.75 mg/kg, with 24-hr occluded dermal exposure. Animals were
observed for 21 days (instead of the usual 14 days) after exposure. Deaths occurred between days
5 and 19. Symptoms (which included bloody nasal discharge) and necropsy findings (hemorrhage
in the thoracic cavity and large intestine) were consistent with anticoagulant activity. There were
mortalities at each dose level (0.25 mg/kg: 4/10; 0.50 mg/kg: 6/10; 0.75 mg/kg: 9/10). There
were no indications of skin irritation in any of the animals. The dermal LD50 of chlorophacinone
technical was calculated to be 0.329 mg/kg (95% confidence interval 0.21-0.52 mg/kg) for males.
Females were not tested. This was because .males had been previously observed to be more
sensitive to the anticoagulant effects of chlorophacinone than females. With a dermal LD50 below
200 mg/kg, technical chlorophacinone is in Toxicity Category I (MRID 41702801) by the dermal
exposure route.
There were no indications of skin irritation from dermal exposure to technical
chlorophacinone at doses'which resulted in mortality (this is the dermal LDSO study indicated
above, in MRID 41702801). The test material is in toxicity category IV in terms of its dermal
irritation potential.
In an inhalation LC50 study in rats, groups of young adult Sprague-Dawley rats, 7-
9/sex/exposure level, were exposed (nose only) for 4 hours to analytically-determined
concentrations of 1.33, 10.3, 11.5 or 14.5 /*g/L (the respective nominal values were 72.3, 88.63,
440 and 166 jtg/L), with a subsequent 21-day observation. "To minirnize human .exposure,
continuous observation of the animals during the 4-hour exposure was not maintained."
Observations were made at 0.5, 1 and 2.5 hours during the exposure period. Between
observations some animals turned in the restrainers and, as a result, died from suffocation. The
deaths from suffocation were considered stress-related. All animals that died within the first 5
hours showed no clinical signs of hemorrhage. At the lowest concentration level (1.33 jtig/L)
there were no compound-related mortalities in 5 males and 7 females; but mortalities accompanied
by signs of anticoagulant activity occurred on post-exposure days 3-8 in rats exposed to the higher
concentrations (10.3 fig/L: 4/6 males, 2/8 females; 11.5 jtg/L: 8/8 males, 5/6 females; 14.5
fjig/L: 2/5 males and 3/6 females). The inhalation LC50 for males = 7.00 jig/L, with 95%
confidence limits (C.L.) of 0.83 - 59 /ig/L. For females, the inhalation LC50 = 12.0 pig/L, with
95% C.L. of 7.8 - 18 pig/L; and the combined LCSO = 9.3 jig/L, with 95% C.L. of 2.3 - 38
jig/L. Chlorophacinone technical (analyzed concentration: 101%) is in Toxicity Category I
(inhalation LC50 at or below 50 jtg/L) based on the LC5Q values in both sexes (MRID 41981102).
In an eye irritation study in rabbits, 0.1 g technical chlorophacinone (99.88%) was instilled
in the conjunctiva! sac of the left eye in each of 6 female New Zealand white rabbits, with no
subsequent eye wash. Eyes were scored at 1, 24, 48 and 72 hours after exposure, but there were
no indications of any irritation (all scores zero). Technical chlorophacinone (99.88%) is in
Toxicity Category IV in terms of eye irritation potential (MRID 41874001). It is noted that the
rabbits were only observed for 72 hours following ocular exposure, and the possibility exists that
if observations had been continued mortalities might have subsequently been noted.
16
-------
A dermal sensitization study (MRID 41578601) of male Hartley strain guinea pigs with
cWorophacinone technical (99.88%), using the Buehler procedure and a 3-weekinduction period
with 2 inductions/week was conducted. A first attempt was made using a dosage level of 0.2
g/animal/induction, but after one induction there was 40% mortality in the test group. In a second
attempt, 0.01 g/animal/induction was used as a dose level. Subsequently, the dosage amount was
reduced to Q.005 g/animal/induction using new animals. This part of the study was also
terminated "due to high mortality in the test group." The final assay attempt utilized a dosage
level of 0.003 g/animal/induction. Dosing chambers were secured with hypoallergenic tape, and
following each 6-hour exposure period, the application site was wiped to remove as much of the
test material as possible. Even so, two animals died during the induction period (on days 8 and
13). There were no indications of dermal irritation at the application sites during either the
induction phase or following challenge. This study adequately demonstrates that technical
chlorophacinone is not a dermal sensitizer as a result of exposure to non-lethal doses.
(5) Diphacinone and its sodium salt Acute Toxicity
Results of the acute toxiciry studies conducted with technical diphacinone are summarized
below in Table 10:
Table 10 - Acute Toxicity Values of Technical Diphacinone
Route
Oral
Oral
Dermal
Inhalation
.Eye Irritation
Skin Irritation
Dermal
Sensitization
Species
Rat
Rat
Rabbit
Rat
Rabbit
Rabbit
Guinea Pig
Results
LD50 (M) = 2.5 (1.32-3. 44) mg/kg
LD50 (F) .= 2. 1 (1 .55-2.86) mg/kg
combined = 2.3 (1.86-2.88) mg/kg
LD50 (M) = 6.8 mg/kg LD50 (F) = 8.0 mg/kg
combined = 7.0 (5.2-9.5 mg/kg
LD50 (M) = 3.6 (0.6-20.8) mg/kg LD50 (F) = not done
LC50 (M) < 0.6 Mg/L LC50 (F) < 0.6 Mg/L
, Moderate irritation clearing "by day 4
Slight erythema clearing within 48 hours, but 4/6 rabbits
died between days 8 and 10
neither a dermal irritant nor a sensitizer at a non-lethal dose
level (2.5 mg/day) ,
Toxiciry
Category
I
I
I
I '
m
IV
N/A
MRID
00060605
42245202
42507001
43000401
42245203
42132501
In an oral LD50 study^^(MRID 00060605) technical diphacinone (purity not specified), was
administered as a suspension in corn oil (volumes of 10 mL/kg were administered at all dosage
levels) to Spartan rats (5/sex/dose level), at dose levels of 0, 0.79, 1.25, 1.98, 3.15,,5.00, 7.94,
12.60, 20.01, 31.76, 50.40 or 201.7 mg/kg, with a subsequent 14-day observation. The
following mortality pattern was observed as outlined in Table 11,
17
-------
Table 11 - Dose Levels and Mortality in an Oral LDrn Study with Diphacinone
,: Dose Level
;> (rag/kg)
0.79
1.25
1.98
3.15
5.00
7.94 .
12.60
20.01
31.76
50.40
201.70
Males Deaths
/Rats Dosed.
0/5
0/5
2/5
3/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
Females Deaths
/Rats Dosed
0/5
1/5
1/5
5/5
5/5
5/5
5/5
4/5
5/5
5/5
5/5
Combined Deaths
/Rats Dosed
0/10
1/10
3/10
8/10
10/10 .
10/10
10/10
9/10
10/10
10/10
10/10
Days after dosage
deaths occurred :
-
6 ;
4
3-7
3-6
3-7
4-6
3-8
4-9
3-7
3-6
Data extracted from tables 4, 5 and 6 of MRID 00060605
Symptoms occurred at all doses, and were not necessarily associated with subsequent
mortality. These included clear or colored nasal discharge, soft stool and/or diarrhea (possibly
associated with the corn oil vehicle used), decreased motor activity and occasional drying of the
corneal surface. Symptoms at higher dose levels included lacrimation, ataxia, cyanosis and
bloody exudate from nose and eyes. Hemorrhage into the body cavities and of various organs
was observed in animals which died. The acute oral LD50 for males was calculated as 2.50
mg/kg, with 95% confidence limits of 1.82-3.44 mg/kg. For females, it was 2.10 mg/kg, with
95% confidence limits of 1.55-2.86 mg/kg. The combined oral LD50 for both sexes was
calculated as 2.31 mg/kg (95% confidence limits of 1.86 to 2.88 mg/kg). These results place
technical diphacinone in Toxicity Category I (MRID 00060605) by the oral exposure route. The
study defines such a high degree of toxicity for technical diphacinone that the Agency can accept
the findings, even in the absence of information as to the purity of the test material.
In a second oral LD50 study (MRID 42245202), technical diphacinone (reported as having
"at least 98% purity") was administered as a 0.2% w/w suspension in corn oil to groups of 5
rats/sex/dose level. The dose levels were 4, 6, 8 or 10 mg diphacinone/kg body weight, with
observation for 14 days after dosage. Signs of toxicity included nasal staining (usually red),
paleness, red staining on the tail. Most animals that survived (including 2/3 at the highest dose
level) appeared healthy throughout the test period. Necropsy findings of animals which died
during the 14-day observation period were consistent with anticoagulant activity (such as red fluid
in the thoracic and/or abdominal cavities, apparent testicular hemorrhage). The acute oral LD50
for males was calculated as 6.8 mg/kg, and for females 8 mg/kg. The combined oral LD50 for
both sexes was calculated as 7 mg/kg (95% confidence limits of 5.2 to 9.5 mg/kg). The results
of this second oral LD50 study (MRID 42245202) are reasonably consistent with those of the first
(MRID 60605), as both define a Toxicity Category I hazard potential for technical diphacinone
by the oral exposure route, although the second study indicates somewhat less toxicity (or perhaps
the strain of rat used in the second study was less susceptible). See Table 12 below.
18
-------
Table 12 - Dose Levels and Mortality in a Second Oral LDgn Study with Diphacinone
i Dose Level (mg/kg)
4
6 .
8
10
; Males Deafts/Rats-
Dosed
1/5
. 3/5
, 3/5
4/5
Females Deaths/Rat$
Dosed
1/5
3/5
' ' . 1/5
.3/5 :
Combined Deaths/Rats
Dosed
2/10
6/10
4/10
7/10
Days after dosage
deaths occurred
5
3-9
3-7
3-7
Data extracted from tables 1, 2, 5, 8 and'11 of MRID 42245202
f
i . ./-".'
It is notedthat the mouse is considerably less susceptible to the toxic effects of diphacinone
than other mammalian species (see discussion in Mutagenicity section under MRID 42406801).
The NIOSH Registry of Toxic Effects of Chemical Substances 1985-86 reports a mouse LD50 for
diphacinone as 300 mg/kg, and the rat LD50 as 1.5 mg/kg. This is also supported by a report
from the open literature (Correll et. al., 1952) which states that the acute oral LD50 for
diphacinone was found to be 3 mg/kg for rats, 340 mg/kg for mice, and 35 mg/kg for rabbits.
"/''. .'"'. ' .-"
In a dermal LD50 study (MRID 42507001) with male New Zealand white rabbits,
diphacinone technical (97.4%) was dissolved in acetone and the appropriate amount of the test
substance solution was applied to the foil side of Scotch Pak pads. , The acetone was allowed to
evaporate, and the Scotch Pak pad, test substance side down, was applied to the application site,
with 24-hour occluded exposure. In a range-finding trial, dose levels of 0, 1, 5, 10, 25 or 50
mg/kg were administered to groups consisting of 1 animal/sex/dose level. The findings in this
range-finding study were used to set the doses in the subsequent definitive study. Females at the
three highest dose levels -10, 25, .or 50 nig/kg - died. Those at the two lower dose levels -. 1 and
5 mg/kg - survived. Deaths occurred on days 7-13. Males at all dose levels died. The
performing laboratory suggested mat only male rabbits should be used for the LD50 determination,
as they had been the more sensitive sex. The doses for the dermal LD50 determination were 0.05,
0.20 and 0.80 mg/kg, with subsequent 21-day observation. The'following mortality pattern was
observed as outlined in Table 13.
Table 13 - Dose Levels and Mortality in a Dermal
Dose Level (mg/Jtg)
0.05
0.20
0.80
Males Deaths/Rabbits Dosed
0/10
1/10
2/10 ,
Days after dosage deaths occurred
-
- 4 -
" 4 .
Study with Diphacinone
Data extracted from tables HA, IIB and EC of MRID 42507001.
The animals that died (both in the preliminary range-finding and subsequent LD50
determination studies), showed symptoms (hemorrhage, discoloration of various organs) indicative
of anticoagulant activity. No clinical signs were observed at the lowest dose level (0.05 mg/kg).
Symptoms at the two higher dose levels included somnolence, loss x>f fluids, absence of feces and
vasoconstrictibn. Based on the mortality, the estimated dermal LD50 in male rabbits is 3.6 mg/kg.
These results place technical diphacinone in Toxicity Category I (MRID 42507001) by the dermal
exposure route.' .
19
-------
In an inhalation LC50 study in rats (MRID 43000401), a group of young adult Sprague-
Dawley rats, 5 of each sex, were exposed (whole body) for 4 hours to a time-weighted average
aerosol concentration (gravimetrically determined) of 6 p,g/L, with subsequent 14-day
observation. The mass median aerodynamic diameter was 2.3 /*m, with a geometric standard
deviation of ฑ2.1 pun. The percentage of particles < 4.0 jtm was equal to 78%. Mortality
occurred (days 4-8) in 5/5 males and 4/5 females. Symptoms (including red staining of abdominal
and urogenital regions, reddish material around ears and in cage tray) and necropsy findings
(hemorrhage in the thoracic cavity and/or cranial cavity and/or various organs) were consistent:
with anticoagulant activity. The dose in the LC50 study was based on findings in a preMminary
range-finding study, in which groups of one rat/sex/exposure level were exposed for one-hour to
concentrations of 0, 0.01, 0.11, or 1,1 mg/L, with subsequent 7-day observation. All the males
died (deaths occurred days 4-7), as did the female exposed to the lowest concentration (0.01
mg/L). However, the two females exposed to the two higher concentrations (0.11 and 1.1 mg/L)
showed an array of symptoms (decreased activity, labored breathing, distended abdomen) on day
7 similar to those observed in other rats in the day or so before they died. These females
underwent scheduled euthanasia. Diphacinone technical (percentage active ingredient not
reported) is in Toxicity Category I (inhalation LC50 at or below 50 jtg/L) based on the LC50 value
of less than 6 /tg/L in both sexes (MRID 43000401).
In an eye irritation study with New Zealand white rabbits (MRID 42245203), an attempt:
was made to place as much technical diphacinone (with at least 98% active ingredient) as possible
into the conjunctival sac of one eye of each of nine rabbits. The report notes that the test material.
at 0.1 g exceeded the capacity of the rabbits' eye. The treated eyes of 3 rabbits were irrigated
approximately 20-30 seconds after instillation of the test material. The eyes of the remaining 6
rabbits were not washed. No corneal opacity was observed, although some eyes showed iritis,
and all eyes (washed and unwashed) showed some conjunctival irritation, with clearing by day 4.
Technical diphacinone is in Toxicity Category HI in terms of eye irritation potential (MRID
42245203). It is noted that the rabbits were only observed for 96 hours following ocular
exposure, and the possibility exists that if observations had been continued mortalities might have
subsequently been noted.
In a dermal irritation study with New Zealand white rabbits, 0.5 g of undiluted technical*
diphacinone (with at least 98% active ingredient) was applied to a single intact site, with 4-hour
occluded exposure. Barely perceptible erythema was observed at 2 treated sites one hour after
patch removal and at one treated site at 24 hours, with no evidence.of erythema at 48 or 72 hours.
No occurrence of edema was observed. The Primary Dermal Irritation Score was reported to be
0.09. Technical diphacinone (at least 98% active ingredient) is in Toxicity Category IVin terms
of its primary dermal irritation potential. However, the report also notes "There were no signs
of gross toxicity, adverse pharmacological effects or abnormal behavior during the test period.
However, it should be noted that 4 of 6 rabbits died after the last scoring interval (i.e. between
days 8 and 10 post-dosing). These spontaneous deaths may have been due to the anticoagulant
properties of the test product."
In a dermal sensitization study (MRID 42132501) with Hartley albino male guinea pigs
with diphacinone technical (96.57%), the test material was administered as a topical application
20
-------
at various dose concentrations. The test article was kept in contact with the skin surface for a six
hour period. After the initial exposure, the test article was administered on alternate days three
days a week such that each animal received 10 sensitizing treatments. Following the tenth
treatment, animals were rested for two weeks, and then given an eleventh (challenge) dose.
The major problem in this dermal sensitization study was on determining a non-lethal dose
level. In the initial assay application of 500 mg caused death and/or severe hemorrhage from the
external nares in some animals and evident discomfort in others, with the result that all surviving
animals were euthanized. Further testing at doses of 5, 10, 20, 40 or 80 mg with two male guinea
pigs/dose resulted in all animals either dying or being euthanized on or about the seventh day after
the initial dose. Additional dosing at 0.1, 0;5, 1.0. or 2.5 mg with two animals/dose resulted in
the death of one animal in the 0.5 mg group. As a result, the final dose selected was 2.5 mg in
10 guinea pigs (one of these animals died 13 days after the initial.dose). Signs of dermal irritation
were not observed in any of the guinea pigs at any dose level during the study, and there were no
indications of any sensitization reaction in the survivors of the final assay (dose level: 2.5
ing/animal). There were 3 guinea pigs in a positive control group (each received 2.5
mg/application). One of these positive control animals died before the challenge, application, but
positive responses were elicited in the remaining 2 guinea pigs. The findings of this study (MRID
42132501) adequately demonstrate that technical diphacinone at a non-lethal exposure level is
neither a dermal irritant nor a sensitizer. -
b. Subchronic Toxicity
(1) Brodifacoum Subchronic Toxicity
The Agency has no record that any subchfonic toxicity studies on brodifacbum have been
received and/or reviewed. However, it is noted that there are a number of multiple-dose studies
which the Agency has,received (including a: special study Brodifacoum: Blood Kinetics Study in
the Pregnant Rat, MRDD 42641902, see below), which include prothrombin time measurements,
which appears to be the most sensitive indicator of toxicity for the anticoagulants.
! , > . ,
Although the current lexicological data base is sufficient for the purposes of this RED,
because of the potential for non-purposeful dermal exposure, and to more accurately assess the
margins of exposure associated with potential incidental exposure, a 21-day dermal toxicity study
(Guideline 82-2) is required as confirmatory data. Such a study must include prothrombin and
activated partial thromboplastin time measurements, including ipre-exposure, as well as on days
7, 14 and 21 of exposure.
(2) Bromadiolone Subchronic Toxicity
In a 90-day study, groups of beagle dogs (4/sex/dose) received bromadiolone in gelatin
capsules at variable daily doses for different lengths of time. The dosages were low-dose, 5/10
,u.g/kg; mid-dose, 10/15/20 jug/kg; and high-dose, 15/25/50/100 /ig/kg. The control dogs
received starch in gelatin capsules. The high-dose animals died or were sacrificed moribund prior
.''- ;- 21 :'.-. ''': .
-------
to die study's termination. In addition, the high-dose animals also showed signs of loose, bloody
stools following the 15 jttg/kg dosing. After five days of following 100 /ig/kg dosing high-dose
animals also showed signs of hypothermia, respiratory difficulties, pale mucosa, drowsiness,
atonia, bloody urine, hematomas, and external hemorrhage. Both mid- and high-dose dogs had
increased prothrombin time and hematuria. Histological examination showed that in high-dose
groups, 4/4 male or female dogs had hemorrhage, congestion and/or edema of the spleen,
kidneys, lungs, urinary bladder, small intestine, liver, thyroid, and skin. No compound-related
histological lesions were found in mid- and low-dose dogs. Based upon the clinical and
hematological findings, the LOEL for subchronic toxicity of bromadiolone was 15 fig/kg; NOEL,
10 j4g/kg (MRID 92196013).
In a multiple-dose toxicity study, groups of female rats (10/dose) received bromadiolone
(technical grade) by gavage at doses of 6.4, 12.4, or 24.8 jtg/kg for 20 days. By study day 13,
the mid- and high-dose rats were all dead, and 8/10 rats in the 6.4 jig/kg group were also dead
by day 20. The clinical signs included hemorrhage in the orbital sinus, nasal cavity, and nail
beds, anorexia, and polydypsia. At necropsy, the dead rats showed general internal bleeding and
hemorrhagic spots in liver, intestinal tract, and kidneys. No NOEL for subchronic toxicity could
be established for bromadiolone (MRID 00107035).
The above two studies are classified as supplementary and do not meet the data
requirements for a subchronic toxicity study in dogs and rats (Guideline No. 82-1). However,
when the data from the 90-day dog study and the 20-day rat study are analyzed together with the
results from rat and rabbit developmental toxicity studies, the results provided sufficient
information for the understanding of the subchronic toxicity of bromadiolone. Additional
subchronic toxicity tests would probably not yield much more new information. Therefore, a new
subchronic toxicity study in either the rat or dog is not requested at this time.
(3) Bromethalin Subchronic Toxicity
Sprague Dawley rats (10/sex/group) received daily gavage doses of 0 (25% polyethylene
glycol in H2O), 5, 25, or 125 micrograms/kg/day (ug/kg/day) of bromethalin technical for 13
weeks. Parameters evaluated included daily observation, weekly body weight and food
consumption, ophthalmoscopy, clinical pathology, necropsy, organ weights, and histopathology.
. The NOEL is 25 /tg/kg/day. The LOEL is 125 ptg/kg/day, based on spongy degeneration
(leukoencephalomyelopathy) observed in most of the central white fiber tracts of the brain,
cerebellum, pons, brain stem, and thoracic spinal cord of both sexes and optic nerves of males.
There were no effects on mortality, clinical chemistry, ophthalmoscopy, body weight, food
consumption, clinical pathology and histopathology of other tissues (MRID 43582102).
In a second 90-day study, groups of 4 male and 4 female beagle dogs were orally dosed
by gavage for 90 days at levels of 6, 5, 25, 125, or 200 ug/kg/day with bromethalin technical.
Observations included daily clinical evaluations, ophthalmoscopy, body weight, food
consumption, clinical pathology evaluations at weeks 6 and 13, necropsy, organ weights and
histopathology. The NOEL is 25 fig/kg/day. The LOEL is 125 /ug/kg/day based on spongy
22
-------
degeneration observed in nervous tissue components (cervical, thoracic, and lumbar spinal cord,
brain stem, right and left optic nerves, frontal and median brain, pons, and cerebellum) in both
sexes of dogs. At the high dose, 3 male dogs displayed the following neurotoxic signs before
death or being sacrificed moribund: salivation and hypoactivity, followed by trembling,
myoclonia, hyperesthesia, groaning, and decubitus. Other measured parameters were considered
comparable between control and treated dogs of both sexes (MRID 43582101).
The above two subchronic toxicity studies in rats and beagle dogs are not guideline-type
subchronic neurqtoxicity studies. However, these studies will satisfy the data requirements for
a 90-day neurotoxicity screening battery because a NOEL and a LOEL was established in both
studies. , .
(4) Chlorophacinone Subchromc Toxicity
In a subchronic study (MRID 92018013), groups of 10 Sprague-Dawley rats/sex/dose were
gavaged at 0, 10, 20 or 40 fig/kg 7 days/week for 113 days. A group was also dosed at 5
jug/kg/day, but was terminated at 77 days due to lack of evident toxicity. Additional groups were
tested at 80 and 160 jig/kg, but all animals died between days 3 and 13. At 40 jtg/kg/day deaths
occurred in 10/10 males (mortalities occurred days 29-82) and 4/10 females (days 69-111); 4/10
males (but 0/10 females) died at 20 /^g/kg/day (deaths occurred on days 105-111). "The -dominant
clinical signs that were responsible for death of animals were related to the anticoagulant activity
of Chlorophacinone." Although 1/10 males and 1/10 females died in the 10 >g/kg/day group,
these deaths were ascribed to intubation error. At termination (112-113 days), hematology
(including "coagulation time") and clinical chemistry parameters were determined from the 0, 10,
20 or 40 /Kg/kg/day groups (but not the 5 /tg/kg/day group, which was terminated at 77 days).
In the 10 y^g/kg/day animals, males showed a 28% increase (p < 0.01) in coagulation time, while
females showed a 6% increase (p < 0.05); at 20 >g/kg/day males showed a > 100% increase (p
< 0.01) in coagulation time and females an 11% increase (p < 0.05); at 40 /tg/kg/day females
showed a > 100% increase.
The FBFRA 88 Phase 2 and 4 Data requirements for all anticoagulant rodenticides Included
a generic data request for a 14-day feeding study in the rat to determine a NOEL and LOEL for
signs of toxicity and coagulation parameters. This information was requested to more adequately
define and evaluate the effects that would result from accidental ingestion of this type of
rodenticide. While MRID 92018013 does not adequately satisfy the Guideline requirements for
a 90-day feeding or gavage study (Guideline 82-1), sufficient information is provided to satisfy
the generic data request for a 14-day feeding study.
At the 5 /tg/kg/day dose level there was no mortality or signs of toxicity during the 77-day
exposure period. Coagulation values were not evaluated at this dose level. However clotting
times were increased by 28% and 6% for males and females, respectively, at the 10 ^g/kg/day
levels at termination (113 days). Based on these findings, HED considers 5 jig/kg/day as a NOEL
in a subchronic oral study, with a LOEL of 10 jig/kg/day (increased coagulation times for both
males and females, with males more sensitive than females).
"' .;' 23 ' ''.'.'''-'
-------
In a 21-day dermal toxicity study (MRID 42237402), a formulated product (tracking
powder) containing 0.2% chlorophacinone was applied dermally with 6 hr occluded exposure/day,
5 days/week at 0.08, 0.40 or 2.0 mg/kg (these doses are in terms of the active ingredient,
chlorophacinone) to 5 rabbits/sex/dose. The 0.2% product was used instead of the technical
material because of difficulties (encountered in a preliminary range-finding study) in accurately
weighing out and working with small quantities of this highly toxic compound. At 2 mg/kg/day,
there was mortality (with "widespread" internal hemorrhage) in 4/5 males (deaths occurred on
days 14-18) and 1/5 females (one death occurred on day 21). Prothrombin (PT) times were
markedly increased on day 21 in surviving animals (the one male had a PT time of 9.0 seconds,
while controls had a mean of 6.0. The females had a mean PT time of 17.7 seconds, as compared
to a control mean of 5.9). Moderate to severe centrilobular liver necrosis was observed in 3/5
males and 1/5 females. There was no mortality at 0.4 mg/kg, but prothrombin times were
markedly increased'on day 21 (males: 7.7 vs. a control value of 6.0 seconds; females: 9.5 vs. a
control value of 5.9). There were no indications of any effect at 0.08 mg/kg/day.
The following table from the report (in MRID 42237402) summarizes the measurements
for prothrombin time (PT) and activated partial thromboplastin time in seconds (APTT):
Table 14 - Prothrombin and Activated Partial Thromboplastin Times in a 21-Day Subacute
Dermal Study in Rabbits - Statistically Significant Findings
Sex
Parameter
Dosage (mg/kg/day)
Pretreatment
Termination
Week -2
Week-1
Week-0
Week - 0
Week -3
Hematology Data - PT/APTT Mean Values
Males
Group 1
0
Group 2
0.08
Group 3
0.4
Group 4
2.0 .
Females
Group 1
o
Group 2
' 0.08
Group 3
0.4
Group 4
.2.0
Prothrombin time (PT) in seconds
6.4
6.3
6.6
6.0
6.4
6.3
6.3
6.0
6.4
6.3
6.3
7.7
6.4
6.2
6.3
9.0
6.3
6.2
6.4
5.9a
6.1
6.1
6.3
6.4b
6.3
6.3
6.2
9.5ฐ
6.4
6.4
6.5
17.7C
Activated partial thromboplastin time (APTT) in seconds
32.5
32.4
52.3
24.5
22.9
28.3
59. T
67.0C
"Examination of the female animals in the concurrent control, for the Week 3 interval, showed a statistically significant
decrease based on their own three pretreatment values. This slight decrease in the control female value gave rise to the
statistical significance in the Group 2 female value.
''Analysis of variance indicated a significant difference from the control value, p <. 0.05; further statistical analyses,
using repeated measures analysis of variance and dependent measures t-test procedures, indicated that this value did
not vary significantly from the mean prothrombin time recorded at pretreatment intervals for those animals.
"Significantly increased, p z 0.05
The subchronic dermal LOEL is 0.4 mg/kg/day, based on increased prothrombin times
in both sexes on day 21. The subchronic dermal NOEL is 0.08 mg/kg/day.
This subchronic dermal study in the rabbit is classified as acceptable (Guideline), and
satisfies the guideline requirement for a subchronic dermal toxicity study (ง82-2).
24
-------
(5) Diphacinone and its sodium salt Subchronic Toxicity
In a 21-day dermal toxicity study (MRID 00074637), diphacinone (99.8%, moistened with
0.9% physiological saline) was applied (6-hr occluded exposure) five days a week for three
weeks, at dosage levels of 0, 0.1, 1.0 or 10.0 mg/kg to groups consisting of four male and four
female New Zealand white rabbits/dose level. The skin of two males and two females in each
group was abraded. The skin of the remaining rabbits was left intact. Most of the animals exposed
to diphacinone showed no dermal irritation. The dermal irritation which did occur in 1 or 2
animals/group was slight. However, all of the animals exhibited yellow staining of the test site
after a few exposures. ,
Mortalities or sacrifice in extremis occurred in 1/8 controls, 1/8 in the, 0.1 mg/kg/day
group, 5/8 at 1.0'mg/kg/day, and 6/8 at 10.0 mg/kg/day. Symptoms included clear nasal
discharge, pale skin and/or mucous membranes, and hypothermia. On gross pathology,
"hemorrhagic areas in different sites were present in the stomach, mouth, ear, muscle, soft
tissues, thoracic and abdominal cavities, cecum, colon, kidney and bladder.of some animals.
These lesions were more frequent in the 1.0 mg/kg and 10.0 mg/kg Diphacinone groups, only one
case was present in the control group and one in the 0.1 mg/kg Diphacinone group." Blood
samples we,re taken at preexposure, and on day 19. Determinations included hematocrit,
hemoglobin, erythrocyte count, total leucocyte count, platelets, mean corpuscular volume, mean
corpuscular hemoglobin and mean corpuscular hemoglobin concentration. However, there were
no measurements of clotting time. .
Finally, while this 21-day dermal toxicity study (MRID 00074637) is classified as
acceptable (satisfying the guideline requirement for a subchronic dermal toxicity study ง82-2),
with a subchronic dermal NOEL of 0.1 mg/kg/day, and a subehronic dermal LOEL of 1.0
mg/kg/day (based on mortality accompanied by indications of anticoagulant activity), it is noted
that there are indications in the report of possible anticoagulant activity ("hemorrhagic areas") in
one control and one 0.1 mg/kg rabbit. In addition, there were no clotting time determinations
(such as prothrombin and/or activated partial thromboplastin times).
In a 21-day subchronic study (MRID 00077319), groups of 2 Swiss Webster mice/sex/dose
level were intubated (using a 10 mg/mL solution of technical diphacinone in propylene glycol)
. at 0.1, 0.5, 1.0, 2.5, 5.0, 10.0 or 20.0 mg/kg/day for 20 days. All the mice dosed at 5, 10 or
20 mg/kg/day died during the first 7 days of the test period, and symptoms (bleeding, paleness)
were generally consistent with anticoagulant activity. Three out of 4 intubated at 2.5 mg/kg died
by day 14 (with symptoms of bleeding) with only one female surviving to termination. .While
there were no mortalities at 1.0 mg/kg, hemorrhages, sub-cutaneous accumulation of blood or
external bleeding was noted at this dose level. No effects were observed at 0.5 mg/kg/day.
" - The observations in this study were subsequently used to set the dose levels (0, 0.1, 0.5,
1.0 or 2.5 mg/kg) in a mouse developmental toxicity study (also in MRID 00077319), which
utilized 15 pregnant females/dose level. All animals dosed at 2.5 mg/kg/day died (days 4-10 of
dosing). There was a considerable proportion of the fetuses in each female of this group
''' 25 -.--.
-------
undergoing resorption (6/10, 4/10, 7/12, 3/11, and 4/12). At 1.0 mg/kg/day one pregnant female
died on day 10 (2/10 fetuses were being resorbed).The LOEL in the 20-day feeding study is 1.0
mg/kg/day (occurrence of subcutaneous accumulation of blood, hemorrhages and external
bleeding, with no mortalities), although no measurements were made for clotting time. While the
single-dose LDSO for the mouse is about 300 mg/kg, the toxicity of diphacinone in this species is
enhanced when administration takes place over a period of several days.
At the 0.5 mg/kg/day dose level there was no mortality or signs of toxicity during the 20-
day exposure period, and no mortalities (or other effects) were observed at this dose level in the
subsequently conducted mouse developmental toxicity study. The LOEL is 1.0 mg/kg/day (based
on the occurrence of subcutaneous accumulation of blood, hemorrhages and external bleeding.,
with no mortalities in the initial 20-day study, and the occurrence of mortality in 1/5 pregnant
females at this dose level in the subsequently conducted mouse developmental toxicity study). It
is noted that no information is given in this study as to clotting times. While the information in
MRID 00077319 is useful, it is not adequate to satisfy the FIFRA 88 Phase 2 and 4 data
requirements for anticoagulant rodenticides for a 14-day feeding study in the rat to determine a
NOEL and LOEL for signs of toxicity.
In a single dose toxicity study (MRID 43260702), male and female Sprague-Dawley rats
(5/sex) received technical diphacinone (99.0%) as a single oral gavage dose in corn oil at doses
of 0, 0.13, 0.20, 1.0 or 2.5 mg/kg. In a 14-day oral toxicity study (MRID 43260701) groups of
5 rats/sex/dose received technical diphacinone (99.0%) by oral gavage in corn oil once a day for
14 days at doses of 0, 0.025, 0.040, 0.085 or 0.175 mg/kg/day. The purpose of these
experiments were to demonstrate a NOEL and LOEL for overt signs of toxicity, lethality, and
anticoagulant effects in young adult Sprague-Dawley rats following single and repeated dosage
with technical diphacinone. Following single doses at up to 2.5- mg/kg (HDT), there were no
overt clinical signs of toxicity. Following repeated dosing, there were no signs of toxicity at the
0.025, 0.040 or 0.085 mg/kg/day dose levels. At the 0.175 mg/kg/day dose level, there were
increased incidences of dyspnea, lethargy, hemorrhage from the nose, ptyalism, and few feces.
At this dose level 3/5 males died (2/5 were found dead and one was sacrificed in extremis). All
of the female rats in this dose group had died by day 11. The following Prothrombin (PT) and
Activated Partial Thromboplastin Times (APTT) were observed as outlined in Tables 15, 16, 17
and 18.
Table 15 - Prothrombin Time in Seconds in Rats Following a Single Dose of Diphacinone
Diphacinone (mg/kg)
Males - 24 hrs after dosing
Males - 96 hrs after dosing
Females - 24 hrs after dosing
Females - 96 hrs after dosing
< ..' ' Pxothrqmbin Time inj$ecojads
0
15.5 ฑ 0.9
14.0 + 0.3
15.1 ฑ 0.3
14.4 ฑ 0.2
0.13
15.1 + 0.5
14.5 ฑ 0.3
14.8 ฑ 0.4
14.6 ฑ 0.4
0.20
15.2 ฑ 0.2
14.3 ฑ0.5
15.6 ฑ 0.5
14.4 ฑ 0.3
1.00
56.6 ฑ 9.2
14.3 ฑ 0.3
30.9 ฑ 6.6
14.0 ฑ 0.3
2.50
70.7 ฑ 8.1
22.9 ฑ 16.6
Sl.fc ฑ14.9
15.1 ฑ 0.9
'Data taken from pages 51-58 of the report (MRID 43260702)
26
-------
Table 16 - Activated Partial Thromboplastin Time in Seconds in Rats Following a Single
Dose of Diphacinone8
Diphacinone (mg/kg)
Males - 24 hrs after dosing
Males - 96 hrs after dosing
Females - 24 hrs after dosing
Females - 96 hrs after dosing
- Activated Partial Prothrombin. Time in Seconds
0
24.5 ฑ2.6
21.7 ฑ.3.1
20.3 ฑ 1.6
21.4 ฑ 3.9
0.13
22.1 ฑ 3.5
21.2;ฑ 2.7
19.3 ฑ 1.1
1-9.8 ฑ 2.0
0.20
24.0 ฑ1.3
19.4 + 2.8
32.1 ฑ 6.6
18.4 ฑ,0.5
1.00
49.8 + 18.3
21.1 + 1.7'
39.6 + 3.6
20.6 + 1.7
2.50
- 42.2 + 5.3
30.3 + 11.0
33.9 + 7.8
29.3 + 4.5
"Data taken from pages 51-58 of the report (MRID 43260702)
Table 17 - Prothrombin Time in Seconds in Rats Following Repeated Doses of Dinhacinone3
. - '
Diphacinone (mg/kg/day)
Males - 24 hrs after last dose
Males - 96 hrs after last dose
Females - 24 hrs after last dose
Females - 96 hrs after last dose
Prothrombin Time in Seconds
0
14.0 ฑ 0.2
14.4 ฑ 0.4
14.3 + 0.3
14.4 ฑ 0.8
0.025
14.2 ฑ 0.2
14.4 ฑ 0.3
14.6 + 0.3
14.6 ฑ 0.3
0.040
14.4 + 0.2
14.0 ฑ 0.7
14.4 + 0.2
14.3 + 0.4
0.085
15.2 + 0.7
14.1 + 0.4
14.4 + 0.3
14.7 + 0.1
'Data taken from pages 51-58 of the report (MRID 43260702)
b All animals were dead by day 11
0.175
20.0 ฑ 1,3
14.3 + 0.4
-b
-b
Table 18 - Activated Partial Thromboplastin Time in Seconds in Rats Following Repeated
Doses of Diphacinone3
* .
Diphacinone (mg/kg/day)
Males - 24 hrs after last dose
Males - 96 hrs after last dose
..Females - 24 hrs after last dose
Females - 96 hrs after last dose
Activated; Partial Thromboplastin Time m Seconds -
0 '
20.2 + 1.1
20.4 ฑ 2,0 ,
20.7 ฑ1.9
21.4 + 2.9
0.025
20.0 + 1.2
20.3 + 1.0
- 19.7 ฑ0.8
20.2 + 0.9
0.040
22.0 ฑ1.2
19.9 ฑ 1.0
20.6 ฑ 0.7
20.2 ฑ 0.5
0.085
25.9 ฑ2.1
19.9 ฑ 0.9
24.4 ฑ 2.1
20.0 ฑ 0.9
0.175
38.3 + 11.0
19.7 + 0.7 .
~b
-b
*Data taken from pages 51-58 of the report (MRID 43260702)
bAll animals were dead by day 11 ' '
The LOEL from single dose administration is 0.20 mg/kg, based on increased activated
partial thromboplastin time in female rats. The NOEL from single dose administration is 0.13
mg/kg. The LOEL from repeated dose administration is 0.085 mg/kg/day, based on increased
prothrombin and activated partial thromboplastin times in male and female rats. The NOEL from
repeated dose administration is 0.040 mg/kg/day. The information in MRIDs 43260701 and
43260702 satisfies the FIFRA 88 Phase 4 Data requirements to determine effects in the rat (and
defining: the NOELs and LOELs for signs of toxicity and coagulation parameters) following a
single dose and following repeated oral dosage over a 14-day period.
c. Chronic toxicity
Given the exclusively non-food uses of these chemicals, no chronic studies were required.
27'
-------
d. Carcinogenicity
Given the exclusively non-food uses of these chemicals, no carcinogenicity studies were
required.
'
e. Developmental Toxicity
(1) Brodifacoum Developmental Toxicity
In a developmental toxicity study (MRID 00052443, along with additional data in MRID
40307202), brodifacoum (92.5%) was administered to 30 Alderley Park, Wistar-derived mated
female rats/dose level by gavage in 10% v/v ethanol:water at dose levels of 0 (vehicle only),
0.001, 0.01 or 0.02 mg/kg/day from days 6 through 15 of gestation. There was blood in the uteri
of one 0.01 and three 0.02 mg/kg females. This was considered to be possibly related to the
administration of brodifacoum. There were no indications of any dose-related developmental
effects associated with exposure to brodifacoum at doses up to and including 0.02 mg/kg/day.
The dose level of 0.02 mg/kg/day is considered adequate, based on the occurrence of 100%
mortality at a nominal value of 0.05 (analytical value of 0.35) mg/kg/day in a preliminary study,
and blood measurements in a special study (Brodifacoum: Blood Kinetics Study in the Pregnant
Rat, MRID 42641902, see below).
The rat maternal toxicity NOEL is 0.001 mg brodifacoum/kg/day (based on the equivocal
finding of blood in the uteri of one 0.01 and three 0.02 mg/kg females).
The rat developmental NOEL is 0.02 mg brodifacoum/kg/day (HDT).This developmental
toxicity study in the rat is classified as acceptable (Guideline) (83-3a), and satisfies the guideline
requirement for a developmental toxicity study in the rat.
In a special study (MRID 42641902), mixtures of unlabeled brodifacoum (98.7%) and
radiolabeled brodifacoum (radiochemical purity > 95 %) were administered to Alderley Park,
Wistar-derived mated female rats by gavage at nominal doses of 0.0125 mg/kg (Group A: 24 rats,
starting on day 1 of gestation, with sacrifice by exsanguination of 3 rats on days 1, 3, 5, 7, 9, 11,
13, 16) or 0.02 mg/kg (Group. B: 15 rats, starting on day 7, with sacrifice of 3 rats on days 7,
9, 11, 13 and 16). The test material was administered as a suspension in polyethylene glycol 600.
Terminal blood samples were analyzed for brodifacoum levels.
The following mean nanogram (ng.) equivalents of brodifacoum/gram of maternal blood
were observed:
Group A (0.0125 mg/kg/day, days 0-16): day 1: 0.560; day 3: 0.924; day 5: 1.556; day
7: 1.809; day 9: 2.015; day 11: 2.795; day 13: 2.168; day 16: 3.396.
Group B (0.02 mg/kg/day, days 7-16): day 7: 0.691; day 9: 1.362; day 11: 3.087; day
13: 2.427; day 16: 4.488.
28
-------
The relative proportions of mean blood brodifacoum levels in group B rats as compared
to group A rats were the following: Day 7: 0.382; Day 9: 0.666; Day 11: 1.10; Day 13: 1.12;
and Day 16: 1.32. ,
This study showed a steady increase of blood brodifacoum levels with continued dosage
of both 0.0125 mg/kg/day and 0.02 mg/kg/day, consistent with findings of a previously reviewed
metabolism study (MRID 00080235). In that study, three rats were given a single oral dose of
0.25 mg labeled brodifacoum and retained a mean of 77.73 % of the initial dose (mean total label
recovery was 91.51%) after 10 days. The combination of high toxicity and body accumulation of
brodifacoum would have eventually resulted in mortalities at these dosage levels.at some time after
16 days. The study is classified:as acceptable (Non-guideline) as it is riot a required guideline
study. It is acceptable for the purposes for which it was intended as a special study, and the
findings adequately justify the dosing schedule and doses used in the rat developmental toxicity
study (MRID 00052443 and 40307202; summarization in MRID 92195013),
In a developmental toxicity study in rabbits (MRIDs 00052442 and 40307201),
brodifacoum (92.5%) was administered to 15 mated female Dutch rabbits/dose level by gavage
in 5% v/v ethanol:water at dose levels of 0 (0.5% v/v aqueous Tween 80), 0 (5% v/v aqueous
ethanol, the vehicle used with brodifacoum), 0.001, 0.002 or 0.005 mg brodifacoum/kg/day from
days 6 through 18 of gestation. Ten of the 15 rabbits receiving 0.005 mg/kg/day died or were
humanely euthanized. Ail were found to have, internal hemorrhage. Nine of these does had loss
of blood (in some cases heavy) from the vagina. All of the implants of one doe (#47; euthanized
on day 16) in the 0.005 mg/kg/day group are reported to have had a hemorrhagic appearance, but
, otherwise there were no indications of any dose-related developmental or toxic effects associated
with exposure to brodifacoum at doses up to and including 0.005 mg/kg/day. Because only three
Utters (and only 20 fetuses) were available from the 0.005 mg/kg/day group at 29 days (and taking
into consideration the hemorrhagic appearance of the implants of #46), the NOEL for fetal
toxicity is 0.002 mg/kg/day, and the LOEL is 0.005 mg/kg/day. The only possible indication of
toxicity in the 0.002 mg/kg/day does was the occurrence of a small hemorrhage beneath the lid
of one eye*on gestation day 14 in one rabbit (#44) which was not pregnant, but a similar finding
was not reported for the 0.005 mg/kg/day females. In addition, the prothrombin time was
significantly increased at 0.005 mg/kg/day on day 20 relative to controls (to 26.5 [seconds?] from
14.5) in a preliminary range-finding study. The following table shows the prothrombin time
measurements (presumably in seconds) on day 20 in a preliminary range-finding study.
Table 19 - Prothrombin Time in the Preliminary Developmental Toxicity Range-Finding
Study in the Rabbit (Day 20)*
Mean
SD .
No. of samples
Control
- 14.5
2.0
. 4
,. 0.001 mg/kg/day -
17.4
_ , - \
1 '.-.
0,005 mg/kg/day
26.5**
5.1
3
** Statistically significant at the 1 % level (Student's t-test) compared with the control group
*Data extracted from appendix 1 of MRID 00052442 (p. 31)
29
-------
The rabbit maternal'NOEL is 0.002 mg brodifacoum/kg/day. The LOEL is 0.005
mg/kg/day (based on 75% mortality associated with hemorrhage in pregnant females at this dose
level). The developmental toxicity NOEL is 0.002 mg/kg/day, as only 3 litters (with a total of
20 fetuses) were available for evaluation at 0.005 mg/kg/day). It is reported that all of the
implants from a 0.005 mg/kg/day doe which was euthanized on day 16 had a hemorrhagic
appearance. This developmental toxicity study in rabbits is classified as acceptable (Guideline
83-3b).
(2) Bromadiolone Developmental Toxicity
Groups of pregnant Sprague-Dawley rats received bromadiolone (technical grade) in
aqueous vehicle by gavage from gestation days (gd) 6 through 16 at doses of 0, 17.5, 35, and 70
tig/kg bw/day. There was an increase in the incidence of vaginal bleeding, hypotonicity, pale
eyes, and deaths in 70 /^g/kg dams. None of the above findings were seen in the controls or the.
two lower dose groups. No developmental toxicity was found in the test animals. The NOEL
for developmental toxicity was 70 ^g/kg (HOT). Based on the increased incidence of vaginal
bleeding, hypotonicity, pale eyes, and deaths, the LOEL for maternal toxicity was 70 jtg/kg. The
NOEL was 35 fig/kg. This study satisfies the data requirements'for a developmental toxicity
study in rats (Guideline No. 83-3(a); MRID No. 92196014).
Groups of artificially inseminated New Zealand White rabbits received bromadiolone
(99.8% purity) in aqueous media by gavage from gestation days (gd) 6 through 18 at doses of 0,
2, 4, and 8 /ig/kg bw/day. Vaginal bleeding was found in 8/19 does of the 8 /j,g/kg group, in
1/19 does of the 2 /tg/kg group, and none in the 4 ^g/kg group and the controls. Since
bromadiolone is an anticoagulant, the vaginal bleeding seen in the 2 (j-g/kg group could be
conservatively considered as a compound-related effect in spite of the lack of a dose-related
response. The prothrombin times of the highest dose group and the controls were comparable at
sacrifice (11 days after dosing). This result was consistent with that seen in an antidote study
where bromadiolone (up to 5.6 mg/kg bw) did not affect the prothrombin times of rats which
received bromadiolone in the diet 2 weeks prior to the prothrombin time measurement (Tox.
Document No. 009423; MRID No. 420933-01). Under the conditions of this study,
conservatively, the incidence of vaginal bleeding seen in the lowest dose group (2 jcig/kg) was
considered as a threshold effect. The Peer Review/RfD Committee had analyzed the results of
. this study, and considered the 2 fig/kg as the "threshold" NOEL. The LEL was 4 fig/kg. There
was no developmental toxicity in any dose group, and the NOEL for developmental effect was
8 jtig/kg (HDT). This study satisfies the data requirements for a'developmental toxicity study in
rabbits (Guideline No. 83-3(b); MRID No. 92196015).
(3) Bromethalin Developmental Toxicity
A developmental toxicity study was conducted with Harlan Wistar rats (25 rats/group).
Rats were orally gavaged on gestation days 6 through 15 at a dosing volume of 5 ml/kg with 0
(vehicle, PEG-200), 0.1, 0.3, or 0.5 mg/kg/day bromethalin technical. Surviving dams were
sacrificed on gestation day 20, necropsied and reproductive findings were recorded. The NOEL
for developmental toxicity is 0.5 mg/kg/day (HDT). There were no compound-related external,
visceral or skeletal effects in bromethalin-treated fetuses in comparison to controls on either a
litter or fetal basis.
30
-------
The NOEL for maternal toxicity is 0.3 mg/kg/day and the LOEL is 0.5 mg/kg/day.
Several effects occurred at the 0.5 mg/kg/day including four deaths-during gestation (gestation
days 12, 16, 17, and 17). Three high-dose females.revealed upper respiratory tract infections
which was regarded as secondary due to physiological stress from treatment. Additionally, in 10
of the 25 high-dose females, including the four which died, clinical'signs consisting of hind leg
weakness and decreased muscle tone were seen. Other observations included poor grooming,
weakness, ventral soiling, chromodacryorrhea, decreased respiration, labored respiration,
hypothermia, hind leg paralysis, prostration and dehydration. - '
During the dosing period, high-dose dams had a 30.2% decrease in weight gain in
comparison to controls. During the post dosing period, weight gain in the high-dose females was
decreased by only 11.7% in comparison to controls. Due to the substantial decreased weight gain
during the dosing period, the high-dose females experienced a 13.9% decrease in weight gain for
the entire gestation period in comparison to controls. These decreased weight gains are
considered to be treatment-related. Food consumption was decreased by 8.7% in high-dose
animals in the post dosing period in comparison to controls. The observed decrease in weight
gain during the post dosing period may be because of decreased food consumption. The food
consumption was comparable between controls and treated groups, including the high-dose group
at other times (MRID 00086731).
** ' -
A second developmental toxicity study was conducted with Dutch Belted rabbits
(15/group). In this study, rabbits were orally gavaged at a volume of i ml/kg with bromethalin
at doses of 0 (PEG-200, vehicle), 0.10, 0.25, or Oi 50 mg/kg/day during gestation days 6 through
18. Surviving does were sacrificed on gestation day 28 and reproductive parameters were:
determined. The NOEL for developmental toxicity is 0.5 mg/kg/day (HDT). There were no
compound-related external, visceral or skeletal effects in bromethalin-treated fetuses in
comparison to controls on either a litter or fetal basis.
The NOEL for- maternal toxicity is 0.10 mg/kg/day. Clinical signs of toxicity were
observed in two females at 0.25 mg/kg/day and 5 females in the 0.50 mg/kg/day group. These
signs included nasal discharge, loss of muscle tone, weakness, decreased respiration, coolness,
and prostration. Two high-dose does died; one on gestation day 16 arid one on day 21. The two
high-dose does that died had clinical signs before death. One female that died had pneumonia and
an empty gastrointestinal tract, and the other had an acute upper respiratory tract infection.
Additionally, two high-dose does, one mid-dose doe and one low-dose doe aborted. The two
high-dose and the one low-dose does that aborted had gastric trichobezoars in an otherwise empty
gastrointestinal tract. The mid-dose doe which aborted had an empty gastrointestinal tract. The
clinical signs, abortions and deaths at the top dose and the clinical signs at the mid-dose are
considered compound-related. Mid and high-dose animals had decreased weight gains during the
dosing period, which are considered compound-related. Food consumption was comparable
between control and treated does during gestation. Although values for the mid-dose animals
were lower than controls, this finding was not dose-related and is not considered compound-
related (MRID 00101545).
(4) Chlorophacinone Developmental Toxicity
In a preliminary range-finding study in rats (MRID 43349501) chlorophacinone
(analytically determined concentration 101%) was administered at days 6-15 of gestation at doses
- - '... - - 31 '' " ' . - ' ,.
-------
of 0, 1, 5, 25, 50, 100 or 200 jtg/kg/day to groups of 8 mated Sprague-Dawley female rats.
Mortalities occurred at 100 and 200 jtg/kg/day. Five rats/dose level in the 0, 1, 5, 25 and 50
/ig/kg/day groups were sacrificed on gestation day 16, and prothrombin and activated partial
thromboplastin times were determined (Refer to Table 20).
It is noteworthy that while there was clotting in at least one sample from the controls and
3 lowest dose groups, this apparently did not occur in the 5 samples from rats of the 50 jtg/kg/day
group. -
Table 20 - Prothrombin (PT) and Activated Partial Thronlboplastin Times (APTT) in a
Preliminary Rat Developmental Toxicity Study
Prothrombin Time (sec)1
Activated Partial Thromboplastin Time (sec)a
'Dose LeverG*.g/kg/day)
0
12.2 ฑ 0.6
N=4b
15.5ฑ2.1
1
12.9 ฑ 1.3
N=2b
23.9ฑ12.4
, '5
12.8 ฑ 0.3
N=4b
16.1 + 1.4
25
12.6 ฑ 0.4
N=3b
16.2+1.3
50
13.0 ฑ 0.2
N=5
17.0ฑ0.9
"Reported as the mean + S.E.M.
bdecrease in N is due to the clotting of some of the samples on which the analysis could not: be done.
In the subsequent developmental toxicity study (also in MRID 43349501) chlorophacinone
(analytically determined concentration: 101% a.i.) was administered to groups of 25 Sprague-
Dawley female rats/dose level by gavage at doses of 0 (vehicle only), 12.5, 25, 50 or 100
jtig/kg/day on gestation days 6-15 inclusive. The test compound was administered as a suspension
in com oil. Eighteen high-dose (100 /ig/kg/day) rats died or were sacrificed moribund (gestation
days 12-16) with necropsy findings (blood in vagina and amniotic sacs, blood in stomach and/or
small and/or large intestines) indicative of anticoagulant effects. There were no indications of
maternal toxicity at 50 pg/kg/day. Treatment-related effects for developmental anomalies, were
noted at the lowest dose and above as increased fetal and litter incidences of distended ureter
(Refer to Table 21).
Table 21 - Fetal and Litter Incidences of Treatment Related Effects in a Rat Developmental
Toxicity Study (doses in
# pups/# litters examined
Control 0
205/25
Low 12.5
186/24
Low Mid 25
206/25
High Mid 50
196/24
High 100
55/7
"" ., Hfydroureter:
Bilateral
Left
Right
TOTAL INCIDENCE
% Incidence
4/4
2/2
0/0
6/6
2.9/24.0
8/4
3/3
0/0
11/5
5.9/20.8
23/10
3/3
0/0
26/11
12.6/44.0
21/9
5/4 ,
III
21 111
13.8/40.7
12/3
0/0
1/1
13/4
23.6/57.1
; Distended ureter: "r
Bilateral
Left
TOTAL INCIDENCE
% Incidence
1/1
1/1
2/2
1.0/8.0
2/2
4/3'
6/4
3.2/16.7
3/2
3/3
6/5
2.9/20.0
4/4
6/6
10/7
5.1/25.9
1/1
1/1
2/2
3.6/28,6
, : . N Total ureter anomaly;
incidence:
% Incidence
8/6
3.9/24.0
17/10
9.1/41.7
32/13
15.5/52.0
37/14
18.9/51.9
15/5
27.3/71.4
32
-------
At the highest dose (100 y^g/kg/day) there was an increased total incidence (16/55 fetuses
in 5/7 litters; controls: 14/205 fetuses in 10/25 litters) of enlarged lateral ventricle. At 50
jtg/kg/day there was an increased incidence of extra rib on lumbar vertebrae I (not noted at 100
/ig/kg/day; however, fewer litters were available for examination). For malformations, there'
were increased fetal and litter incidences of bilateral hydroureter at 25 >g/kg/day.
' The rat maternal toxicity NOEL = 50 pig/kg/day.
The rat maternal toxicity LOEL= 100 /^g/kg/day (based on mortality)
The rat developmental NOEL is < 12.5 ^g/kg/day. .
The rat developmental LOEL is < 12.5 ^g/kg/day (increased incidences of hydroureter,
distended ureter and total ureter anomaly).
This developmental toxicity study in the rat is classified as acceptable and satisfies the
guideline 83-3(a) requirement for a developmental toxicity study in the rat.
In a preliminary range-finding developmental toxicity study in rabbits (MRID 43570801).
chlorophacinone (analytically determined concentration 101%) was administered at 0, 1, 2, 5, 10,
50 or 100 #g/kg/day to groups of 5 mated female rabbits. In addition, there were five satellite
groups, each containing 3 rabbits dosed at 0, 1, 2, 5 or 10 /ig/kg/day. The dosing period was
from gestation days 7 through 19; satellite females were sacrificed on gestation day 20 and their
blood was .analyzed for Prothrombin Time (PT) and Activated Partial Thromboplastin time
(APTT) measurements. Both the mean PT and APTT were elevated in the 10 jag/kg/day females
(refer to Table 22). ,_ '
Table 22 - Prothrombin (PT) and Activated Partial Thromboplastin Times (APTT) in a
Preliminary Rabbit Developmental Toxicity Study Chlorophacinone Qag/kg/day)
No, of female rabbits bled
ProthrombJn Time (sec)4
'Activated Partial thromboplastin Time (sec)3
- 0
.3
8.1 ฑ. 0.5
26.5 ฑ 5.7*
1 i
3
7.8 ฑ 0.2
26.6 + 3.7
2
3
7.9 ฑ0.r
23.2 +.1.5
5
3
- 8.7 ฑ 0.6
26.4ฑ 4.9
' 10
3
11.6 ฑ 2.1
53.0 +14.3
f
"Reported as the mean + S.E.M.
*p<0.05; Jonckheere's Test (significant by trend test)
Table from page 167 of MRID 43570801.
In the subsequent developmental' toxicity study in rabbits (MRID 43570801),
chlorophacinone (analytically determined concentration reported as 101%) was administered to
16 New Zealand white rabbits/dose level by oral gavage at dose levels of 0, 5, 10, 25 or 75
/tg/kg/day from gestation days 7 through 19, inclusive.
There was maternal mortality in 13/16 high mid (25 /ig/kg/day) and 16/16 high dose (75
/^g/kg/day) rabbits, with hemorrhage (neck, thoracic cavity, vagina, uterus, amniotic sacs, and
GI tract). Increased incidences of external bleeding around the mouth, ears, and urogenital
system, along with pale eyes, ears, lips/gums, lethargy and blood in the pan beneath the cage,
were noted in the two highest dose groups. No evidence of treatment-related fetotoxicity was
33
-------
noted in the cesarean section observations. However, due to the low number of surviving litters
(3) at 25 /a.g/kg/day, and the lack of surviving litters at the highest dose (75 /ug/kg/day),
developmental toxicity cannot be assessed at these doses, and 10 jtg/kg/day will be considered as
the NOEL for developmental toxicity. This developmental toxicity study in the rabbit is classified
as Acceptable (Guideline 83-3(b), and satisfies the guideline requirement for a developmental
toxicity study in the rabbit.
The rabbit maternal toxicity NOEL is 5 #g chlorophacinone/kg/day. The LOEL is 10
/ig/kg/day (based on increased prothrombin and activated partial thromboplastin times in the
preliminary range-finding study. These measurements were not made in the subsequent
developmental toxicity study). The rabbit developmental toxicity NOEL is 10 /tg/kg/day, based
on the lack of sufficient fetuses/litters at the next highest dose level (25 jug/kg/day) available for
evaluation. This developmental toxicity study (Guideline 83-3(b) in the rabbit is classified as
acceptable.
, _ \
(5) Diphacinone and its sodium salt Developmental Toxicity
In a developmental toxicity study in rats (MRID 42834801), technical diphacinone (purity
>97%) in corn oil was administered via gavage to groups of 25 mated female Sprague-Dawley
rats/dose level at 0, 10, 25 or 75 ^g/kg/day on gestational days 6-15, inclusive. There were no
effects on maternal body weight or weight gain. Reddish vaginal discharge, reddish urogenital
Staining and/or reddish fluid in the cage/tray were observed in one dam from the control group,
two dams at 10 jctg/kg/day, three dams at 25 jtg/kg/day, and six dams at 75 ^g/kg/day. One dam
(with these symptoms) in the 75 /tg/kg/day group was euthanized in extremis on day 15. A NOEL
was not established for maternal toxicity then, as there was a dose-related increase in incidence
of clinical signs of the anticoagulant effects of diphacinone through all dose levels. No
compound-related altered growth and/or developmental anomalies were observed. There was an
increased number of early resorptions and resorptions/dam at 75 /ig/kg/day (52 and 2.2 ฑ 1.8,
respectively, compared to control values of 33 and 1.4 ฑ 1.5). These increases were not
statistically significant, and were within the upper limit of historical control data. However, 33 %
mortality was observed at 100 jcig/kg/day in a range-finding study, and the increased number of
resorptions is consistent with what was observed in a mouse developmental toxicity study (MRID
00077319) at a dose level (2.5 mg/kg/day) at which 5/5 pregnant females died.
The rat maternal toxicity NOEL < 10 jctg/kg/day.
The rat maternal toxicity LOEL= 10 #g/kg/day (based on signs consistent with
anticoagulant activity)
The rat developmental NOEL =- 25 ^g/kg/day.
The rat developmental LOEL = 75 /ig/kg/day (based on an increased incidence of
resorptions)
This developmental toxicity study in the rat is classified as acceptable, and satisfies the
guideline (Guideline 83-3(a) requirement for a developmental toxicity study in the rat).
34
-------
It is noted that no clotting time measurements were obtained in this rat developmental
toxicity study, and that there is no rabbit developmental toxicity study. The Agency has received,
for brodifacoum and chlorophacinone, both rat and rabbit developmental toxicity studies. For
both of these anticoagulants, the rabbit is the more sensitive species, particularly with respect to
mortality. . .
f. Mutagenicity
Results of mutagenicity studies for brodifacoum, bromadiolone, bromethalin,
chlorophacinone and diphacinone and its sodium salt indicate the following:
Salmonella typhimuriurn. There were no indications of an increased number of revertants
at the histidine locus in any of the strains used. .
In Vivo Testing. While .different species were used such as Chinese hamsters and mice,
results were consistent and there was no evidence of induced mutagenicity response to any
strains at any non-activated or activated dose levels.
In Vitro Testing. Testing was performed for chlorophacinone and bromadiolone. Based
on this testing it can be concluded that at doses up to and including those associated with
cytotoxicity (50 ^g/ml), did not induce a clastogenic response in human lymphocytes
under the conditions of this assay either in the presence or absence S9.
Appendix C of this document, provides the MRID numbers and names of studies used to
support these mutagenicity findings.
"'.""ป'* . ' -l ". ' - .
g. Metabolism
(1) Brodifacoum Metabolism
In the first part of a metabolism study (MRID 44021705) brodifacoum, 3-[3-(4'-bromo-
[ 1,1' -biphenyl] -4-yl)-1,2,3,4-tetrahydro-1 -naphthalenyl] -4-hydroxy-2H-1 -benzopyran-2-one,
radiochemical purity >98%, radiolabeled (14C) in the benzene ring of the benzopyran, was
administered to 3 previously bile-duct cannulated Crl:CD(SD)BR strain male rats as a single oral
administration at a nominal dose level of 10 mg/kg body weight, well above the LD50 value of 0.3
mg/kg. The rats had been pre-dosed with vitamin Ka in their drinking water, but showed
symptoms of anticoagulant toxicity before sacrifice at 48 hours. Bile, urine and feces were
collected at pre-dose, 6, 12, 24, and 48 hr post-dose, and radioactivity was determined in these
samples, as well as in the livers and residual carcasses. The metabolite profiles of 14C-
brodifacoum in bile and bile extracts were examined by chromatographic and spectroscopic
techniques.
Total mean recovery of radioactivity was 102.9 ฑ 8.1%. Recovery from feces
(presumably unabsorbed brodifacoum) was 36.11 ฑ 8.83%; from liver was 14.79 ฑ 0.41; from
the residual carcass: 42.85 ฑ 5.06%. The mean from ;bile (all 3 animals) was 6.40 ฑ 5.45%,
but one rat had poor bile flow, possibly from blockage in the cannula. The two remaining
animals had a mean 9.53 % of the label in bile.
'-'''' ' 35 . "
-------
The major (and only identified) metabolite of brodifacoum in bile was the glucuronide
(attachment to the 4-hydroxy moiety of brodifacoum), which accounted for 39.43 to 77.28% of
the total radioactivity in individual bile samples, while brodifacoum represented 0.00 to 24.95%
of the total activity. Further characterization appeared to split the glucuronide peak into 2
components, and while the cis:trans ratio of parent material was 70:30, the ratio in the
glucuronide was reversed (30:70). One unidentified metabolite (region 10) ranged from 1.59 to
21.7% total radiolabel.
Although only one metabolite (the glucuronide) is identified, it is the parent compound
which is of lexicological concern, and the registrant has adequately demonstrated in previously
submitted studies (refer to MRIDs 00080235 and 42007502) that a high proportion of
unmetabolized compound is retained, particularly in the liver.
In a second study (in vitro perfusion, also in MRID 44021705) the lower vena cava of a
single male rat was ligated. The hepatic portal vein was then cannulated and the liver was cleared
of blood and the bile duct cannulated. The liver was perfused and, after equilibration, 14C-
brodifacoum, at a dose of 10 mg/kg, was added to the main perfusate reservoir. Bile and
perfusate were collected at pre-dose, 1 minute (perfusate only), 1, 2, 3, 4 and 6 hr post-dose.
The radioactivity present in bile, perfusate, terminal perfusate supernatant, supernatant filtrate and
liver was determined. There was 74.32% recovery after 6 hours, with 59% of the total in
perfusate, and 15.19% in liver. Metabolite profiling was attempted, but no metabolites were
identified. All radioactivity in the perfusate supernatant was bound to perfusate proteins, with no
activity being measured in the aqueous filtrate.
In a metabolism study (MRID 42007502), groups of male rats received single oral doses
of MC-labeled brodifacoum at different dose levels (Group 2: 0.02 mg/kg; Group 3: 0.15 mg/kg;
Group 4: 0.35 mg/kg), and blood was taken from 1-3 rats/group at various intervals following
this dosage. The following Kaolin Cephalin .Time (KCT) and Prothrombin Time (PT)
measurements were made as outlined in Table 23 below:
36
-------
Table 23 - Kaolin Cephalin and Prothrombin Time in a Metabolism Study in Male Rats
Time after
Dosing
6hr
12 hr
18 hr
24 to
48 hr
' ?2Jhr
96 hr
Day8
Day 14
Day 28
Day 56
> Day 84
Week 13
Week 26
Week 39
Weefc52
, Week 65 :
Week 78
Week 91
N Week 104
r Clotting times (seconds)
Group 2; Q.OZjng/fcg
KCT
-
- '
-
14.9a ฑ4.2
-
. -
- - -
- - .
-
14.9a ฑ1.1
-"
1 -
14. la ฑ1.1
. -
16.6 ฑ 4.3
16.7 ฑ 3.3
-
16.8 ฑ2.6
14.7 ฑ 3.0
PT
'.;- :
-
-
13.0a ฑ1.8
-
-
. -
.'-
12.7a ฑ0.3
, -
. - '
15.4aฑ0.6
' - '
13.5 ฑ 1.2
." -
13.5 ฑ 0.8
'
14.6 ฑ 0.4
11.1 ฑ 1.0
Group 3i 0*15 ttig/kg
KCT
-
,- ' .
-
15.8 ฑ 4.8
'. -
. -
-'
.
14.0 ฑ1.1
21.3 ฑ 2.9
16.2aฑ 2.4 '
- - .
16r5 ฑ 1.4
12,3b
15.0 ฑ1.7
15.6 ฑ 6.2
, 18.0 ฑ 3.2
18.6 ฑ 1.3
19.8 ฑ 2.2
13.2 ฑ 0".5
PT
-
13.0 ฑ 1.1
-
.
-
' -.
14.3 ฑ 0.2
13.6 + 0.6
12.7aฑ0.6
-
13.8 ฑ 0.2
*16.1b
13.8 ฑ 0.5
12.7 ฑ1.2
13.2 ฑ 0.5
12.8 ฑ 1.2
15.1 ฑ 1.5
10.9 ฑ 0.6
Group 4: 0,35 mg/kg
KCT
'ND
ND
43.7 ฑ2.1
58,9 ฑ 7.6
113.7ฑ10.6
92.8 ฑ49:4
32.3 ฑ7.2
2l.3aฑ2.4
15.4 ฑ 4.5
20.2 ฑ 2.9
19.6aฑ 2.2
17.2 ฑ 2.9
-
-
-
-
- --
-
-
PT
14.3 ฑ 1.7
20.7 ฑ 3.7
37.2 ฃ 5.4
95. 5" ฑ2.7
147.6 ฑ 6.9
39.7 ฑ19.4
18.8 ฑ 2.0
15.8aฑ 1.2
17.4 ฑ 0.5
13.4 ฑ 0.4
13.3aฑ 0.2
12.5. ฑ 0,4
-
'
'-. -
.
-
-
- .
-
The standard deviation (SD) is derived from data obtained with 3 animals per group.
a2 values only .
b single value only
ND = not determined .
Table taken from p. 26 of MRID 42007502. '
The results given above clearly show an increase in clotting time in rats which had
received a single oral dose of 0.35 mg/kg. Assuming the effect was manifested as a doubling of
the normal clotting time (to approximately 30 seconds for kaolin cephalin and/or prothrombin
times), effects were evident as soon as 18 hours after dosage, and were still present at 96 hours
post-dosage. In addition, the metabolism study in MRID 42007502 demonstrates that considerable
amounts of the radiolabel are retained in the .liver following dosage (refer to the Table 24).
37
-------
Table 24 - Percentage of radioactivity retained in the liver following single-dose
administration of 14C Brodifacoum
Time after dosing
Day 1
Week 4
WeekS
Week 12
Week 13
Week 39
Week 65
Week 91 '
Week 104
Group 2; 0,02 Big/kg
Mean SD
47.33 ฑ10.87
39.16 ฑ 3.50
-
,
34.01 ฑ 2.49
20.33 ฑ 0.42
15.97 ฑ 2.33
10.57 ฑ 1.08
11.78 ฑ 0.97
Group 3: 0.15 mg/kg
Mean SD
29.71 ฑ 4.40
37.07 ฑ 1.94
30.86 ฑ 4.23
-
31.74 ฑ 5.13
22.02 + 2.83
15.36 ฑ 3.03
12.39 ฑ 3.08
11.74 ฑ 1.64
Group 4; 0,35 mg/kg
Mean SD
28.92 ฑ 1.79
23.47 ฑ 1.21
23.00 ฑ 0.09
21.24 ฑ 3.19
-
-
-
Table from data on pages 30-32 of MRID 42007502.
It is concluded that overall there is sufficient metabolism data (including excretion,
distribution, retention half-life and amounts retained'within different organs). This metabolism
study in the rat, taken with previously submitted metabolism studies (in MRlDs 00080235 and
42007502) is classified as acceptable. The combination of these studies is adequate to satisfy the
85-1 data (metabolism study) guideline requirement.
Groups of male Sprague-Dawley rats received a single dose (0.2 mg/kg bw) of
brodifacoum, bromadiolone, or flocoumafen by gavage. A control group consisting of 9 male
rats which received nothing was also included in the study. The results showed that the levels
of brodifacoum in the liver declined very slowly during the duration of the study as indicated by
the difference between day 1 (1.107 jig/g) and day 200 (0.539 j^g/g). During the first 28 days
after dosing, the decline of the liver concentrations of bromadiolone and flocoumafen was faster
than that of brodifacoum as indicated by the t1/2's of these 3 chemicals at the first 28 days
(brodifacoum: t1/2, 63 days; bromadiolone: t1/2, 17 days; flocoumafen: t1/2, 6 days). The decline
of the liver concentrations of these 3 test chemicals occurred in a "bi-exponential manner". The
second t1/2's were estimated to be 282, 318, and 159 days for brodifacoum, bromadiolone, and
flocoumafen, respectively. In general, oral administration of any of these 3 chemicals would
result in substantial retention of the chemical in the liver for a very long time. The initial report
of this study contained deficiencies which were rectified in subsequent supplemental date
submission. This study satisfies the data requirement for a modified metabolism study on
bromadiolone (Guideline No. 85-1; MRID No. 42596801).
(2) Bromadiolone Metabolism
Groups of male Sprague-Dawley rats received a single dose (0.2 mg/kg bw) of
brodifacoum, bromadiolone, or flocoumafen by gavage. A control group consisting of 9 male
rats which received nothing was also included in the study. The results showed that the levels
of brodifacoum in the liver declined very slowly during the duration of the study as indicated by
the difference between day 1 (1.107 ^g/g) and day 200 (0.539 /tg/g). During the first 28 days
38
-------
after dosing, the decline of the liver concentrations of bromadiolone and flocoumafen was faster
than, that of brodifacoum as indicated by the t1/2's,pf these 3 chemicals at the first 28 days
(brodifacoum: t1/2, 63 days; bromadiolone: t1/2, 17 days; flocoumafen: t1/2, 6 days). The decline
of the liver concentrations of these 3 test chemicals occurred in a "bi-exponential manner". The
second t1/2's were estimated to be 282, 318, and 159 days for brodifacoum, bromadiolone, and
flocoumafen, respectively. In general, oral administration of any of these 3 chemicals would
result in substantial retention of the chemical in the liver for a very long time. The initial report
of this study contained deficiencies which were rectified in subsequent supplemental data
submission. This study satisfies the data requirement for a modified metabolism study on
bromadiolone (Guideline No. 85-1; MRID No. 42596801). ,
(3) Bromethalin Metabolism
A metabolism study was conducted in Fischer 344 rats following oral administration: of
14C-bromethalin at 1 mg/kg. Blood samples were taken from the orbital sinus at 0.25, 0.5, 1, 2,
4, and 24 hours, and at 2, 3, 4, 6, 8, 11, 14, 17, and 21 days after dosing. Based on radiolabeled
material, the plasma half-life was 134 hours (5.6 days). The half-life of the distributive phase
suggested distribution in total body water. The T J/2 of bromethalin is 5.6 days. The major
metabolite formed in the rat is desmethyl bromethalin. The study (MRID 0004724) was classified
as acceptable.
' ' ** ' ' - -
(4) Diphacinone and its sodium salt Metabolism
In a metabolism study (MRID 92049009), the disposition of 14-C diphacinbne was studied
in Sprague-Dawley! rats, Swiss albino mice, and Diphacinone-tolerant Norway rats.
Sprague-Dawley rats received single oral doses of 0.18, 0.4 mg/kg (group A, 2 rats/group), 0.5,
or 1.0 mg/kg (group B, 1 rat/group) labeled diphacinone and urine and feces collected up to 3
days post-dose (group A) or 8 days post-dose (group B). Swiss mice (1 mouse/group) received
0.6 mg/kg labeled diphacinone by oral intubation or sandwich method and urine and feces
collected up to.4 days post-dose. Norway rats (1 rat) received 4 consecutive doses of 3.5 mg/kg
labeled diphacinone and 1 dose of 6.1. mg/kg labeled diphacinone. Blood samples were obtained
. at 4, 6, 7, and 8 hours after the last dose and at 26 hours (time of sacrifice). A group of 10
diphacinone-tolerant Norwegian rats received 1.5 mg/kg labeled diphacinone in DMSO daily for
2-3 days to obtain enough excreta for metabolite identification. Because 4 different batches of
labeled diphacinone were prepared for this study (label in different positions for each batch), eight
Sprague-Dawley rats (2 females/group) received approximately 42 fj,g of labeled diphacinone from
each labeled batch as a single oral dose, and^TLC autoradiograms from these 4 labels were
compared. ,
Absorption appeared fairly rapid but was only estimated in one rat, as judged by the blood
levels measured over time. Distribution data showed that the liver,'muscle, blood, fat, and lung
were the tissues demonstrating the greatest retention of the test chemical in the order liver
(14-25% of the dose), muscle (0.18-4.4% of the dose), fat (0.55-1.16% of the dose), and lung
(0.04-0.5% of the dose). Rats appeared to show greater retention than mice of test chemical, but
data were inconclusive based on limited numbers of animals and poor experimental design.
'" - - - . r :
-. ; '' - ..'" '39 ' '.
-------
Half-life, as estimated in the single Norway rat, was stated as 17 hours, but is likely an
underestimation. Elimination of diphacinone derived radioactivity was primarily in feces, with
between 47-77% of the dose in feces of rats, and 69-73% of the dose in mice. At least five
metabolites of diphacinone were identified in urine, feces, and/or liver. These metabolites
represent hydroxylated products of diphacinone occurring on the phenyl and indandionyl rings.
This study is classified as unacceptable and does not satisfy the guideline requirement 85-1
for a metabolism study in rats. The unacceptable classification is based on the following
deficiencies observed in this study:
1) Inadequate number of animals per dose group.
2) Four different radiolabeled parent compounds were administered in this study.
Distribution data show that blood, liver, muscle and fat contained the highest amount of
radioactivity, but the percentages found might depend on the label position. The excretion
of only two different radiolabeled compounds was followed to any degree.
3) Inadequate experimental design for analysis of half-life.
4) Inadequate data on recovery of radioactivity from dosed animals.
5) No stated rationale for doses used.
j
The Agency requires metabolism data more adequately defining the half-life of
diphacinone in the rat, as well as retention data for the liver.
(5) Chlorophacinone Metabolism
Agency records indicate only one metabolism study (MRID 00155540) on chlorophacinone
has been received. Several experiments were conducted, including blood kinetics (2 experiments
with a determination of radioactivity in organs 4 and 48 hours following dosage; urinary, fecal
and biliary excretion).
In the first blood kinetics assay, four rats each received orally 1 mg of 14C-labeled
chlorophacinone. The following mean blood concentrations were measured as outlined in Table
25 below:
Table 25 - Mean blood concentration of chlorophacinone (in /tg equivalents) following oral
administration of 1 mg chlorophacinone
Mean Blood Cone.
Sflroin,
1.4
ifar.
2.4
2hr.
4.1
4hr,
6.4
<5hr.
6.4
Shr.
5.9
24 hi.
1.8
48 hr, "
0-3 !
Chromatography and autoradiography demonstrated that the chlorophacinone remained
unchanged in plasma, with a blood half-life of about 10 hours.
40
-------
Organs of the rats used in the first blood kinetics study were assayed for radioactivity.
The following results were obtained as outlined in Tabler 26 below:
Table 26 - Mean concentration of chlorophacinone Qtg/g of organ)
"Organ
Liver
Kidney
Lung
Heart .
Muscle (thigh)
Fat , '
Carcass '
4 hours
1 31.1
6.6
, 4.5
3.1
2.0 "
1.2
5.2
48 hours
2,9
1.2 .
0.4
0.2 .
0.1
0.7
0.3
In a second blood kinetics study, two rats each received 1.43 mg of 14C-labeled
chlorophacinone/day for 3 days. Blood samples were taken at various times following the third
dose, with the following blood concentration measurements as outlined in Table 27 below,'
Table 27 - Mean blood concentration of chlorophacinone (in fug equivalents) following three
daily oral administrations of 1.43 mg chlorophacinone
Mean Blood Cone.
30 nan. :
7-1.
IJhr.
8.9
2hr,
10.2
4nr>
11.5
6Jir<
12.2.
8hr.
14.2
In an elimination assay, two rats were used. One received 1.43 mg of 14CMabeled
chlorophacinone and the second received 1.28 mg 14G-labeled chlorophacinone. Daily assays
were made of urine, feces arid CO2 for four days. The rats were sacrificed and radioactivity was
measured in blood, organs and carcass. Urine and feces were extracted and measured by TLC
and autoradiography. ;
Urine and CO2 radioactivity were less than 1 % of the total dose. Most of the radioactivity
was excreted in the feces (94.7% in one rat and 108.6% in the other over the 4-day period).
Excretion reached 90% in the first two days. . ,
In a biliary excretion assay, two rats were used. Each received 1.4 mg of chlorophacinone
intraduodenally. Bile was collected for 8 hours and total radioactivity was measured. TLC and
autoradiography were performed on the bile directly before and iafter hydrolysis with
glucuronidase. , ; ,
Two hours after administration of chlorophacinone in the duodenum, biliary elimination
was constant. At the end of 8 .hours, an average of 26% of the administered radioactivity was
eliminated in the bile.
The information provided in MRID 00155540 adequately addresses the guideline
requirements 85-1 for a metabolism study for a highly toxic anticoagulant with no chronic
41
-------
exposure. Although it is reported that there is over 90% excretion in the two days following
dosage, the findings in the subchronic study (MRID 92018013) indicate there is a potential for
bioaccumulation (or cumulative toxicity). In the subchronic study, there were mortalities at 40
jig/kg/day in 10/10 males (deaths occurred days 29-82) and 4/10 females (deaths on days 69-111),
and there were also mortalities at 20 ^g/kg/day in 4/10 males (deaths on days 105-111).
h. Other Toxicological Considerations
(1) Brodifacoum - Other Toxicological Considerations
In an antidotal study (MRID 42007501), four male beagle dogs each received a single oral
dose of 5 mg/kg brodifacoum (96.8%). Prothrombin times for each of the dogs were then
monitored over a period of five weeks. "Doses of 2 mg/kg vitamin Kj were administered to dogs
by the intramuscular route whenever their prothrombin times were elevated to levels consistent
with a life-threatening effect on coagulation." Individual dogs required 12-15 vitamin Kt
treatments in the period from days 2 to 29 post-dosing. All four dogs survived to the end of this
study (5 weeks after the test material was administered). However, based on elevations in
prothrombin time, vitamin Kj had to be administered to one dog on day 29. This dog had also
been treated with vitamin Kt on days 23 and 24 as well as on previous occasions, and the last
prothrombin time measurement for this dog was on day 34. The possibility exists that this dog
would have required additional vitamin Kj treatments after day 34.
(2) Bromadiolone - Other Toxicological Considerations
In an antidotal treatment study, groups of male Crl:CDR rats (10/dose) were exposed to
bromadiolone baited peUets (0.005% a.i.) for 24, 48, or 78 hours. The estimated mean total
bromadiolone doses were 5.69, 9.76, and 15.63 mg/kg for 24-, 48-, and 72-hour groups,
respectively. At the end of the exposure period, the first 5 surviving rats of each group were
given vitamin Kx at 5 mg/kg. Initially, a loading dose was given subcutaneously, and
subsequently, vitamin K! was administered daily by gavage for 13 days. The survivors were
sacrificed at 8 to 10 days after discontinuing the vitamin Kx treatment.
The animals which did not receive vitamin K: died in each exposure group. The deaths
. frequently occurred within 3 to 4 days of the study. The clinical and gross pathology findings
were hemorrhage-related toxicity in all test-article treated animals. The death rates in vitamin Ka
treated animals were 1/5, 2/5, and 5/5 in the 24-, 48-, and 72-hour exposure groups, respectively.
With vitamin Kj treatment, the clinical findings (hemorrhagic-related toxicity) were resolved by
the 5th day of the antidote treatment, and the decrease in body weight observed during the
bromadiolone treatment was also restored in the surviving animals. At the 2nd week of the study,
the prothrombin times of the vitamin Kx treated animals were essentially comparable to those of
the controls. However, for the 48-hour exposure group, the prothrombin time was slightly
decreased relative to that of the control.
The results demonstrate that vitamin Kj treatment, as employed in this study, can restore
the clotting process of an animal which is exposed to bromadiolone below an estimated total dose
of 15.63 mg/kg body weight during a 72 hour period. However, the antidotal treatment may not
completely prevent death (i.e. all the rats died in 72-hour exposure groups with vitamin K1
42
-------
treatment) when rats are exposed to bromadiolone even at the lowest exposure dose (5.69 mg/kg)
in this study. This study satisfies the data requirements .-for an antidotal study (Guideline 86-1-
MRID No. 42093301). - '
(3) Bromethalin - Other Toxicological Considerations
The following information is in the Agency's files and are supportive of the endpoint of
toxicological concern identified in the above studies.
Ph.D. Dissertation entitled "Bromethalin-Based Rodenticides: Mode of Action, Toxicity,
Clinical Effects, and Treatment Efficacy in Rats, Dogs, and Cats", by D. Dorman,
University of Illinois, Dept. of Veterinary Biosciences (MRID 42759602).
- This dissertation is a summary of information found in the literature. According to the
summary page of the dissertation, "The purpose of these studies was to define the toxicity of
bromethalin-based rodenticides, develop treatments, and determine new modes of action of
bromethalin Sublethal doses of bromethalin to dogs and cats resulted in delayed CNS
depression, hind-limb ataxia, paresis, and paralysis. Higher doses given to dogs resulted in rapid
severe muscle tremors and generalized seizures. Bromethalin toxicosis was also associated with
increased cerebrospinal fluid pressure and cerebral edema. Bromethalin toxicosis produced acute
and chronic EEG changes. Predominant abnormal EEG changes included spike and spike-and-
'wave EEG patterns; high voltage slow wave activity; photoconvulsive or photoparoxysmal
irritative responses, and marked voltage depression. Histologic lesions included diffuse white
matter spongiosis, mild microgliosis, and optic nerve vacuolization. Ultramicroscopic
examination of brainstem revealed occasional swollen axons, intramyelenic vacuolization, and
myelin splitting at the intraperiod line."
The Toxicitv and Mechanism of Action of Bromethalin HURTD 42795603).
This publication is a journal article with only summary data. The study authors state "
Doses in excess of the LDSO (2 mg/kg in rats) will cause death within 8:12 hours and it is preceded
"by one to three episodes of clonic convulsions with death usually due to respiratory arrest.
Multiple low doses or sublethal intoxication yield hind leg weakness and loss of tactile sensation
. in rodents. Histopathology of the brain and spinal cord of these animals revealed a spongy
degeneration of the white matter which was shown upon ultramicrbscopic examination to be
intramyelenic edema. ...Mechanistic studies showed that bromethalin is rapidly converted to the
desmethyl analog which is an extremely potent uncoupler of oxidative phosphorylation. It was
theorized that if this occurs in the central nervous system, a fluid imbalance may ensue due to
insufficient adenosine triphosphate (ATP). Fluid buildup in the cranium was determined by
measuring cerebrospinal fluid pressure (CSFP), brain and spinal cord moisture, and cation
concentrations."
Toxicitv and Efficacy of Bromethalin fMRID 42795604)
This report is a published journal article with no raw data. The study authors state "Acute
oral LDjo values range between 1 and 13 mg/kg for several mammalian and avian species.
' . ' 43- , -
-------
Results of experiments designed to determine the physiological and biochemical mechanism of
action suggest that treatment with bromethalin results in the uncoupling of oxidative
phosphorylation in central nervous system mitochondria."
(4) Chlorophacinone - Other Toxicological Considerations
In an antidotal study (MRID 41981101) groups of 10 male rats were offered pelleted end-
use product (containing 0.005% chlorophacinone) as their sole dietary source of food for 24, 48
or 72 hours. Reported mean dose levels were 5.28, 4,73 and 5.03 mg chlorophacinone/day.
About 1-2 hours after the end of their respective exposure periods, five males in each group
received a subcutaneous injection of 5 mg/kg vitamin Kl5 followed by vitamin K! by daily oral.
gavage (5 mg/kg/day) for the next 13 days. Animals were sacrificed 8-10 days after the last oral.
dose of vitamin K^' Five animals in each dose group did not receive vitamin Kj treatment.
All rats that ate the chlorophacinone-containing pellets and did not receive vitamin K! died.
All rats treated with vitamin Kx after 24-hour exposure to the chlorophacinone diet survived, as
did 3/5 rats fed the chlorophacinone-containing diet for 48 hours. All of the vitamin Kj-treated
rats which had been fed the chlorophacinone-containing diet for 72 hours died.
While vitamin Kx has been shown to be a somewhat effective treatment following
chlorophacinone ingestion, there were some mortalities among the rats which were given vitamin
KI at 48 hours. This suggests a potential hazard if incidents occur involving pets or small children
in which it is not known or realized that ingestion has occurred. It is noted that this antidotal
study does not include prothrombin times. Such information, while not necessary for purposes
of reregistration, could be useful to the Agency in defining hazards associated with exposure to
chlorophacinone.
(5) Diphacinone and its sodium salt - Other Toxicological
Considerations
A collection of published articles (in MRIDs 42791201, 42791202, 42791203) from the
literature has been submitted to support the use of Vitamin Kx as an antidote in treating
diphacinone poisoning.
In one report (Mount, M. E. and B. F. Feldman, 1983. The Mechanism of Diphacinone
Rodenticide Toxicosis in the Dog Clarified and Its Therapeutic Implications. Am. J. of Vet. Res.
44(11): 2009-2017; in MRID 42791201) the clinical effectiveness of Vitamin Kx therapy in
reversing anticoagulant effects of two rodenticides in male dogs was investigated. Warfarin and
diphacinone were administered in the diet twice daily for 3 days. Warfarin was fed to one dog at
a,total dose of 5 mg (a.i.)/kg and diphacinone was fed to three dogs at 2.5 mg (a.i.)/kg. These
doses would generally be lethal for repeated exposure. Evidence of coagulopathy was observed
by day 3, and Vitamin K: therapy was initiated for all dogs on day 6 at divided doses 3 times/day
over a 5-day interval. One warfarin and one diphacinone-dosed dog received 2.5 mg Kj/kg/day,
while the other two diphacinone-dosed dogs received 5 mg K^/kg/day. All animals survived to
the termination of the study.
44
-------
' . A single regime of vitamin Kt (2.5 mg/kg/day for 5 days) was effective in reversing
hypoprothrombinemia of the warfarin-treated dog. However, this regimen was ineffective for
diphacinone-treated dogs, which required either 5 mg vitamin Kj/kg/day administered in repeated
doses 3 times/day on days 6-10 and 16-20, or 2.5 mg vitamin K^ in repeated doses on days 6-10,
16-20 and 26-30. In addition, one diphacinone-dosed dog received fresh plasma with the first
vitamin K! injection. '
The three diphacinone-exposed dogs had prolonged bleeding at venepuncture sites the last
day of treatment. All dogs became clinically ill within the subsequent 3 days. Bleeding was
-observed in the diphacinone-exposed dogs as long as 2 weeks following exposure. An important
finding was that the vitamin K-enzyme complex was inhibited in diphacinone-exposed dogs for
approximately 30 days as indicated by routine coagulation screen tests.and coagulation factor
inhibition. No hepatic dysfunction was observed. There was a statistically significant reduction
(p < 0.00,1) in pancreatic exocrine function although the resulting values were within the
laboratory's reference range. . ,
According to the published paper in MRID 42791201:
"The liver synthesizes the vitamin-K dependent coagulation proteins, factors II, VII, IX, and X, to inactive
precursor forms dependent upon vitamin K for activation by a postribosomal protein modification. The
. inactive precursor proteins contain several glutamic acid residues which serve as the site for vitamin K
function. These amino acids are carboxylated to form gamma-carboxyglutamic acid (Gla) residues which are
responsible for activation of the coagulation protein. Calcium binding is dependent upon this cluster of
carboxylic groups; without calcium binding the factor is nonfunctional. Hence, vitamin K serves as an
essential,cofactor for the enzyme that carboxylates protein-bound glutamic acid residues to Gla.
The molecular role of vitamin K in the carboxylation event is unclear. The carboxylase enzyme has been
studied and its activity measured. A reductase, epoxidase (carboxylase-epoxidase enzyme), and epoxide
reductase enzymes are also closely associated with the metabolic role of vitamin K... This...collectively
represents the vitamin K-enzyme complex. This term is used since the complete biochemical mechanisms of
vitamin K metabolism are not completely understood. The site of the biochemical lesion caused by
anticoagulant rodenticides is the epoxide reductase enzyme... . The carboxylase-epoxidase enzyme
interaction.. .is not understood but results in Gla formation and conversion of vitamin K to the inactive
epoxide. The epoxide can then be reconverted to the vitamin K quinone through the epoxide reductase
enzyme... Without this enzyme vitamin K cannot be recycled. This results in rapid depletion of body stores
of vitamin K..."
The material in MRID 427912201 satisfies the guideline data requirement (ง86-1) for an
antidotal study.
Diphacinone (as "Dipaxin") has been investigated and used as a therapeutic anticoagulant
in humans (Correll, J.; Coleman, L.; Long, S.; Willy, R., 1952). According to this report, a
single oral dose of 16 mg given to a healthy man weighing oyer 200 Ibs resulted in no significant
change in prothrombm determinations over a period of 48 hours. A second man of similar weight
was given 32 mg, and changes in the prothrombin time were evident within a period of 4 hours.
The maximum effect was seen at about 16 hours, with decrease in prothrombin time at 30 hours,
and recovery to normal at 70 hours. A third patient, a 95-lb 22-year-old man received 32 mg as
' ' ' .. '/'-.. 45 ' ' . ' .
-------
a single dose; definite increase of prothrombin time was measurable within 23 hours, and a
"therapeutic" effect (prothrombin time > 15 seconds) was evident within 48 hours. Following
this single dose, 12 days were required for the prothrombin time to return to normal range. The
dosage was then repeated, and prothrombin time was prolonged to 31 seconds (normal is about
12 seconds) within 36 hours. The following day, the patient received 50 mg of vitamin K
intravenously. One hour later the prothrombin time was 26 seconds; 2 hours later it was 19
seconds, and approximately normal prothrombin values had been restored at 7 hours.
Dipaxin was given to a 30-year-old woman with post-operative venous thrombosis.
Definite prolongation of the prothrombin time (to approximately 22 seconds) developed 24 hours
after a single 32-mg dose. Repetition of this dose on the third day brought prolongation of the
prothrombin time into the optimal therapeutic range (24-36 seconds), where it was maintained by
5 mg of Dipaxin daily. On the day of the last dose (day 13) the prothrombin time was 26
seconds, returning to normal range 3-4 days later.
Additional information on clinical investigations of Dipaxin in humans are given in Katz
et al. 1954 (in which it is stated that "The prothrombopenic action of Dipaxin is readily
counteracted with vitamin Ka administered either orally or intravenously) and Field et al. 1952
(in which it is stated that, in man: "This agent induces an effective hypoprothrombinemia in single
doses of as little as 4 mg... After single doses of 20 mg a marked hypoprothrombinemia was
usually evident in 48 hours which persisted from 6 to 10 days... The recommended starting dose
is about 20 mg... The maintenance of adequate clinical hypoprothrombinemia was obtained with
daily doses of 2 to 4 mg. Hypoprothrombinemia was readily overcome with vit. K2, the natural
vitamin being more effective than the synthetic...".
2. Exposure Assessment
a. Dietary Exposure
These chemicals are non-food use pesticides. Therefore, it is unlikely that there will be
any exposure to food sources or to residues in ground or surface water contamination.
b. Occupational and Residential Exposure
The following assumptions were made:
All formulations are 0.005% a.i. (note: some end-use products formulations have a higher
percent a.i., but using these would make a comparison of MOEs more difficult). In order
to calculate MOEs for a higher percent a.i. the calculations would be adjusted accordingly;
A child weighs 10. kilograms; and ' ซ.
Poison specialists estimate that a child would consume approximately 5 grams in one bite.
These assumptions were extracted from the various rodenticides in this RED.
46
-------
Using bromethalin as an example, the exposure (dose), and resulting MOE, a 10 kilogram.
child would receive from 5 grams of bromethalin at 0.005% active ingredient (a.i.) is:
5 grams X 1000 mg/gram-= 5000 mg
5000 mg X .00005 (percent a.i.) = 0.25 mg technical a.i. in 5 grams
0.25 mg / 10 kg = 0.025 mg/kg (note: for any 0.005% formulation this number will
remain consistent for the listed fodenticides.
MOE = NOEL / Exposure; NOEL = 0.025 mg/kg
MOE = 0.025 mg/kg/0.025 mg/kg = 1
Table 28 summarizes the relative MOEs for the chemicals in the Rodenticide Cluster and
for zinc phosphide. Normally any MOE less than one is expressed as: < 1. However, for
comparison purposes the actual MOE has been put in the table. The Agency acknowledges that
there is little confidence in the significant figures of results less than one.
Chemical
Bromeflialin
Brodifacoum .
Bromadiolone
Chlorophacinone
Diphacinone
Zinc Phosphide
a j. of
Typical BP
0.05%
0.05%
0.05%
0.05%
0.05%
2.0%
Tox, Bndpoint
0.025 mg/kg/day
0.002 mg/kg/day
0.002 mg/kg/day
O.OQ5 mg/kg/day
0.13 mg/kg/day
5 mg/kg
Amount consumed
in one bite
5 grams
5 grams
5 grams ,
5 grams
5 grams
5 grams
Amottrtf of technical
consumed fa one Tjite
-------
Based on the use patterns and potential exposures described above, six major handler
exposure scenarios were identified for brodifacoum: (1) placing bait packs; (2) loading bait boxes
or bait stations with meal bait, grain bait, bait pellets, or other food-based bait from larger
containers; (3) breaking paraffinized slabs, cakes, and blocks into pieces and placing the pieces
at bait stations; (4) securing large paraffin blocks at bait stations in sewers; (5) applying bait by
hand; and (6) applying bait (e.g., pellets) in broadcast treatments using ground equipment.
It is unclear from labels and other available information (1) the extent to which it is
necessary, due to size or design of packages, for handlers to directly handle or contact the bait
during bait station loading (which may result in dermal exposures); or (2) the extent to which it
is possible for dusts associated with meal baits, grain baits, or pellets to result in inhalation
exposure to handlers during bait station loading. Although the vapor pressure of brodifacoum is
relatively low (9.8 X 10~7 Torr), the Agency is concerned about potential inhalation of
participates, fine particles and dusts associated with baits which could be inhaled resulting in
ingestion/oral exposure.
Calculations of daily exposure to pesticidal active ingredients by handlers are used to assess
risk to those handlers. There are no handler exposure data available for the use patterns
associated with brodifacoum mixing, loading, and application.
(b) Post-Application Exposures & Assumptions
EPA has determined that there is a potential for exposure to users and others following
applications of brodifacoum, particularly in residences. EPA has concerns about possible post-
application exposures if: (1) baits are not placed out of reach of children or are not placed in
tamper-resistant bait stations, as specified in labeling; (2) baits are available to homeowners in
packages which are not tamper re resistant or child resistant and could be accessible to- children
prior to application; and, (3) baits are brightly colored or.packaged in a way in which they could
be appealing to children or mistaken by children for food or candy.
(c) Occupational and Residential Characterization
Risk from Dermal and Inhalation Exposures
There are no exposure data currently available for calculating risks to handlers resulting
from exposures to brodifacoum. However, EPA has several concerns about the risks to handlers
of brodifacoum products, particularly commercial handlers (1) handling large quantities of
product; (2) handling dusty, non-paraffinized products; or (3) applying products by hand. These
concerns are based on (1) very high acute toxicity; (2) potential dermal absorption of
toxicologically significant amounts; and, (3) absence of exposure data for all scenarios considered.
(2) Bromadiolone Occupational and Residential Exposure
Assessment
At this time some products containing Bromadiolone are intended primarily for
homeowner use, and some are intended primarily for occupational use.
48
-------
(a) Handler Exposures & Assumptions
EPA has determined that there is a potential exposure to applicators or other handlers
during typical use patterns associated with bromadiolone. Specifically, the Agency is concerned
about potential dermal and inhalation exposures to handlers during the loading and application of
bromadiolone at bait stations.
Based on the use patterns and potential exposures described above, four major handler
exposure scenarios were identified for Bromadiolone: (1) placing bait packs at bait stations; (2)
loading bait boxes or bait stations with meal bait or bait pellets from larger containers; (3)
breaking pafaffmized slabs, cakes, and blocks into pieces and placing the pieces at bait stations;
and (4) securing large paraffin blocks at bait stations in sewers.
It is unclear from labels and other available information (1) the extent to which it is
necessary, due to size or design of packages, for handlers to directly handle or contact the bait
during bait station loading, which may result in dermal exposures; or (2) the extent to which it
is possible for dusts associated with meal baits or pellets to result in inhalation exposure to
handlers during bait station loading. , . /
ป ' ... - . -f
/
Calculations of daily exposure to Bromadiolone by handlers are used to assess risk to those
handlers.
(b) Post-Application Exposures and Assumptions
EPA has determined that there is a potential for exposure to consumers and others
following applications of bromadiolone, particularly in residences. EPA has concerns about
possible post-application exposures if (1) baits are hot placed out of reach of children or are hot
placed in tamper-resistant bait stations, as specified in labeling; (2) baits are available to
homeowners in packages which are not tamper resistant and could be accessible to children; or
(3) baits are brightly colored or packaged in a way in which they could be appealing to children
or mistaken by children for food or candy.
(3) Bromethalin Occupational and Residential Exposure
At this time, some products containing bromethalin are intended primarily for occupational
use, and some products are intended primarily for residential use.
An occupational and/or residential exposure assessment is required for an actiye'ingredient
if (1) certain lexicological criteria are triggered and (2) there is potential exposure to handlers
(mixers, loaders^ applicators) during use or to persons entering treated sites after application is
complete.
(a) Handler Exposures and Assumptions
The Agency has determined that there is potential for exposure to applicators of other
handlers during typical use-patterns associated with bromethalin. Specifically, the Agency is
49
-------
concerned about potential accidental oral and inhalation exposures to handlers resulting from the
loading and application of bromethalin at bait stations.
Occupational Handler Exposures
Based on the use patterns described above, four major handler exposure scenarios were
identified for occupational handlers of bromethalin: (1) placing bait packs and bait cups at bait
stations; (2) loading or recharging bait stations and bait trays with loose baits (meal baits, bait
pellets, etc.); (3) putting loose baits into plastic or paper bags for placement in rodent burrows;
and (4) removing baits that have not been touched by target rodents for relocation or disposal.
,, ^ ' / l ' '
Frequency of handling activities and amount of product handled are expected to vary
among handlers; some occupational handlers may use bromethalin products several times in a 90-
day period resulting in possible intermediate-term exposures, while others may use bromethalin
infrequently resulting in possible short-term exposures.
No data are currently available for any of the occupational handler exposure scenarios
identified. It is unclear from labels and other available information the extent to which exposure
is possible or likely during the activities associated with each exposure scenario.
Homeowner Handler Exposures
Because bromethalin products are available to homeowners, the Agency has determined
that there is potential for exposure to applicators or other residential handlers during typical use-
patterns associated with bromethalin. Specifically, the Agency is concerned about accidental oral
and inhalation exposures to homeowner handlers during the loading and application of bromethalin
at bait stations.
Residential handlers are expected to have fewer than seven days of exposure during a 90-
day period.
f i '
Based on the use patterns and potential exposures described above, four major handler
exposure scenarios were identified for residential handlers of bromethalin: (1) placing bait packs
and bait cups at bait stations; (2) loading or recharging bait stations and bait trays with loose meal
baits or bait pellets; (3) putting loose baits into plastic or paper bags for placement in rodent
burrows; and (4) removing baits that have not been touched by target rodents for relocation or
disposal.
No data are currently available for any of the homeowner handler exposure scenarios
identified. It is unclear from labels and other available information the extent to which exposure
is possible or likely during the activities associated with each exposure scenario.
(b) Post-Application Exposures amd Assumptions
The Agency has determined that there is a potential for exposure to residential and others
following applications of bromethalin, particularly in residential areas, the Agency has special
50
-------
Concerns about possible post-application exposures if (1) baits are not placed out of reach of.
children or are not placed in tamper-resistant bait stations as specified in product labeling; (2)
baits are available to homeowners in packages which are not child resistant and could be
accessible to children; or (3) baits are brightly colored or packaged in a way in which they could
be appealing to children or mistaken by children for food or candy.
Occupational Post-Application Exposures
,The Agency has determined that there is potential for occupational post-application
exposure to bromethalin. Accidental exposures may occur in a variety of industrial and other
occupational settings if bromethalin baits have ,not been applied in tamper-resistant bait stations
or ready-to-use packages and workers come into contact with or handle the bait material. Because
exposures of this nature are expected to be infrequent and relatively short in duration, at this time
the Agency does not expect such exposures to significantly affect worker risk. Furthermore,
based on available incident data, the Agency believes it is unlikely that adult workers mistake
bromethalin baits for food.
Residential Post-Application Exposures <-.'
The Agency has determined that the potential f5r post-application residential exposure
exists following residential applications made either by users or professional pest control operators
(PCOs). .'.-'.
For adults, the Agency has determined that there is potential for user post-application
exposure to bromethalin for situations similar to those described above for workers. Accidental
exposures may occur following applications in residential settings if baits have not been applied
in tamper-resistant or child resistant bait stations and consumer handle or otherwise come in
contact with bait material, or if adults in residential settings mistake bromethalin baits for food.
For the reasons described above for workers, the Agency does not expect such post-application
exposure scenarios to pose a significant risk to an adult user, but recommends confirmation from
the registrants). . '
The Agency has special concerns, however, about possible post-application exposures to
. children if (1) baits are not placed out of reach of children or are not applied in tamper-resistant
or child resistant bait stations as specified in product labeling; and (2) baits are brightly colored
or packaged in a way^ in which they could be appealing to children or be mistaken by children for
food or candy. These concerns are supported by the high number of accidental child ingestion
incidents relative to the number of adult ingestion incidents for rodenticide baits in general, and
for bromethalin specifically'. ,
(c) Occupational and Residential Risk
Characterization
Calculations of daily dose of bromethalin are used to assess occupational and residential
risks resulting from bromethalin use. Because the Agency currently has no data on occupational
or residential exposures to bromethalin, the Agency is unable to calculate daily doses.
' ' . -.- .. 51 . ; ' -
-------
The Agency has risk concerns for persons exposed to bromethalin in both occupational and
residential scenarios. These concerns are based on (1) very high acute toxicity (category I for
acute oral toxicity); (2) very low short-term and intermediate-term NOELs (0.1 mg/kg/day and
0.025 mg/kg/day respectively); (3) the potential for acute, short-term, and intermediate-term
exposures for occupational handlers, and for acute and short-term homeowner exposures; (4) a
relatively high number of incidents associated with rodenticide baits in genera).; and (5) an absence
of exposure data for all exposure scenarios considered.
(4) Chlorophacinone Occupational and Residential Exposure
At this time some products containing chlorophacinone are intended primarily for
homeowner use and some are intended primarily for occupational use.
(a) Handler Exposures & Assumptions
EPA has determined that there is a potential exposure to applicators or other handlers
during typical use-patterns associated with chlorophacinone: Specifically, EPA is concerned about
potential dermal and inhalation exposures to handlers during the mixing of concentrate into baits
and loading and application of chlorophacinone. .
Because the vapor pressure of chlorophacinone is low (3.6 X 10"6 Torr), the potential for
exposure resulting from inhalation of chlorophacinone vapors is not a significant concern despite
a very low LC^ (0.007 mg/L). However, if fine particles become airborne during the handling
of chlorophacinone baits, individuals may inhale these particles. Because these particles could
potentially be ingested, such exposure would contribute to the individual's risk resulting from
accidental ingestion/oral exposure.
Based on the use patterns and potential exposures described above, eight major handler
exposure scenarios were identified for chlorophacinone: (1) mixing concentrate into baits (if end-
use products which are concentrates that are intended to be mixed with food based do not exist,
then this scenario can be eliminated), (2) placing bait packs; (3) loading bait boxes or bait stations
with meal bait, grain bait, bait pellets, or other food-based bait from larger containers; (4)
breaking paraffinized slabs, cakes, and blocks into pieces and placing the pieces in bait stations;
(5) securing large paraffin blocks in bait stations in sewers; (6) applying bait by hand; (7)
applying bait (e.g., pellets) in broadcast treatments using ground equipment; and (8) pouring and
applying tracking powders (For some workers involved in major applications, exposure could last
8 hours a day, 5 days a week), and (9) spray application in orchards at 0.2 Ib a.i./acre.
It is unclear from labels and other available information (1) the extent to which it is
necessary, due to size or design of packages, for handlers to directly handle or contact the bait
during bait station loading (which may result in dermal exposures); or (2) the extent to which it
is possible for dusts associated with meal baits, grain baits, tracking powders, or pellets to result
in inhalation exposure to handlers during bait station loading.
52
-------
(b) Post-Application Exposures & Assumptions
Occupational and Residential
EPA has determined that there is a potential for exposure to consumers and others
following applications of chlorophacinone, particularly in residences. EPA has concerns about
possible post-application exposures if (1) baits are not placed out of reach of children or are not
placed in tamper-resistant bait stations, as specified in labeling; (2) baits are available to
consumers in packages which are not tamper resistant and could be accessible to children prior
to application; and (3) baits are brightly colored or packaged in a way in which they could be
appealing to children or mistaken by children for food or candy. These factors, among others,
can be expected to lead to numerous exposures among small children Under Note to Physicians,
many of the labels recommend that Vitamin Kx be administered intravenously (IV) or
intramuscularly (IM). The veterinary literature states that vitamin Kt can cause anaphylactic
reactions if given IV and extensive hemorrhage after IM administration. Sheldon Wagner, M.D.,
a consultant,to OPP, confirmed that Vitamin K: should not be given IV unless there is a
hemprrhagic crisis. IM administration is normally acceptable in humans. The recommendation
for IV administration should be deleted from the label.
(5) Diphacinone and its sodium salt Occupational and
Residential Exposure
Because EPA currently has no data on occupational or residential exposures to
diphacinone, the Agency is unable to; calculate daily doses. EPA has risk concerns for persons
exposed to diphacinone in both occupational and residential scenarios. These concerns are based
on (1) very high acute toxicity (short- and intermediate - term NOEL of 0.1 mg/kg/day based
on developmental toxicity); (2) potentially high (e.g., 100 percent) dermal absorption values; (3)
an absence of exposure data for all exposure scenarios considered; and (4) a relatively high
number of incidents associated with diphacinone use as compared to non-anticoagulant pesticides.
(a) Handler Exposures & Assumptions
There are no exposure data currently available for calculating risks to handlers resulting
.from exposures to diphacinone. However, the Agency has several concerns about the risks to
handlers of diphacinone products, particularly commercial handlers (1) handling large quantities
of product, (2) handling dusty, non-paraffinized products, including the concentrate and tracking
powder formulations, or (3) applying products by hand. .
The Agency recommends that all labels for occupational-use products require commercial
handlers to wear gloves while handling all diphacinone formulations that are not contained in a
tamper-resistant bait stations or in place packs. This would reduce dermal exposure to
diphacinone and diminish the potential oral exposure that could result from hand-to-mouth
transfer. Though no exposure data are available, the Agency believes that both tamper-proof bait
stations and place packs greatly reduce the potential for dermal contact with diphacinone. ;
53
-------
In addition, the Agency recommends that occupational handlers (commercial applicators)
wear protective eyewear and a dust/mist respirator when handling diphacinone powder or other
non-paraffinized diphacinone formulation, such as meal or grain-based baits, unless those
formulations are contained in tamper-resistant bait stations or place packs. The eyewear and
respirator would reduce the possibility of inhalation and ingestion of dusts resulting from the '
pouring and application of these products and reduce the potential ocular exposure that could
result from contact with such dusts.
(b) Post-Application Exposures & Assumptions
There are no data currently available to address post application exposure for diphacinone.
Only the following rough calculations are possible.
The dose a 10 kg child could receive from a 43 gram packet (average packet size) of
diphacinone at (0.005%) equals 0.215 mg/kg. Assuming a NOEL of 0.13 rng/kg, this exposure
will result in a Margin of Exposure (MOE = NOEL/Exposure) of 0.6, more than 167 fold less
than the acceptable MOE of 100.
r
3. Risk Assessment .
a. Occupational and Residential
The Agency has determined that there is a potential exposure to applicators and other
handlers during typical use patterns associated with these chemicals. Specific concerns are those
of dermal and inhalation exposure to handlers during the loading and application of the chemicals.
The Agency is therefore recommending that gloves be worn when handling formulations not
already contained in tamper-resistant bait stations or place packs. In addition the Agency is
requiring all those who handle powder formulations or any other non-parafinized formulations to
wear a dust mask or respirator and protective eyewear during open pouring and application.
The Agency has special concerns, however, about possible post-application exposures to
children if (1) baits are not placed out of reach of children or are not applied in tamper-resistant
or child resistant bait stations as specified in product labeling; and (2) baits, are brightly colored
. or packaged in a way in which they could be appealing to children or be mistaken by children for
food or candy. These concerns are supported by the high number of accidental child ingestion
incidents relative to the number of adult ingestion incidents for rodenticide baits in general, and
for bromethalin specifically.
EPA is concerned about the continued risk of human exposure, especially to children, to
rodenticides used in residential settings. In fact, EPA has gone on record, over the years, to
express its concern regarding human exposures and incidents to rodenticides used in and around
the home. PR Notice 94-7, Label Improvement Program for the Revision of Use Directions for
Commensal Rodenticides and Statement of the Agency's Policies on the Use of Rodenticide Bait
Stations, issued by the Agency on September 16, 1994, required registrants of certain rodenticide
54
-------
products claimed to control commensal rodents to revise the labeling of such products to bear
certain statements concerning "tamper-resistant bait stations." It also informed rodenticide
registrants, applicants, and other interested persons of EPA's continued concern for the safe use
of rodenticides. Moreover, PR Notice 94-7 outlined EPA's policies regarding the isolation'of
commensal rodenticides from children, dogs, other pets, domestic animals, and non-target
wildlife. PR Notice 94-7, in part, stated the following:
"Historically, more than 1000 incidents of human exposure to rodent poisons have been reported annually
in the U.S. Numbers of human incidents reported have increased greatly in recent years with the advent of
a new reporting network. In 1988, more than 10,000 rodenticide incidents were reported in the American
Association of Poison Control Center's National Data Collection System. Nearly 90 % of these cases involved
children under six years of age. Nearly all of such exposures are classed as accidents. The human exposure
incidents that are reported may represent less than half of those which occur. Well over 80% of reported
human rodenticide exposures involve anticoagulant compounds. , >
Young children thought to have been exposed to rodenticides are often given some medical attention, although
symptoms of poisoning usually are not observed, especially in cases involving anticoagulants which act very
slowly. Although young children have been killed by rodenticides, most rodenticide-related deaths of humans
result from intentional ingestions by persons much older than five years of age.
While reports summarizing incidents typically do not indicate exactly how exposures have occurred, it is likely
that most accidents are related to improper use rather than to improper storage. Accidents of both types are
preventable. EPA believes that the large numbers of exposure incidents provide evidence that current policies
for promoting bait protection have not been sufficient and, therefore, that tougher, more explicit policies are
needed. EPA has not been persuaded by contentions that the relatively low incidences of serious human
illnesses caused by accidental exposures to compounds such as warfarin justify selective relaxations of
requirements for bait protection..."
Based on available data, young children experience excessive exposures to anticoagulant
rodenticides. An analysis of pesticide ingestions in 1989 in children less than 6 years of age
compared the number of ingestions to the number of containers reported in U.S. homes in 1990.
When 83 active ingredients were ranked, the top 5 products responsible for childhood ingestion
per 1000 containers were all anticoagulant rodenticides. The ratio of eases for these rodenticide
baits was up to a 100 times higher than the median for all pesticides.
A relatively large percentage of children accidentally exposed to anticoagulant rodenticides
are treated in health care facilities. For 99 percent of all,cases, however, only minor or no
adverse health effects are reported. In some published reports, it has been claimed that children :
exposed to anticoagulants often are-given unnecessary treatments as a precautionary measure.
Over several years, some 36 percent of the victims of all anticoagulant rodenticide cases reported
to poison control centers are brought to health care facilities for treatment.
Furthermore, rodenticides are acutely toxic to humans. Margins of Exposures (MOEs),
when bait is ingested, are less than one. Generally, the Agency considers a MOE of 100 or above
to be protective of the public's health. The Agency, for example, has calculated the dose a 10
kg child receives from a 43 gram packet (standard commercial package). The Agency's
calculation resulted in a MOE of 0.6 (using the diphacinone NOEL of 0.13 mg/kg).
'. .. . ' 55 ...- ', " .
-------
Rodenticides, when used as currently sold and marketed, are responsible for a high number
of accidental exposures each year. In the recent past, poison control centers have enhanced their
ability to capture incident data. Even with improved data collection, the high number of human
unintentional or accidental exposures to rodenticides remain constant each year, or may be
increasing. From the number of exposures to children, it is clear that children under six years-old
are disproportionately more at risk to the continued use of these products in and around the home.
Based on these facts, EPA is concerned regarding the risk of exposure to these chemicals to the
public, particularly children.
Ingestion of an entire 43 gram packet by a one year old is unlikely. Poisoning specialists
estimate the risks to children by assuming a one year old child weighing 10 kg would get one
swallow (approximately 5 grams). This provides an estimated dose of 500 mg/kg. For
diphacinone and other anticoagulants formulated at 0.005% active ingredients, the dose would be
0.025 mg/kg. Therefore, the margin of exposure from the lowest dose causing clinical effects
in adults (0.1 mg/kg) to the dose if a child consumed one swallow (O.I/.025) would be 4.0. In
other words, if a child consumed four swallows, the child would be expected to experience
clinical effects. Note this assumes that children are no more sensitive to anticoagulants than
adults, which may not be the case.
1995 data collected by the American Association of Poison Control Centers (AAPCC)
show 17,187 human exposures to all rodenticides. Of these numbers, 14,710 (~ 86%) exposures
were attributed to the anticoagulant rodenticides. Of concern to EPA is the number of exposures
to children less than six years-old; in 1995, there were a total of 14,900 or approximately 87%
of the total exposures. Six thousand four hundred and fifty (6,450) of the total number of human
exposures to rodenticides, were significant enough to result in treatment at a health care facility.
1996 data collected by the AAPCC indicate that 17,601 rodenticide exposures occurred
to humans. The anticoagulant rodenticides (brodifacoum, bromadiolone, chlorophacinone,
diphacinone and its sodium salt, and pival and its sodium salt), accounted for 14,836 or over 84%
of the total exposures. Of these exposures, 13,362 (90%) occurred in children less than six years-
old. Approximately 5,300 exposures resulted in people seeking treatment at a health care
facility.
C. Environmental Assessment
1. Ecological Toxicity Data
Primary toxicity to mammals is very high for all five of these rodenticides. Primary
toxicity to birds is high to very high for the single-feeding compounds (brodifacoum,
bromadiolone, bromethalin) but mostly moderate for the multiple-feeding compounds
(diphacinone, chlorophacinone). Toxicity to aquatic organisms ranges from moderate to very
high.
Some secondary toxicity data exist for avian and mammalian predators and/or scavengers
for some but not all of these rodenticides. These studies are required to support rodenticides used
56
-------
in the field and around Buildings in non-urban (i.e., rural, suburban areas). The available
laboratory and/or field data indicate that rodents poisoned with brodifacoum or bromadiolone baits
can kill avian and mammalian secondary consumers. Sufficient data also exist to indicate that
0.01% a.i. diphacinone bait is secondarily hazardous to birds and mammals and that 0.01% a.i.
chlorophacinone bait is hazardous to mammalian predators. Avian data are not available for
0.01% a.i. chlorophacinone bait. Adequate secondary data are not available for birds and
mammals for 0.005% a.i. chlorophacinone and diphacinone bait or bromethalin and is being
required in this RED. These data are required to support .all uses except those bait placements
limited to indoors and immediately against the outside walls of buildings.
a. Toxicity to Terrestrial Animals
(1) Birds, Acute and Subacute
(a) Brodifacoum - Birds, Acute and Subacute
An acute oral toxicity study using the technical grade of .the active ingredient (TGAI) is
required to establish the toxicity of brodifacoum to birds. The preferred test species is either
mallard duck (a waterfowl) or bobwhite quail (an upland gamebird). Results of this test are
summarized in Table 29 below, .
Table 29 - Brodifacoum Avian Acute Oral Toxicity
Species
Mallard duck (Anas platyrhynchos)
!%a.Li
97.6
LD^
{nag/kg) i
0.26
Toxicity
Category ,
Very highly toxic
MRIDNo,
Author, Year
41563303 Ross, 1980
Study
Classification1
Core
'Core (study satisfies guideline). Supplemental (study is scientifically sound, but does not satisfy guideline)
Since the LD50 falls two orders of magnitude below the 10 mg/kg standard, brqdifacoum
is very highly toxic to avian species on an acute oral basis. The guideline (71-1) is fulfilled
(MRID 41563303).
Two subacute dietary studies using the TGAI are required to establish the toxicity of
brodifacoum to birds. The preferred test species are the mallard duck and bobwhite quail.
' Results of these tests are summarized in Table 30 below.
Table 30 - Brodifacoum Avian Subacute Dietary Toxicity
i Species
Northern bobwhite quail
(Colinus virginianus) .
Mallard duck
(Anas platyrhynchos)
% a.i.
97.6
97.6
40-Day LCS8. '
0.8
2
Toxicity Category
Very Highly
Toxic
Very Highly
Toxic
MKBDNo. '.
Aethor, Year
124477.
Fink, 1978
124476
Fink, 1978
Stady ,
Classification.
Core
Core
'Test organisms observed an additional three days while on untreated feed.
'57
-------
Since the LC50 is an order of magnitude less than 10 ppm, brodifacoum is very highly toxic
to avian species on a subacute dietary basis. The guideline (71-2) is fulfilled (MRIDs 124477 and
124476).
,('"
(b) Bromadiolone - Birds, Acute and Subacute
An acute oral toxicity study using the technical grade of the active ingredient (TGAI) is
required to establish the toxicity of bromadiolone to birds. The preferred test species is either
mallard duck (a waterfowl) or bob white quail (an upland gamebird). Results of this test are
summarized in Table 31 below.
Table 31 - Bromadiolone Avian Acute Oral Toxicity
Species
Northern Bob-white
(Colinus virginianus)
Northern Bobwhite
'% a,i.
99.75
99.75
LDjft(TOg/kg)
170
138
Toxidiy Category
Moderately toxic
Moderately toxic
MRID Author, Year
257770 Roth, 1985
41707301 Shapiro
Study Ckssification
Core
Core
Because the LD50 is in the range of 51 to 500 mg/kg, bromadiolone is considered
moderately toxic to birds on an acute oral basis. The guideline (71-1) is fulfilled (MRID 257770,
417073-01)).
Two subacute dietary studies using the TGAI are required to establish the toxicity of
bromadiolone to birds. The preferred test species are mallard duck and bobwhite quail. Results
of these tests are summarized in Table 32 below.
Table 32 - Bromadiolone Avian Subacute Dietary Toxicity
'Species
Northern Bobwhite (Colinus virginianus)
Mallard (Anas platyrhynchos)
Mallard
% a.i.
99.75
99.75
94.4
LC50
(ppm) I
37.6
158
440
ToxicHy
Category
Highly toxic
Highly toxic
Highly toxic
MRID
Auflior, Year
257770 Roth, 1985
257770 Fletcher, 1985
249995 Beavers, 1979
Study
Classification:
Core
Core
Core
Because the LC50 values are in the range of <50 to 500 ppm, bromadiolone is highly to
very highly toxic to birds on a subacute dietary basis. The guideline requirements are fulfilled
(MRID 257770, 249995).
(c) Bromethalin - Birds, Acute and Subacute
An acute oral toxicity study using the technical grade of the active ingredient is required
to establish the toxicity of bromethalin to birds. The preferred test species is either the mallard
duck or the bobwhite quail. Results from these tests are summarized in Table 33 below.
58
-------
Table 33 -Bromethalin Avian Acute Oral Toxicity
Species
Bobwhite quail (Colinus virginianus)
Bobwhite quail
%
a.i.
96.3
96.3
Ufa
{mg/kg)
4.6
11.0
Toxicay'Category
Very highly toxic
Highly toxic
MRID " -
Author, Year
246173 vanLier, 1981
86741 vanLier, 1981
Study
Classification
Core
Core
These results indicate that bromethalin is highly to very highly toxic to birds on an acute
"oral basis. The guideline requirement (71-1) is fulfilled (MRIDs 246173, 86741, and 86745).
Two subacute dietary studies using the technical grade of the active ingredient are required
to establish the toxicity of bromethalin to birds. The preferred test species are mallard duck (a
waterfowl) and bob white quail (an upland gamebird). Results of these tests are summarized in
Table 34 below., , ,
Table 34 - Bromethalin Avian Subacute Dietary Toxicity
Species
Bobwhite quail (Colinus virginianus)
Mallard duck (Anas platyrhynchos)
% a.i.
96.3
96.3,
LC5fr
(pprn)
210
620
Toxicity
Category
Highly toxic
Moderately toxic
MRID,
Author, Year
86745 van Lier, 1981
26526 van Lier, 1981
Study
Classification
Core
Core
These results indicate that bromethalin is moderately to highly toxic to avian species on
a subacute dietary basis. The guideline requirement (71-2) is fulfilled (MRID 86745 and 26526).
(d) Chlorophacinone - Birds, Acute and Subacute
An acute oral toxicity study using the technical grade of the active ingredient (TGAI) is
required to establish the toxicity of chlorophacinone to birds. The preferred test species is either
mallard duck (a waterfowl) or bobwhite quail (an upland gamebird). Results of this test are listed
in Table 35 below.
Table 35 - Chlorophacinone Avian Acute Oral Toxicity
Stiecies
Northern bobwhite quail
, (Colinus virginianus)
% a.i.
100
">ป,
(mg/fcg)
2582
Toxicity
Category
moderately
toxic
MRID No.
{Author/Year) ' " s
41513101
(Fletcher and Pedersen 1989)
Study "_ '
Classification
core
1 birds were observed for 30 days after dosing
? all mortality (28 of 50 birds dosed) occurred within 5 days
Because the LD50 is in the range of 51 to 500 mg/kg, chlorophacinone is considered
moderately toxic to birds on an acute oral basis. The guideline (71-1) is fulfilled (MRID
41513101). ."".,!
59
-------
Two subacute dietary studies using the TGAI are required to establish the toxicity of
chlorophacinone to birds. The preferred test species are mallard duck and bob white quail.
Results of these tests are summarized in Table 36 below.
Table 36 - Chlorophacinone Avian Subacute Dietary Toxicity
Species
Northern bobwhite quail
(Colinus virginianus)
Mallard duck
(Anas platyrhynchos)
% a,i.'
100
100
5-Day LC50
(ppm)1
562
1723
Toxicity
Category
highly
toxic
highly
toxic
IMRIDN0. - \
\ {Author/Year)
41513102
(Fletcher and Pedersen 1989)
41513103
(Fletcher and Pedersen 1989)
Study
Classification
core
core
1 birds were observed an additional 25 days while on untreated feed
2 all mortality (37 of 60 birds dosed) occurred within 9 days
3 all mortality (28 of 60 birds dosed) occurred within 22 days
Because the LCSO values are in the range of 50 to 500 ppm, chlorophacinone is considered
highly toxic to birds on a subacute dietary basis. The guideline (71-2) is fulfilled (MRIDs
41513102,41513103).
(e) Diphacinone and its sodium salt - Birds, Acute
and Subacute
An acute oral toxicity study using the technical grade of the active ingredient (TGAI) is
required to establish the toxicity of diphacinone to birds. The preferred test species is either
mallard duck (waterfowl) or bobwhite quail, (upland gamebird). Results of this test are
summarized below.
Table 37 - Diphacinone and its sodium salt Avian Acute Oral Toxicity
Species
Northern bobwhite quail
(Colinus virginianus)
% a,i.
96.9
lAo (tag/kg)3
400 < LD50 <2000
Toxacity
Category
moderately
toxic
MRtt) No.
(Author/Year)
42245201
(Campbell et al. 1991)
Study
Classification
supplemental
1 quail were observed for 21 days after a single oral dose
A reliable LD50 was not determined in this study. The 95% confidence interval ranged
from 0 to ซ>, in part because test concentrations were separated by a factor of 5X rather than the
1.6X separation recommended in the study guideline. Visual inspection of the data indicate that
the LDso is less than 2000 mg/kg but greater than 400 mg/kg. Therefore, until an adequate study
is submitted, 400 mg/kg will be used as a conservative estimate of the LD50. The guideline (71-1)
is not fulfilled.,
Two subacute dietary studies using, the TGAI are required to establish the toxicity of
diphacinone to birds. The preferred test species are mallard duck and bobwhite quail. Results
of these tests are summarized in Table 38 below.
-------
Table 38 - Diphacinoneand its sodium salt Avian Subacute Dietary Toxicity
Species
Northern bobwhite quail
(Colinus virginianus)
Mallard duck
(Anas platyrhynchos) ,
% a.i
96.9
96.9
5-Day LC&
(ppm)1
>50002
9063
Toxicity
Category
practically
nontoxic
moderately toxic
MRID No.
(Aufttor/Year)
42408801
(Long et al. 1992) ,
42408802
(Longetal. 1992)
Study
Classification
core
core
'test organisms (10/level; 6 test,concentrations, 3 control groups) were observed an additional 20 days while on
untreated feed. .'',
2all mortality (10% at 5000 ppm, 30% at 1667 ppm, and 10% at 185 ppm) occurred within 18 days.
3 all mortality. (20 of 60 birds dosed) occurred within 16 days. ' .
Because the lowest LC50 value is between 501 to 1000 ppm, diphacinone is considered
moderately toxic to birds on a subacute dietary basis. The guideline (71-2) is fulfilled (MRID
42408801,42408802). '
(2) Birds, Chronic Toxicity
Avian reproduction studies are not required for these rodenticides, except for one product.
Chronic exposure of birds is not expected for rodenticides used inside and along the .outside Walls
of buildings. Only chlorophacinone and diphacinone have field uses, but applications are either
made outside the avian breeding season or bait is applied in enclosed bait stations or other sites
(e.g., rodent burrows) inaccessible to nontarget wildlife. The one exception is chlorophacinone
product CA890023. Its use according to label directions could subject birds to repeated or
continuous exposure during or preceding the breeding season, because it allows an uninterrupted
supply of unprotected bait to be maintained for up to four weeks. , ,
(3) Mammals
Wild mammal testing is required on a case-by-case basis, depending on the results of lower
tier laboratory mammalian, studies, intended use pattern, and pertinent environmental fate
characteristics. In most cases, rat or mouse toxicity values obtained from the Agency's Health
Effects Division (HED) substitute for wild mammal testing. These toxicity values are reported
in Tables 39 through 43 below.
(a) Brodifacoum - Mammals, Acute and Chronic
Table 39 - Brodifacoum Mammalian Acute Oral Toxicity
Species Study Duration
Laboratory rat (Rattus norvegicus)
%a.i.
97.6
Toxicity Value
tf 0.418 mg/kg? 0.561 mg/kg
MRID No,
426875
Since the acute and dietary toxicities are much less than 10 mg/kg, brodifacourn is very
highly toxic to mammals on an acute and a dietary basis. , ,
61
-------
(b) Bromadiolone Mammals, Acute and Chrome
laoie au - jsromaaioione Mammalian Ural Toxicit
Species
White lab rat (Rattus norwegicus)
Substitute for wild rodents
White lab mice
(House mouse, Mus musculus)
Substitute for wild rodents
Beagle dogs
Substitute for wild canids
90 day gavage
Beagle dogs
Maximum tolerated dose
Cat - Substitute for wild felids
Maximum tolerated dose
(Continued)
Pig
Ground squirrel
%a.i.
0.005
1.0
Doc.#
007425
2.5 g/1
Unknown
Unknown
Unknown
Unknown
0.005%
LDio{mg/kg)
1.1 (female)
60 (TEP?)
1.75
.56 -.84
(in /^g/kg/day)
NOEL = 8
4 of 6 diedฎ 20
6 of 6 diedฎ 50
10 rag/kg
25 mg/kg
5 mg/pig/day
killed 3 pigs in 8,
9 & 10 days
Died
r
Toxidjy
Category-
Very highly toxic
Moderately toxic
Very highly toxic
Very highly toxic
n/a
n/a
n/a
n/a
n/a
MRID
226423
241703
007425
009423
254001
Chempar, 1981
254000
Chabert, 1975
254000
Chabert, 1975
257769
Lyon Vet.
School, 1984
264384
Study
^Classification
Supplemental
Minimum
Minimum
Minimum
Supplemental
Not rated
Not rated
Not rated
Not rated
The available mammalian data indicate that bromadiolone is moderately to very highly
toxic to mammals on an acute oral basis (MRID 226423 and 241703).
(c) Bromethalin - Mammals, Acute and Chronic
Toxicity
Table 41 - Bromethalin Mammalian Oral Toxicity
Species .
Laboratory rat
(Rattus norvegicus)
Laboratory rat
Laboratory Mouse
(Mus musculus)
Laboratory Mouse
House cat
(Fells domesticus)_
Domestic dog
(Canis familiaris)
%a.L
TGAI in Acacia
0.005%
TGAI in Acacia
0.005%
TGAI in
PEG-200
TGAI in
Acacia
TGAI in
PEG-200
TGAI in
PEG-200
Test type
Acute oral
Acute oral
Acute oral
Acute oral
Acute oral
Acute oral
LDse (mg/kg)
? = 9.1
d* = 1Q.7
? = > 500
(> 2.5 a.i.)
?-= 8.1
d< = 5.3
$ = 28.9
d- = 35.9
18
.4.8
Classification
Minimum
Minimum
Minimum
Minimum
Minimum
Minimum
Toxicity Category
Very highly toxic
Very highly toxic
Very highly toxic
Very highly toxic
Highly toxic
Very highly toxic
MRID
241521
246172
241521
241521
241521
241521
62
-------
The results indicate that bromethalin is highly to very highly toxic to small mammals on
an acute oral basis. . ," .
(d) Chlorophacinone - Mammals, Acute and Chrome
Toxicity
Species
Laboratory rat (Rattus norvegicus)
% a.L
100
LDj0 (nag/kg)
6.21-2
Toxicity Category
Very highly toxic
MRID No.
418753-01 '
d-= 3.15 mg/kg, ? = 10.95 mg/kg
2 mortalities occurred 4 to 9 days after treatment
The results, indicate that Chlorophacinone is very highly toxic to small mammals on an
acute oral basis.
(e) Diphacinone and its sodium salt - Mammals,
Acute and Chronic Toxicity
Table 43 - Diphacinone and its sodium salt Mammalian Oral Toxicity
Species
Laboratory rat (Rattus norvegicus)
Coyote (Canas latrans)
Mongoose (Herpestes auropunctatus)
%&.i. - :
96.9
not reported
not reported
LD5&
-------
Since the LCSO is in the range 0.1 to 1 ppm for the bluegill and is an order of magnitude
less than 0.1 ppm for the trout, brodifacoum is highly toxic to very highly toxic to freshwater fish
on an acute basis. Although all the studies were "supplemental," they were accepted as fulfilling
the Guidelines' requirement (72-1), because of the use pattern and the extremely low solubility
of brodifacoum (MRID 088011, 124474, and 124473).
(b) Bromadiolone - Freshwater Fish Acute Toxicity
Table 45 - Bromadiolone Freshwater Fish Acute Toxicity
Species
Rainbow trout
Bluegill sunfish
%a.i.
94.4
94.4
LC50 ppm a.i.
0.24 .
,3.0
MRID
232567 Stiefer, 1978
232567 Stiefer, 1978
Toxicity Category
Moderate
Moderate
Study Classification
Fulfills Guideline Requirement
Fulfills Guideline Requirement
The results of the 96-hour bluegill sunfish and rainbow trout acute toxicity studies indicate
that bromadiolone is moderately toxic to fish. The guideline requirements are fulfilled (MRID
232567).
(c) Bromethalin Freshwater Fish Acute Toxicity
Table 46 - Bromethalin Freshwater Fish Acute Toxicity
Species :;
Bluegill sunfish
(Lepomis macrochirus)
Rainbow trout
(Oncorhynchus myldss)
%&.L
99
99
LC50
Species
Rainbow trout
(Oncorhynchus mykiss)
Bluegill sunfish
(Lepomis macrochirus)
% a.i.
100
100
96-hour
nVQ>pb)
450
710
Toxicity
Category :
highly toxic
highly toxic
MRID No.
(Author/Year)
42356103
(Machado 1992)
42356102
(Machado 1992)
Study,
Classification
core
core
*Using flow-through (measured) testing
Because the LC50 falls in the range of 100 to 1000 ppb, Chlorophacinone is considered
highly toxic to freshwater fish on an acute basis. The guideline (72-1) is fulfilled (MRID
42356102,42356103).
64
-------
(e) Diphacinone and its sodium salt - Freshwater Fish
Acute Toxicity
Table 48 - Diphacinone and its sodium salt Freshwater Fish Acute Toxicity*
Species
Rainbow trout
(Oncorhynchus mykiss)
Bluegill sunfish
(Lepomis macrochirus)
%a.i.
95.8
95.8
9j6~hour
LCW (ppm)
2.6
,7.5
Toxicity Category
moderately toxic
moderately toxic
MBlDNo,
(Author/Year)
43249502 (Machado 1994)
43249501 (Machado 1994)
Study
Classification
core
core
*Using flow-through (measured) testing
Because the LC50 falls in the range of 1 to 10 ppm, diphacinone is considered moderately
toxic to freshwater fish on an acute basis. The guideline (72-1) is fulfilled (MRID 42356102,
42356103).
(2) Toxicity to Freshwater Invertebrates
(a) Brodifacoum - Acute Toxicity to Freshwater
Invertebrates
A freshwater aquatic invertebrate tpxicity test using the TGAI is required to establish the
toxicity of brodifacoum to aquatic invertebrates. The preferred test species is Daphnia magna.
Results of this test are summarized in Table 49 below.
Table 49 - Brodifacoum Freshwater Invertebrate Acute Toxicity
Species
Waterflea,
(Daphnia magna) Static
%a,i/
97.6
48-hour
lIAo/BCs, (pprn)
0.98 nominal
Toxicity '
Category
Highly Toxic
MRID No.
Author, Year
128442 Gerry, 1978
Study Classification
Supplemental, but
satisfies requirements
Since the LC50 falls in the range 0.1 to 10 ppm, brodifacoum is.Highly Toxic to aquatic
invertebrates on an acute basis. Although the study was "Supplemental," it was accepted as
fulfilling the Guidelines' requirement (72-1),, because of the use pattern and the extremely low
solubility of brodifacoum (MRID 128442). . . .
(b) Bromadiolone- Acute Toxicity to Freshwater
Invertebrates
The minimum testing required to assess the hazard of a pesticide to freshwater
invertebrates is a freshwater aquatic invertebrate toxicity test, preferably using first instar
Daphnia magna or early instar amphipods, stoneflies,, mayflies, or midges. The available
information is summarized in Table 50 below.
65
-------
Table 50 - Bromadiolone Freshwater Invertebrate Acute Toxicity
Species
Waterflea (Daphnia magna)
Waterflea
%a.i.
Unknown
98.7
EC5Q
(ppro)
0.24
2
Toxicdty Category
Highly toxic
Moderately toxic
MRID Author, Tear :
232567 LeBlanc, 1977
420933-02 Boeri, 1991
Study Classification
Core
Core
Because the EC50 falls in the range of 0.1 to 10 ppm, bromadiolone is considered
moderately to highly toxic to freshwater invertebrates on an acute .basis. The guideline
requirement is fulfilled (MRID 232567, 420933-02).
(c) Bromethalin - Acute Toxicity to Freshwater
Invertebrates
A freshwater aquatic invertebrate toxicity test using the technical grade of the active
ingredient is required to establish the toxicity of bromethalin to invertebrates. The preferred test
species is Daphnia magna. Results of this test are summarized in Table 51 below.
Table 51 - Bromethalin Freshwater Invertebrate Acute Toxicity
Species
Waterflea (Daphnia magna)
Waterflea
% a.L
96.3
99
EC50{ppb)
2.0
5.1
Toxicity Category-
Very highly toxic
Very highly toxic
MRID Author, Year
86751 van Lier, 1981
42733503 Conner, 1993
Study Classification
Supplemental
Supplemental
The results indicate that bromethalin is very highly toxic to aquatic invertebrates on an
acute basis. The guideline requirement (72-2) is fulfilled (MRIDs 86751 and 42733503).
. (d) Chlorophacinone - Acute Toxicity to Freshwater
Invertebrates
A freshwater aquatic invertebrate toxicity test using the TGAI is required to establish the
toxicity of Chlorophacinone to aquatic invertebrates. The preferred test species is Daphnia
magna. Results of this test are summarized in Table 52 below.
Table 52 - Chlorophacinone Freshwater Invertebrate Acute Toxicity
Species
Waterflea (Daphnia magna)
% a.i.
100
48-hour
EC5tt(ppb)
640
Toxicity
Category
highly toxic
MRID No. (Author/Year)
42356101 (Putt 1992)
Study Classification
core
*Using Flow-through (measured) testing
Because the EC50 is between 100 to 1000 ppb, Chlorophacinone is considered highly toxic
to aquatic invertebrates. The guideline (72-2) is fulfilled (MRID 42356101).
66
-------
(e) Diphacinone and its sodium salt - Acute Toxicity
to Freshwater Invertebrates
A freshwater aquatic invertebrate toxicity test using the TGAI is required to establish the
toxicity of diphacinone to aquatic invertebrates. The preferred test species is Daphnia mdgna.
Results of this test are summarized in Table 53 below. . . . ' ' .
Table 53 - Diphacinone and its sodium salt Freshwater Invertebrate Acute Toxicity55
Species
Waterflea (Daphnia magna)
!%a,l
98.7
48-h0ttrEC50
(ppm)
1.8
ToxMty
Category
moderately toxic
MRID No. (Author/Tear)
42282201 (Putt 1992)
Study
Classification
core
*Using Flow-through (measured) testing .
Because the EC50 in the range of 1 to 10 ppm, diphacinone is considered moderately toxic
to aquatic invertebrates on an acute basis. The guideline (72-2) is fulfilled (MRID 42282201).
c. Birds and Mammals, Secondary Toxicity Tests
, The Agency requires data to determine if vertebrate pesticides labeled for outdoor use pose
a hazard to secondary consumers. A whole body residue analysis with a target species is initially
required to determine the toxicant load in the carcass of a primary consumer. If a significant
toxicant load occurs, secondary poisoning studies with a mammalian predator and a predacious
bird are required. If the toxicant load is not significant, the secondary studies are not required.
For chlorophacinone, studies are required on the 0.005% a.i. bait only if a hazard exists for the
0.01% a.i. bait. The study in Table 54 was previously submitted.
Table 54 - Mammalian Secondary Toxicity
Species
Coyote
(Canis .
latrans)
Food/Test Material
Ground squirrels poisoned
with 0.01 %
Chlorophacinone bait over .
a 6-day period .
Food Amount
1 dead ground
squirrel/day for
5 consecutive
days1
Results '\
3 of 7 coyotes died (1
adult, 2 subadult) during
the 30-day posttreatment
period
MRID No. ;
(Aa&or/Year) \
427609-02
(Marsh and
Howard 1986)
Study
Classification
core
'the coyotes were held an additional 30 days for observation >
Three coyotes died from multiple feedings on ground squirrels poisoned with 0.01 % a.i.
bait. One of four adults died of internal hemorrhagmg, whereas the other three-remained healthy
with no observable symptoms. Of the three subadults tested, two died of internal hemorrhaging;
the survivor remained healthy. The amount of toxicant ingested secondarily was not determined.
The study, is adequate to indicate that rodents poisoned with 0.01% Chlorophacinone baits pose
a secondary hazard to coyotes and presumably other mammalian carnivores and scavengers. No
whole body residue analysis or avian data have been submitted.
Because the 0.01 % a.i. bait resulted in secondary mortality to coyotes, a study is required
using the 0.005% a.L bait. The data requirement (70-A-SS) for a secondary poisoning study with
67
-------
a mammal is fulfilled for the 0.01% a.i. bait (MRID 427609-02) but is outstanding for the
0.005% a.i. bait. The data requirements for a secondary poisoning study (70-B-SS) and whole
body residues in a target species (70-C-SS) are not fulfilled for the 0.01% a.i. and 0.005% a.i.
bait.
d. Terrestrial Field and Simulated Field Testing
The studies summarized in Table 55 below were submitted to support Chlorophacinone
registrations for California ground squirrel control or for vole control in orchards.
Table 55 - Chlorophacinone Terrestrial and Simulated Field Tests
Target Species
California Ground
Squirrel
(Spermophilus
beecheyi)
California Ground
Squirrel
California Ground
Squirrel
Pine vole
(Mkrotus
pinetorum)
Treatment
0.01% a.i. and
0.005% a.i.
grain baits
bait station
with 0.005%
a.i. grain bait
0.005% a.i.
pelleted bait
1 ground
spray at 0.3 Ib
ai/acre
NontajcgetKjfll , - '
poisoning confirmed in 14/15 mice and 2/2
woodrats examined on 5 0.01% a.i. bait plots
and 9/13 mice and 3/3 woodrats on 5 0.005%
a.i. bait plots1
poisoning confirmed in 3/3 mice examined on
2 bait plots1
poisoning confirmed in 2 dead rabbits (residue
levels of 0.011 and 1.16 ppm in GI tract)
No mortality or adverse affects were observed
in six captive opossums exposed for 14 days to
sprayed ground vegetation in an orchard
MRID No.
(Author/Year)
43.9222-01
(Baroch 1996)
439222-02
(Baroch 1996)
416493-01
(Poch 1991)
234579
(Libke et al.
1972)
Study
Classification
supplemental2
supplemental2
supplemental2
supplemental3
'poisoning was indicated by blue-dyed bait in the GI tract, blue stain in fatty tissues, subdermal hematomas, and/or
internal hemorrhaging
Jthe study was an efficacy test that provided some information on nontarget hazards
3sample size (6 opossums) was small
The food bait studies were designed primarily to assess efficacy of 0.01 % a.i. and 0.005%
a.i. Chlorophacinone baits to the California ground squirrel in the field. The orchard spray study
was designed to determine if opossums exposed to sprayed ground vegetation in an orchard setting
were adversely effected. All four studies were too limited in scope for a broad evaluation of the
potential impacts of Chlorophacinone on nontarget species. However, the information obtained
indicates that Chlorophacinone baits pose a primary risk to some nontarget species, especially
granivorous rodents. In two of the food baiting studies (MRID Nos 43922201, 43922202), an
effort was made to collect carcasses found during spot-baiting trials with 0.01 % a.i. and 0.005 %
a.i. grain baits and a bait station trial in which 0.005% a.i. grain bait was available in bait
stations. Based on the presence of blue dye incorporated into the bait and/or signs of internal or
external hemorrhaging, 91% (130/143) of the ground squirrels recovered and 86% (31/36) of
nontarget mice (Peromyscus spp., Perognathus inornatus) and woodrats (Neotoma fuscipes)
examined were poisoned. There was no evidence that the. 4 rabbits (Sylvilagus auduboni), 2
pocket gophers (Thomomys bottae), or 1 mourning dove (Zenaida macrourd) found were
poisoned. Although no evidence was found to indicate that birds consumed baits or that avian and
68
-------
mammalian predators and scavengers were adversely effected in any of these studies, none were
designed to assess such risks. In another study (MRID No. 416493-01) designed to assess efficacy
of 0.005% a.i. chlorophacinone bait against the California ground squirrel, two dead rabbits were
recovered. Both had bait in the GI tract. How the rabbits were exposed is not known;
presumably, they entered bait stations or gleaned spilled bait. . . .
e. Birds and Mammals, Secondary Toxicity Tests
The Agency requires data to determine if vertebrate pesticides labeled for outdoor use pose
a hazard to secondary consumers. .A whole body' residue analysis with a target species is required
to determine the toxicant load in the carcass of a primary consumer. Secondary poisoning studies
with a mammalian predator and a predacious bird are required only if-a biologically significant
toxicant load exists. The studies summarized in Table 56 below were previously submitted or
published. '-.-', ;
Table 56 - Diphacinone Avian and Mammalian Secondary Toxicity
Species
"" ' >
Barn owl (Tyta alba)
Great-horned owl
(Bubo virgirdanus)
Saw-whet ovfl(Aegottus
acadicus)
Golden eagle
(Aquila chrysaetos)
Rat
(Rattus norvegicus)
Mink (Mustella vison),
Dogs
Ermine (Musteld
erminea)
Striped skunk
(Mephitis mephitis)
JNIo.
Tested
2
3 ,
1
7
'72
3
3
2
5
Pood/
Test Material
wild rats poisoned
with 0.005% a.i. .
grain bait1 or deer
mice poisoned with
0.01 % a.i. grain bait?
sheep muscle
containing 2.7 ppm
Diphacinone
muscle tissue from
captive coyotes killed
with a single oral
dose
*
nutria5 poisoned with
0.01 % a.i. carrot bait
deer mice (2/day)
poisoned with 0.01 %
a.i; grain bait2
.Days
Dosed
10-
10
5,
5-10
6
5-18
6-10
5
5 '
Results
both barn owls survived with
no apparent signs of
intoxication; 2 great horned
owls died after 14 days; the
saw-whet owl died after 7
days3
all survived, but prothrombin
times and hematocrit values
were temporarily affected
coyote muscle containing 0.5
ppm Diphacinone killed 4 of 8
rats; muscle with <0.5 ppm
Diphacinone caused no
mortality . .
mink died on days 5,8, and
18; dogs died days 6, 6, and
10
1 ermine died after eating 10
mice in 7 days, the other ate
only 2 mice and survived; all
skunks survived
&GODN6.
! (Author/Year}
40077202
(Mendenhall
andPank
1980)
(Savarie et
al. 1979)6
(Savarie et
al. 1979)6
(Evans and
Ward 1967)7
002467
(Pankand
Hirata 1976)
Study
Classification
supplemental4
n/a .
n/a
supplemental4
supplemental4
'dead rats (Rattus spp.) fed to barns owls were given a free choice of poisoned bait or untreated lab. chow for. five days
Mead mice (Peromyscus maniculatus) fed to great-horned owls, saw-whet owls, ermine, and striped skunks had received 10 daily doses of 1 g
oat groats containing 0.01 % Diphacinone ' , , -
^eS great-horned owls, including the survivor, and the saw-whet owl were necropsied at the end of the test and all displayed severe symptoms
of anticoagulant poisoning; coagulation times were elevated from 0.5 to 1.5 min. prior to exposure to 22 to 34+ min. on day 8; coagulation had
only partially recovered (6 min.) by day 15 in the owl that survived. .
4 small sample size and uncertain dosage levels "'--.' " "
, sMyocastor coypus
'in E.E. Kenaga (ed.), Avian and Mammalian Wildlife Toxicology, ASTMSTP 693, pp. 69-79 ;
7J. Amer. Veterinary Med. Assoc. 151:856-861" ,
Collectively, these studies indicate that some birds and mammals are susceptible to
secondary poisoning from consuming diphacinone residue in animal tissue. The toxicant loads
69
-------
of the rats, mice, and nutria fed to raptors, mustelids, and dogs are not known but were
sufficiently high to cause mortality in most species. The relationship between target loads in
poisoned target species and the levels presented in coyote and sheep muscle was not established.
Moreover, the amount of toxicant present in the coyote muscle was found to be considerably
lower than that contained in the small intestine, liver, kidney, and heart tissues. The data are
adequate to demonstrate that avian and mammalian predators may be killed from consuming target
species poisoned with 0.01% a.i. bait. Therefore, the data requirements for secondary toxicity
tests with a mammal (70-A-SS) and bird (70-B-SS) are fulfilled for the 0.01% a.i. bait but not
for the 0.005% a.i. bait. Because toxicant loads in a target species have not been determined, that
data requirement (70-C-SS) also is not fulfilled for the 0.005% a.i. bait.
2. Environmental Fate
a. Environmental Fate and Transport
(1) Brodifacoum Environmental Fate and Transport
Based on the use pattern of brodifacoum, only hydrolysis (161-1), aerobic soil metabolism
(162-1), and mobility (163-1) data are required. The Agency has valid data for hydrolysis,
aerobic soil metabolism, and 30-day unaged mobility. The degradates and their accumulation and
decline pattern were not identified in the aerobic soil metabolism study. However, because
brodifacoum is typically applied in bait stations and/or only in and around structures, bait is only
50 ppm (0.005%) a.i., and brodifacoum is immobile in soil, potential contamination of surface
and ground water is low. Therefore, degradate identification, accumulation and decline, aged
column leaching, field dissipation, and adsorption/desorption data are not required.
Brodifacoum is stable to hydrolysis at pH 5, 7, and 9, persistent in soil (t-1/2 = 157
days), and immobile in soil columns. Unaged column leaching studies indicated that parent
brodifacoum is immobile in columns of British sand, sandy clay loam, silty clay and clay; 78-94%
of the applied radioactivity remained in the layer of unaged soil and < 0.32 % was recovered in
the leachate. Valid Kds were not obtained, but they are expected to be relatively high because
of the immobility indicated in the column leaching studies. Brodifacoum is persistent, but little,
if any, contamination of surface and ground waters is expected because of its use pattern and
immobility in soil.
(a) Brodifacoum Degradation
Hydrolysis: Brodifacoum is stable to hydrolysis at pH 5, 7, and 9. The guideline
requirement (161-1) is fulfilled. (MRID 42237701).
(b) Brodifacoum Metabolism
Aerobic Soil Metabolism: Brodifacoum degraded with a half-life of 157 days in sandy
clay loam soil incubated in the dark at 21 C and 75% of 0.33 bar moisture capacity. No volatile
70
-------
degradates other than 14CO2 were identified; 14CO2 comprised 36% of the applied radioactivity at
52 weeks posttreatment. Up to eleven [14CJcompounds,other than [14C]brodifacoum were isolated
from the soil extracts at 2.07 to 17.34% of the applied (0.008 to 0.067 ppm), but none were
identified. Identification and accumulation and decline of a major metabolite (17.34% of applied)
is not required for currently registered uses because of the limited potential for metabolite contact
with the soil. The guideline requirement (162-1) is fulfilled. (MRID 42579401)
' . . (c) . Brodifacowm Mobility
Unaged Column Leaching: Based on column leaching experiments, aged 30 days
brodifacoum residues (89-97% as brodifacoum) were relatively immobile in columns of sand'
sandy clay loam, silty clay, or clay soils from Great Britain that were leached with 20 inches of
0.01 M calcium chloride solution. Following leaching, 78.8 - 94.8% of the applied radioactivity
remained in the layer of aged soil and _<0.32% was recovered in the leachate. No degradates
were identified in the soil or leachate. The test material was aged for 30 days, but after 30 days
the major brodifacoum degradates had not been formed, and parent brodifacoum remained
essentially intact. Therefore, this study satisfied requirements for unaged column leaching rather
than aged column leaching for which the study was originally designed. Due to the very limited
potential for contact with the .soil, aged column leaching data are not required. The guideline
requirement (163-1) is fulfilled. (MRID 42568301)
Adsorption/Desorption: These data are considered to be of uncertain value and should
not be used to predict the environmental behavior of brodifacoum residues. This study is
unacceptable because acetone was used as a co-solvent, resulting in brodifacoum concentrations
far in excess of possible concentrations in the field. Brodifacoum is soluble in acetone at up to
20,000 parts per million. Brodifacoum was applied to a 2 g soil/20 ml water slurry at 0.9 - 4.5
ppm, although the study author stated that brodifacoum solubility in water is <0.1 ppm in 0.01
N CaCl2 solution. It is not possible to extrapolate these results into realistic solubility ranges, or
to discount the likelihood that brodifacoum was partitioned out of the aqueous solution and into
the acetone co-solvent. Also, Freundlich K values were not calculated. (MRID 42024501)
(2) Bromadiolone Environmental Fate and Transport
Based on the use pattern of bromadiolone, only hydrolysis (Guideline 161-1), aerobic soil
metabolism (Guideline 162-1), and mobility adsorption/desorption (163-1) data are required. Fish
bioaccumulation data also are available. The data requirement for adsorption/desorption is not
fulfilled, but the available data are sufficient to characterize the environmental fate of
bromadiolone for the labeled rodenticide use. The data requirement for field dissipation studies
was waived, because terrestrial non-food use is limited and because baits are typically placed
indoors or in bait stations. Additional data may be required if other uses are registered.
Sufficient information exists for a qualitative environmental fate assessment. Parent
bromadiolone is not persistent to aerobic soil metabolism (t1/2 = 14 days) and can generally be
considered immobile except in soils of low organic matter and clay, such as sand. Parent
bromadiolone was classified as immobile, based on aged (30 days) and unaged soil column
71
-------
leaching studies. Ninety-nine % of the leached radioactivity was bromadiolone isomers. Parent
KjS are 5.4 (silt loam) and 13.2 (loamy sand). Bromadiqlone was stable to hydrolysis in pH 5,
7 and 9 buffer solutions.
Although the parent compound is not persistent and is essentially immobile except in soils
low in organic matter and clay, two of the major degradates identified in the aerobic soil
metabolism study are persistent. These degradates, #1 and #3, reached 19 and 25% of the applied
in 120 and 270 days, respectively. Another degradate, bromadiolone ketone, reached 19% of the
applied in 14 days. No mobility information is available for the degradates. Additional
information to determine the IQs would be necessary for a more comprehensive fate assessment.
However, the available data are sufficient to categorize the environmental fate of bromadiolone
for the labeled rodenticide use.
Bromadiolone can leach in soils low in organic matter and clay; leaching was observed in
a soil column (silt loam) with 0.5% organic matter and 3.2% clay. Movement is correlated with
clay and organic matter content; sand soil, with little or no organic matter and clay, leached 62%
of the total radioactivity with the solute. However, because bromadiolone is applied as a food bait
(pellets, place packs, or paraffmized blocks), leaching is expected to be minimal.
(a) Bromadiolone Degradation
Hydrolysis: Bromadiolone parent is stable to hydrolysis at 5, 7, and 9. The data
requirement for hydrolysis is satisfied. (MRID 42237501)
(b) Bromadiolone Metabolism
Aerobic Soil Metabolism: The half-life of the parent is 14 days. Two major degradates,
#1 [l,3-diphenyl-5(4'-bromo-biphenyl) pentane-1-ol] and #3 [l,3-diphenyl-5(4'-bromo-biphenyl)
pentane-l,5-diol] are persistent. The mobility and toxicity of these two degradates are unknown.
The data requirement for aerobic soil metabolism is satisfied. (MRID 43594301)
(c) Bromadiolone Mobility
Leaching/AdsorptionyDesorption: The parent is generally immobile except in soils low
. in organic matter and clay. Aged and unaged column leaching studies showed no movement of
radioactive bromadiolone; 97% of radioactivity remained in the top one inch. Two major
degradates identified in the "new" aerobic soil metabolism'study (MRID 43594301) have not been
tested for mobility.
Bromadiolone can leach in soils low in organic matter and clay. Leaching was observed
in a soU column (silt loam) with 0.5% organic matter and 3.2% clay. Movement of bromadiolone
is correlated with clay and organic matter content. Sandy soil (little or no organic matter and clay)
leached 62% of the total radioactivity with the solute.
72
-------
Two major degradates, #1 [l,3-diphenyl-5(4'-bromo-biphenyl) pentane-1-ol] and #3 .[1,3-
diphenyl-5(4l-bromo-biphenyl) pentane-l,5-diol], detected in the aerobic soil metabolism study
(MRID 43594301) are persistent. The mobility and toxicity of these two degradates are unknown.
Therefore, the adsorption/desorption data requirement is not satisfied; however, the available data
are sufficient to characterize the environmental fate of parent Bromadiolone. Leaching data is
needed on the two major degradates noted above. (MRID 43000702, 42237501, 161972 161973
161988) .
(d) Bromadiolone Accumulation
Accumulation in Fish: Bioaccumulation concentration factors (BCFs) of 160X and 1658X
were obtained for edible and non-edible tissues in bluegill sunfish, respectively. The BCF for the
non-edible portion was 11.3 higher than the edible portion and 3.2 higher that the value obtained
for the whole fish. Twenty-four percent, 35.8% and 16% of Bromadiolone residues were
retained in whole, edible tissues, and non-edible tissues, respectively; after 14 days of depuration.
Total bluegill mortality during the 44 day test 43.9% (36/82 fish) and only 1.2% for the control.
The study for fish bioaccumulation is scientifically valid and is considered supplemental. The data
requirement is not satisfied because radioactive residues in the fish tissues were not identified.
The identification of extractable residues at concentrations >.-10% is a critical element of the fish
accumulation study. One of the primary reasons this study is conducted is to identify the residues
that accumulate in fish after exposure to a constant leveliof a pesticide. (MRID 00161965)
(3) Bromethalin Environmental Fate and Transport
Based on the use pattern and because bromethalin is formulated as a pelleted rodenticide,
it is probable that any contact with soil and water will be minimal. Therefore, only hydrolysis
' (Guideline 161-1), aerobic soil metabolism (Guideline 162-1) and leaching (Guideline 163-1) data
are required at this time. No data were submitted to assess the mobility of bromethalin.
However, leaching data are required. ."...:..
The available data are sufficient for a ;cursory environmental fate assessment for the
current use pattern. The data submitted indicate that bromethalin is stable to hydrolysis and is
persistent (half-life = 178 days) to aerobic soil metabolism. Data are not available to assess the
. mobility of parent bromethalin or its major degradate. However, because bromethalin is
formulated as a pelleted food bait, total usage of the active ingredient is low, and field uses do not
exist, ground water leaching and surface runoff are. expected to be minimal. ,
(a) Bromethalin Degradation
Hydrolysis: [14G]bromethalin, at approximately 1 ppm, was stable in aqueous buffered
pH 5, 7, and 9 solutions that were incubated at 25 ฐC in the dark for 30 days. At 35 days post-
treatment, bromethalin comprised 91.2-99.9% of the radioactivity in.the three buffer solutions
and was the, only [14C]compound detected. At the conclusion of the study, the material balance
for the three solutions was 93.0-100.0% of the applied radioactivity. The data requirement'
(Guideline 161-1) is fulfilled. (MRID 42438701). .
73
-------
(b) Bromethalin Metabolism
Aerobic Soil Metabolism: Parent compound accounted for 102.4% of the applied
radioactivity at the start and decreased to 22.3% by the end of the study. The calculated half-life
for parent compound was 178 days (y = -0.0039x + 4.38, r == -0.954). The parent compound
would be expected to be relatively stable to microbial/chemical degradation in the soil.
Up to 15.4% of the applied radioactivity was non-extractable residues; while up to 5.1%
of the applied radioactivity was 14C-volatiles, including 2.2% CO2. Because the concentration of
volatiles was so low, no attempt was made to characterize them. Unknown degradates ranged up
to 3.6% of applied. One degradate at a concentration of 43.8% of the applied was identified as
desnitrobromethalin. The data requirement (162-1) is fulfilled. (MRID 43007901)
!
(c) Bromethalin Mobility
Leacbing/adsorption/desorption: The leaching/adsorption/desorption data requirement
(Guideline 163-1) is not fulfilled. Mobility data for bromethalin parent are needed. Furthermore,
a major degradate detected in the aerobic soil metabolism study, desnitrobromethalin, comprising
43% of the applied, also appears to be persistent and its mobility is unknown. Leaching data also
are needed for this degradate. Because bromethalin is formulated as a pelleted rodenticide
primarily for use in and around buildings; it is probable that contact with soil and water will be
minimal.
(4) Chlorophacinone Environmental Fate and Transport
Data have been submitted for hydrolysis (Guideline 161-1), photolysis in water (Guideline
161-2), photolysis on soil (Guideline 161-3), aerobic soil metabolism (Guideline 162-1), and
leaching-adsorption/desorption (Guideline 163-1). These studies are acceptable and can be used
to fulfill their respective environmental fate data requirements. No additional data are required
to support the reregistration of Chlorophacinone.
Based on the available data, Chlorophacinone appears to be veiy immobile and readily
degradable in the environment. It has the following characteristics: (1) low water solubility (34
ppm at 25ฐ); (2) stable to hydrolysis at pH 5, 7, and 9; (3) very susceptible to direct photolysis
in water (half-life of 37 minutes at pH 7); (4) moderately susceptible to photodegradation on soil
(half-life of 4 days); (5) moderately degradable in a sandy clay loam soil under aerobic conditions
(half-lives of 21-45 days); (6) expected to be very immobile in soil (K^ = 341; K^ = 43,411);
(7) volatilizes slowly from water and soil (vapor pressure = 3.6xlO"6 mm Hg; Henry's Law
constant = 5.2X10"8 at m-m3/mol); and (8) does not accumulate in fish at-a significant level (Kow
-94).
Results from the aqueous photolysis, the soil photolysis, and the aerobic soil metabolism
studies suggest that Chlorophacinone degrades very rapidly to o-phthalic acid and p-
chlorophenylphenyl acetic acid through the cleavage of the indandione ring. The carboxylic acid
on the o-phthalic acid was further cleaved and transformed into carbon dioxide.
74
-------
In the field, chlorophacinone is expected to be bound very tightly with soil. Most of the
chemical is expected to remain in the. top soil layers, and its potential to reach ground water is
very low. Surface water contamination may occur in less-permeable areas and in areas near water
bodies. The mechanism for chlorophacinone to reach surface waters would likely be via
adsorption to eroding soil, as opposed to .dissolution in runoff water. Because of its high
adsorption coefficient, most chlorophacinone would be partitioned in the suspended and bottom
sediments instead of in the water column. Chlorophacinone might drift into surface waters from
its use as a spray in orchards. However, because the spray is applied at a low height, near ground
level, the resulting drift may be decreased by the surrounding orchard trees.
(a) Chlorophacinone Degradation
Hydrolysis: Indan-labeled [14C] chlorophacinone at 1.07 ppm was relatively stable in
sterile aqueous buffered solutions (pH 5, 7, and 9) incubated in the dark at 254^1 C for 30 days.
Two degradates (p-chlorophenyl acetic acid and o-phthalic acid) were detected from all three
solutions. In the pH 5 solution, chlorophacinone was 113% of the applied immediately
" posttreatment, 88.5% of the applied at 14 days, and 96% of the applied at 30 days, p-
Chlorophenylphenyl acetic acid was a maximum 0.4% of the recovered at 14 days, and o-Phthalic
acid was a maximum 0.7% of the recovered at 30 days. In the pH 7 solution, chlorophacinone
was 98.5-112.5% of the applied at 0 through 14 days and 84.1-85.9% of the applied at 30 days.
p-Chlorophenylphenyl acetic "acid and o-phthalic acid were each a maximum 0.2% of the
recovered during the study. In the pH 9 solution, chlorophacinone was 68.4-81.2% of the applied
at all sampling intervals. p-Chlorophenylphenyl acetic acid and o-Phthalic acid were each a
maximum 0.4% of the recovered during the study. The material balances determined prior to
partitioning ranged from 94 to 105% of the applied. The hydrolysis data requirement (Guideline
161-1) is fulfilled. (MRID 42205501)
Photodegradation in Water: Indan-labeled [14C] Chlorophacinone at approximately 1 ppm
degraded with a half-life of 37 minutes in pH 7 buffered solutions continuously irradiated with
a xenon arc lamp for 24.hours at 23.9-25.9 C. In contrast, Chlorophacinone was _>_97.4% of the
applied at all sampling intervals in dark controls incubated at 25 JL! C for 24 hours. During the
study, material balances were 94.6-103.3% of the applied for the irradiated samples and _>ilOO%
for the dark controls. . ' -'
Photodegradation on Soil: Ring-labeled [14C] Chlorophacinone at 10,8 ppm
phdtodegraded with a half-life of 4 days on sandy clay loam soil irradiated with an artificial light
source (xenon lamp) for up to 30 days at 19.9-26.9 C. By comparison, [14C]Chlorophacinone
degraded with a half-life of 95 days in the dark controls. Two major degradates (o-phthalic acid
and p-chlorophenylphenyl acetic acid) were identified. In the irradiated samples, chlorophacinone
was 95.7-99.1% of the applied immediately posttreatment, 77.7-90.5% at 1 day, 60.4-66.2% at
2-3 days, 40.0-41.9% at 5-9 days, and 24.7% at 14 days, o-phthalic acid was, 0.4% of the
applied immediately posttreatment, 20.9-23.9% at 1 day, 37.1% at 5 days, and 45.5% at 14 days.
g-chlorophenylphenyl acetic acid was a maximum of 4.1-4.2% in irradiated samples at 3 days.
The material balances were 85.9-122.7% in the irradiated samples and 94.3-121.0% in the dark
controls. The photodegradation on soil data requirement (161-3) is fulfilled. (MRID 42452301)
75
-------
(b) Chlorophacinone Metabolism
Aerobic Soil Metabolism: Indan-labeled [l,3-14C]Chlorophacinone at 9.7-10.5 ppm
degraded with observed half-lives of 45 days in sandy clay loam soil (flushed once daily with
humidified air) and 26 days in sandy loam soil (flushed once weekly). During incubation, both
soils were maintained in the dark at 24-26 C and 75 % of field capacity at 0.33 bar. CO2 was the
major volatile degradate, and two nonvolatile degradates (o-phthalic acid and p-
chlorophenylphenyl acetic acid) were isolated from the soils.
In the sandy clay loam soil, [14C]Chlorophacinone comprised 99.0-101% of the applied
immediately post-treatment, 55..7-57.9% at 30 days, 19.9-27.3% at 91 days, and 13.7-21.8% at
182 days. o-Phthalic acid was a maximum 3.6-5.4% of the applied at 91 and 182 days post-
treatment, and p-chlbrophenylphenyl acetic acid was a maximum 1.6-1.9% at 91 days. CO2, the
only volatile compound, totaled 21% of the applied at 30 days post-treatment, 36% at 91 days,
and 50% at 182 days. Unextracted soil [14C]-residues were a maximum of 11% of the applied at
182 days post-treatment. Material balances were 99-101% of the applied at 0 and 1 day post-
treatment, 92-98% at 3 through 21 days, 86-89% at 30 days, 72-78% at 91 days, and 82-88% at
182 days.
In the sandy loam soil, [14C] Chlorophacinone comprised 90.6-94.1% of the applied
immediately post-treatment, 40.3-41.8% at 14 days, 26.3-26.4% at 30 days, and 12.6-12.8% at
70 days. o-Phthalic acid was a 6.6-9.8% of the applied at 14 through 70 days posttreatment, and
p-chlorophenylphenyl acetic acid was a maximum 5.3-5.4% at 14 days. 14CO2 totaled 34% of the
applied at 14 days posttreatment, 50% at 30 days, and 64% at 70 days. Unextracted soil [14C]-
residues were 8-10% of the applied at 14 through 70 days post-treatment. Material balances were
> 95% of the applied at all sampling intervals.
The aerobic soil metabolism (162-1) data requirement is fulfilled. (MRID 43159801)
(c) Chlorophacinone Mobility
Leaching/Adsorption/Desorption: The submitted study on the adsorption/desorption of
Chlorophacinone is acceptable. The Leaching-Adsorption/Desorption (Guideline 163-1) data
requirement is fulfilled. Results from this study are summarized below: ,
The study's author stated that based on batch equilibrium studies, [14C]chlorophacinone
was determined to be relatively immobile in four soils. Freundlich K^ values were 56 for the
sand soil, 126 for the loam soil, 183 for the sandy clay loam soil, and 1000 for the clay soil (the
averaged ฃ^=341); K^ values were 95745, 26900, 15600, and 35400, respectively, for the four
soils (the averaged 1^=43,411). Adsorption increased with increases in clay and soil organic
matter content. (MRID 42666001)
(5) Diphacinone and its sodium salt Environmental Fate and
Transport ,
Data have been submitted for hydrolysis (Guideline 161-1), aerobic soil metabolism
(Guideline 162-1), and leaching-adsorption/desorption (Guideline 163-1). The hydrolysis and
76
-------
leaching-adsorption/desorption studies are supplemental and do not fulfill the guideline
requirements. The data are sufficient to make a cursory assessment of the environmental fate of
diphacinone. However, in order to make a quantitative environmental fate assessment, acceptable
hydrolysis,and leaching/adsorption/desorption data are needed.
Based on the available data, diphacinone appears to be relatively immobile and moderately
degradable. It has the following characteristics: (1) low water solubility (30 ppm at 25ฐC); (2)
stable to hydrolysis at pH 7 and 9 but susceptible to hydrolysis at pH 5 (half-life of 44 days); (3)
moderately degradable in a sandy loam soil under aerobic conditions (half-lives of 28 to 32 days);
(4) is expected to be immobile in soil; (5) volatilizes slowly, from water and soil (vapor pressure
= 1.2 x 10"8 mm Hg; Henry's Law constant- 1.8 x 1(3ฐ atm-mVmol); and (6) does not
accumulate in fish at a significant level (Kow = 43).
Results from the aerobic soil metabolism study suggest that diphacinone degraded to
diphenylglycolic acid relatively rapidly. The degradate was further cleaved and transformed-into
carbon dioxide.
Based on laboratory studies, diphacinone is expected to be bound very tightly with soil in
the field. Most of the chemical would remain in the top soil layers and its, potential to reach
ground water is very low. Surface water contamination may occur in less-permeable areas and
in areas near water bodies, The mechanism for diphacinone to reach surface waters would likely
be via adsorption to eroding soil rather than dissolution in runoff water. Although no adsorption
coefficient is available, most diphacinone is expected to be partitioned in the suspended and
bottom sediments instead of in the water column. /
(a) Diphacinone and its sodium salt Degradation
Hydrolysis: At a concentration of 10 ppm, Diphacinone was hydrolytically stable at pH
7 and pH 9, but degraded at pH 5 with a half-life of 44 days. However, degradates resulting from
hydrolysis at pH 5 were not quantified, nor were they identified other than by reference to a 1977
study (Velsicol Project No. 408398). The 1977 study was unacceptable when submitted and after
a current reevaluation. Therefore, it cannot be used to identify the degradates detected in the
current study. The current study is supplemental but does not fulfill the guideline requirement
for a hydrolysis study (Guideline 161-1). Identification of residues present at levels > 10% of
. the applied is a critical element of the hydrolysis study; Failure to identify one or more
significant degradates may result in gaps in the understanding of the environmental fate of the
chemical and its degradation products. (MRID 43582401)
(b) Diphacinone and its sodium salt Metabolism
Aerobic Soil Metabolism: Radio-labeled (benzyl ring or both phenyl rings)
[14C]Diphacinone, at a concentration of 2 pg/g, was metabolized with a half-life of 28.3 to 31.7
days, respectively, in sandy loam soils incubated aerobically in the dark at 25 ฑ 1ฐC for 3.5
months. The major degradate (defined as .>jLO% of the applied) detected in the phenyl ring-
labeled study was identified as diphenylglycolic acid and was present at a maximum of 24.5% of
the applied at one month after application. Diphenylglycolic acid was also detected in the benzyl
ring-labeled study at a very low concentration (_< 10% of the applied).
' ' ' 77
-------
Benzyl ring-labeled [14C]Diphacinone in soil extracts decreased from 86.4% of the applied
radioactivity at day 0 to 39.2% of the applied by day 14 post-treatment, and to 9.6% of the
applied by 3.5 months post-treatment. By 3.5-month's post-treatment, 42.5% of the applied
radioactivity was accounted for as 14CO2. Material balances during the study ranged from 93.1
to 104.1%.
Phenyl ring-labeled [14C]Diphacinone in soil extracts decreased from 87.1 % of the applied
radioactivity at day 0 to 41.6% of the applied by day 7 post-treatment, and to 6.5% of the applied
by 3.5 months post-treatment. By 3.5 months post-treatment, 37.3% of the applied radioactivity
was accounted for as 14CO2. Material balances during the study ranged from 88.6 to 103.1.
ปป''- '
The guideline requirement for an aerobic soil metabolism study (162-1) is fulfilled
(MRID 42035001)
(c) Diphacinone and its sodium salt Mobility
Leaching/Adsorption/Desorption: Diphacinone was relatively immobile in columns (60
cm in length) packed with sandy loam, silt loam, sand, and loamy sand soils to a depth of 30 cm.
Prior to leaching, the columns had been topped with loamy sand soil that had been treated with
technical diphacinone and incubated in a closed container in the dark for 30 days at 18-30ฐC. The
columns were leached with 20 inches of distilled water.
Diphacinone was detected only in the 0-6 cm layer in the columns with sandy loam and
silt loam soils. In the sand soil, diphacinone was detected in the 0-6 cm layer (at 117.1% of the
applied) and in the 6-12 cm layer (at < 3 % of the applied). Diphacinone was present in the 0-6
cm layer of the loamy sand soil at 76.1% of the applied, and was also present in the 6-12 cm, 12-
18 cm, and 18-24 cm layers at 3.4%, 4.8%, and 4.4% of the applied, respectively. Diphacinone
was not detected in any of the leachates collected from the four soil columns.
No adsorption values were reported. However, results from the aged column leaching
study suggest that diphacinone is relatively immobile in the environment.
Results from this study (MRID 435824-02) are supplemental. The guideline requirement
.for a leaching-adsorption/desorption study (Guideline 163-1) is not fulfilled primarily because
degradates, including CO2> were not identified or quantified. Identification of residues present
at levels _>_ 10% of the applied is a critical element of the leaching/adsorption/ desorption study.
One reason this study is conducted is to determine the mobility of parent and its degradates in soil.
Failure to identify one or more significant degradates may result in gaps in the understanding of
the mobility of the chemical and its degradation products and their leaching potential in ground
water. A new study is required.
j
3. Ecological Exposure and Risk Characterization
Risk characterization integrates the results of the exposure and ecotoxicity data to evaluate
the likelihood of adverse ecological effects. The means of integrating the results of exposure and
.78
-------
ecotoxicity data is called the quotient method. Risk quotients (RQs) are calculated by dividing
exposure estimates by ecotoxicity values, bom acute and chronic.
RQ = EXPOSURE/TOXICITY ,
RQs are then compared to OPP's levels of concern (LOCs). LOCs are criteria used by
OPP to indicate potential risk to nontarget organisms and the need to consider regulatory action.
The criteria indicate that a pesticide used as directed has the potential to cause adverse effects on
nontarget organisms. LOCs currently address the following risk presumption categories: (1)
acute high - potential for acute risk is high; regulatory action may be warranted in addition to
restricted use classification; (2) acute restricted use - the potential for acute risk is high but may
be mitigated through restricted use classification; (3) acute endangered species - the potential for
acute risk to endangered species is high; regulatory action may be warranted; and (4) chronic risk
- the potential for chronic risk is high; regulatory action may be warranted.
The ecotoxicity test values (i.e., measurement endpoints) used in the acute and chronic
RQs are derived from the results of required studies. Examples of ecotoxicity values derived
from the results of short-term laboratory studies that assess acute effects are: (1) LC50 (fish and
birds); (2) LD50 (birds and mammals); and (3) EC50 (aquatic invertebrates). For birds, the NOEC
value is used as. the ecotoxicity test value in assessing chronic effects.
Risk presumptions, RQ methods, and LOCs are summarized in Table 57 below.
Table 57 - Risk Presumptions for Terrestrial and Aquatic Organisms
Risk Presumption
i-
Acute High Risk
Acute Restricted Use
Acute Endangered Species
Chronic Risk
Birds and Mammals
^,,RQMefliod ;
EECVLCSO or LD50/day2
EEC/LCSO or LD^/day
EEC/LCSO or LD30/day
EEC/NOEC
,LOC
0.5
0.2
0.1
1
Aquatic Organisms
- RQ Method
EEC3/LC50orEC50
EEC/LC50 or EC50
EEC/LC50 or ECSO
EEC/MATC or NOEC
LOG,
0.5
0.1
0.05
1
'EEC = Estimated Environmental Concentration (ppm) on avian and mammalian food items (short grass; tall grass;
broadleaved plants and small insects; seeds, pods, large insects)
fog toxicant consumed/day -f- [LD50 X bird wt (kg)], where tox. consumed/day = amount food eaten X % a.i, in the
' food - .-
3EEC = aquatic Estimated Environmental Concentration (ppm or ppb)
a. Brodifacoum Ecological Exposure and Risk Characterization
/ -
Brodifacoum is a single dose rodent poison for use inside and along the outside walls of
buildings. It is very highly toxic to mammals and birds on an acute basis and a dietary basis.
It also is very highly toxic to aquatic organisms, but, due to its extremely low solubility,
it is not believed that enough brodifacoum would dissolve in water to create a hazard to nontarget
animals. Its use pattern is not likely to bring it into contact with water. There are uses for
79
-------
sewers; however, these products are "weather resistant" pafaffinized blocks and are not expected
to dissolve in the water.
The possibility of plants or bees being unduly exposed to brodifacoum is so small that no
plant or bee toxicity studies were required. Since it is being used only inside and along the
outside walls of buildings, endangered species will not likely be put at risk.
This risk characterization is based upon the definition of the use pattern "inside and along
the outside walls or buildings." The pattern should be put on the label.
If the use pattern is extended, nontarget hazard and secondary poisoning studies will be
needed to characterize the risks. The question of endangered species risks would have to be
reassessed because it is highly likely that additional species would be exposed. If the Agency can
not determine measures to protect those additional species, consultation with the 'Fish and Wildlife
Service may be necessary.
The available toxicity data on the TGAI are interpreted to mean that brodifacoum is very
highly toxic to birds (LD50 = 260 ^g/kg; LC50 = 800 ppb), very highly toxic to mammals (LDSO
= 0.41 mg/kg, male rat), and highly to very highly toxic to freshwater organisms (LC50 = 25
ppb). If the use pattern is extended, nontarget hazard and secondary poisoning studies will be
needed to characterize the risks.
*
(1) Brodifacoum Exposure and Risk to Nontarget Terrestrial
Animals
There are several terrestrial field studies that were submitted during the initial registration
process. They were interpreted as showing that brodifacoum has a primary and secondary
nontarget poisoning potential. The reregistration of brodifacoum is for indoor, transportation,
and sewer uses only. Therefore, field and secondary poisoning studies are not required and the
old studies and the literature were not reviewed. If field uses are requested, additional studies will
be required.
(a) Brodifacoum Exposure and Risk to Birds
Brodifacoum's avian toxicity is two orders of magnitude more toxic than is required for
the category very highly toxic. It poses a very high hazard to any birds that consume it. If it
would be used outdoors it would be a presumptive hazard to birds. However, it is only used
indoors, in vehicles, and in sewers, therefore, birds are not expected to be unduly exposed to it.
(b) Brodifacoum Exposure and Risk to Mammals
Brodifacoum is two orders of magnitude more toxic than is required for the category very
highly toxic. It poses a very high hazard to any mammals that consume it. If it would be used
outdoors it would be a presumptive hazard to mammals. However, it is only used indoors, in
vehicles, and in sewers, therefore, wild mammals are not expected to be unduly exposed to it.
80
-------
(2) Brodifacoum Exposure and Risk to Nontarget Aquatic
Animals
Brodifacoum is an order of magnitude more toxic than is required for the category very
highly toxic for the rainbow trout and is highly toxic to the bluegill sunfish. It is only used
indoors, in vehicles, and sewers. The sewer use is for a paraffinized bait and is not expected to
contaminate water., It is not expected that it will come into contact with aquatic animals. The
solubility of brodifacoum is 10 mg/1. If it was put in water it would dissolve sufficiently to
produce a concentration of 0.01 ppm, enough to Mil some aquatic animals, although it would be
below the LC50. Since brodifacoum has no aquatic uses, it is not expected to enter a body of
water in a large enough quantity to cause significant contamination. It is not believed that
brodifacoum will pose an undue hazard to aquatic organisms.
(3) Brodifacoum Exposure and Risk to Nontarget Plants and
, Insects
The possibility of plants or bees being unduly exposed to brodifacoum is so small that no
plant or bee toxicity studies were required. Since it is being used only outside and,along the
outside walls of buildings, endangered species will not likely be put at risk.
(4) Brodifacoum Endangered Species Concerns
Brodifacoum was addressed by the U.S. Fish and Wildlife Service in its Biological
Opinion of March 1993. Uses considered were control of Norway rats, roof rats, and house mice
in and around urban, industrial, commercial, agricultural, and public buildings and in and around
transport vehicles (ships, trains, and aircraft and related port buildings. The service made a
"jeopardy" or "no jeopardy" determination for the 20 "may affect" species listed below in Table
58. Other species were considered either not at risk of exposure or not likely to be affected.
81
-------
Table 58 - USFWS 1993 Biological Opinion for Brodifacoum
, Species
- Jeopardy
No Jeopardy
" ' ^Mammals:
Alabama beach mouse (Peromyscus polionotus ammobates)
Anastasia Island beach mouse (Peromyscus polionotus phasma)
Choctawhatchee beach mouse (Peromyscus polionotus allophrys)
Southeastern beach mouse (Peromyscus polionotus niveiventris)
Perdido Key beach mouse (Peromyscus polionotus trissyllepsis)
Florida salt marsh vole (Microtus pennsylvanicus dukecampbelli)
Salt marsh harvest mouse (Reithrodontomys raviventris)
Fresno kangaroo rat (Dipodomys nitratoides exillis)
Giant kangaroo rat (Dipodomys igens)
Morro Bay kangaroo rat (Dipodomys heermanni morroensis)
Stephen's kangaroo rat (Dipodomys stephensi)
Tipton kangaroo rat (Dipodomys nitratoides nitratoides)
Point Arena mountain beaver (Aplodontia rufa nigra)
Carolina northern flying squirrel (Glaucomys sabrinus coloratus)
San Joaquin kit fox (Vulpes macrotis mutica)
Louisiana black bear (Ursus americanus luteolus)
X
X
X
X
X
X
X
X
X
X
,
X
X
X
.X
X
X
' - Birds;
Audubon's crested caracara (Caracara cheriway audubonii)
San Clemcnte loggerhead shrike (Lanius ludovicianus meamsi)
Hawaiian hawk (Buteo solitarius)
X
X
X
':.'' ,-, ' Reptiles;
Eastern indigo snake (Drymarchon corais couperi)
X
b. Bromadiolone Ecological Exposure and Risk Characterization
(1) Bromadiolone Exposure and Risk to Nontarget
Terrestrial Animals
(a) Bromadiolone Exposure and Risk to Birds and
Nontarget Mammals
Because bromadiolone is a rodenticide, risk is presumed for any small mammals that feed
on bait. Mortality of captive subadult coyotes fed poisoned ground squirrels also indicates a
potential for secondary poisoning of predators if secondary exposure occurs. However,
bromadiolone is used outdoors only in urban areas. Such placements can be made only around
buildings or in sewers, and all placements around buildings must be in protective bait stations or
in areas inaccessible to nontarget wildlife. Due to paucity of nontarget wildlife (i.e., non-
domestic animals) in urban areas, minimal risk is expected. In non-urban areas, bromadiolone
baits can be used only indoors therefore, minimal exposure of nontarget species is expected.
82
-------
(2) Bromadiolone Exposure and Risk to Nontarget Aquatic
Animals ,
Based on where and how bait is applied, little if any bromadiolone is expected in water
bodies. Additionally, because it is extremely insoluble, Bromadiolone is not expected to pose a
major risk to aquatic organisms.
(3) Bromadiolone Endangered Species Concerns
The U. S. Fish and Wildlife Service addressed bromadiolone in its Biological Opinion
issued in March of 1993., The uses addressed were control of Norway rats, roof rats, and house
mice in urban areas in and around the periphery of homes, industrial, commercial and public
buildings, alleys, arid cargo areas of ships, trains, and aircraft. Table 56 below summarizes the
results of the USFWS opinion. The U.S. Fish and Wildlife Service made a "jeopardy" or "no
jeopardy" determination for the 12 "may affect" species listed in the jeopardy tables. Other
species were considered either not a risk of concern or not likely to be affected.
Table 59 - USFWS 1993 Biological Opinion for Bromadiolone
Species
Jeopardy
No Jeopardy
' Mammals: _ -,
Alabama beach mouse (Peromyscus polionotus ammobates)
Anastasia Island beach mouse (Perpmscus polionotus phasma)
Choctawhatchee beach mouse (Peromyscus polionotus allophrys)
Southeastern beach mouse (Peromyscus polionotus niveiventris)
Perdido Key beach mouse (Peromyscus polionotus trissyllepsis)
Salt marsh harvest mouse (Reithrodontomys raviventris)
Fresno kangaroo rat (Dipodomys nitratoides exillis)
Morro Bay kangaroo rat (Dipodomys heermanni morroensis)
Stephen's kangaroo rat (Dipodomys stephensi)
Tipton kangaroo rat (Dipodomys nitratoides nitratoides)
Point Arena mountain beaver (Aplodontia rufa nigra)
San Joaquin kit fox (Vulpes macrotis mutica)
X
X
X
X
X
X
x
x
-. x
X
X
X
c. Bromethalin Ecological Exposure and Risk Characterization
(1) Bromethalin Exposure and Risk to Nontarget Terrestrial
Animals
Because bromethalin is used exclusively in and around buildings or in sewers, primary
exposure of birds is expected to be minimal. Bait applications must be contained in protected bait
stations or made in areas inaccessible to nontarget wildlife. Because bromethalin is a rodenticide,
83
-------
risk is presumed for any small mammals that feed on the bait. Bait applications around buildings
in non-urban areas is likely to expose some small mammals.
The Agency's incident data base has no records of wild animals being killed from feeding
on rodents poisoned with brometHalin. However, secondary toxicity data are needed before
secondary risks can be adequately assessed from bait applications of bromethalin around buildings.
(2) Bromethalin Exposure to Plants and Insects
No data were required.
(3) Bromethalin Exposure and Risk to Nontarget Aquatic
Animals
Risks to aquatic organisms are presumed to be minimal. Bromethalin is very highly toxic
to aquatic organisms, but its use in and around buildings, cargo vessels, alleys, and sewers is
likely to result in minimal contamination of aquatic environments. Some potential for contact
with water exists for the sewer use, especially in overflow sewers or if bait blocks are not
properly wired above the water line. However, because bromethalin has an extremely low
solubility hi water and sewer baits are formulated as "weather-resistant" paraffinized blocks, very
little, if any, exposure of aquatic organisms is anticipated from sewer use.
(4) Bromethalin Endangered Species Concerns
The U.S. Fish and Wildlife Service addressed Bromethalin in its Biological Opinion
issued in March of 1993. The use patterns included control of Norway rats, roof rats and house
mice in and around homes, commercial, industrial and agricultural buildings and airports, landing
strips and urban alleys. The Service made a "jeopardy" or "no jeopardy" determination for the
14 "may affect" species listed in Table 55. Other species were considered either not at risk of
exposure or not likely to be affected.
84
-------
Table 60 - USFWS 1993 Biological Opinion for Bromethalin
Species , ' "f ',
Jeopardy
No Jeopardy
Mammals:
Alabama beach mouse (Peromyscus polionotus ammobates)
Anastasia Island beach mouse (Peromyscus polionotus phasma)
Choctawhatchee beach mouse (Peromyscus polionotus allophrys)
Southeastern beach mouse (Peromyscus polionotus ntveiventris)
Perdido Key beach mouse (Peromyscus polionotus trissyllepsis)
Florida salt marsh vole (Microtus pennsylvanicus dukecampbelli)
Salt marsh harvest mouse (Retihrodontomys raviventris)
Fresno kangaroo rat (Dipodomys nitratoides exillis)
Giant kangaroo rat (Dipodomys igens)
Morro Bay kangaroo rat (Dipodomys heermanni morroensis)
Stephen's kangaroo rat (Dipodomys stephensi)
Tipton kangaroo rat (Dipodomys 'nitratoides nitratoides)
Point Arena mountain beaver (Aplodontia rufa nigra)
Carolina northern flying squirrel (Glaucomys sabrinus coloratus)
X
"X
X
X .
X
, X
X
X
X
X
, * ^
X
x
X
X
d. Chlorophacinone Ecological Exposure and Risk
Characterization
(1) Chlorophacinone Exposure and Risk to Nontarget
Terrestrial Animals .
Field and Rural vs Urban/Suburban Risks: The risk assessment for nontarget wildlife
pertains to field uses and to bait applications in rural and urban/suburban areas where bait can be
applied around buildings (e.g., barns, houses, sheds) for commensal rat and mouse control.
Chlorophacinone can be used to control rats and mice around buildings in urban areas. However,
due to the paucity of wildlife (i.e., non-domestic animals) in urban areas, primary and secondary
risks are expected to be minimal.
EECs: The estimated environmental concentration (EEC) of a pesticide on potential food
items of birds and mammals immediately after a foliar application is compared to the most
, sensitive avian or mammalian LC50 value to assess potential risk. Based on the findings of
Hoerger and Kenaga (1972) as modified by Fletcher et al. (1994), predicted 0-day maximum and
mean residues of a pesticide expected on selected .avian or mammalian food items immediately
following a direct single application at 1 Ib a.i./acre are listed in Table 61. For Chlorophacinone,
the only spray:application is for vole control in orchards. One spray application at 0.2 Ib a.i./acre
is permitted per year,(a repeat application is allowed if rainfall occurs within 12 hours of
application). Therefore, EECs resulting from a Chlorophacinone spray are presumed to be 20%
of the values summarized in Table 61 for a 1 Ib a.i./A application.
85
-------
Table 61 - EECs1 on Potential Avian and Mammalian Food Items After a Single Pesticide
Spray Application of 1 Ib a.L/A and a Chloriphacinone Orchard Spray of 0.2 Ib a.i./A
Food Items
Short grass
Small insects
Seeds, Fruits, Large insects
1 Ib a.i./A pesticide appl.
Maximum EEC (ppm)
240
135
15
Mean EEC (ppm)
85
, 45
7
0,2 Ib z,L/A CMorophacinone appl.
Maximum EEC (ppm)
48
27
3
Mean EEC (ppm)
17
9
1
'Predicted maximum and mean EECs based on on Hoerger and Kenaga (1972) as modified by Fletcher et al. (1994)
' / '
(a) Chlorophacinone Birds
Acute primary risk (spray application): Acute RQs for a single spray application of
chlorophacinone are summarized in Table 62 below.
Table 62 - Avian Acute RQs for a Single Ground Spray Application of Chlorophacinone1
Site/ Appl. Rate
(Iba.i,/A)
Orchard2
(0-2)
Food Item
Short grass
Small insects
Seeds, Fruits, Large insects
Maximum
EEC (ppm)
48
27
3
Mean EEC
(ppm)
17.00
9.00
1.00
Max. Acute RQ
OSBC/LCj,)
0.86***
0.48*** '
0.05
Mean Acute RQ
(EEC/LC50)
0.30**
0.16*
0.02
1 Single ground spray application of chlorophacinone are based on maximum and mean EECs and a bobwhite quail
LCjo of 56 ppm.
2 OR, UT, WA, WV (vole control)
"'exceeds LOCs for acute high risk (0.5), restricted use (0.2), and endangered species (0.1)
"exceeds LOCs for acute restricted use (0.2) and endangered species (0.1)
"exceeds the LOG for endangered species (0.1)
t
Based on maximum EECs for a single application, the avian acute high risk, restricted use,
and endangered species, LOCs are exceeded for birds feeding on^hort grass, restricted use and
endangered species LOCs are exceeded for insectivores. Based on mean EECs, restricted use and
endangered species, LOCs are exceeded for short grass. Moreover, the endangered species LOG
is exceeded for birds feeding on small insects.
Acute primary risk (food baits): The potential for primary exposure of seed-eating birds
to food baits exists primarily for field applications of unprotected loose bait (i.e., aerial or ground
broadcast or hand applied pellets or treated whole grains). Minimal exposure is expected for
applications where bait is placed in protected bait stations or areas inaccessible to nontarget
wildlife, if place packs or paraffinized bait blocks are used, and for underground applications for
control of pocket gophers. Birds that are mainly herbivorous or insectivorous are not expected
to be at risk from grain-based food baits.
RQs for loose food baits are based on the number of LD50 doses potentially consumed by
a bird in one day. RQs are calculated for three separate weight classes of birds: 500-1000 g
(e.g., waterfowl), 100-200 g (e.g., upland gamebird), and 20-50 g (e.g., passerine). Acute RQs
for applications of chlorophacinone food baits are summarized in Table 63 below.
86
-------
Table 63 - Avian (Granivore) Acute RQs (LD^/day) for Chlorophacinone Food Baits, Based
on a Bobwhite Quail LD5ft of 258 mg/kg
Site
Crop and noncrop areas (bare ground)4;
Forestry5
Orchard6; Tree plantation7;
Noncrop areas, ditch banks,
rights of way8; Noncrop areas or
unspecified9
Bait {% a,i,)
0.01
0.005
Body Wt
Class; (g)
20-50
100-200
500-1000
.. 20-50
100-200 ,
500-1000
AmtFood
Eaten (g)1
3.50
9.00
18,00
3.50
9.00
18.00
rug a.L
consumed/day
, 0.35 ;
0:90
,1.80,
0.18
. ,0.45
;.' 0.90
Acute RQ23
(LD5(>s/day)
0.07
0.04
0.01
0.04
0.01
0.01
'estimates of food consumption as a function of body size are based on information provided by Kenaga (1972) and
Dunning (1984) for the mallard, bobwhite quail, and red-winged blackbird
2LD50s/day = mg toxicant consumed/day 4- [LD50 (mg/kg) * bird wt (kg)]
3only the highest RQ value is tabulated
4 ground squirrel control (CA, MT) ' ,
5 deer mouse control (CA) ' -
6 vole control (CT, MD, MI, MO, NC, NY, OH, OR, PA, SC, VA, VT, WA, WV)
7 vole control (ID, NC)
8 vole control (OR) . .
9 ground squirrel, vole, chipmunk, woodrat, and/or jackrabbit control (CA, OR)
Avian acute LOCs are not exceeded for applications of loose bait when risk is based on
the/number of LD50s potentially consumed by; granivorous birds in one day. However,
chlorophacinone is a multiple-feeding anticoagulant, and risk to birds that feed on bait for several
days is likely greater than predicted by RQ values based on a single feeding. Avian dietary tests
indicate that chlorophacinone is more toxic when ingested over a 5-day period than when
administered in a single dose. For this scenario, EECs on grains or pellets are 50 ppm (0.005%
a.i.baits) and 100 ppm (0.01% a..i baits). Acute RQs based on avian dietary toxicity are
summarized in Table 64 below for granivorous birds.
Table 64 - Avian (Granivore) Acute RQs For Chlorophacinone Food Baits, Based on a
Bobwhite Quail LCsn of 56 ppm
Site
Crop and noncrop areas (bare ground)1; Forestry2
Orchard3; Tree plantation4; Noncrop areas, ditch banks,
rights of way5
Bait (% a.l)
0.01
0.005
EEC(ppm)
> 100
50
Acute RQ (EEC/LCio)
^ yg**#
0.89***
1 ground squirrel control (CA, MT)
2 deer mouse control (CA) ,
3 vole control (CT, MD, MI, MO, NC, NY, OH,, OR, PA, SC, VA, VT, WA, WV)
4 vole control (ED, NC) " . .
5 vole control (OR)
*** exceeds LOCs for acute high risk (0.5), restricted use (0.2), arid endangered species (0.1)
Acute high risk, restricted use, and endangered LOCs are exceeded for granivorous birds
for above-ground applications of both 0.01% a.i.and 0.005% a.i. loose food baits when risk is
87
-------
based on dietary toxicity. The Agency is not aware of any bird poisoning incidents due to
chlorophacinone, nor was any avian mortality observed during efficacy field studies in which
small mammal mortality was reported. However, any possible means of reducing primary
exposure of birds are important, such as use of protective bait stations, which the Agency
addressed in PR Notice 94-7, issued September 16, 1994. The quality of bait stations and the care
taken by applicators to secure stations and ensure that bait is not exposed outside bait
compartments are important in minimizing exposure of bait to granivorous birds. Stations should
be adequate to prevent destruction by wildlife (e.g., raccoons, bears) and/or livestock and protect
bait in adverse weather conditions. Stations should be designed with internal bait compartments
that minimize spillage and be well secured or anchored. Applicators should be encouraged to use
stations with baffles, mazes, and/or small entrance holes that deter birds from entering the bait
compartment, and they must ensure that bait spilled outside stations is disposed of properly.
Where bait stations may not be feasible, use of products formulated in place packs or paraffinized
blocks would help reduce primary exposure of birds.
Chronic risk: Chronic risk is presumed to be minimal for uses where baits are
inaccessible (e.g., in bait stations, place packs, or burrows), not likely to be eaten (e.g.,
paraffinized blocks), if only one application is made, or if applications are made outside or not
immediately preceding the breeding season of birds. Based on these criteria, applications of one
chlorophacinone product (SLN CA890023) may result in chronic exposure to granivorous birds,
because baiting directions specify that "An uninterrupted supply of bait should be maintained as
long as any bait is taken, which may be 1 to 4 weeks." Chronic risk from this use cannot be
assessed, however, until avian reproduction studies are submitted. This study is required unless
label changes are made to eliminate potential chronic exposure.
Secondary risk: Data are lacking to assess potential secondary risks to avian predators
and scavengers that may feed on rodents poisoned with chlorophacinone. Two field studies
conducted primarily to determine the efficacy of 0.005% ai.and 0.01% a.i. chlorophacinone food
baits to the California ground squirrel also attempted to evaluate potential nontarget hazards. No
mortality of avian predators or scavengers was observed in either study. However, the evaluation
was based almost exclusively on locating carcasses on treatment plots. Because predatory and
scavenging birds are highly mobile and wide-ranging and chlorophacinone takes several days to
kill, birds might die away from study sites and not be found. Pre- and post-treatment population
censusing of granivorous birds, use of radio telemetry for following and determining fates of
raptors and scavengers, and extensive carcass searches on and away from study plots are needed
to adequately assess secondary risks to birds. Therefore, these efficacy studies are considered
inadequate for evaluating secondary risks to birds from field uses and from commensal rat and
mouse control in rural areas. Potential risks will be evaluated when the required laboratory
secondary toxicity tests are submitted.
(b) Chlorophacinone Mammals
Acute primary risk (food bait): Because rodents, moles (insectivores), and jackrabbits
(lagomorphs) are target species and chlorophacinone is very highly toxic to small mammals, the
88
-------
Agency presumes acute high risk to any small mammals that feed on chlorophacinone baits or
sprayed food items (e.g., grass, seeds, insects) over a period of several days. Field studies
conducted against ground squirrels on the San Joaquin range in California confirm this
presumption of high acute risk. Small nontarget mammals, principally mice and woodrats, were
found poisoned on plots baited with,0.01% a.i. and 0.005% a.i. Chlorophacinone grain baits.
The findings indicated, however, that nontarget mortality might be reduced if 0.005% a.i.bait is
used rather than 0.01% a.i. bait. Of the 47 nontarget individuals located on spot-baited plots, 27
(57%) were found on plots treated with 0.01% a.i. bait and 20 (43%) on the plots treated with
0.005% a.i. bait. Evidence of poisoning was found in 80% (16/20) of the individuals necropsied
on the 0.01% a.i. plots but only 60% (12/19) of those necropsied on the 0.005% a.i. plots.
Primary risk to larger mammals are reduced for applications requiring protected bait
stations, providing that the stations are adequately constructed and secured. Bait stations are
designed with openings only large enough to accommodate adults of the target species. Larger
species cannot gain entrance to the bait compartment, although smaller species are able to enter
and thus have access to the bait. Care should be taken to ensure that bait spillage is minimized
and that any bait spilled is immediately removed and not left exposed on the ground. The two
dead rabbits found in one field study may have been small enough to enter the bait stations, or
more likely they gleaned bait spilled outside the stations.
Acute primary risk (spray application): Sprayed ground vegetation in and around the
perimeter of orchards is potentially hazardous to herbivores, and insectivores may be adversely
effected by feeding on contaminated insects. Vegetation sprayed at 0,2 lb a.i./acre
crilorophacinone apparently is lethal to voles, which are the target species. Mortality occurs when
voles consume sprayed vegetation or when they groom fur contaminated from contact with
sprayed vegetation. Although opossums exposed for 14 days to sprayed vegetation did not die or
exhibit any adverse effects, sample size (n = 6) was small. Moreover, opossums are omnivorous.
and their susceptibility to chlorophacinone may not reflect that of smaller mammalian herbivores
that might feed exclusively on green vegetation.
Secondary risk: A secondary hazards study in which poisoned ground squirrels were fed
to captive coyotes demonstrates that rodents poisoned with 0,01% a.i. chlorophacinone bait pose
a risk to coyotes and presumably other species. In that study, three of seven coyotes died from
. consuming -one poisoned squirrel per day for five consecutive days. In the efficacy studies
conducted on the San Joaquin Range in California, carcasses of California ground squirrels
poisoned with 0.01% a.i. and 0.005% a.i. grain baits were available at burrow entrances and in
open areas on the ground surface away from burrows. It is conceivable that coyotes and other
predators (e.g., fox, bobcats, mustelids) could easily find and consume one ground squirrel per
day'over a 5-day period. Although no dead predators were found in those studies, the techniques
used and the search effort for effected nontarget species was not adequate for wide-ranging
species. . . ,
An adequate assessment of secondary risks to mammalian predators and scavengers cannot
be completed until required secondary toxicity tests are conducted for the 0.005% a.i. bait.
However, findings from the California ground squirrel field trials indicate that carcasses of
ground squirrels poisoned with 0.005% a.i. bait may contain considerably less chlorophacinone
89
-------
residue than those poisoned with 0.01 % a.i.. bait. Analysis of whole carcass tissue residues found
mean residueloads of 0.62 (0.048-1.88) mg chlorophacinone in the 10 squirrel specimens exposed
to 0.01% a.i. bait. Mean residue loads were 0.19 (0.032-0.744) and 0.16 (0.043-0.415) mg
chlorophacinone in squirrel specimens exposed to 0.005% a.i.bait on spot-baited plots and plots
with bait stations, respectively. The hazard of these residue loads is undetermined in the field,
although some captive coyotes in the secondary hazards study were killed from exposure to
ground squirrels poisoned with 0.01% a.i. chlorophacinone bait. Because the residue levels in
poisoned squirrels exposed to 0.005% a.i. bait were only about one-third of those in squirrels
exposed to 0.01% a.i. bait, secondary risks from 0.005% a.i. bait likely are less than for 0.01%
a.i. bait.
(2) Chlorophacinone Exposure and Risk to Nontarget
Aquatic Animals
EFED calculates aquatic EECs using the Generic Expected Environmental Concentration
Program (GENEEC). The EECs are used for assessing risk to aquatic organisms. GENEEC uses
basic environmental fate data and pesticide label application information to estimate EECs from
treatment of 10 hectares. The model calculates the concentration (i.e., EEC) of pesticide in a 1-
hectare, 2-m deep pond, taking into account adsorption to soil or sediment, degradation in soil
before washoff into the water body, and degradation within the water body. The model also
accounts for direct deposition of spray drift into the water body (assumed to be 1 % of the
application rate for a ground spray). The interval between applications is included in the
calculations for multiple applications. The environmental fate values used in the model for
chlorophacinone are: soi!KoC'= 43,411, solubility = 34ppm, aerobic soil metabolism half-life
= 45 days, hydrolysis = >30 days (stable), and the water photolytic half-life = 0.03 days.
Aquatic EECs and RQs for the most sensitive aquatic organism (rainbow trout) are summarized
in Table 65 below for those use sites for which the product label specified an application rate in
pounds per acre.
Table 65 - Aquatic EECs and Acute RQs For Freshwater Organisms1
Site
Orchard2
Orchard3;
Crop and noncrop areas (bare ground)4
Type of
AppEcation
ground spray
food bait
Appl. Rate
(So ajL/A)
0.2
0.001
No. Appl. /Appl.
Interval (days)
1
2(1)
1
2(30)
Initial EEC
(PP1>>
0.271
0.616
0.001
0.002
Acute RQ
(EEC/LC^
< 0.001
0.001
< 0.001
< 0.001
1 Aquatic EECs and acute RQs for freshwater organisms are based on a rainbow trout LC50 of 450 ppb of
chlorophacinone ' -
2OR,UT, WA, WV
3 MI, NC
4CA, MT
The results indicate that no aquatic acute LOCs are exceeded for freshwater organisms at
maximum registered application rates for orchard ground spray (vole control) or applications of
0.01% a.i. food bait. RQs for the 0.005% a.i. bait and other freshwater organisms would be even
lower. Therefore, minimal risk to freshwater organisms is expected.
90
-------
(3) Chlorophacinone Endangered Species Concerns
The U.S. Fish and Wildlife Service addressed Chlorophacinone in its Biological Opinion
of March, 1993. That Opinion is based on its use for control of Norway rats, roof rats, and
house mice in and around homes, industrial, and agricultural buildings; pocket gophers in
underground runways; mice and voles in Idaho and Delaware; orchard mice in Delaware,
Connecticut, and Arizona; control of deer mice in noncrop areas of Florida; ground squirrel
control in Arizona; control of deer mice, house mice, and pocket gophers in California; and
indoor control of bats. The Service made a "jeopardy" or "no jeopardy" determination for the
28 "may affect" species listed below. Other species were considered either not at risk of exposure
or not likely to be affected. See Table 66 below.
Table 66 - USFWS 1993 Biological Opinion for Chlorophacinone
Species ,
Jeopardy
No Jeopardy
Mammals: -
Alabama beach mouse (Peromyscus polionotus ammobates)
Anastasia Island beach mouse (Peromyscus polionotus phasma)
Choctawhatchee beach mouse (Peromyscus polionotus allophrys)
Southeastern beach mouse (Peromyscus polionotus niveiventris) '
Perdido Key beach mouse (Peromyscus polionotus trissyllepsis)
Amaigosa. vole (Microtus califomicus scirpensis)
Florida salt marsh vole (Microtus pennsylvanicus dukecampbelli)
Hualapai Mexican vole (Microtus mexicanus hualpaiensis)
Salt marsh harvest mouse (Reithrodontomys raviventris)
Fresno kangaroo rat (Dipodomys nitratoides exiltis)
Giant kangaroo rat (Dipodomys igens)
Morro Bay kangaroo rat (Dipodomys heermanni morroensis)
Stephen's kangaroo rat (Dipodomys stephensi)
Tipton kangaroo rat (Dipodomys nitratoides nitratoides)
Point Arena mountain beaver (Aplodontia rufa nigra)
Utah prairie dog (Cynoniys parvid en s) -
Carolina northern flying squirrel (Glaucomys sabrinus coloratus)
San Joaquin kit fox (Vulpes macrotis mutica)
Gray wolf (Canis lupus)
Florida panther (Felis concolor coryi)
Jaguariindi (Felis yagouaroundi cacomitli)
Ocelot (Felis pardalis)
Grizzly bear (Ursus arctos horribillis)
Louisiana black bear (Ursus americanus luteolus)
X
X
X
X
X
X
X
X
'X '
X
X
x . .
X
,x
X
X
X
.
X
X
X
1
X
X'
"
X
X
BIRDS - '
Audubon's crested caracara (Caracara cherrway audubonii)
X
- - " - REPTILES
Eastern indigo snake (Drymarchon corals couperi)
Puerto Rican boa (Epicrates inomatus)
Virgin Islands tree boa (Epicrates monensis (=inornatus) grand)
X
- X
X
91
-------
e. Diphacinone and its sodium salt Ecological Exposure and Risk
Characterization
LOCs for diphacinone address the following risk presumption categories: (1) acute high -
potential for acute risk is high; regulatory action may be warranted; (2) acute restricted use - the
potential for acute risk is high but may be mitigated through restricted use classification; and (3)
acute endangered species - the potential for acute risk to endangered species is high; regulatory
action may be warranted. The ecotoxicity test values (i.e., measurement endpoints) used in
calculating. RQs are derived from laboratory studies. Risk presumptions, RQ methods, and LOCs
are tabulated below for birds. RQs are not determined for mammals; because diphacinone is a
rodenticide, high risk is presumed.
(1) Diphacinone and its sodium salt Exposure and Risk to
Nontarget Terrestrial Animals
The risk assessments for birds and small mammals pertains to field uses and to bait
applications in rural and suburban areas where baits can be applied around buildings (e.g., barns,
houses, sheds) for control of commensal rats and mice. Diphacinone can be used to control rats
and mice around buildings, alleys, sewers, and transport vehicles (trains, ships, aircraft) in urban
areas. However, due to the paucity'of wildlife (i.e., non-domestic animals) in urban areas,
primary and secondary risks are expected to be minimal.
(a) Diphacinone and its sodium salt - Birds
Table 67 - Acute Risk Presumptions for Birds
Risk Presumption
High Risk
Restricted Use
Endangered Species
RQ
EEC'/LCSO or LD50/day2
EEC/LC50 or LD50/day
EEC/LC50 or, LD50/day
LOG
0.5
0.2
0.1
'EEC = Estimated Environmental Concentration (ppm) on avian and mammalian food items (short grass; tall grass;
broadleaved plants and small insects; seeds, pods, large insects)
^g toxicant consumed/day * [LD50 Xbird wt (kg)], where tox. consumed/day = amount food eaten X % a.i. in the
food
Primary risk: The potential for primary exposure of seed-eating birds exists primarily
for field applications of unprotected loose bait (i.e., aerial or ground broadcast or hand applied
pellets or treated whole grains). Minimal exposure is expected for applications where bait is
placed in protected bait stations or areas inaccessible to nontarget wildlife, if place packs or
paraffmized bait blocks are used, and for underground applications for control of pocket gophers.
Birds that are mainly herbivorous or insectivorous are not expected to be at risk from grain-based
food baits.
RQs for loose food baits are based on the number of LD50 doses potentially consumed by
a bird in one day. RQs are calculated for three separate weight classes of birds: 500-1000 g
(e.g., waterfowl), 100-200 g (e.g., upland gamebird), and 20-50 g (e.g., passerine). Acute RQs
for applications of diphacinone food baits are summarized in Table 68 below.
92
-------
Table 68 - Avian (Granivore) Acute RQs (LD5ns/day)*
Site-
Unspecified sites4;
Forestry5
Orchard6;
Unspecified sites7
Bait {% a,i)
0.01
0.005
Bpdy Wt ,
Class (g)
20-50
100-200
500-1000
, 20-50
100-200 -
500-1000
. Ami Food
'Baten (g)1
3.50
9.00
18.00
3.50
9.00
18.00
mg a.i.
consumed/day
0.35
0.90
1.80
0.18
0.45
0.90
Acute RQ2'3'
(LD^s/day)
0.05
0.02
O.Ol'
0.02 .
0.01 ,
0.01
+the number of LDJ0s potentially ingested per day are determined only for those use sites where loose, unprotected baits
are available (i.e., broadcast or hand-applied, uncovered baits)
'estimates of food consumption as a function of body size are based on Kenaga (1972) and Dunning (1984) for the
mallard, bobwhite quail, and red-winged blackbird
2LDsos/day = mg toxicant consumed/day -s- [LD50 (mg/kg) * bird wt (kg)] .
3only the highest RQ value is tabulated
4ground squirrel control (CA)
5deer mouse control (CA) '
6vole control (CT, GA, ID, MA, MI, NC, NH, OH, OR, PA, SC, UT, VA, VT, WA, WV)
7rats, mice, voles, woodrats, jackrabbits (CA)
"Acute RQs (LD50s/day) are based on a Diphacinone Bobwhite Quail LD50 of 400 mg/kg.
Acute LOCs are not exceeded when RQs are based on the number of LD50 doses
potentially ingested in a day. However, diphacinone is a multiple-feeding anticoagulant, and risk
to birds that feed on bait for several days is likely greater than predicted by RQ values based on
a single feeding. Therefore, it may be more appropriate to assess risk based on the 5-day dietary
toxicity value. For this scenario, EECs on grains or pellets are 50 ppm (0.005%. a.i. baits) and
100 ppm (0.01% a.i. baits), Acute RQs based on subacute dietary toxicity are summarized in
Table 69 below.
Table 69 - Avian (Granivore) Acute RQs For Diphacinone Food Baits1
Site?
Unspecified sites2; Forestry3
Orchard3; Unspecified sites5
Baft<5ฃa.i)
0.01
0.005
EEC (ppm)
100
50
Acste RQ (EEC/JLC50)
0.11***
0.06***
+RQs are calculated only for those use sites where loose, unprotected baits are available (i.e., broadcast or exposed
baits) ,.-
1 Acute RQs For Diphacinone Food Baits are based on a Mallard LC50 of 906 ppm.
2ground squirrel control (CA) ,
3deer mouse control (CA)
Vole control (CT, GA, ID, MA, MI, NC, NH, OH, OR, PA, SC, UT, VA, VT, WA, WV)
5rats, mice, voles, woodrats, jackrabbits (CA)
"'exceeds the endangered species LOG
Acute high risk and restricted use LOCs are not exceeded for food bait applications when
the RQ is based on the subacute dietary toxicity. However, the endangered species LOG is
exceeded for granivores for field and "around" building applications of 0.01% a.i. bait in
California.
93
-------
Secondary risk: Potential secondary risks exist for some avian predators and scavengers
that feed on poisoned rodents. As indicated by a supplemental study, rats and mice poisoned with
0.01% a.i. diphacinone baits can be hazardous to owls and presumably other raptor species that
feed on poisoned animals. Such exposure is likely to occur for the uses of 0.01 % a.i, diphacinone
bait for field uses and around buildings in California. Most field baits and those used to control
commensal rats and mice around buildings are 0.005 % active ingredient. Risk from 0.005 % a.i.
bait cannot be assessed until secondary toxicity data become available. However, based on the
secondary hazard reported for the 0.01 % active ingredient bait, risk is presumed for the 0.005%
a.i.bait until data are available to refute that presumption.
(b) Diphacinone and its sodium salt - Mammals
Primary risk: Because diphacinone is a rodenticide with label claims for control of
rodents (rats, mice, voles, ground squirrels, pocket gophers, muskrat, chipmunk), lagomorphs
(jackrabbit), and carnivores (mongoose), the Agency presumes acute high risk to any small
mammals that feed on diphacinone baits. Primary risk is likely to be highest for field uses,
because more wildlife is apt to be exposed in orchards and other areas than around buildings
where rats and mice are baited. The Agency also presumes that risk from 0.01% a.i. baits is
greater than that for 0.005% ai.baits. High risk to small carnivores also may exist from products
containing flavorings such as "meat and blood" and "fish", because the odors and taste of such
'flavorings may attract and enhance bait consumption by species that might not otherwise be
attracted to grain-based bait.
Primary risk can be reduced for mammals larger than the target species if protected bait
stations are used for applying bait. Well designed bait stations have entrance holes just large
enough for adults of the target species but too small for larger nontarget species. However,
because smaller species can enter bait compartments and feed, high risk is presumed for any
granivorous mammals in the treatment area that are smaller than the target species.
Secondary risk: Studies conducted by the Denver Wildlife Research Center indicate that
animals poisoned with 0.01 % a.i. diphacinone bait pose a risk to secondary consumers. In one
study (Evans and Ward 1967), 0.01% a.i. carrot baits were fed to nutria for 10 days. Dead nutria
(skinned carcass, liver, heart, and lungs) were frozen and subsequently thawed and fed to three
. mink and three mongrel dogs. The three mink died after 5 to 18 days exposure, and the three
dogs died after 6 to 10 days. The authors concluded that nutria poisoned with 0.01% a.i..
diphacinone bait could pose a secondary risk to some nontarget species. In another study, one of
two ermine died after eating 10 poisoned mice in 7 days.
Savarie et al. (1979) administered a single oral dose of diphacinone (7 dosage levels) to
10 captive coyotes. The LD50 was 0.6 mg/kg, with animals dying 6 to 17 days.after dosing.
Skeletal muscle from dead coyotes was ground, mixed with 25% oatmeal, reground, and
refrigerated until 30 g samples were fed to groups of laboratory rats (8 rats per group) to indicate
the potential for secondary hazard. Four of eight rats died 6 to 8 days after feeding on meat
mixture containing 0.5 ppm diphacinone. Rats feeding on meat mixtures of less than 0.5 ppm
94
-------
survived with no clinical signs of toxicity. However, as the authors emphasized, the amount of
residue in liver, kidneys, heart, and small intestine exceeded 0.5 ppm in many or most of the dead
coyotes, and selective feeding on these tissues by secondary consumers could result in increased
risk of poisoning; ,
The Agency currently lacks secondary hazards data to assess risk to mammalian predators
and scavengers that might feed on rodents poisoned with 0.005% a.i. diphacinone baits. These
data are needed to assess risks from the various field uses and for use against commensal rats and
mice around buildings in rural areas. However, based on the demonstrated secondary toxieity of
0.01% a.i. baitj the Agency presumes secondary risks to mammals from applications of 0.005%
a.i. baits. Secondary risks will be reconsidered when toxicity data are submitted.
(c) Diphacinone and its sodium salt - Exposure and
Risk to Nontarget Plants and Insects
No data were required.
(2) Diphacinone and its sodium salt Exposure and Risk to
Nontarget Aquatic Animals
Minimal risk to aquatic organisms is expected from the current uses of.diphaeinone.
Outdoor products are food baits, most of which are pelletized and/or paraffinized, and the amount
of active ingredient applied per acre is very low. Applications made in bait stations further limit
contact of bait with soil. The available environmental fate data indicate that most diphacinone will
be tightly bound to soil, and little contamination of surface waters is expected. Moreover,
diphacinone has a low solubility in water (30 ppm) and is only moderately toxic to aquatic
organisms (EC50/LC5oS = 1.8-7.5 ppm). Diphacinone salt, which is highly soluble in water, can
be dissolved in water and applied as a liquid bait; however, it is limited to indoor use for rat and
mouse control.
(3) Diphacinone and its sodium salt Endangered Species
Concerns
The U.S. Fish and Wildlife Service addressed Diphacinone in its Biological Opinion of
March, 1993. The use patterns included commensal and field rodent control in and around
buildings, in orchards, cropland, pasture, rangeland, ornamentals, forest, rights-of-way, along
ditches and banks of waterways, garbage dumps, and sewers. The Service made a "jeopardy" or
"no jeopardy" determination for the 34 "may affect" species listed below. Other species were
considered either not at risk of exposure or not likely to be affected. See Table 70 below.
95
-------
Table 70 - USFWS 1993 Biological Opinion for Diphacinone
Species
Jeopardy
No Jeopardy
Mammals:
Alabama beach mouse (Peromyscus polionotus ammobates)
Anastasia Island beach mouse (Peromscus polionotus phasma)
Choctawhatchee beach mouse (Peromyscus polionotus allophrys)
Southeastern beach mouse (Peromyscus polionotus niveiventris)
Perdido Key beach mouse (Peromyscus polionotus trissyllepsis)
Amargosa vole (Microtus califomicus scirpensis)
Florida salt marsh vole (Microtus pennsylvanicus dukecampbelli)
Hualapai Mexican vole (Microtus mexicanus hualpaiensis)
Key Largo cotton mouse (Peromyscus gossypinus allapaticola)
Salt marsh harvest mouse (Reithrodontomys raviventris)
Fresno kangaroo rat (Dipodomys nitratoides exillis)
Giant kangaroo rat (Dipodomys igens)
Morro Bay kangaroo rat (Dipodomys heermanni morroensis)
Stephen's kangaroo rat (Dipodomys stephensi)
Tipton kangaroo rat (Dipodomys nitratoides nitratoides)
Point Arena mountain beaver (Aplodontia. rufa nigra)
Silver rice rat (Oryzomys palustris natator (=Oryzomys argentatus)
Utah prairie dog (Cynomys parvidens)
Carolina northern flying squirrel (Glaucomys sabrinus coloratus)
Delmarva fox squirrel (Sciurus niger cinereus)
Key Largo woodrat (Neotomaflorida.no. smalli)
Lower Keys rabbit (Sytvilagus palustris hejheri)
Black-footed ferret (Mustela nigripes)
San Joaquin kit fox (Vulpes macrotis mutica)
Gray wolf (Canis lupus)
Florida panther (Felis concolor coryi)
Jaguarundi (Felis yagouaroundi cacomitli)
Ocelot (Felis pardalis)
Grizzly bear (Ursus arctos horribillis)
Lousiana black bear (Ursus americanus luteolus\
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
1
.. '
X
', . , Birds,' ,
Audubon's crested caracara (Caracara chertway audubonii)
X
% , Reptiles:
Eastern indigo snake (Drymarchon corais couperi)
Puerto Rican boa (Epicrates inornatus)
Virgin Islands tree boa (Epicrates monensis (=inornatus) granti)
X
X
X
96
-------
IV. RISK MANAGEMENT AND REREGISTRAHON DECISION
\ - ' -
A. Determination of Eligibility
Section 4(g)(2)(A) of FIFRA requires the Agency to determine, after submission of
relevant data concerning an active ingredient, whether products containing the active ingredient
are eligible for reregistration. The Agency has previously identified and required the submission
of the generic (i.e., active ingredient specific) data required to support reregistration of products
containing brodifacoum, bromethalin, bromadiolone, chlorophacinone, diphacinone and its sodium
salt, and pival and its sodium salt, as active ingredients. The Agency has completed its review
of these generic data, and has determined that the data are sufficient to support reregistration of
all products containing these chemicals, except pival and its sodium salt. Appendix B identifies
the generic data requirements that the Agency reviewed as part of its determination of
reregistration eligibility of brodifacoum, bromethalin, bromadiolone, chlorophacinone, and
diphacinone and its sodium salt. Appendix B also lists the submitted studies that the Agency found
acceptable. -
The data identified in Appendix B are sufficient to allow the Agency to assess the
registered uses of brodifacoum, bromethalin, bromadiolone, chlorophacinone, and diphacinone
and its sodium salt, and to determine that these chemicals can be used without resulting in
unreasonable adverse effects to humans and the environment when labeled and used as specified
in this RED document. The Agency, therefore, finds that all products containing brodifacoum,
bromethalin, bromadiolone, chlorophacinone, and diphacinone and its sodium salt as the active
ingredient are eligible for reregistration. The reregistration of particular products is addressed
in Section V of this document.
With the exception of:pival and its sodium salts, the Agency made its reregistration
eligibility determination based upon the target data base required for reregistration, the current
guidelines for conducting acceptable studies to generate such data, published scientific literature,
data from the American Association of Poison Control Centers, etc. and the data identified in
Appendix B. Although the Agency has found that all uses of these chemicals are eligible for
reregistration, it should be understood that the Agency may take appropriate regulatory action,
and/or require the submission of additional data to support the continued registration of products
. containing brodifacoum, bromethalin, bromadiolone, chlorophacinone, and diphacinone and its
sodium salt, if new information comes to the Agency's attention or if the data requirements for
registration (or the guidelines for generating such data) change..,.
The chemical pival and its sodium salts was suspended by the Agency in December 1994
for failure of the registrant, Motomco, Incorporated, to respond to the Agency's Data Call-In
Notice (DCI) and submit the required data to support the continued registration. The Agency,
during the reregistration process for this rodenticide cluster RED, again solicited the registrant
to submit the required data to support the reregistration. The registrant chose not to support the
reregistration ofpival and its sodium salts. Therefore, the Agency has determined that pival and
its sodium salts are ineligible-for reregistration, and will remain suspended. In the future, the
Agency may seek cancellation of the registration for pival and its sodium salt.
97
-------
1. Eligibility Decision
Based on the reviews of the generic data for the active ingredients brodifacoum,
bromethalin, bromadiolone, chlorophacinone, and diphacinone and its sodium salt, the Agency
has sufficient information on the health effects of these chemicals and on their potential for
causing adverse effects in fish, wildlife, and the environment. The Agency has determined that
these chemicals, labeled and used as specified in this Reregistration Eligibility Decision document,
will not pose unreasonable risks or adverse effects to humans or the environment. Therefore, the
Agency concludes that products containing brodifacoum, bromethalin, bromadiolone,
chlorophacinone, and diphacinone and its sodium salt, are eligible for reregistration.
2. Eligible and Ineligible Uses
The Agency has determined that all uses of brodifacoum, bromethalin, and bromadiolone
are eligible for reregistration.
The Agency has determined that all uses of chlorophacinone and diphacinone and its
sodium salt are eligible for reregistration, with the exception of certain field bait uses. The
Agency has determined that field-bait uses containing .005% chlorophacinone and diphacinone
and its sodium salt are eligible for reregistration.
The Agency has determined that field-bait uses containing more than .005%
chlorophacinone and diphacinone and its sodium salt are ineligible for reregistration. Field tests
have adequately demonstrated that products with lower-concentrations of these active ingredients
are sufficiently efficacious for target pest species, and that the uses with higher concentrations
have the potential to cause unnecessary secondary poisonings to avian and mammalian consumers.
The Agency has also determined that all uses of pival and its sodium salt are ineligible for
reregistration and are to remain suspended.
B. Regulatory Position
1 v ' : -
The following is a summary of the regulatory positions and rationales for brodifacoum,
bromethalin, bromadiolone, chlorophacinone; and diphacinone and its sodium salt. Where
labeling revisions are imposed, specific language is set forth in Section V of this document.
1. Summary of Risk Assessment Conclusions
a. Human Health Risk
(1) Dietary
These chemicals are non-food use pesticides. Therefore, tolerance reassessment is
unnecessary. Also, it is unlikely that there will be any dietary exposure to humans via food
sources or via drinking water through contamination of ground or surface water.
98
-------
(2) Residential and Occupational Risk
(a) Residential
- ' " VC . ':
EPA is concerned about the continued risk of human exposure, especially children,
resulting from the continued use of rodenticides in residential settings. In fact, EPA has gone on
record, over the years, to express its concern regarding human exposures and incidents to
rodenticides. PR Notice 94-7, Label Improvement Program for the Revision of Use Directions
for Commensal Rodenticides and Statement of the Agency's Policies on the Use of Rodenticide
Bait Stations, issued by the Agency on September 16, 1994, required registrants of certain
rodenticide products claimed to control commensal rodents to revise the labeling of such products
to bear certain statements concerning "tamper-resistant bait stations." It also informed rodenticide
registrants, applicants, and other interested persons of EPA's continued concern for the safe use
of rodenticides. Moreover, PR Notice 94-7 outlined EPA's policies regarding the isolation of
commensal rodenticides from children, dogs, other pets, domestic animals, and non-target
wildlife. PR Notice 94-7, in part, stated the following:
"Historically, more than 1000 incidents of human exposure to rodent poisons have been reported annually
in the U.S. Numbers of human incidents reported have increased greatly in recent years with the advent of
a new reporting,network. In 1988, more than 10,000 rodenticide incidents were reported in the American
Association of Poison Control Center's National Data Collection System. Nearly 90% of these cases involved
children under six years of age. Nearly all of such exposures are classed as accidents. The human exposure
incidents that are reported may represent less than half of those which occur. Well over 80% of reported
human rodenticide exposures involve anticoagulant compounds.
Young children thought to have been exposed to rodenticides are often given some medical attention, although
symptoms of poisoning usually are not observed, especially'in cases involving anticoagulants which act very
' slowly. Although young children have been killed by rodenticides, most rodenticide-related deaths of humans
result from intentional ingestions by persons much older than five years of age.
While reports summarizing incidents typically do not indicate exactly how exposures have occurred, it is likely
mat most accidents are related to improper use rather than to improper storage. Accidents of both types are
preventable. EPA believes that the large numbers of exposure incidents provide evidence that current policies
for promoting bait protection have not been sufficient and, therefore, that tougher, more explicit policies are
needed. EPA has not been persuaded by contentions that the relatively low incidences of serious human
illnesses caused by accidental exposures to compounds such as warfarin justify selective relaxations of
requirements for bait protection..." ,
Data collected by the American Association of Poison Control Centers (AAPCC) for 1995
report 17,187 human exposures to all rodenticides. Of these numbers, 14,710 (86%) exposures
were attributed to the anticoagulant rodenticides. Of concern to EPA is the number of exposures
to children less than six years-old; in 1995, there were a total of 14,900 or approximately 87%
of the total exposures. When the total number of human exposures to rodenticides was analyzed,
6,450 were significant enough to result in treatment at a health care facility.
Data collected by the AAPCC for 1996 report that 17,601 rodenticide exposures occurred
to humans. The anticoagulant rodenticides (brodifacoum, bromadiolone, chlorophacinone,
99
-------
diphacinone and its sodium salt, and pival and its sodium salt), accounted for 14,836 or over 84%
of the total exposures. Of these exposures, 13,362 (90%) occurred in children less than six years-
old. Approximately 5,300 exposures resulted in people seeking treatment at a health care
facility.
%
Furthermore, rodenticides are acutely toxic to humans. Margins of Exposures (MOEs),
when bait is ingested, are less than one. Generally, the Agency considers a MOE of 100 or above
to be protective of the public's health. The Agency, for example, has calculated the dose a 10
kg child receives from a 43 gram packet of rodenticide (standard commercial package). The
Agency's calculation resulted in a MOE of 0.6 The lexicological endpoint for diphacinone, was
0.13 mg/kg/day.
Rodenticides, when used as currently sold and marketed, are responsible for a high number
of human incidents and accidental exposures each year. In the recent past, poison control centers
have enhanced their ability to capture incident data. Because of improved data collection, it
appears that the high number of human unintentional or accidental exposures to rodenticides
remain constant each year, or may be increasing. From the number of rodenticide exposures to
children, it is clear that children under six years-old are disproportionately more at risk from the
continued use of these products in residential settings. Based on these facts, EPA is concerned
regarding the risk of exposure to these chemicals to residential users, particularly children.
(b) Occupational (Mixer/Loader/Applicator)
The Agency has determined that there is potential exposure to applicators and/or other
handlers during typical use patterns associated with these chemicals. Specifically, the Agency is
concerned about potential dermal and inhalation exposures to handlers during the loading and
application of these chemicals.
Based on the use patterns and potential exposures described above, major handler
exposure scenarios were identified such as: (1) placing bait packs; (2) loading bait boxes or bait
stations with meal bait, grain bait, bait pellets, or other food-based bait from larger containers;
(3) breaking parafinized blocks into pieces and placing the pieces in bait stations; (4) securing
large paraffin blocks in bait stations used in sewers; (5) applying bait by hand; and (6) applying
bait, e.g. pellets in broadcast treatments using ground equipment; and (6) spraying.
It is unclear from labels and other available information (1) the extent to which it is
necessary, due to size or design of packages, for handlers to directly handle or come in contact
with the bait during loading into the bait stations (which may result in dermal exposures); or (2)
the extent to which it is possible for dusts associated with meal baits, grain baits, or pellets to
result in inhalation exposure to handlers during loading into bait stations. Hence, the Agency is
concerned about potential dermal exposure and inhalation of fine particles, and dusts associated,
with baits which could be inhaled resulting in an inhalation and/or oral exposure. As a result, the
Agency is requiring more stringent PPE for all occupational uses of these chemicals as discussed
below and in Section V of this RED document.
100
-------
b. Risk to Household Pets
As with human exposures, EPA is concerned about the increased risk posed to household
pets to rodenticides used in residential settings. When used as currently sold and marketed,
rodenticides account for a high number of incidents and accidental exposures to household pets
every year. PR Notice 94-7 stated in part that:
"Dog incidents account for more than 80% of the reported exposures of nontarget animals to commensal
rodenticides. Most dog exposures are believed to be accidental. The annual number of incidents of animals
being, exposed to rodenticides is not known, but over 4,000 rodenticide-related inquiries were made to the
Illinois Animal Poison information Center in each of the years from 1986 to 1988, with a high of 6,272
inquiries having been made in 1987.
Symptoms of rodenticide poisoning are detected more frequently in reported animal cases than in child cases.
A larger percentage of asymptomatic exposures of animals may go undetected as pets and livestock generally
are not watched as closely as children. Dogs may die as a result of rodenticide exposures, especially if acute
poisons are involved. Extended Vitamin Kl therapy may be needed for dogs that have been exposed to
certain anticoagulants, such as brodifacoum or diphacinone, which are retained in the body for a relatively
long time. For animal exposures reported in 1987 (and probably in other years as well), the animal's owner
typically was the source of the rodenticide.. Most of these exposures were accidental and 'occurred in or
around human residences."
The American Association of Poison Control Centers (AAPCC) reported 41,854 animal
exposure cases (mostly dogs and cats)in 1990, Of these,' 3,157 involved rodenticides (8.4%).
Most rodenticide 'poisonings are due to careless placement or overuse of baits, and, much less
often, failure to discard poisoned rodents and malicious poisonings. There were a total of 454
deaths reported in animals in 1990, of which 39 (9.2%) were due to anticoagulant rodenticides,
the second leading cause of death after ethylene glycol and related compounds.
c. Environmental Risk
(1) Environmental Fate
In general, these rodenticides 'are very similar in their holistic environmental fate
characteristics. However, they differ in specific environmental fate characteristics as discussed
earlier in this RED document. ,
Based on environmental chemistry data, and the use pattern, use of these rodenticides is
not expected to result in contamination of surface and ground water. Although persistent, these
chemicals tend to be relatively immobile in soil and fairly insoluble in water. Most are applied
as a pelleted bait used in and around buildings. They are primarily used in protective bait stations
when used outdoors, therefore, their environmental fate risk is negligible.
(2) Ecological Effects
Primary toxicity to mammals is very high for these rodenticides. Primary toxicity to birds
is mostly high to very high for the single feeding rodenticides (brodifacoum, bromadiolone, and
bromethalin). It is mostly moderate for the multiple feeding compounds (diphacinone and
101
-------
chlorophacinone). Toxicity to aquatic organisms ranges from moderate to very high. Chronic
data are not available for any of the rodenticides.
For only a few of these chemicals do some secondary toxicity data exist for avian and
mammalian predators and their scavengers. These studies are required to support the use of
rodenticides in fields, and "around" buildings in non-urban (i.e., rural, suburban) areas.
Available laboratory and/or field data indicate that rodents, poisoned with brodifacoum or
bromadiolone baits, can kill avian and mammalian secondary consumers. Sufficient data exist to
indicate that diphacinone bait (0.01%) is secondarily hazardous to birds and mammals and
chlorophacinone bait (0.01 %) is hazardous to mammalian predators. Avian data are not available
for chlorophacinone bait at 0.01 %. Adequate data are not available for birds and mammals for
chlorophacinone and diphacinone bait or for bromethalin (all at 0.005%).
2. Summary of Rodenticide Benefits
Although the Agency is concerned about the risk posed to humans, especially children, and
non-target animals by the use of these products as they are currently sold and marketed, EPA also
recognizes the important public health benefits of rodenticides. Specifically, the Agency
considered the benefits from rodent control as it relates to prevention of disease transmission,
property damage, and attacks on humans.
Rodenticides are one of the most efficient available means for controlling existing
infestations of large numbers of rodent pests. These agents also may be the method of choice in
controlling certain smaller rodent infestations and often are needed to control individuals which
cannot be removed by use of traps.
People control rodent pests primarily because these animals: (1) are associated with the
spread of many types of serious diseases; (2) bite humans; (3) damage private and commercial
property; (4) destroy and contaminate millions of tons of agricultural crops annually, both, in the
field and in storage; and, (5) are generally unwelcome in homes, schools, places of business, and
other areas occupied or frequented by humans.
The diseases vectored by rodents include: plague, Rickettsial diseases (e.g., murine
typhus, Rickettsialpox), leptospirosis, rat bite fever, Salmonellosis, hantavirus, Lyme disease,
gramilocytic Ehrlichosis, relapsing fever, and others. Rodents transmit diseases either directly
or indirectly, via ectoparasites such as fleas, ticks or mites, or bodily waste products and
secretions.
Many rodent-transmitted diseases recently have been held in check through the private and
public use of rodenticides, along with other pest and disease control and management practices.
Improved pest management, including coordination of rodenticide use and other rodent abatement
practices, is a principal reason why numbers of cases and deaths associated with many rodent-
transmitted diseases have been much lower in the latter part of the 20th Century than was the case
in prior decades. For example, there were 3,700 reported cases of murine typhus in the U.S. in
102
-------
1942 but only 12 reported cases in 1987. In recent decades, however, "new" rodent-transmitted
diseases such as Lyme disease and hantavirus have emerged, primarily in rural and semi-rural,
areas in the U.S. Of these diseases, the HPS hantavirus strains appear to be the most serious,
with a composite fatality rate of approximately 45% for the 170 + human cases reported since
1993.
The number of cases of rats biting humans has been estimated to be 14,000 per year.
More recent information is not available on a nationwide basis.
Rodents damage structures by gnawing on integral parts and by contaminating them with
bodily waste products and other secretions. Rodents can gnaw through wood, concrete, asphalt,
sheet rock, plumbing, and soft metals. Rodent damage to electrical wiring has been cited as the
probable cause for certain fires and explosions, as well as an instance of shutting down the
Internet. When buildings, including residences, are heavily infested, poisoning generally is an
integral component of successful abatement programs. ,
Field rodents such as ground squirrels, voles, and native mice and rats cause significant
damage to crops and rangelands. Certain crops, such as sugarcane, are heavily damaged in the
field by commensal rats and mice. Commensal rodent species are responsible for much of the
pest damage to stored food and feed in the United States. Chlorophacinone, diphacinone, and zinc
phosphide play an important role in the management of rodents associated with agricultural crops.
In general, commensal rats and mice are not "liked" by humans. This may be a factor in
rodenticide use; however, disease concerns and desires to protect self and property are present
in most cases in which rodenticide baits are used.
Rodenticide baits also are used in certain special circumstances, such as managing .or
eradicating non-native rodent species at sites where such rodents jeopardize the continued
existence of certain threatened or endangered species. Control programs of this nature are run
by government agencies and typically are limited to offshore islands or other refuge areas.
EPA has consulted with the Center for Disease Control (CDC), Rodent Control offices in
several states (New York; Philadelphia, Pennsylvania; Boston, Massachusetts; Arlington,
. Virginia; and Chicago, Illinois), and a nationally recognized rodent expert regarding public
health benefits and the Agency's risk mitigation measures. Based upon these discussions, the
Agency has decided that its reregistration eligibility determination and the risk mitigation
measures specified in this document are in the public interest as per FIFRA Section 3(c)(5).
3. Risk Mitigation Overview
As discussed earlier in this RED document, the Agency is concerned about the risks posed
to humans, particularly children, household pets, and non-target animals, from the continued use
of these products as they are currently sold, marketed, and used.
103
-------
While an effective antidote is available, treatment must occur in time. Furthermore,
treatment can be traumatic for children, and there are costs both for time and treatment, In
addition, the Agency's concerns are heightened by the number of incidents and exposures,
reported annually, to these chemicals involving humans (particularly children less than six years-
old), and household pets. The Agency, however, is also aware of the public health benefits these
chemicals provide. As a result of the Agency's concerns, the following risk mitigation measures
are necessary for all registrations of brodifacoum, bromethalin, bromadiolone, chlorophacinone,
and diphacinone and its sodium salt.
a. Reducing Risk for Children and Household Pets
The Agency has concluded that the rodenticides, containing the active ingredients subject
to this RED document, which are used in residential settings, schools, recreation areas, and other
places that children may frequent, pose the greatest risk of accidental exposure and incidents to
humans, particularly children, and household pets. As set forth below, the Agency is requiring
the following risk mitigation measures for rodenticide active ingredients subject to this RED
document used in residential settings, schools, recreation areas, and other places children may
frequent. In addition, outside the scope of this RED process, the Agency is requiring the
identical risk mitigation measures to the registrations of other rodenticide active ingredients such
as zinc phosphide, warfarin and its salt, difethialone, vitamin D-3, and red squill and, if
necessary, registrations of new rodenticide active ingredients to be used in residential settings,
schools, recreation areas, and other places that children may frequent.
When reviewing these chemicals for their reregistration eligibility, the Agency carefully
considered the acute risk posed by the residential use of these chemicals along with the benefits
for allowing them to remain on the commercial market for consumers to use. EPA concludes that
although these products pose an acute risk to humans and household pets, the Agency has
determined that the continued use of these rodenticides in residential and other settings provide
a critical public health benefit.
The Agency recently became aware of incident data which suggests that there may be a
potential incident problem involving the active ingredient .brodifacoum. At this time the Agency
is reviewing the data; no final conclusions have been reached. Additionally, through the "Notice
of Availability" for this document, the Agency requests state incident data for all rodenticides to
better understand the extent of this potential problem. After review, the Agency may impose
additional restrictions on the use of brodifacoum and/or other active ingredients.
b. Incremental Risk Reduction
In order to address the risk concerns posed by the use of these products and still maintain
the benefits afforded by their use, the Agency developed a two-phased approach to mitigating risk.
The first phase involves measures which can be put in place in the short term that will serve to
identify when an exposure has occurred, lessen the number of exposures, and monitor exposures.
104
-------
The second phase will move toward eliminating the opportunity for exposures in the long
term. Ideally, the Agency would have preferred to impose measures which would have
immediately eliminated opportunities for exposures; however, it recognizes that new technologies
may not exist and may need'to be developed to accomplish this while still maintaining the efficacy
of the product. The Agency has, therefore, developed this phased approach to allow time for the
development and testing of a new technology. The innovation of the new technology will be
coordinated by a Stakeholder group. The two phases to risk mitigation, the time frames, and
reporting requirements are described in detail below.
(1) Phase One: Short-Term Risk Mitigation Measures
(a) Indicator Dye and Bittering Agent
All registrants of rodenticides, other than those with products used exclusively at
agricultural sites, must incorporate an indicator dye into their formulations. The dye is intended
to help identify whether a child or household pet has consumed a rodenticide by dying their mouth
and/or hands a bright color. EPA believes the dye will play an important role in identifying when
an exposure has occurred, thereby helping to determine if treatment is required.
Typically, it is very difficult for parents and guardians of children and pet ownejs to
discern whether an exposure or ingestion has actually occurred. This uncertainty may lead to
unnecessary treatment at a medical facility as a precautionary measure. In turn, the Agency
believes this measure will also enable parents and guardians of children and pet owners to seek
medical or veterinarian attention sooner rather than later and avoid a serious medical problem.
All registrants of rodenticides, other than those with products used exclusively at
agricultural sites, must incorporate a bittering agent into their formulations to make the bait less
palatable to humans. EPA believes that the bittering agent may cause some children to expel the
bait if placed in the mouth. The Agency is fully aware that children younger than one year old
do not have fully formed taste buds and may not be fully protected by this measure. However,
this measure should prevent some exposures to, children older, than one year of age. Likewise,
the EPA is also aware that this measure may not affect exposures to non-target household animals.
EPA recognizes that many of the formulations currently contain a dyef All registrants may
. present data demonstrating that the current dye meets the intent of this requirement. ' - '
(b) Improved Labeling Requirements
EPA is requiring a number of label revisions to rodenticide registrations. These
requirements are set forth in Section V of this RED document and are in addition to those in PR
Notice 94-7 that have already been implemented.
Labels which currently allow placement of rat and mouse baits "in and around buildings"
must be amended to "indoors and against the outside walls of buildings." Rat and mouse bait
placements will be allowed "around" buildings only if registrants demonstrate in secondary
toxicity studies that secondaryBrisks to birds and mammals are minimal.
105
-------
Under "Note to Physicians," a few of the labels recommend that Vitamin Kj be
administered intravenously (TV) or intramuscularly (IM). The veterinary literature states that
vitamin Kx can cause anaphylactic reactions if given IV and extensive hemorrhage after IM
administration. Sheldon Wagner, M.D., a consultant to OPP, confirmed that Vitamin Kt should
not be given IV unless there is a hemorrhagic crisis. IM administration is acceptable in humans.
The recommendation for IV administration must be deleted from the label.
(c) Annual Submission of American Association of
Poison Control Centers (AAPCC) Data
Under the authority of FIFRA section 3(c)(2)(B), the Agency is requiring registrants of
rodenticides subject to this RED document, to submit to the Agency annual American Association
of Poison Control Centers' (AAPCC) data. The Agency is requiring AAPCC data for the years
1999 through 2009. Registrants are encouraged to share the cost of generating data, whenever
appropriate. If needed, the Agency may ask registrants of rodenticides for additional annual
submission of AAPCC data. These data will enable the Agency to determine whether the
imposed risk mitigation measures are reducing incidents/exposures to humans, in particular
children. AAPCC data obtained by the Agency for 1995 and 1996 will serve as baseline data.
The American Association of Poison Control Centers is located at 3201 New Mexico Avenue
NW, Suite 310, Washington, D.C. 20016. They can be reached by telephone on (202) 362-7217
and by fax on (202) 362-8377.
(d) Restricted Use Classification for Tracking
Powders
When rodents migrate, through tracking powder during their daily activities they contact
and accumulate the rodenticide on their bodies and/or fur. Afterward, the rodents ingest the
poison while grooming. If enough rodenticide is consumed, death occurs.
EPA has determined that the use of these chemicals as tracking powders in and around
residences, schools, recreation areas, and other places that children may frequent, pose a
significant risk to children, household pets, and non-target animals. EPA believes that children
and pets can easily come in contact with rodenticides used as tracking powders simply based on
, their use patterns and use locations. To protect children and non-target animals from exposure,
all products formulated as tracking powders must remain classified and labeled as restricted use
because of acute toxicity and undue secondary risk to non-target species. Certified applicators
receive training on the importance of following label directions and overall application, and,
therefore are more likely to apply the product correctly. Moreover, tracking powder products
must bear a strong precautionary statement and new restrictions limiting placement of powder to
locations not accessible to children, household pets, and non-target animals.
EPA is also concerned about the potential exposure (inhalation and dermal) to the certified
applicators of these types of product formulations. Due to the low inhalation LC50 value and the
possibility of users inhaling or ingesting powders during pouring and application, EPA is limiting
106
-------
use of the powder formulations to use by certified applicators, EPA is requiring protective
eyewear and dust/mist respirators for such users r in addition to. other personal protective
equipment.
Within eight months after receipt of this RED document, the EPA is requiring that all
products with tracking powder uses, including field and residential uses, containing brodifacoum,
bromadiolone, brbmethalin, chlorophacinone, and diphacinone and its sodium salt.be classified
as restricted use pesticides. '
. (e) Restricted Use for Field Products
All products labeled for field uses, except for those limited to manual underground baiting,
must be reclassified and relabeled as restricted use because of acute toxicity and undue secondary
risk to non-target species.
(f) Field Uses of Chlorophacinone and Diphacinone
and its sodium salts
Within eight months after the receipt of this RED document, all products containing
chlorophacinone and diphacinone and its sodium salt ~ at active ingredient percentages higher
than 0.005% must remove all field-use claims from the label. This is required because of acute
toxicity and undue secondary risk to non-target species. This requirement does not apply to
products limited to manual, underground applications in field situations (pocket gophers and
moles), if this limitation is stated clearly and unambiguously on the products' labels.
(g) Time Frames & Reporting Requirements
PHASE ONE: The Agency is aware that all mitigation measures required during Phase
One may not be feasible within the eight-month time frame usually accorded by the RED process
to submit labeling changes. While registrants will still be required to submit revised labeling as
detailed in Section V within the 8 month time frame, the Agency recognizes that the formulation
changes required by the addition of the indicator dye and bittering agent may take longer. The
timing for the incorporation of the dye and bittering agent in rodenticide products will be an
, outcome of a meeting convened by the Agency before the first Stakeholder meeting (as discussed
below in Phase Two).
Data from the American Association of Poison Control Centers (AAPCC) must be
submitted within one year after the end of the reporting year. For example, 1999 AAPCC data
must be submitted to the Agency on or before December 31, 2000. The Agency will schedule
a meeting with registrants before the initial Stakeholder meeting to provide registrants with clear
guidance on the format, content, and parameters of the data obtained from the AAPCC.
(2) Phase Two: Long-Term Risk Reduction
As discussed previously in this RED document, the Agency believes that the required risk
mitigation measures outlined in Phase One should be followed by further exposure/risk reduction
107
-------
measures for rodenticides. EPA is also aware that a safer technology is efficacious and equally
effective to eliminate human and household pet exposures may not currently exist. However, the
Agency will require the development of and movement into a new, safer household rodenticide
use technology. The EPA is convinced that this technology can be developed. Therefore, Phase
Two of the Agency's risk mitigation approach, is the requirement to move rodenticides into a
safer use technology. To achieve this end, within 90 days of the issuance of the REDs, the Agency
will form a Stakeholder group and hold a series of meetings to discuss means of significantly
reducing exposures to children and pets. The Stakeholder group will consist of members from
industry, states, CDC, CPSC, AAPCC, rodent control experts, members of environmental
groups, and the medical community.
The Agency will conclude the Stakeholder process within nine months from the issuance
of the REDs. The Agency expects, at the conclusion of this process, to have a recommendation
on how to further mitigate risk to children and household pets and an implementation plan to
achieve significant risk reduction. Agency ideas include: (a) placing rodenticides in bait
containing, disposable (non-refillable), child-resistant bait stations, or some other technology, (b)
development and implementation of an exhaustive, educational outreach program for consumers
and enhanced training for PCOs, (c) tamper-resistant bait stations, and (d) additional labeling
improvements, e.g., foreign language labeling, icons on labeling such as "Mr. Yuk," and skull
and crossbones. ,
c. Risk Mitigation Measures for Products Intended for
Occupational Use
(1) Gloves
To reduce dermal exposure, the Agency has determined that all labels for occupational-use
products will require commercial handlers to wear gloves while handling these rodenticide
chemicals that are not already contained in place packs. This requirement will be overturned if
registrants submit data which indicate there is no dermal exposure.
EPA is requiring all occupational handlers (commercial applicators) who handle
formulations that are not already contained in place packs to wear gloves.
(2) Protective Eyewear and Inhalation Protection
The Agency has determined that occupational handlers (commercial applicators) must wear
protective eyewear, and a dust mask/mist respirator when handling non-parafinized formulations
of these chemicals such as, meal or grain-based baits, unless these formulations are contained in
place packs or the registrants can determine via data that there is no inhalation exposure. The
respirator would reduce the possibility of inhalation and ingestion of dusts resulting from the
pouring and application of these products. Moreover, the protective eyewear would reduce the
potential ocular absorption that could result from contact with such dusts.
108
-------
In addition, the Agency is requiring all occupational handlers who handle powder
formulations or any other non-paraffinized formulation of chlorophacinone to wear a dust/mist
respirator and protective eyewear during open pouring and application unless registrants submit
data which indicate there is no inhalation exposure.
There are no handler exposure data available for the use patterns associated with
chlorophacinone mixing, loading, and application.
4. Endangered Species Statement .
The Agency has developed a program (the "Endangered Species Protection Program") to
identify pesticides whose use may cause adverse impacts on endangered and threatened species,
and to implement mitigation measures that will eliminate the adverse impacts. At present, the
program is being implemented on an interim basis as described in a Federal Register notice (54
PR 27984-28008, July 3, 1989), and is providing information to pesticide users to help them
protect these species voluntarily. As currently planned, the final program will call for label
modifications referring to required limitations on pesticide uses, typically as depicted in county-
specific bulletins or by other site-specific mechanisms as specified by state partners. A final
program, which may be altered from the interim program, will be described in a future Federal
Register notice. The Agency is not imposing label modifications at this time through the RED.
Rather, any requirements for product use modifications will occur in the future under the
Endangered Species Protection Program.
The pesticides included in this RED have been subject to a formal consultation with the
Fish and Wildlife Service, as noted following each active ingredient. Additional consultation with
the Fish and Wildlife Service and/or the National Marine Fisheries Service may be necessary to
determine if steps need to be taken to protect newly listed species or from proposed new uses of
. these pesticides. . ;
Most of the species determined by the Fish and Wildlife Service to be jeopardized or
otherwise potentially affected by these pesticides occur in California, Florida, Hawaii, or Texas.
Under the Endangered Species Protection Program, these states are working with the Agency and
the Fish and Wildlife Service to provide locally based protection to listed species. Interim
. protective measures are being implemented or are under development. For the few species in
other statesr_the Agency is developing protective measures to be provided to pesticide users in
interim county bulletins. .
V. ACTIONS REQUIRED OF REGISTRANTS
This section specifies the data requirements and responses necessary for the reregistration
of both manufacturing-use and end-use products.
109
-------
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregistration of brodifacoum, bromethalin,
bromadiolone, chlorophacinone, and diphacinone and salt for the above eligible uses has been
reviewed and determined to be substantially complete. The following studies are required to be
conducted on the generic ingredients.
a. Brodifacoum
21-Day Dermal - rabbit/rat [82-2]
Estimation of Dermal Exposure at Outdoor Sites [231]
Estimation of Inhalation Exposure at Outdoor Sites [232]
Estimation of Dermal Exposure at Indoor Sites [233]
Estimation of Inhalation Exposure at Indoor Sites [234]
b. Bromadiolone
Leaching/Adsorption/Desorption [ 163-1 ]
Estimation of Dermal Exposure at Outdoor Sites [231]
Estimation of Jnhalatipn Exposure at Outdoor Sites [232]
Estimation of Dermal Exposure at Indoor Sites [233]
Estimation of Inhalation Exposure at Indoor Sites [234]
c. Bromethalin
General Metabolism [85-1]
Leaching/Adsorption/Desorption [163-1]
Estimation of Dermal Exposure at Outdoor Sites [231]
Estimation of Inhalation Exposure at Outdoor Sites [232]
Estimation of Dermal Exposure at Indoor Sites [233]
Estimation of Inhalation Exposure at Indoor Sites [234]
Secondary Poisoning, Mammal [70-A-SS]*
Protocol
Secondary Poisoning, Bird [70-B-SS]*
Protocol
Whole Body Residue, Target Species [70-C-S]*
Protocol
*Studies are not required for "indoors and along the outside walls of buildings", but are required
for any other uses.
d. Chlorophacinone
Avian Reproduction, Quail [71-4(a)]* , ,
Avian Reproduction, Duck [71-4(b)]*
Estimation of Dermal Exposure at Outdoor Sites [231]
Estimation of Inhalation Exposure at Outdoor Sites [232]
110
-------
Estimation of Dermal Exposure at Indoor Sites [233]
Estimation of Inhalation'Exposure at Indoor Sites [234]
Secondary Poisoning, Mammal [70-A-SS]**
Protocol
Secondary Poisoning, Bird [70-B-SS]**
Protocol
Whole Body Residue, Target Species [70-C-S]**
Protocol
*Required to support Product CAS 90023.
**Studies are not required for "indoors and along the outside walls of buildings," but are required
.for any other uses. . ' . !
e. Diphacinone and its sodium salt
General Metabolism [85-1] .. " -
Hydrolysis [161-1]
. Leaching/Adsorption/Desorption [163-1] .
, Estimation of Dermal Exposure at Outdoor Sites [231]
Estimation of Inhalation Exposure at Outdoor Sites [232]
Estimation of Dermal Exposure at Indoor Sites [233]
Estimation of Inhalation Exposure at Indoor Sites [234] .
Secondary Poisoning, Mammal [70-A-SS]*
Protocol
Secondary Poisoning, Bird [70-B-SS]*
Protocol ,
Whole Body Residue, Target Species [70-C-S]*
, Protocol .
*Studies are not required for "indoors and along the outside walls of buildings," but are required
for any other uses.
2. Submission of Poison Control Centers Data
Under the authority of FIFRA section 3(c)(2)(B), the Agency is requiring registrants of.
rodenticides subject to this RED document, to submit to the Agency annual American Association
of Poison Control Centers' (AAPCC) data. The Agency is requiring AAPCC data for the years
1999 through 2009. Registrants are encouraged to share the cost of generating data, whenever
appropriate. If needed, the Agency may ask registrants of rodenticides for additional biannual
submission of AAPCC data. Data from the American Association of Poison Control Centers
(AAPCC) must be submitted within one year after the end of the reporting year. These AAPCC
data requirements are identified in the data requirements listed in Appendix B of this RED
document. The American Association of Poison Control Centers is located at 3201 New Mexico
Avenue, Suite 310, Washington, D.C. 20016. They can be reached by telephone on (202) 362-
.7217 and by fax on (202) 362-8377.
Ill
-------
B. End-Use Products
1. Formulation Changes - Indicator Dye and Bittering Agent
All registrants of rodenticides must incorporate an Agency approved indicator dye and
bittering agent into their formulations. All registrants must submit to the Agency for approval,
a revised CSF and draft labeling reflecting this incorporation into their product's formulation.
The Agency recognizes that the formulation changes required by the addition of the indicator dye
and bittering agent may take longer than the eight months usually provided by RED Document.
The Agency will work with registrants to establish a timeframe for the incorporation of the dye
and bittering agent into rodenticide products at a meeting, or through other means, prior to the
initial stakeholder meeting. At this time, deadlines and submittal procedures for additional
efficacy testing, if required, will also be addressed.
2. Stakeholder Meetings
The Agency is planning to hold the initial stakeholders meeting within 120 days from the
issuance of this RED in Washington, D.C. As mentioned earlier, these meetings will provide an
open forum to develop workable mitigation measures to adequately protect children from
accidental rodenticide exposures. For these meetings to be most efficient and successful, all
interested parties and viewpoints will be welcomed and considered. The outcomes of these
meetings will effect all rodenticide products with residential uses, including those that were
previously reregistered and those that have been registered more recently and, hence, not subject
to reregistration.
3. Tracking Powders Classified as Restricted Use
Within eight months after the receipt of this RED document, the Agency is requiring that
all products, containing brodifacoum, bromethalin, bromadiolone, chlorophacinone, and
diphacinone and its sodium salt, with tracking powder uses, must be reclassified and relabeled as
RESTRICTED USE PESTICIDES.
4. Field Use Classified as Restricted Use
Within eight months after the receipt of this RED document, the Agency is requiring that
all products, containing brodifacoum, bromethalin, bromadiolone, chlorophacinone, and
diphacinone and its sodium salt, with field uses, except for those limited to manual underground
baiting, must be classified and labeled as RESTRICTED USE PESTICIDES.
5. Field Uses of Chlorophacinone and Diphacinone and its sodium salts
Within eight months after the receipt of this RED document, all products, containing
chlorophacinone, and diphacinone and its sodium salt, at active ingredient percentages higher than
0.005%, must remove all field use claims from the label. Products which are limited only to
manual underground bailing in a field use situation are excluded from the above requirement and
must clearly state this limitation on the product label.
112
-------
6. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-specific
data regarding the pesticide after a determination of eligibility has been made. Registrants must
review previous data submissions to ensure that they meet current EPA acceptance criteria, and
if not, commit to conduct new, studies. If a registrant believes that previously submitted data meet
current testing standards, then study MRID numbers should be cited according to the instructions
in the Requirement Status and Registrants Response Form provided for each product.
7. PPE/Engineering Control Requirements for Pesticide Handlers,
For sole active ingredient end-use products that containing brodifacoum, bromethalin,
bromadiolone, chlorophacinone, and diphacinohe and its sodium salt:
Revise the product labeling to adopt the handler personal protective equipment/engineering
control requirements set forth in this section. ,
Remove any conflicting PPE requirements on the current labeling;
a. Products Intended for Occupational Use
The Agency is requiring modifications to the PPE/Engineering Controls requirements on
all end-use products containing brodifacoum, bromethalin, bromadiolone, chlorophacinone, and
diphacinone and its sodium salt that are intended primarily for occupational use.
i .
(1) Formulation Specific PPE Requirements
The Agency is establishing formulation-specific PPE for all occupational uses,of
brodifacoum,-bromethalin, bromadiolone, chlorophacinone, and diphacinone and its sodium salt
end-use products. Remove any conflicting PPE requirements on the current labeling by
eliminating the less stringent requirement. For guidance on choosing glove material, contact the
Chemical Review Manager for the specific chemical in question. Please refer to Table 71 for the
specific label language required. " ' .
(2) Determining PPE Labeling Requirements for End-Use
Products
The PPE that would be established .on the basis of the acute toxicity category of the end-
use product must be compared to the active ingredient specific personal protective equipment
specified above. The more protective PPE must be placed on the product labeling.
For guidance on which PPE is more protective, see PR Notice 93-7.
113
-------
(3) Placement in Labeling
The personal protective equipment requirements must be placed on the end-use product
labeling in the location specified in PR Notice 93-7, and the language of the PPE requirements
must be the same as is specified in PR Notice 93-7.
b. Products Intended for Residential Use
The Agency is not establishing any formulation-specific engineering control or handler
PPE requirements for end-use products intended primarily for homeowner use.
8. Other End-Use Product Labeling Requirements
a. All End-Use Products
Labels which currently allow placement of rat and mouse baits "in and around buildings"
must be amended to "indoors and against the outside walls of buildings." Rat and mouse bait
placements will be allowed "around buildings" only if registrants demonstrate from secondary
toxicity studies that risks to birds and mammals are minimal.
All end-use products should have clear, concise and complete labeling instructions. Proper
labels can improve reader understanding, thereby reducing misuse and the potential for incidents.
Toward this end, the Agency is requiring the labeling modifications listed below.
(1) Directions for Use
Directions for Use must be stated in terms that can be easily read and understood by the
average person likely to use or to supervise the use of the pesticide. It must be presented in a
format that is easy to understand and follow. The Directions for Use section of a pesticide label
must provide the necessary information to answer four major categories regarding the use of the
pesticide. These four questions are:
1) Why is the pesticide being used? For what pest(s) or problem?
2) Where is the pesticide to be applied? (Where should it not be applied?)
3) How is the pesticide to be applied (what special precautions must the user take? how
much should they use?)
4) When should the pesticide be applied?
"DIRECTIONS FOR USE" for products covered by this RED should be organized in the format
generally used for rodenticide products registered in the U.S. This format is outlined below and
appears in format labels such as the one appended to PR Notice 94-7.
DIRECTIONS FOR USE
It is a violation of Federal law to use this product in a manner inconsistent with its labeling.
114
-------
READ TEDS LABEL: Read this entire label and follow all use directions and use precautions.
IMPORTANT: [Insert text from PR Notice~94-7 which applies only to products used to control
commensal rodents, and to end-use concentrates used to-make baits, which may be used to control
commensal rodents in and around buildings.]
MIXING DIRECTIONS: [This section applies only to end-use concentrates.]
USE RESTRICTIONS: [Indicate the species for which control is claimed, the sites where the
product may be used, general restrictions and precautions on use, and any special seasonal,
geographical^ or other prohibitions. Requirements for protective clothing and equipment may be
stipulated here or under "MIXING DIRECTIONS:" or "APPLICATION DIRECTIONS:", if
more appropriate.] .
SELECTION OF TREATMENT AREAS: [This section applies only to products used to control
commensal rodents in and around buildings. Text on current labels should be retained.]
APPLICATION DIRECTIONS: [Indicate the correct placement amounts or rates for product
application and the specific procedures required for such applications. Add information on
follow-up treatments and surveillance of treated areas as appropriate.]
When preparing labels, be sure that this basic format is preserved to ensure that it is clear, to
readers that all of the subsections indicated above are part of the "DIRECTIONS FOR USE".
For products claimed to control a variety of different vertebrate pests, the "DIRECTIONS FOR
USE" may be subdivided by species groupings. If the same basic set of "USE
RESTRICTIONS:" applies to all species groupings for which control is claimed, this subdividing
should occur at the "APPLICATION DIRECTIONS:" level.
If one set of "USE RESTRICTIONS:" is not appropriate for all site/pest combinations claimed,
such as might occur if certain sites or application methods were permitted or appropriate for only
some of the pests claimed, subdivision of the "DIRECTIONS FOR USE" should occur at the
"USE RESTRICTIONS:" level, with each site-pest grouping having separate "USE
RESTRICTIONS:", "MIXING DIRECTIONS" (if appropriate), and "APPLICATION
DIRECTIONS".
For labels which claim control of commensal rodents "in and around buildings" and other site/pest
combinations, the subdivision pertaining to commensal rodent control must include the specific
bait protection text indicated in PR Notice 94-7, except that the "It is a violation ..." and "READ
TEDS LABEL: ..." text may directly precede the subheading which sets directions for controlling
commensal rodents in and around buildings apart from the remainder of the "DERECTIONS FOR
USE". , - . . .
115
-------
(2) First Aid (Statement of Practical Treatment)
The Agency is requiring that all labels with Statement of Practical Treatment sections be
amended so that these sections are entitled, "First Aid." First aid statements must be brief, clear,
simple and in straightforward language so that the average person can easily and quickly
understand the instructions. These statements should be appropriate for all ages or, when
necessary, should include distinctions between the treatments for different ages. Once the Agency
has reviewed the data submitted for the RED, it may require additional changes to the "FIRST
AID" or "NOTE TO PHYSICIAN" statement."
Under Note to Physicians, many of the labels recommend that Vitamin Kx be administered
intravenously (TV) or intramuscularly (IM). The veterinary literature states that vitamin Kj can
cause anaphylactic 'reactions if given IV and extensive hemorrhage after IM administration.
Sheldon Wagner, M.D., a consultant to OPP, confirmed that Vitamin Kj should not be given IV
unless there is a hemorrhagic crisis. IM administration is acceptable in humans. The
recommendation for IV administration must be deleted from the label.
(3) Note to Veterinarian
* '
The Agency is requiring that all labels include a section entitled, "Note to Veterinarian"
which reads: "Contains [active ingredient], an anticoagulant with a half-life in the dog of [give
number, if known] days. For dogs that have ingested or that are suspected of having ingested
[active ingredient], and/or have obvious poisoning symptoms, such as [list major ones, such as
bleeding] or have lowered prothrombin times, give [name of antidotal material] as follows:
[treatment advice]. For anticoagulants with long half-lives, if known, it might be necessary to
check prothrombin times every 3 days until values return to normal.] See 'Note to Physician' for
additional information."
(4) PR Notice 94-7
All registrants of rodenticides within eight months after receipt of this RED document,
must be in compliance with the labeling requirements outlined in PR Notice 94-7, Notice to
Manufacturers, Formulators, Registrants and Users of Pesticides, dated September 16, 1994, if
. they have not already done so. Any rodenticide products not in compliance will be referred to
EPA's Office of Enforcement and Compliance Assurance for action.
116
-------
fill
I
6
bfi
.S
33
u
^beting Changes
i i
*s
1
CP
Cc5
^^
i
js
JS
E"^
1
o
CB
1 Required Labeling
a
-.3
o.
n
i
-
*
.-
i
1
o
p
^
ซ1
a
_9
"o
S
B,
;ง
ฃ>.
ง'
K
o
OH-
CO
BO
O
"53
0
t_i
OS'
i:
s
"Only for formulation into a rodenticide for the following use(s) [fill blank only with those ui
registrant]."
..Q
I
<3 n
ฃ o
2 i
M 3*
0 M
o. g
s ' s
i? g"
w "ca
3 ' "3
1. 1
3 ,<0
3 J
<ง 2
J -1
2 fe ฃ
"This product may be used to formulate products for specific use(s) not listed on the MP labe
complied with U.S. EPA submission requirements regarding support of such use(s). "
"This product may be used to formulate products for any additional use(s) not listed on the M
grower has complied with U.S. EPA submission requirements regarding support of such use(
5r* & ^ ^*
S o ง -a ง"
S ^ .2 - 1 S
g -S 0 .M g^ M
ง -3 5 ฐ & |
^a *ซ **"* w w
-2 ^S O ^ OT M
1 1 1 'ง 1 1
"Si 1 &-2 1
rt e ^ *"^ *^
o ฐ *
*.*3 w
-g E>
o <4~l
3 jn
o O
*S -J
oฃ .13
a> f^
D .3
2
W
(^
o
,
t
Ui
1
a
1
1
I
I
't
1
or
t
1
2
1
o
3
a
ci
.2' ซ>
e ^2
O
s ง
cง .a
' fii f^
5 .3
^
1
i
i
1
"a"
0
a
"ง>*
1 I
5 g
o "73.
Q-
"Do not apply this product in a way that will contact workers or other persons, either directly
may be in the area during application. Keep all other persons out of the treated area during a]
-z?
|I
ง 5
C <3
ffl "
tซ
O O
7- " "" S
' c *n
J*o
. J. .. .
s- -t
! 1
_g ' =g
*ง' o -
*J OT
C3 eo
SD '<
fcH
T3 *S
o ' g
= I 8
j 1 4
i . s g-
^ s , -
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no such instructions fo:
Keep and wash PPE separately from other laundry."
"Users should remove PPE immediately after handling this product. Wash the outside of gkr
wash thoroughly and change into clean clothing."
"Any person who retrieves carcasses or unused bait following application of this product mus
... -., -sf
' M S
' | 1
3 _t)
W
3 S
o'l
1 -a .
03 C3
o
CO
e
cs
'f-<
^
' 1
ซ3
|
1
2
a1
B
0
"All handlers (including mixers, loaders and applicators) must wear:
long-sleeve shirt and long pants,
shoes plus socks,
glovesl, and mixers and loaders must wear a dust/mist filtering respirator (MSHA/JS
"protective eyewear."
2 |'
is^^.g'
ง]ง:ง S j| .
g 3 ป S g
'S -8 | 1 s
S | a S3 "g; S
y ^* "S ^ "2
52 S o o o
*3 P '&4 SH fS-i
-------
1
i
M
P*
Required Labeling
J
"co*
<ซ H
a ซ
g i
a -a
2 <3
ง "2
ra a
_,
a
e
T-4
i
H
1
a,
L-i
"All handlers, including mkers/loaders and applicators, must wear:
- long sleeve shirt and long pants,
- shoes plus socks,
gloves,
- a dust/mist filtering respirator (MSHA/NIOSH approval numb<
protective eyewear."
Tracking powder
formulations
a
.2 a>
oฃ ^
a ^ S4
.<2 | ง .s a
^ ฐ ^ o3
cฐ ^.sฐ1 o
ฃ ,ง g ^"a
o >>-9 "5
t2> 00 Q<"t5 S
f 1 1 1 ฐ
*g <5 o "?; -3
fa Q 4-1 P
c a >- ft
i C " H O
a _. =5 o . M
O ^3 CO /"> *-* "0
;3 O > W ca G
S
S
1|
a H
>i
G
ซJ
a
S
M o
a to
B-g.
T3< S*
"So BO
li ^
59''
C 2
o 3
ง ^
. ^^ o
.1 ซ
g g
I ^
.& "ป
^i
"All handlers, including loaders and applicators, must wear:
long sleeve shirt and long pants,
shoes plus socks, and
gloves.
In addition, persons loading the pellets or baits into aircraft or mechanical ground <
pushed or hand-held equipment, such as a push-type spreader or cyclone spreader,
(MSHA/NIOSH approval number prefix TC-21 C) and protective eyewear. "
CO
a
~3
'ซง
o
1
&
^
w g
s ง
S 3
5 ซ
a -S
O O
" B
ll
ffi vS-
c
0
?3
u
"All handlers (including mixers, loaders and applicators) must wear:
long-sleeve shirt and long pants,
shoes plus socks,
gloves,
a dust/mist filtering respirator (MSHA/NIOSH approval number prefix 1
| 0-s
End-use pellet or prem
bait formulation with a
acute inhalation toxicit
Category I or II
L-l
CO
a
a
I ~
a g
.ง |
a S
05 03
"Do not contaminate water when disposing of equipment wash water or rinsate. "
.1
Products mixed or app
via equipment
a
o a>
ฃ3 OT
a o
5 g
O *3
3-2
ง g
D .a
CO
Q
^1
C8 g<
"H -2
E ง
S c
8 -B
CO CO
.ปH .-^
"5 9
3> s>
o -o
a "S
J .9
"ป ฐ
S S
j= 0
& a
CO g
S ซ
So ^
fe o
t< C
"Do not use in edible product areas of food or feed processing plants, restaurants o
prepared or processed. Do not contaminate food/feed or food/feed handling equipi
ป5 g>
For use in indoor
commercial establishm
(does not apply to trad
powders)
^
1
I
"Si
i
"o
o
D
ซS
I
I
1
4>
-------
1
V
a
S
on
Required Labelii
a
o
ts
_ฃ<
i
o
s
D
^
00
^n
-s
3
ca
60
. a
ucts must be relabeled to read:
)ors and 'against the outside walls of buildi
13
R< !!
OOT3
s ง
1 2
rt ""O ,
"S ง
|-a
M) fl CO
g ca 60
ง 1 s
04 *O|^
CO
1.
w
.1
Q
ซ
a
ฃ
o
S
=3
S
J2-
C
S
*y
.c
i '
1
t-l
o
of
"G
s- -
00
S3 ,
CO
g
12
G Q>
S^ -5
O ซ
8ft 1
Igs ง
2 f") T3
*- C-- 4>
information on this pesticide product (inc:
:ide Telecommunications Network at 1-801
not apply this product by any method not
11 a
y ฃL< 3 '
2 I
o ^ S
'f> & ง
o ง -ฐ S
"a 6 >> =0
<ซ s 1 1
G> O E SI
ฃ
1
_g
- o
C
"o
e
1 . -ฐ
^ 3
S -o*
S 1
M 3
.9 60
co p
3 1
o J
O *S
S Jง
.0 &
s
i 1
oo S3
a
c 2ฃ
1 s-
t-t
o -3
CO CO
ฃ "3
1 'i
rt Q
1 ^
S <5
o . -^
ce water is present or
ight be poisoned if the;
!
1 ซ- 1 1 -
III >
Q -S ?< (
"^ CX( *3 *^g
^ S "7^ ง
1 ll f.
ง11 "
.ง S.- = -P
If-life in the dog of [g;
and/or have obvious j
le of antidotal material
prothrombin times ev
Co " C3 ^
J~ '53? co o
03 ง ฃ, J=
ll-li
itains [active ingredient], an anticoagulant
ire suspected of having ingested [active ing
ing] or have lowered prothrombin times, |
half-lives, if known, it might be necessary
ician' for additional information."
O *-ป Qi 60 S?
U 5 Jg a S
y -S J3 S2, &*
I
-------
D. Existing Stocks
Registrants may generally distribute and sell products bearing old labels/labeling for 26
months from the date of the issuance of this Reregistration Eligibility Decision (RED). Persons
other than the registrant may generally distribute or sell such products for 50 months from the
date of the issuance of this RED. However, existing stocks time frames will be established
case-by-case, depending on the number of products involved, the number of label changes, and
other factors. Refer to "Existing Stocks of Pesticide Products; Statement of Policy"; Federal
Register. Volume 56, No. 123, June 26, 1991.
The Agency has determined that registrants may distribute and sell brodifacoum,
bromethalin, bromadiolone, chlorophacinone, diphacinone and its sodium salt products bearing
old labels/labeling for 26 months from the date of issuance of this RED. Persons other than the
registrant may distribute or sell such products for 50 months from the date of the issuance of this
RED. Registrants and persons other than registrants remain obligated to meet pre-existing
Agency imposed label changes and existing stocks requirements applicable to products they sell
or distribute.
120
-------
VI. APPENDICES
-------
8
<
8?
o
g-
eu
i
u
a
o
(N
cs
z
z
z
g
z
s
OQ
z
z
g
IS
I
is
CO
5
z
g
z
I
o
u
a
o
o
|
i"
23
^ ปn
^ to '
< I s
zซ S:
3 ซ ซ
| 2 |
,S N .3
B
SI
5
a
a
in
E-
I
g
I
a
B ~
3 '
a I
-------
rt
R
-'
o
1
1
s
,_,
1
^
Case 2755 [Brodifacoum] Chemical
si'
3
G "J
_O M
I 1 ง ' "
5 Iง
w .S
s Q - '
2
GO
o
"S
3
i 3* '
ca
s S* s
*? /sf
s-i ,1"
s "
a-8?i.--
K g 8 ^
Ills
"* S a S
*2 S,"
lit*
"3 (Sl o
CO ^ ><
SjS * Q
< o If!".
^ J s i ฐ
Ctf ^ ^
ง ฐ
g, ,
fllf
ฉ'ซ ~ ฐ '
,
[2 S3 ^^
w f .
^ 73
SITE Application Type, Application
Timing, Application Equipment -
Surface Type (Antimicrobial only)
cy Influencing Factor (Antimicrob:
r
Z'
5
USES ELIGIBLE FOR REREGISTE
NON-FOOD/NON-FEED (con't)
O
*fj
3
Q
O E2
'Bj. Z
0 g
'ซ CO
8 Z
Q
I'
O
a> CO
D z
. to '
Z
.0
i
!!
ซl
ซ
^-^
^
"ง- ง
CO
ta .
AGRICULTURAL/FARM PREMIS
B/S
v
^j4
U
Q
O
g
Z
o
z
o
" ง
S
co H
g . 5
CO
Z
00 o
o
g ' 0
* 5
* a
u . w
as w
\o '
ซ * p
_J
. G
z , S
ง
P/T
COMMERCIAL TRANSPORTATK
'-
S
u
CO
Z
Z '
^
g
g '
g
ฃ
^
S
o
's
oa
s '
g
1
i.
a
oa
u
u
co"
c?\
U
%
g
g
" ^
CO
Z
CO
2
.0
i
ii -
in , ซ>
ซ.l
C
^
f_
U
c*T
o\
CJ
g
g
g
g
Z
to
Z
ฃ
O
s
?1
$
1
s
u
u
u
u
8
g
.
g
-UC
E-06 Ib
ง
g
1
g
o
Q
Z
'ง
I
a
co
cs
g
ง'
.
ft int
2.513E-06
ft interval
tion
S
-------
<
u
tx.
1
S
u
5
a",
u
CN
s z
o
2;
ง
O
ง g
c. z
EGISTRATION
GIBLE FOR
ex
a
IAL PREMIS
ONAL/INDO
TIT
MMERaA
UC
S ฐ
si
<-
z
z
S
z
s
z
g
B) g
ฐl
^ s
m 5
<
Z
50
ca
' AJ
51
B5
-------
<
X
-
o
<
u
o
O
-------
.
nly
ES
s
u
s
u
S
o
cs
z
s
ง
S
I
o
Q
8
O
W
z
S
=?
ta
S s
dซ
CO C*
S-
73- W S
S| I
il ^l:
z z
S S
* *
S . ฃ
ฃ 2
1 &! ง
C i-t ฃ ปn
o
S 1
o s
[I] O,
S S-
ง i
I
Oi
1
52
1
S
J
I
-------
\Q
S 9i
sง
is
if
H
04
g
la
ซฃ
kj
I
1
<
1
1
a
1
T-H -
Case 2755 [Brodifacoum] Chemical
If
||1
.a &
a0
2
CO
0
JS
'S
1
4? -rf
S ^
.s 1" |
H- "?;
Sis.
s ^^
D "^? "^
K ง .M m
ซ J ง
a* fl w Q<
S 3 o o^
"* -2 ซ 5
^1 ?
'"ง ฎ1 ^ o1
10 s S
lisa -
"^ S S 'flj-'S
x >-^ 2 -5 ti
SS 3 1
05 ^ S '
S o
*!li
4s s |
S s S .ง '
3ซ~f
1 Is
S3 g
<ซ -3
SITE Application Type, Application
Timing, Application Equipment
Surface Type (Antimicrobial only)
cy Influencing Factor (Antimicrobi
-
1
USES ELIGIBLE FOR REREGISTR
NON-FOOD/NON-FEED (con't)
'
r\
^
u
c-
"g
&
8
g
.0
eฃ
o
|--a
i- %
O Z
.l'-M
z
CO
"i ซ
-3- 2:
f-^-
J
iTCONTRC
UC
a
It
55
PUBLIC BUILDINGS/STRUCTURE
B/S
'
fj
j
u
%
2'
%
CO
* .
2
2
*
-Ha
\O "
II
CO *^
1.
S "
z
S
Q
O
g
g
i
s
Use Gro
B
> .S
co "ซ
ttt ^
O n.
< &l
B3 "ซ
OR
-------
o
s
oo
cs
-------
ON
CN
J3
E
ฃ
C93 : Do not apply directl
CAC : Keep out of lakes, s
CAT : Do not place in loca
* NUMBER IN PARENTH
re fo
-------
<
U
<
U
fr ป
o
co
a
o
o
u.
CA
z
S
oi
O -1
o
i s
U.
ง
ง
lic
Ap
z
CO
Z
B
z
*
s
<> .s
ง
s
ซ vo
w '-
!
I
g
g
ES
LE
US
PRE
L/FA
eg
a
s-s
ea m
S
Q
o
1
en
S
s
I
G
U.
I
g
<
8 I
06 i
3 ซ
3.333E
linear ft
uc
3.350E-06 Ib
ft interval
ง
g
!
u
S
tu
_:
D
U,
I
m
S -
-------
cs
0
s
0
_J
E-
' 1
?
CK
III'.
^ ^?
>-< ^ ^^
JVH
TJ <
glfl
il.il
& 3 o g
Jซ ฐ
^^
"S (E9* u*
<ซ ฎ X ฃ
_; X 4| g
ง3 ^ Jj Q 0
^ !< S'ITU
J5 "^^ C5 *S y
^ *c
ง 0
"3< i.
9* 3 ง ^?
^ 1-4 0 JS
S S S S
3-05 ~ ฐ
1 s
12 if
_j ' .S
..I S"o
SITE Application Type, Applicat
Timing, Application Equipment
Surface Type (Antimicrobial on
cy Influencing Factor (Antimicl
-.
;
-
I :,
fj
E
USES ELIGIBLE FOR REREGK
FOOD/FEED USES (con't)
c-
"g
,8,
ง
g
CJ
0
o
i-
_
1
o
8"
D
^-
g
J
ri .
Q
S
S
ia
g
N FACILITIES.
O
P
COMMERCIAL TRANSPQRTA
u
0
CO
, Z
1 <
z
s
CO
S
it
ฃ
ง
ia
o
CO
co'
<
s
,<-
>.
Bait application, When needed, E
u
o
u
.<
o
u
CJ
<
u
s
2 %
S o
g
z.,
g.
S W
<
Z
S3
m
B
SI"
ง1
a .s
z .s
-ss
^S
en
en-
B
B
ฃ
UC
50E-061b
interval
fc: ,
.2
S 5
i
Q
.1
z,
i
s
-------
I
GBLE FOR
>D/NON-
i
FE
o
o
u
<
u
u
<
u
u
<.
u
u
<
o
<
z
o
g
B B
.
P/T
g
o
i
Id
ฃ2.
a
s
3 B
B
I
1
Bs
i I
s a
CO
=>
I
CO
m
Q
O
g
Q
ง
I
I
z
S'
D 1
K W
I 1
1 I
O 03
g
B
<
Z
-------
I
O
CO
ง
J5
*-t
I
Report Run Date: 08/12/97 -
PRO Report Date: 07/06/95
-
f-
04
O
ง
^j*
%
|
s
< "
1
"o
' "5 -
g
B
0
o
cs
^*
.a
i
Case 2760 [Bromadiolone] Ch(
'
If :
1|1
3 =f
2
00
"S
o
<1> -tf1
& ^
.s ||
~ "i:
<; _gj ซ
tt ฃ S-
0)
^lla
>s w ^ -t*
So"
fill
^ 'Cง >ป
ซ . "-*
Jiff
ฐ @ ^ s*
Sili
3 * vป "
f - A
if
1 s 1 1
SITE Application Type, Applic
Timing, Application Equipme
Surface Type (Antimicrobial
cy Influencing Factor (Antim
0
^
1
USES ELIGIBLE FOR REREC
NON-FOOD/NON-FEED (con
u
u
o
g
CA
0
0 "
Q
Z %
H,
s
B CO
O Z
'I
CO.
12''
CO
*
D .0
i s
1 ง
O u-i
2 co
1 "
1 1
Z < B
co Z .3-
1 *
3 ฃ2
u ซ
B. -o
Z ง
< ซ
COMMERCIAL TRANSPORT
Bait application, When needed,
-
CJ CJ
< 'u " ' < ,
ฐ O u ฐ
Q
0
g
Z
' - ซ!
O
O
CO CO. 71
Z g 2 Z g,
0 0 8
^-t o ^^ o
CO ' CO , &
Z I* Q Z D
Z Z
CO ; 'CO
2 g g -Z
S1
' s
CO co CD
* g' g Z i
CO CO
z , g g z i
? B,VI i
gซ Sis
C*l is V^ Ci [13
<ซ> S m s S
<" .S ซn .S 0-
" ' ' * 1
g '* ^ g 1
' , . US
ซ B. fc' ฃ ^
, - 1
-.." i
s
-i
u
o
g
*H
g
CO
Z-
CO
Z
g
50E-06H) *
ซn
<
2 .
t
ffl
.1
A
ei'
1
M
1
1
u
<
u
<
u.
CO
en
BJ
' Z
g
g
g
g
3.333E-06 11
linear ft
<
B
g
* -B
z *
z z
!50E-061b '
w
"ซ
|:
e
"g
i
1
ft interval
3.350E-06 11
.g
interval
G
3.350E-06 11
' g
interval
&
B.
B.
Bai
Bai
-------
C_d
1
<
K
Q
ง
Cl*
<
I
^s
g
I
u
60 [Bronuidiolonel '
R
J
3j
5 - s
ilง
.s .S
s^
J
t5;
ปS
<5*
ill
g "^
f" 'S
ซll*
g. g ง a,
** 2 1"^
>< *^*
ll1!
w a a
^f-^Q o
< S 3 ป a
a 1 s 1 &
5* S w C=
cc ง S
S o
i-4
< ^ 3 f
i|ll
cation Form(s)
ซnt - Ra
only)&Effica- 1
licrobial only) ol
lr! 5 S
pplicationType, Ap
5, Application EquJ[
e Type (Antimtcn*
lucncing Factor (An1
<.f 31
gill-
CO
3ISTRATION
i'0
a s
iLIGIBLEFORRES
DOD/NON-FEED((
HJ ฃ
S- *
S ง
1
g
Q
O
O
IX,
Z
1
WD
W
S
ฃ
H.
g
I
ฃ?
0
1
5
91
&}
1
ง
CU
JNAL/INDUSTRIAL
H
ERCIAL/INSTITOl
1
u
CO
Z
Z
S
S
S
4(.
ฃ
VO
O
0
en
CO
*3
< 3
Z .3
ซ
1
1
TB
S
1
s
n
u
<
CJ
W -3 W
^ .3
c
25
ra
ca
g
D
c
.2
ra
a
g
ง
S
O
en
Z
S,
<
i
I
S
8
g
I
g
o
Q
Z
I
Q
B
S
ง
o
EC
Id
i
B
B
งป
w 1
o -g
2 -S
-------
*o
S.
x di
S 0 0
"I ฉ^ ^
X ai
~ >* S o
f^S0 &
^ s a -S1 ^3
ซ S g .| 5-
ง a ฃ S
So1Js
1 ฐ
*K,
S S " .
^li*
sSS g
Sa||
"s"
1 If
fill
till
< งง:ง-
ซ w -a r
1: ง i |
H a e s
ct g < ซ
- ^.^ g
If ง|
3 *S *"
[i] S ซ
ฃซซ.ป
-
r
I ^
U d
m S
S "
ง Q
OS ง
1 i
m z:
USES ELIGH
NON-FOOD/
""
. u
5
J
p
ง
i .. g
u
os
OS
0 OT
S z
I-H
&4 ^
_O
S
B g
S
*
. B
W
CO
W
ฃ <^
8
S ra
I i
i -|
2 1
kOUSEHOLI
Bait applicati(
0
<
u
<
u
<
u
* z
2 o
S
g
B
o'
a
m -S
.5
ง
CQ
.|
II
o
<
u
S
z
z
CO
Q.
O
O
B,
Z
o
z
o
o
Q
z
"*
I1
O
5
o
!3
CO
Z
ซ
g
CO
^
g
en
z
g.
s
ta
<: a
^z .s
ซ
S^
S-
B
I
.a
OS
ca
-------
o
<
u
o
<
o
"s
u
o
CJ
cS
<
<
u
<
o
<
ill
B=a
p.,
q
B
Z
B
-------
ง
a
II
is
lic
Ap
Ty
G
D/NON-F
LI
OO
NON-F
<
o
o
<
CJ
en
ง
ta
ง
o
I
j
I
2
O
z
g
UJ
S
w
S
<
o
ง
oi
O
ซ .3
S - S
-------
a
S
t
o
<
CJ
<
o
o
<
CJ
<
<
<
II
g
l
oo
I
z
ง
B
B
B
S*
ซn 5!
tx] S
^!
m "~
CJ
Oi
f-
B
ง|
Ml
ซ" fa
ซ ง
m.s
ง
USES ELIGIBLE FOR REREG
(con'
NON
NON-F
i-
I
o
o
B
03 .2
ง ^
S- -g"
so 'ซ
-------
X
8
w
a.
cu
a
ซ sr
ซ ซ
11
8
3
,1 It
i-sS
:I1
o 2
ง3
igo
igs
o
co *
en
I S
t, w
s* *
s a
is 1
ซ .a> J
S a 3
I * L
O S a. O
z
S S
5U'
ซ a
11'
1ง
< Q
'^1
ซJ ซ ซ
CJ o u
o S 5
z.il
3 " "
U
&*'>
:|^ a
IfS
111
s a
- i
-------
'a
o
, 2 o J
2
u
"ป1
-------
GUIDE TO APPENDIX B
Appendix B contains listings of data requirements Which support the reregistration for active
ingredients within the case 2665 covered by this Reregistration Eligibility .Decision Document.
.It contains generic data requirements that apply to Rodenticide Cluster active ingredients in all
products, including data requirements for which a "typical formulation" is the test substance.
The data table is organized in the following format:
1. Data Requirement (Column 1). The data requirements are listed in the order in which
they appear in 40 CFR Part 158. the reference numbers accompanying each test refer to the test
protocols set in the Pesticide Assessment Guidelines, which are available from the National
Technical Information Service, 5285 Port Royal Road, Springfield, VA 22161 (703) 487-4650.
2. Use Pattern (Column 2). This column indicates the use patterns for which the data
requirements apply. The following letter designations are used for the given use patterns:
A Terrestrial food .
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food
J Forestry
K Residential
L Indoor food
M Indoor non-food *
N Indoor medical
O Indoor residential
3. Bibliographic citation (Column 3Y. If the Agency has acceptable data in its files, this
' column lists the identifying number of each study. This normally is the Master Record
Identification (MRTD) number, but may be a "GS" number if na MRID number has been
assigned. Refer to the Bibliography appendix for a complete citation of the study.
141
-------
142
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Brodifacoum
REQUIREMENT
PRODUCT
61-1
61-2A
61-2B
62-1
62-2 .
62-3
63-2
63-3
63-5
63-7
63-8
63-9
63-11
63-12
63-13
CHEMISTRY
Chemical Identity
Start. Mat. & Mnfg. Process
Formation of Impurities
Preliminary Analysis
Certification, of limits "
Analytical Method
Color :
Physical State
Melting Point
Density
Solubility .
Vapor Pressure
Octanol/ Water Partition
PH
Stability
USE
PATTERNS
- All
All
All
All
All
All
All
All
All
All
All
All
All
All"
All
CITATION(S)
129706
129706 ;
129706
129706 .
129706
129706
41892201
41892201
41.892201, 41892202
41892201
41892201,41892202
41892202
418.92202
41892201 . ','.,'
41892201
ECOLOGICAL EFFECTS
71-1A
71-2A
71-2B ..
72-1A :
72-1 C
72-2A
Acute Avian Oral - Quail/Duck
Avian Dietary - Quail
Avian Dietary - Duck
Fish Toxicity Bluegill
Fish Toxicity Rainbow Trout
Invertebrate Toxicity
C, F, K ,
C,F,K
C,F,K
C,F,K
C,F,K
C,F,K
41563303
124477
124476
124472
88011 .
128442
143
-------
Data Supporting Guideline Requirements for the Reregistration of Brodifacoum
REQUIREMENT
USE
PATTERNS
CETATION(S)
TOXICOLOGY
81-1
81-2
81-3
81-4
81-5
Acute Oral Toxicity - Rat
Acute Dermal Toxicity -
Rabbit/Rat
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation -
Rabbit
83-3A Developmental Toxicity - Rat
83-3B Developmental Toxicity - Rabbit
85-1 General Metabolism
86-1 Domestic Animal Safety
ENVIRONMENTAL FATE
161-1 Hydrolysis
162-1 Aerobic Soil Metabolism
163-1 Leaching/Adsorption/Desorption
All 42687501,4021701
All 42223201,44021702
All 43110501
All 66938
All 44021703
L 52443, 40307202, 42641902
L 52442,40307201
L 80235^42007502,42596801,44021705
42007501
C,F, K 42237701
C, K 42579401
C, F,K 42024501,42568301
144
-------
Data Supporting Guideline Requirements for the Registration of
Bromadiolone
REQUIREMENT
PRODUCT
61-1
61-2A
61-2B
62-1
62-2
62-3 ' ..
63-2
63-3
63-4
63-5
63-7
63-8
63-9
.63-11 >
63-13
CHEMISTRY
Chemical Identity
Start. Mat. & Mnfg. Process
Formation of Impurities
Preliminary Analysis
Certification of limits
Analytical Method
Color
Physical State
Odor
Melting Point
Density
Solubility
Vapor Pressure
Octanol/Water Partition
Stability
USE PATTERN CITATION(S)
All
AU
AU
AU '
AU
AU
AU
AU
AU
AU
AU
AU
AU
AU
AU
41717001, 41884701
41717001,41884701
41690802,41717001
41514101, 41717002
41514101,41717002
41514101, 41717002, 41849601
41849601, 42395901, 42667801
'41849601, 42395901, 42667801
41849601, 42395901, 42667801
42395901,42667801
41849601, 42395901, 42667801
42395901,42667801
42395901,42667801
42395901, 42667801
42395901, 42667801
ECOLOGICAL EFFECTS
71-1A
71-2A
71-2B
72-1A
72-1 C
72-2A
Acute Avian Oral - Quail/Duck
Avian Dietary - Quail
Avian Dietary - Duck
Fish Toxicity Bluegill
Fish Toxicity Rainbow Trout
Invertebrate Toxicity
C,K
C,K
C,K
C,K
C,K
C, K
257770, 41707301
257770
249995,257770
232567
232567
232567
145
-------
Data Supporting Guideline Requirements for the Reregistration of
Bromadiolone
REQUIREMENT USE PATTERN CITATION(S)
TOXICOLOGY
81-1
81-2
81-3
81-4
81-5
81-6
82-1A
82-1B
83-3A
83-3B
85-1
86-1
Acute Oral Toxicity - Rat
Acute Dermal Toxicity - Rabbit/Rat
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation - Rabbit
Dermal Sensitization - Guinea Pig
90-Day Feeding - Rodent
90-Day Feeding - Non-rodent
Developmental Toxicity - Rat
Developmental Toxicity - Rabbit
General Metabolism
Domestic Animal Safety
All
All
All
All
All
All
L
L
L
L
L
, 41900001
42673701
41976901
88113
88112
41847401
107035
92196013
92196014
92196015
42596801
42093301
ENVTRO3S1MENTAL, FATE
161-1
162-1
163-1
Hydrolysis
Aerobic Soil Metabolism
Leaching/ Adsorption/Desorption
C,K
C, K
C,K
42237501 .
43594301
161972, 161973, 161988, 42237501,
43000702, 43594301
146
-------
Data Supporting Guideline Requirements for the Reregistration of Bromethalin
REQUIREMENT
USfe PATTERN CITATION(S)
PRODUCT
61-1.
61-2A
61-2B
62-1
62-2
62-3
63-2
63-3
63-4
63-5
63-7
63-9
63-11
CHEMISTRY
Chemical Identity
Start. Mat. & Mnfg. Process
Formation of Impurities
Preliminary Analysis
Certification of limits
Analytical Method
Color
Physical State
Odor
Melting Point
Density
Vapor Pressure
Octanol/Water Partition
All
All
All
All
. All
All
All
All
All
All
All
AH
All
42333401, 42403001
40617001,42333401
42333401,42403001
- .26519, 86718, 86719, 40797401,
42403002 . . '
42433401
42403002 .
41599601
41599601
41599601.
41599601
41599601
41979600
41599603
ECOLOGICAL EFFECTS
71-1A
71-2A
71-2B
72-1A
72-1C
72-2A
Acute Avian Oral - Quail/Duck
Avian Dietary - Quail
Avian Dietary - Duck
Fish toxicity Bluegill
Fish Toxicity Rainbow Trout
Invertebrate Toxicity
All
All.
All
All
All
All
86741, 246173
86745
26526
42733501 ,
42733502
86751, 42733503 .
147
-------
Data Supporting Guideline Requirements for the Reregistration of Bromethalin
REQUIREMENT
USE PATTERN CITATION(S)
TOXICOLOGY
81-1 Acute Oral Toxicity - Rat
81-2 Acute Dennal Toxicity - Rabbit/Rat
81-3 Acute Inhalation Toxicity - Rat
81-4 Primary Eye Irritation - Rabbit
I ,
81-5 Primary Dermal Irritation - Rabbit
81-6 Dermal Sensitization - Guinea Pig
81-7 Acute'Delayed Neurotoxicity - Hen
82-1A 90-Day Feeding - Rodent
82-1B 90-Day Feeding - Non-rodent
82-5B 90-Day Neurotoxicity - Mammal
83-3B Developmental Toxicity - Rabbit
85-1 General Metabolism
86-1 Domestic Animal Safety
ENVIRONMENTAL FATE
161-1 Hydrolysis
162-1 Aerobic Soil Metabolism
All 26524, 241521, 246172
All 26524
All 26524
All 26524
All 26524
All 41653001
All 101543
All 43582102
All 43582101
All 42793101
All 86731, 101545
All , 4724
All 42759602,42759603,42759604
All 42438701
All 43007901
148
-------
Data Supporting Guideline Requirements for the Reregistration of Chlorophacinone
REQUIREMENT
PRODUCT
61-1
61-2A
61-2B
62-1
62-2
62-3
63-2
63-3
63-4
63-5
63-7
63-8
63-9
63-10
63-11
63-13
CHEMISTRY
Chemical Identity
Start. Mat. & Mnfg. Process
Formation of Impurities
Preliminary Analysis
Certification of limits
Analytical Method
Color
Physical State
Odor
Melting Point
Density '
r> Solubility
Vapor Pressure
Dissociation Constant
Octanol/Water Partition
Stability
USE PATTERN CITATION(S)
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
Other Submissions
Other Submissions
Other Submissions
41922901
419229Q1
41922901
42237401
42237401
42237401
42237401
42237401
42237401
\
42237401
42237401
42237401
42237401 ' . " . -
ECOLOGICAL EFFECTS
71-1A
71-2A
71-2B
72-1A
724 C
72-2A
Acute Avian Oral r Quail/Duck
Avian Dietary - Quail
Avian Dietary - Duck
Fish Toxicity Bluegill ,
Fish Toxicity Rainbow Trout
Invertebrate Toxicity
All
All
All
.All
All
All
41513101
41513102
41513103
42356102
42356103
42356101
149
-------
Data Supporting Guideline Requirements for the Reregistration of Chlorophacinone
REQUIREMENT USE PATTERN
CITATION(S)
TOXICOLOGY
81-1
81-2
81-3
81-4
81-5
81-6
82-1A
82-2
83-3A
83-3B
85-1
86-1
Acute Oral Toxicity - Rat .
Acute Dermal Toxicity -
Rabbit/Rat
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation -
Rabbit
Dermal Sensitization - Guinea
Pig
90-Day Feeding - Rodent
21 -Day Dermal - Rabbit/Rat
Developmental Toxicity - Rat
Developmental Toxicity - Rabbit
General Metabolism
Domestic Animal Safety
All
All
All
All
All
All
All
All
All
All
All
All
41875301
41702801
41981102
41874001
41702801
41578601
92018013
42237402
43349501
43570801
155540
41981101
ENVIRONMENTAL FATE
161-1
161-3
162-1
163-1
SPECIAL
70-A-SS
Hydrolysis
Photodegradation - Soil
Aerobic Soil Metabolism
Leaching/ Adsorption/Desorption
STUDIES
Secondary Toxicity Study
All
All
All
All
All
42205501
42452301
43159801
42666001
42760902
i
150
-------
Data Supporting Guideline Requirements for the Reregistration of Diphacinone and
' "/ , ^ Salt ' .
REQUIREMENT USE PATTERN CITATION(S)
PRODUCT
61-1
"61-2A.
61-2B
62-1
62-2
62-3
63-2
63-3
63-4
63-5
63-7
63-8
63-9
63-10
63-11
63-12
63-13
CHEMISTRY
Chemical Identity
Start. Mat. & Mnfg. Process
Formation of Impurities,
Preliminary Analysis
Certification of limits
Analytical Method
Color
Physical State
Odor
Melting Point
Density
Solubility
Vapor Pressure
Dissociation Constant
Octanol/Water Partition
pH
Stability
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
41613401, 41727801, 41612801,
42136001, 42360601
41613401, 41612801, 42136001
41613401, 41612801, 42136001,
42136002,42360601
41613402,^41727802, 41612802,
42136002
41613402. 41612802, 42136002
41613402, 41612802, 42136002
41727803,42360601
42360601
134837
134837
. 134837 ' ._
134837, 134839
41612802, 134837
41612802
41612802, 134840
41612802
41612802,42136003
ECOLOGICAL EFFECTS
71-1B
71-2A
71-2B
72-1A
72-1 C
72-2A
Acute Avian Oral - Quail/Duck
TEP
Avian Dietary - Quail
Avian Dietary - Duck
Fish Toxicity Bluegill
Fish Toxicity Rainbow Trout
Invertebrate Toxicity
All
All "
All
All
All
All
42245201
42408801 . . . '
42408802
43249501
43249502
42282201
TOXICOLOGY
151
-------
Data Supporting Guideline Requirements for the Reregistration of Diphacinone and
Salt
REQUIREMENT
USE PATTERN CITATION(S)
81-1 Acute Oral Toxicity - Rat
81-2 Acute Dennal Toxicity -
Rabbit/Rat
81-3 Acute Inhalation Toxicity - Rat
81-4 Primary Eye Irritation - Rabbit
81-6 Derm'al Sensitization - Guinea Pig
82-2 21-Day Dermal - Rabbit/Rat
83-3A Developmental Toxicity - Rat
84-2B Structural Chromosomal
Aberration
85-1 General Metabolism
86-1 Domestic Animal Safety
ENVTRO^jMENTAL FATE
161-1 Hydrolysis
162-1 Aerobic Soil Metabolism
SPECIAL STUDIES
70-13-SS Secondary Toxicity Study
All 43260701, 43260702, 42245202,
60605
All 42507001
All 43000401
All 42245203
All 42132501
All 074637,77369
All . 077319,42834801
All 42406801
All 92049009
All ' 42791202
All 43582401
All 42035001
All 40077202
152
-------
153
-------
GUIDE TO APPENDIX C
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies
considered relevant by EPA in arriving at the positions and conclusions stated
elsewhere in the Reregistration Eligibility Document. Primary sources for studies in
this bibliography have been the body of data submitted to EPA and its predecessor
agencies in support of past regulatory decisions. Selections from other sources
including the published literature, in those instances where they have been considered,
are included.
2. UNITS OF ENTRY. The unit of entry in this bibliography is called a "study". In the
case of published materials, this corresponds closely to an article. In the case of
unpublished; materials submitted to the Agency, the Agency has sought to identify
documents at a level parallel to the published article from within the typically larger
volumes in which they were submitted. The resulting "studies" generally have a
distinct title (or at least a single subject), can stand alone for purposes of review and
can be described with a conventional bibliographic citation. The Agency has also
attempted to unite basic documents and commentaries upon them, treating them as a .
single study.
3. IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted
numerically by Master Record Identifier, or "MRID number". This number is unique
to the citation, and should be used whenever a specific reference is required. It is not
related to the six-digit "Accession Number" which has been used to identify volumes of
submitted studies (see paragraph 4(d)(4) below for further explanation). In a few
cases, entries added to the bibliography late in the review may be preceded by a nine
character temporary identifier. These entries are listed after all MRID entries. This
temporary identifying number is also to be used whenever specific reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry
consists of a citation containing standard elements followed, in the case of material
submitted to EPA, by a description of the earliest known submission. Bibliographic
conventions used reflect the standard of the American National Standards Institute
(ANSI), expanded to provide for certain special needs.
a Author. Whenever the author could confidently be identified, the Agency has
chosen to show a personal author. When no individual was identified, the
Agency has shown an identifiable .laboratory or testing facility as the author.
When no author or laboratory could be identified, the Agency has shown the
first submitter as the author.
b. Document date. The date of the study is taken directly from the document.
When the date is followed by a question mark, the bibliographer has deduced
the date from the evidence contained in the document. When the date appears
\
154
-------
BIBLIOGRAPHY
MRID CITATION
as (19??), the Agency was unable to determine or estimate the date of the
document.
/ . . '...,
c. Title. In some cases, it has been necessary for the Agency bibliographers to
create or enhance a document title. Any such editorial insertions are contained
between square brackets.
d. Trailing parentheses. For studies submitted to the Agency in the past, the
trailing parentheses include (in addition to any self-explanatory text) the
following elements describing the earliest known submission:
(1) Submission date. The date of the earliest known submission appears .
immediately following the word "received."
(2) Administrative number. The next element immediately following the
word "under" is the registration number, experimental use permit
number, petition number, or other administrative number associated
with the earliest known submission.
(3) Submitter, The third element is the submitter. When authorship is
defaulted to the submitter, this element is omitted.
(4) Volume Identification (Accession Numbers). The final element in the
trailing parentheses identifies the EPA accession number of the volume
in which the original submission of the study appears. The six-digit
accession number follows the symbol "CDL," which stands 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.
155
-------
BIBLIOGRAPHY
MRID
CITATION
Brodifacoum Bibliography
> . , - '
00052442 Hodge, M.C.E.; Banham, P.B,; Richards, D.; etal. (1980) Brodifacoum: Teratogenicily Study in
the Rabbit: Report No. CTL/P/ 459. Includes undated method entitled: The determination of
Brodifacoum in dosing solutionsmethods A and B. (Unpublished study received Mar 7, 1980
under 10182-28; prepared by Imperial Chemical Industries, Ltd., submitted by ICI Americas, Inc.,
Wilmington, Del.; CDL:242118-A)
00052443 Hodge, M.C.E.; Banham, PJB.; Richards, D.; etal. (1980) Brodifacoum: Teratogenicity Study in
the Rat: Report No. CTL/P/437. Includes undated method entitled: The. determination of
Brodifacoum in dosing suspensions. (Unpublished study received Mar 7, 1980 under 10182-28;
prepared by Imperial Chemical Industries, Ltd., submitted by ICI Americas, Inc., Wilmington, Del.;
CDL-.242118-B)
00066938 Parkinson, G.R.; Lefevre, V.K.; Jaggers, S.E. (1978) Brodifacoum: Skin and Eye Irritation: Report
No. CTL/P/404. (Unpublished study received Aug 15, 1978 under 10182-26; prepared by Imperial
Chemical Industries, Ltd., submitted by ICI Americas, Inc., Wilmington, Del.; CDL:234655-E)
00080235 Bratt, H.; Hudson, P. (1979) Brodifacoum: Absorption, Excretion and Tissue Retention in the Rat:
Report No. CTL/P/462. (Unpublished study received Jul 22, 1981 under 10182-38; prepared by
Imperial Chemical Industries, Ltd., England, submitted by ICI Americas, Inc., Wilmington, Del.;
CDL:245704-E)
00088011 Hill, R.W.; Maddock, E.G.; Hart, B.; et al. (1976) Determination of the Acute Toxicity of PP581
to Bluegill Sunfish (Lepomis macrochirus): Report BL/B/1771. (Unpublished study received Jan
3, 1978 under 10182-EX-10; prepared by Imperial Chemical Industries, Ltd., submitted by ICI
Americas, Inc., Wilmington, Del.; CDL:232750-F)
00124472 Hill, R. (1979) Determination of the Acute Toxicity of PP 581 to Rainbow Trout..: BL/B/1877.
(Unpublished study received Feb 27, 1979 under 10182-26; prepared by Imperial Chemical
Industries, Ltd., Eng., submitted by ICI Americas, Inc., Wilmington, DE; CDL:237703-C)
00124476 Fink, R.; Beavers, J.; Grimes, J.; etal. (1978) Forty-day Dietary LC50-MallardDuck:
Technical Brodifacoum: Project No. 123-128. Final rept. (Unpublished study received Feb 27,
1979 under 10182-26; prepared by Wildlife International, Ltd. and Washington College,
submitted by ICI Americas, Inc., Wilminton, DE; CDL:237703-H)
00124477 Fink, R.; Beavers, J.; Grimes, J.; et al. (1978) Forty-day Dietary LC50-Bobwhite Quail:
Technical Brodifacoum: Project No. 123127. Final rept. (Unpublished study received Feb 27,
1979 under 10182-26; prepared by Wildlife International, Ltd. and Washington College,
submitted by ICI Americas, Inc., Wilmington, DE; CDL:237703-I)
00128442 Getty, C.; Wilkinson, W.; Sealey, C. (1978) Brodifacoum: Toxicity of the Liquid Concentrate
Pelleted Bait and Technical Material to First Lastar Daphnia magna: Report Series RJ0046B.
(Unpublished study received Mar 29, 1974 under 10182-26; prepared by Imperial Chemical
Industries Ltd., Eng., submitted by ICI Americas, Inc., Wilmington, DE; CDL:237909-A)
156
-------
MRID
BIBLIOGRAPHY
''"" i -'.. - /
CITATION
00129706 Tandy, M.; Duffin, M. (1978) Brodifacoum: Detailed Analysis of Technical Materials Sent for
Toxicological Studies: Report Series RJ 0029C. (Unpublished study received Jul 19, 1979 under
10182-26; prepared by Imperial Chemical Industries, Ltd., Eng., submitted by ICI Americas,
Inc., Wilmington, DE; CDL:238840-B)
40307201 Litchfield, M. (1980) Brodifacoum: Teratogenicity Study in the Rabbit: Individual Animal Data:
Supplement: Lab Project ID: CTL/P/459S. Unpublished study prepared by ICI Central
Toxicology Lab. 35 p.
40307202 Litchfield, M. (1980) Brodifacoum: Teratogenicity Study in Hie Rat: Individual Animal Data:
Supplement: Lab Project ID: CTL/P/437S. Unpublished study prepared by ICI Central
Toxicology Lab. 96 p.
41563303 Ross, D.; Roberts, N.; Fairley, C. (1990) Brodifacoum: The Acute Oral Toxicity (LD50) OF
Brodifacoum to Mallard Duck; Lab Project Number: ICI 308 WL/791275. Unpublished study
prepared by Hunting don Research Centre. 24 p.
41892201 Wbllerton, C.; Husband, R. (1991) Brodifacoum TGAI-Physico-Chemical Data File: Lab
Project Number: RJ0960B: 90JH232. Unpublished study prepared by ICI Agrochemicals,
Jealott's Hill. 17 p.
41892202 WoUerton, C; Husband, R. (1991) Pure Brodifacoum-Physico-chemial Data Files: Lab Project
Number: RJ0959B: 89JH361: PP581PR01. Unpublished study prepared by ICI Agrochemicals,
Jealott's Hill Research. 29 p.
42007501 Hopkins, M. (1991) Brodifacoum: Antidote Study in Dogs: Lab Project Number: CLT/P/3171:
PD0646. Unpublished study preparedby ICI Central Toxicology Lab. 29 p.
42007502 Batten, P.; Bratt, H. (1990) Brodifacoum: Elimination From the Tissues of Rats Following
Administration of Single Oral Doses: Lab Project Number: UR0172: UR0211: CTL/P/1559.
Unpublished study prepared by ICI Central Toxicology Laboratory. 65 p.
42024501 Newby, S.; White, B. (1979) Brodifacoum: Adsorption and Desorption in Soils Measured Under
Laboratory Conditions: Lab Project Number: TMJ 1764 B. Unpublished study prepared by ICI
Agrochemicals 59 p.
42232101. McCall, J. (1991) Brodifacoum Technical: Acute Dermal Toxicity to the Rat: Lab Project
Number: CTL/P/3595: CR2899. Unpublished study prepared by ICI Central Toxicology Lab. .
64 p.
42237701 Jackson, R.; Priestly, I.; Hall, B. (1992) The Determination of the Hydrolytic Stability of
Ccarbon 14-Brodifacoum: Lab Project No. 381420: 8330. Unpublished study prepared by
Inveresk Research International. 77 p.
42568301 Jackson, R.; Hall, B. (1992) Aged Soil Leaching of carbon 14 BrodifacQum: Lab Project
Number: 381986. Unpublished study prepared by Inveresk Research International. 72 p.
157
-------
BIBLIOGRAPHY
MRID
CITATION
42579401 Hall, B.; Priestly, I. (1992) Brodifacoum: Metabolism in Soil under Aerobic Conditions: Lab
Project Number: 381441. Unpublished study prepared by Inveresk Research International. 63 p.
42641902 Lappin, G.; Davies, D. (1992) Brodifacoum: Blood Kinetics Study in the Pregnant Rat:
Supplement MRID 52443: Lab Project Number: CTL/P/3818: UR0394. Unpublished study
prepared by ICI Central Toxicology Lab. 30 p. .
42687501 Duerden, L. (1993) Brodifacoum: Acute Oral Toxicity to the Rat: Lab Project Number:
CTL/P/3918: AR5481: DAC903-08/03. Unpublished study prepared by Zeneca Central
Toxicology Lab. 79 p.
43110501 Parr-Dobrzanski, R. (1993) Brodifacoum: 4-Hour Acute Inhalation Toxicity Study in the Rat:
Lab Project Number: CTL/P/4065. Unpublished study prepared by Zeneca Central Toxicology
Lab. 139 p.
44021701 Lees, D.; Leah, A. (1996) Brodifacoum Formulation Concentrate (0.25 % w/w): Acute Oral
Toxicity to the Rat: Lab Project Number: CTL/P/4672: AR5937. Unpublished study prepared
by Zeneca Central Toxicology Laboratory. 80 p.
44021702 Lees, D.; Leah, A. (1996) Brodifacoum Formulation Concentrate (0.25% w/w): Acute Dermal
Toxicity to the Rat: Lab Project Number: CTL/P/4653: CR3227. Unpublished study prepared
by Zeneca Central Toxicology Laboratory. 64 p.
44021703 Lees, D. (1996) Brodifacoum Formulation Concentrate (0.25% w/w); Skin Irritation to the
Rabbit: Lab Project Number: CTL/P/4617: EB4362. Unpublished study prepared by Zeneca
Central Toxicology Laboratory. 22 p.
44021705 Thomley, K. (1996) (Carbon 14)-Brodifacoum: Metabolism in the Rat: Lab Project Number:
88/126-1011: 88/126. Unpublished study prepared by Coming Hazleton (Europe). 162 p.
158
-------
BIBLIOGRAPHY
MRID
CITATION
Bromodiolone Bibliography
00088112 Shapko, R. (1977) Primary Skin Irritation: Bromadiolone: Report No. T-214. (Unpublished
study received June 20, 1978 under 7173169; prepared by Nutrition International, Inc.,
submitted by Chempar Chemical Co., Inc., New York, N.Y.; CDL:237470-A)
00088113 Shapiro, R. (1977) Eye Irritation: Bromadiolone: Report No. T215. (Unpublished study
received Jun 20, 1978 under 7173-169; prepared by Nutrition International, Inc., submitted by
Chempar Chemical Co., Inc., New York, N.Y.; CDL:237470-B) "
00107035 Shapko, R. (1978) Letter sent to S. Pitehon dated Aug 10, 1978 Teratology study with
bromadiolone technical, anticoagulant. (Unpublished study received Aug 29, 1978 under
7173-169; prepared by Nutrition International, Inc., submitted by Chempar Chemical Co., Inc.,
New York, NY; CDL:235046-A)
00161972 Spare, W. (1981) Leaching Characteristics of Aged Carbon 14-Bromadiolone: Project Number
00151. Unpublished Lipha Report No. 86-019 prepared by Biospherics Inc. 67 p.
00161973 Spare, W. (1980) Carbon 14-Bromadiolone Soil Leaching: Biospherics Project Number
80PL-80-L. Unpublished Lipha Report No. 86-020 prepared by Biospherics Inc. 70 p.
00161988 Spare, W. (1981) Carbon 14-Bromadiolone Soil Adsorption/DesorptionStudy: Project Number
80PL-81-AD. Unpublished Lipha Report No. 86-021 prepared by Biospherics Inc. 48 p.
41690802 Janeriat, Y.; Eavre, G.; Lechevin, J. (1990) Product Chemistry and Disclosure of Ingredients:
Bromadiolone Technical Grade. Unpublished study prepared by Lipha S. A. Ill p.
41717001 Hirfh, K. (1990) Product Identity and Composition of Technical Bromadiolone. Unpublished
study prepared by Bell Laboratories, Inc. 125 p.
41717002 Hirth, K. (1990) Analysis and Certification of Product Ingredients of Technical Bromadiolone.
Unpublished study prepared by Bell Laboratories, Inc. 144 p.
41847401 ' Kuktinski, M. (1990)'Skin Sensitization Test of Bromadiolone Technical Grade (...) in Albino
Guinea Pigs (Modified Buehler Test). Lab Project Number: 025-001. Unpublished study
prepared by Biologic Safety Research. 45 p.
41849601 Joers, D.; Marshall, E. (1991) Product Chemistry Maid Mini Block (0.005% Bromadiolone):
Lab Project Number: 91052: 91050: 91051. Unpublished study prepared by LiphaTech, Inc. 92
' -p- '''-' .-'.-.. '
41849601 , Joers, D.; Marshall, E. (1991) Product Chemistry Maki Mini Block (0.005% Bromadiolone):
Lab Project Number: 91052: 91050: 91051. Unpublished study prepared by LiphaTech, Inc. 92
P- ' : ' - ' .
159
-------
BIBLIOGRAPHY
MRID
CITATION
41884701 Janeriat, Y.; Favre, G.; Lechevin, J. (1990) Product Chemistry and Disclosure of Ingredients
Bromadiolone Technical Grade: Final Report. Unpublished study prepared by Lipha SA. 133 p.
41900001 Mally, Ch.; Porret-Blanc, G. (1987) LM637 (Bromadiolone) Determination of LD5Q of LM 637
Orally in Rats: Lab Project Number: 87.04 .LM 637 RPL. Unpublished study prepared by
Lipha Centre de Recherches. 83 p.
41976901 Holbert, M. (1991) Acute Inhalation Toxicity Study of Bromadiolone in Rats: Lab Project
Number: 7437-90. Unpublished study prepared by StiUmeadpw, Inc. 50 p.
42093301 Markiewicz, V. (1991) Antidotal Treatment Study Following Oral Exposure to Bromadiolone in
Rats: Lab Project Number: HWA 2624102. Unpublished study prepared by Hazleton
Washington, Inc. 233 p.
42237501 Spare, W. (1992) Hydrolysis of Bromadiolone: Lab Project Number: 1414. Unpublished study
prepared by Agrisearch Inc. 62 p.
42237501 Spare, W. (1992) Hydrolysis of Bromadiolone: Lab Project Number: 1414. Unpublished study
prepared by Agrisearch Inc. 62 p.
42395901 Pessehnan, R. (1992) Bromadiolone: Product Chemistry: Lab Project Number: 6001-604.
Unpublished study prepared by Hazleton Laboratories America, Inc. 279 p.
42395901 Pesselman, R. (1992) Bromadiolone: Product Chemistry: Lab Project Number: 6001-604.
Unpublished study prepared by Hazleton Laboratories America, Inc. 279 p.
42596801 Hawkins, D.; Brodie, R.; Clarke, D.; et aT. (1991) Determination of the Residues and the
Half-Life of the Rodenticides Brodifacoum, Bromadiolone, and Flocoumafen in the Livers of
Rats During 200 Days after a Single Oral Dose of Each at a Dose Level of 0.2 mg/kg: Lab
Project Number: HRC/LPA 158/891590. Unpublished study prepared by Huntingdon Research
Centre. 78 p.
42667801 Hake, R. (1993) Physical and Chemical Characteristics of Technical Bromadiolone: Series 63
(Stability): Lab Project Number: BEL/0692/C116. Unpublished study prepared by Bell Labs,
Inc. 51 p.
42667801 Hake, R. (1993) Physical and Chemical Characteristics of Technical Bromadiolone: Series 63
(Stability): Lab Project Number: BEL/0692/C116. Unpublished study prepared by Bell Labs,
Inc. 51 p.
42673701 Myers, R.; Christopher, S. (1993) Bromadiolone Technical: Acute Cutaneous Toxicity in the
Rabbit: Lab Project Number: 92N1112. Unpublished study prepared by Union Carbide
Chemicals (BRRC). 44 p.
43000702 Spare, W. (1993) Leaching Characteristics of Bromadiolone: Lab Project Number: 1422.
Unpublished study prepared by Agrisearch Inc. 123 p.
160
-------
BIBLIOGRAPHY
MRID CITATION
43594301 Misra, B. (1995) Aerobic Soil Metabolism of Bromadiolone: Amended Final Report: Lab Project
Number: ME 9200154. Unpublished study prepared by Pittsburgh Environmental Research Lab,
Inc. 106 p.
43594301 Misra, B. (1995) Aerobic Soil Metabolism of Bromadiolone: Amended Final Report: Lab Project
Number: ME 9200154. Unpublished study prepared by Pittsburgh Environmental Research Lab,
Inc. 106 p. ' . .
161
-------
BIBLIOGRAPHY
MRID
CITATION
Bromethalin Bibliography
42333401 Rose, J. (1992) Product Identity and Disclosure of Ingredients; Description of Beginning
Materials and Manufacturing Process: Bromethalin. Unpublished study prepared by Purina
Mills, Inc. 55 p.
42403001 Rose, J. (1992) Product Identity and Disclosure of Ingredients and Discussion of the Formation
of Impurities: Bromethalin. Unpublished study prepared by Purina Mills, Inc. 15 p.
42333401 Rose, J. (1992) Product Identity and Disclosure of Ingredients; Description of Beginning
Materials and Manufacturing Process: Bromethalin. Unpublished study prepared by Purina
Mills, Inc. 55 p.
42403001 Rose, J. (1992) Product Identity and Disclosure of ingredients and Discussion of the Formation
of Impurities: Bromethalin. Unpublished study prepared by Purina Mills, Inc. 15 p.
00086718 Koenig, D.K.; Loh, A.; Wilson, J.T.; et al. (1981) Test Article Characterization of Bromethalin:
Technical Lot B31-72C-18R. (Unpublished study received Oct 29, 1981 under 1471-121;
submitted by Blanco Products Co., Div. of Eli Lilly and Co., Indianapolis, Ind.;
CDL:246169-F)
41599601 Davis, M. (1990) Physical Characterization of Bromethalin: Final Report: Lab Project Number:
SC900029. Unpublished study prepared by Battelle. 13 p.
41599603 Davis, M. (1990) Determination of the n-Octanol/Water Partition Coefficient of Bromethalin:
Lab Project Number: SC900030. Unpublished study prepared by Battelle. 35 p.
00086741 Cochrane, R.L.; Kehr, C.C.; Van Lier, R.B.L.; etal. (1981) The. Toxicity of Bromethalin
(HU614, Compound 126714) to Bobwhite in a 14-day Acute Oral Study: Study A008-80.
(Unpublished study received Oct 29, 1981 under 1471-121; submitted by Blanco Products Co.,
Div. of Eli Lilly and Co., Indianapolis, Ind.; CDL: 246173-C)
00086745 Kehr, C.C.; Van Lier, R.B.L.; Jordan, W.H.; et al. (1981) The Toxicity of Bromethalin
(EL-614, Compound 126714) to Bobwhite in a Five-day Dietary Study: Study A007-80.
(Unpublished study received Oct 29, 1981 under 1471-121; submitted by Elanco Products Co.,
Div. of Eli Lilly and Co., Indianapolis, Ind.; CDL: 246173-G)
42733501 Conner, B.; Holmes, C.; Swigert, J. (1993) Bromethalin: A 96-Hour Flow-Through Acute
Toxicity Test with the Bluegill (Lepomis macrochirus): Final Report: Lab Project Number:
199A-102. Unpublished study prepared by Wildlife International Ltd. 43 p.
42733502 Conner, B.; Holmes, C.; Swigert, J. (1993) Bromethalin: A 96-Hour Flow-Through Acute
Toxicity Test with the Rainbow Trout (Oncorhynchus mykiss): Final Report: Lab Project
Number: 199A-103. Unpublished study prepared by Wildlife International Ltd. 45 p.
162
-------
BIBLIOGRAPHY
MRID
CITATION
00086751 Kehr, C.C.; Van Lier, R.B.L.; Brannon,;D.R:; et al. (1981) The Toxicity of Bromethalin
(EL-614, Compound 126714) to Bluegills in a 96-hour Static Test: Study F151-80.
(Unpublished study received Oct 29, 1981 under 1471-121; submitted by Blanco Products Co.,
Div. of Eli Lilly and Co., Indianapolis, Ind.; CDL: 246173-M)
42733503 Holmes, C.; Swigert, J. (1993) Bromethalin: A 48-Hour Flow-Through Acute Toxicity Test with
the Cladoceran (Daphnia magna): Final Report: Lab Project Number: 199A-101. UnpubUshed
study .prepared by Wildlife International Ltd. 46 p.
OJ0026524 Van Lier, R.B.L.; Arthur, B.H.'; Ansley, A.D.; et al. (1979) Acute Hazard Evaluation of
Compound 126714 Including Dermal, Ocular, and Inhalation Testing: Study Nos. B-D-59-77,
B-D-74-77, B-E-75-77, R-H-50-77, R-H-52-77, R-H-53-77, R-H-58-77, R-H-59-77,
R-H-64-77. (UnpubUshed study received Dec 13, 1979 under 1471-EX-72; submitted by Blanco
Products Co., Div. of Eli Lily and Co., Indianapolis, Ind.; CDL:241521-G)
41653001 Rock, G.; Sites, D.; Van Lier, R. (1990) A Guinea Pig Sensitization Study with Bromethalin
- . (Compound 12671): Lab Project Number: GOO390. UnpubUshed study prepared by Lilly
Research Labs. 39 p. '
00101543 Cochrane, R.; Kehr, C.; Van Lier, R.; et al. (1982) The Toxicity of Bromethalin (EL-614,
Compound 126714) to Hen Chickens in a 24-day Acute Oral Delayed Neurotoxicity Study: Study
A00981. (UnpubUshed study received Apr 29, 1982 under 1471-121; submitted by Blanco
Products Co., Div. of EU Lilly and Co., Indianapolis, IN; CDL:247447-B)
43582102 Monnot, G. (1987) 13-Week Oral Toxicity Study in the Rat: Bromethahn (CGA 175156): Lab
Project Number: 610209: 601326-D. UnpubUshed study prepared by Hazleton-Institut Francais
de Toxicologie. 277 p.
43582101 Monnot, G. (1987) 13-Week Oral Toxicity Study in the Beagle Dog: Bromethalin (CGA
175156): Lab Project Number: 610203: 601325-D. UnpubUshed study prepared by Hazleton-
Institut Francais de Toxicologie. 273 p.
42793101 ,_. Ponnock, K. (1993) An Acute Neurotoxicity Study of Bromethalin in the Rat Via Oral Gavage
Administration: Lab Project Number: 92-3807. UnpubUshed study prepared by Bio/dynamics,
Inc. 334 p.
00086731 . Miller, B.J.; Van Lier, R.B.L.; Owen, N.V.; et al. (1981) A Teratology Study with Bromethalin
(EL-614, 126714) in die Wistar Rat: Study R02181. (UnpubUshed study received Oct 29, 1981
under 1471-121; submitted by Blanco Products Co., Div. of EU Lilly and Co., Indianapolis,
Ind.; CDL:246172-1)
00101545 MiUer, B.; Van Lier, R.; Owen, N.; et al. (1982) A Teratology Study with Bromethahn
(EL-614, 126714) in the Dutch Belted Rabbit; Study B7141. (UnpubUshed study received Apr
29, 1982 under 1471-121; submitted by Blanco Products Co., Div. of EU LiUy and Co.,
. IndianapoUs, IN; CDL:247447-D) '
163
-------
BIBLIOGRAPHY
MRID CITATION
42438701 Fathulla, R. (1992) Hydrolysis of Ccarbon 141 -Bromethalin in Aqueous Buffer Solutions: Final
Report: Lab Project Number: HWI6416-100. Unpublished study prepared by Hazleton
Wisconsin, Inc. 68 p.
43007901 Fathulla, R. (1993) Aerobic Soil Metabolism of (carbon 14)-Bromeuialin: Final Report: Lab
Project Number: HWI 6416-102. Unpublished study prepared by Hazleton'Wisconsin, Inc. 98
P- .
164
-------
BIBLIOGRAPHY
MRID
CITATION
Chlorophacinone Bibliography
41922901 Labarthe, B. (1990) Chlorophacinone: Analytical Methods; Certification of Limits. Unpublished
.study prepared by LiphaS. A., Lyonnaise Indistrielle Pharamceutique. 26 p.
42237401 Pesselman, R.; Hoffman, M. (1992) Product Chemistry: Chlorophacinone Technical: Lab
Project Number: HLA 6001. Unpublished study prepared by Hazleton Wisconsin. 350 p.
41513101 Fletcher, D. ; Pedersen, C. (1989) Chlorophacinone: 30-Day Acute Oral LD50 Study in
Bobwhite Quail: Lab Project No: 87 QD 106. Unpubh'shed study prepared by Bio-Life
Associates, Ltd. 42 p. "
. 41513102 Fletcher, D.; Pedersen, C. (1989) Chlorophacinone: 30-Day Acute Dietary LG50 Study in
Bobwhite Quail: Lab Project No: 87 QC 105. Unpublished study prepared by Bio-Life
Associates, Ltd. 41 p. .'.--
41513103 Fletcher, D.; Pedersen, C. (1989) Chlorophacinone Primary Dermal Irritation Study: Lab Project
Number: 87 DC 103. UnpubUshed study prepared by Toxicon. 39 p.
42356102 , Machado, M. (1992) Chlorophacinone-Acute foxicity to Bluegill Sunfish (Lepomis
macrochirus) under Flow-through Conditions: Final Report: Lab Project Number: 92-1-4079:
11219.0891.6104.105. Unpubh'shed study prepared by Springborn Labs, Inc. 60 p.
42356103 Machado, M. (1992) .ChlorophacinoneAcute Toxicity to Rainbow Trout (oncorhynchus mykiss)
under Flow-through Conditions: Final Report: Lab Project Number: 91-12-4025: 11219.0891.
6103.108. Unpubh'shed study prepared by Springborn Labs, Inc. 58 p.
42356101 Putt, A. (1992) ChlorophacinoneAcute Toxicity to Daphnids (Daphnia magna) under
Flow-through Conditions: Final Report: Lab Project Number: 91-11-3998:
11219.0891.6105.115: 010190/FIFRA 72-2 DM. Unpublished study prepared by Springborn
Labs, Inc. 64 p. .. - .
41875301 Mally, C.; Porret-Blanc, Q. (1988) LX>50 Evaluation of Chlorophacinone in Solution in PEG
300 Orally to Rats: Lab Project Number: 88.02.LM.91.RP2. Unpublished study prepared by
Lipha Centre de Recherches. 75 p.
41702801 Lilja, H., (1990) Single Dose Dermal Toxicity Study (LD501): Chlorophacinone: Lab Project
Number: 89G-0146D. Unpublished study prepared by Toxikon Corp. 56 p.
41981102 Holbert, M. (1991) Acute Inhalation Toxicity Study of Technical Chlorphacinone in Rats: Lab
Project Number: 7436-90. Unpublished study prepared by Stillmeadow, Inc. 42 p.
41874001 Lilja, H. (1989) Chlorophacinone Primary Eye Irritation in the Rabbit: Lab Project Number:
89G-0148. Unpublished study prepared by Toxikon. 22 p.
165
-------
BIBLIOGRAPHY
MRID
CITATION
41702801 , Lilja, H. (1990) Single Dose Dermal Toxicity Study (LD501): Chlorophacinone: Lab Project
Number: 89G-0146D. Unpublished study prepared by Toxikon Corp. 56 p.
41578601 Shapiro, R. (1990) EPA Guinea Pig Sensitization (Buehler): Chlorophacinone, Technical Grade,
Lot #CLOM010: Lab Project I.D.: T-9990. Unpublished study prepared by Product Safety
Labs. 31 p.
42237402 Hamada, N. (1992) 21-Day Dermal Toxicity Study in Rabbits with Chlorophacinone: Final ,
Report: Lab Project Number: 2624-104,105, 106. Unpublished study prepared by Hazleton
Washington, Inc. 677 p.
43349501 Tyl, R.; Marr, M.; Myers, C. (1994) Developmental Toxicity Evaluation of Chlorophacinone
Administered by Gavage to CD (Sprague-Dawley) Rats: Final Report: Lab Project Number:
65C-5724-01/02: RTI-476: RT93-CPN. Unpublished study prepared by Research Triangle
Institute. 229 p.
43570801 Tyl, R.; Marr, M.; Myers, C. (1995) Developmental Toxicity Evaluation of Chlorophacinone
Administered by Gavage to New Zealand White Rabbits: Final Report: Lab Project Number:
65C-5724-03/04. Unpublished study prepared by Research Triangle Institute. 200 p.
00155540 Belleville, M. (1981) Absorption, Distribution, Metabolism and Excretion Studies in the Rat
Using Carbon-14-Labeled Chlorophacihone: Lipha Report No. 86-001. Unpublished study
prepared by Lipha Research Center. 16 p. ,
41981101 Markiewicz, V. (1991) Antidotal Treatment Study Following Oral Exposure to Chlorphacinone
in Rats: Lab Project Number: 2624103. Unpublished study prepared by Hazleton Washington,
lac. 219 p.
42205501 Spare, W. (1992) Hydrolysis of Chlorphacinone: Lab Project Number: 1415. Unpublished study
prepared by Agrisearch Inc. 76 p^ ,
42452301 Spare, W. (1992) Soil Photolysis of Chlorophacinone: Lab Project Number: 1418. Unpublished
study prepared by Agrisearch Inc,. 98 p.
43159801 Spare, W. (1994) Aerobic Soil Metabolism of Chlorophacinone: Lab Project Number: 1419:
1419R. Unpublished study prepared by Agrisearch Inc. 151 p.
42760902 Marsh, R.; Howard, W. (1986) Ground Squirrel-Coyote Secondary Toxicity Studies with
Chlorophacinone and Bromadiolone (An Administrative Report of Laboratory Findings).
Unpublished study prepared by University of California, Wildlife and Fisheries Biology Lab. 67
p.
166
-------
BIBLIOGRAPHY
MRID
CITATION
00060605
00074637
00077319
00134837 '
41612801
41612802
41727801
41727802
41727803
42035001
42132501
Diphacinone Bibliography
GoldenthaL E.I.;- Wazeter, F.X.; Dean, W.P. (1975) Acute Toxicity Studies in Rats and Rabbits:
IRDC No. 163-349. (Unpublished study received Aug 21, 1978 under 876-EX-36; prepared by
International Research and Development Corp., submitted by Velsicol Chemical Corp., Chicago
I11.;CDL:234818-I)
Laveglia, J.; Myer, J.R.; Peel, B.; etal. (1981) 21-day Dermal Toxicity Study in Rabbits: IRDC
No. 163-678. (Unpublished study received May 22, 1981 under 876-124; prepared by
International Research and Development Corp., submitted by Velsicol Chemical Corp., Chicago
HI.; CDL:245264-A)
Hashmi, A.W.; Jackson, W.B.; Ashton, A.D. (1978?) Studies on the Toxicity and
Teratogenicity of Diphacinone (2-Diphenyl-acetyl-l,3,-indandione) in Swiss Webster Mice.
(Unpublished study received Jun 10, 1980 under 12455-29; prepared by Bowling Green State
Univ., Environmental Studies Center, submitted by Bell Laboratories, Madison, Wis
CDL:243774-A) .
Velsicol Chemical, Corp. (1978) Chemical & Physical Properties: Diphacinone. (Compilation;
unpublished study received Jul 12, 1978 under 876-EX-35; CDL:234419-A)
Hirth, K. (1990) Product Identity and Composition of Technical Diphacinone. Unpublished
study prepared by Bell Laboratories, Inc. 92 p.
Hirth, K. (1990) Analysis and Certification of'Product Ingredients of Technical Diphacinon.
Unpublished study prepared by Bell Laboratories, Inc. 52 p:
Hirth, K. (1990) Product Identity and Composition of Technical Diphacinone. Unpublished
study prepared by Laboratories, Inc. 96 p.
Hirth, K. (1990) Analysis and Certification of Product Ingredients of Technical Diphacinone.
Unpublished study prepared by Bell Laboratories, Inc. 52 p.
Hirth, K. (1990) Physical and Chemical Characteristics of Technical Diphacinone. Unpublished
study prepared by Bell Laboratories, Inc. 83 p.
Nomura, N.; Hilton, H. (1979) The Metabolism of CCarbon 14-Diphacinone to Carbon Dioxide
in Two Hawaiian Sugarcane Soils Under Aerobic conditions. Unpublished study prepared by
Hawaiian Sugar Planters. 27 p.
Bier, C.; Oliviera, P. (1980) Acute Dermal Sensitization in Guinea Pigs Administered Test
Article Diphacinone: Project 9324 and Excretion and Retention of Carbon-14-Diphacinone in
Rats. . . Velsicol Project Number 9324. Corrected report, including Phase 3 summary by J.
Kelley dated 1990 (92049007). Unpublished study prepared by Velsicol Chemical Co. 39 p.
167
-------
BIBLIOGRAPHY
MRID
CITATION
42136001 Lechnir,_R.; Schroeder, C. (1991) Diphacinone: Product Composition, Description of Beginning
Materials, Manufacturing Process and Impurities: Lab Project Number: DS 9002-S(A).
Unpublished study prepared by Derse & Schroeder Assocs., Ltd. 61 p.
* r ' i
42136002 Vielhuber, S. (1991) Analysis of Technical Diphacinone for Diphacinone and Impurities: Lab
Project Number: DS-9002-S(B). Unpublished study prepared by Derse & Schroeder Assocs.,
Ltd. 173 p.
42136003 Lechnir, R.; Viehlhuber, S. (1991) Diphacinone-StabiUty of Test Substance: Lab Project
Number: DS 9002-S(C). Unpublished study prepared by Derse & Schroeder Assocs., Ltd. 72
P-
42245201 Campbell, S.; Hoxter, K.; Smith, G. (1991) Diphacinone Technical: An Acute Oral Toxicity
Study with the Northern Bobwhite: Lab Project Number: 284-103'. Unpublished study prepared
by Wildlife International Ltd. 24 p.
42245202 Shapiro, R. (1990) EPA Acute Oral Toxicity-Defined LD50: Diphacinone Technical, Batch
#T-988: Lab Project Number: T-9687. Unpublished study prepared by Product Safety Labs. 39
P-
42245203 Shapiro, R. (1990) EPA Primary Eye Irritation Test: Diphacinone Technical, Batch #T-988: Lab
Project Number: T-9688. Unpublished study prepared by Product Safety Labs. 20 p.
42282201 Putt, A. (1992) Diphacinone Technical: Acute Toxicity to Daphnids (Daphnia magna) under
Flow-through Conditions: Lab Project Number: 91-9-3938: 12455. 1290. 6100. 115: 90-10A.
Unpublished study prepared by Springborn Labs, Lac. 66 p.
42360601 Douglas, M.; Thompson, J. (1992) DiphacinoheProduct Composition, Chemical Identity and
Discussion of Impurities: Lab Project Number: AL92-09. Unpublished study prepared by
Hacco, Inc. 10 p.
42406801 SanSebastian, J. (1992) In vivo Micronucleus Test with Diphacinone in Mouse Bone Marrow
Erythropoietic Cells: Lab Project Number: PH 309-HA-001-91. Unpublished study prepared by
Pharmakon Research International, Inc. 133 p.
42408801 Long, R.; Foster, J.; Hoxter, K. et al. (1992) Diphacinone Technical: A Dietary LC50 Study
with the Northern Bobwhite: Lab Project Number: 284-101 A. Unpublished study prepared by
Bell Labs, Inc. 32 p.
42408802 Long, R.; Foster, J.; Hoxter, K. et al. (1992) Diphacinone Technical: A Dietary LC50 Study
with the Mallard: Lab Project Number: 284-102B. Unpublished study prepared by Wildlife Intl.
36 p.
42507001 FitzGerald, G. (1992) Acute Dermal Study: Diphacinone Technical: Lab Project Number:
92G-0268. Unpublished study prepared by Toxikon Corp. 22 p.
168
-------
BIBLIOGRAPHY
MRID
CITATION
42834801 Daniel, E. (1993) An Oral Teratology Study in Rats with Technical Diphacinone: Final Report:
Lab Project Number: 3284.3. Unpublished study prepared by Springbom Labs, Lac. 320 p.
43000401 Rush, R. (1993) An Acute Whole-Body Inhalation Toxicity Study in Rats with Technical
Diphacinone: Final Report: Lab Project Number: 3284.4. Unpublished study prepared by
Springbom Laboratories, Inc. 79 p. .
43249501 Machado, M.W. 1994. Diphacinone, sodium salt-prolonged acute toxicity to bluegill sunfish
(Lepomis macrochirus) under flow-through conditions. Conducted by Springbom Laboratories,
Inc., 'Wareham, MA. SLI Report # 94-3-5191. Submitted by HACCO, Inc., Madison, WI
43249502 Machado, M.W. 1994. Diphacinone, sodium salt - prolonged acute toxicity to rainbow trout
(Oncorhynchus myMss) under flow-through conditions. Conducted by Springbom Laboratories,
Inc., Wareham, MA. SLI Report #94-3-5216. Submitted by HACCO, Inc., Madison, WI
43260701 . Rogers, A. (1994) A 14-Day Oral Toxicity Evaluation of Technical Diphacinone in Young Adult
Sprague Dawley Rats: Lab Project Number: 100-056: 6141-101. Unpublished study prepared by
Bell Labs., Inc. 331 p.
43582401 Riekena, C. (1995) Hydrolysis of Technical Diphacinone
(2-(Diphenylacetyl)-lH-indene-l,3(2H)-dione): Lab Project Number: BEL/0894/C143.
Unpublished study prepared by Bell Labs, Inc. 40 p.
169
-------
170
-------
\ _
' UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
. AND TOXIC SUBSTANCES
GENERIC DATA CALL-IN NOTICE
CERTIFIED MAIL
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the
active ingredient(s) identified in Attachment 1 of this Notice, the Data Call-in Chemical Status
Sheet, to submit certain data as noted herein to the U.S. Environmental Protection Agency
(EPA, the Agency). These data are necessary to maintain the continued registration of your .
product(s) containing this active ingredient(s). Within ,90 days.after you receive this Notice
you must respond as set forth in Section HI below. Your response must state:
1 . . how you will comply with the requirements set forth in this Notice and its Attachments
1 through 4; or, , '
2. why you believe you are exempt from the requirements listed in this Notice and in
Attachment 3, Requirements Status and Registrant's Response Form, (see section TTT-
3. L why you believe EPA should not require your submission of data in the manner
specified by this Notice (see section ni-D).
, If you do not. respond to this Notice, or if you do not satisfy EPA that you will comply
with its requirements or should be exempt or excused from doing so, then the registration of
your product(s) subject to this Notice will be subject to suspension. We have provided a list
of all of your products subject to this Notice in Attachment 2, Data Call-In Response Form, as
well as a list of all registrants who were sent this Notice (Attachment 4).
- '171 , '
-------
The authority for this Notice is section 3(c)(2)(B) of the Federal Insecticide" Fungicide
and Rodenticide Act as amended (FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
information is authorized under the Paperwork Reduction Act by OMB Approval No.
2070-0107 and 2070-0057 (expiration date 3-31-99).
This Notice is divided into six sections and five Attachments. The Notice itself contains
information and instructions applicable to all Data Call-in Notices. The Attachments contain
specific chemical information and instructions. The six sections of the Notice are:
Section I - Why You Are Receiving This Notice
Section II - Data Required By This Notice
Section HI ' - Compliance With .Requirements Of This Notice
Section IV - Consequences Of Failure To Comply With This Notice
Section V - Registrants' Obligation To Report Possible Unreasonable
Adverse Effects
Section VI - Inquiries And Responses To This Notice
*
The Attachments to this Notice are:
Attachment 1 - Data Call-In Chemical Status Sheet
Attachment 2 - Data Call-In Response Form
Attachment 3 - Requirements Status And Registrant's Response Form
Attachment 4 - List Of All Registrants Sent This Data Call-in Notice
SECTION! WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient(s) and reevaluated the
data needed to support continued registration of the subject active ingredient(s). This
reevaluation identified additional data necessary to assess the health and safety of the continued
use of products containing this active ingredient(s). You have been sent this Notice because
you have produces) containing the subject active ingredient(s).
SECTION n. DATA REQUIRED BY THIS NOTICE
A. DATA REQUIRED
The data required by this Notice are specified in Attachment 3, Requirements
Status and Registrant's Response Form. Depending on the results of the studies
required in this Notice, additional testing may be required.
B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements
specified in Attachment 3, Requirements Status and Registrant's Response Form.
within the time frames provided.
172
-------
C.. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance With test
standards outlined in the Pesticide Assessment Guidelines for those studies for which
guidelines have been established.
These EPA Guidelines are available from the National Technical Information
Service (NTIS), Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (tel:
703-487-4650).
Protocols approved by the Organization for Economic Cooperation and
Development (OECD) are also acceptable if the OECD-recommended test standards
conform to those specified in the Pesticide Data Requirements regulation (40 CFR ง
158.70). When using the OECD protocols, they should be modified as appropriate so
that the data generated by the study will satisfy the requirements of 40 CFR ง 158.
Normally, the Agency will not extend deadlines for complying with data requirements
when the studies were not conducted in accordance with acceptable standards. The
OECD protocols are available from 2001 L Street, N.W., .Washington, D.C. 20036
(Telephone number 202-785-6323; Fax telephone number 202-785-0350).
- All new studies and proposed protocols submitted in response to this Data Call-
in Notice must be in accordance with Good Laboratory Practices [40 CFR Part
160.3(a)(6)]. -
D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(&(ZtfS) NOTICES
ISSUED BY THE AGENCY :
' .- ^ " *
Unless otherwise noted herein, this Data Call-in does not in any way supersede
or change the requirements of any previous Data Gall-In(s). or any other agreements.
entered into with the Agency pertaining to such prior Notice. Registrants must comply
with the requirements of all Notices to avoid issuance of a Notice of Intent to Suspend
their affected products.
SECTION IE. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice must be submitted to
the Agency within 90 days after your receipt of this Notice. Failure to adequately
respond to this Notice within 90 days of your receipt will be a basis for issuing a
Notice of Intent to Suspend (NOIS) affecting your products. This and other bases for
issuance of NOIS due to failure to comply with this Notice are presented in Section IV-
A and IV-B. ' . _
173
-------
B. OPTIONS FOR RESPONDING TO THE AGENCY
The options for responding to this Notice are: 1) voluntary cancellation, 2)
delete use(s), (3) claim generic data exemption, (4) agree to satisfy the data
requirements imposed by this Notice or (5) request a data waiver(s).
A discussion of how to respond if you chose the Voluntary Cancellation option,
the Delete Use(s) option or the Generic Data Exemption option is presented below. A
discussion of the various options available for satisfying the data requirements of this
Notice is contained in Section ]H-C. A discussion of options relating to requests for
data waivers is contained in Section ffl-D.
There are two forms that accompany this Notice of which, depending upon your
response, one or both must be used in your response to the Agency. These forms are
the Data-Call-in Response Form (Attachment 2) and the Requirements Status and
Registrant's Response Form (Attachment 3). The Data Call-In Response Form must be
submitted as part of every response to this Notice. Please note that the company's
authorized representative is required to sign the first page of the Data Call-in Response
EPJOH and Requirements Status and Registrant's Response Form (if this form is
required) and initial any subsequent pages. The forms contain separate detailed
instructions on the response options. Do not alter the printed material. If you have
questions or need assistance in preparing your,response, call or write the contact
person identified in Attachment 1.
1; Voluntary Cancellation - You may avoid the requirements of this-Notice
by requesting voluntary cancellation of your product(s) containing the active
ingredient(s) that is the subject of this Notice. If you wish to voluntarily cancel
your product, you must submit a completed Data Call-In Response Form.
indicating your election of this option. Voluntary cancellation is item number 5
on the Data Call-In Response Form. If you choose this option, this is the only
form that you are required to complete.
If you choose to voluntarily cancel your product, further sale and
distribution of your product after the effective date of cancellation must be in
accordance with the Existing Stocks provisions of this Notice which are
contained in Section IV-C. ,
2. Use Deletion - You may avoid the requirements of this Notice by
eliminating the uses of your product to which the requirements apply. If you
wish to amend your registration to delete uses, you must submit the
Requirements Status and Registrant's Response Form, a completed application
for amendment, a copy of your proposed amended labeling, and all other
information required for processing the application. Use deletion is option
174
-------
number 7 on the Requirements Status and Registrant's Response Form. You
must also complete a Data .Gall-In Response Form by signing the certification,
item number 8.- Application forms for amending registrations may be obtained
from the Registration Support and Emergency Response Branch, Registration
. Division, (703) 308-8358.
If you choose to delete the use(s) subject to this Notice or uses subject to
specific data requirements, further sale, distribution, or use of your product
after one year from the due date of your 90 day response, must bear an
amended label.
3. Generic Data Exemption - Under section 3(c)(2)(D) of FIFRA, an
applicant for registration of a product is exempt from the requirement to submit
or cite generic data concerning an active ingredient(s) if the active ingredient(s)
in the product is derived exclusively from purchased, registered.pesticide
products containing the active ingredient(s), EPA has concluded, as an exercise
of its discretion, that it normally will not suspend the registration of a product
which would qualify and continue to qualify for the generic data exemption in
section 3(c)(2)(D) of FIFRA. To qualify, all of the following requirements
must be met:
a. The active ingredient(s) in your registered product must be
present solely because of incorporation of another registered product
which contains the subject active ingredient(s) and is purchased from a
source not connected with you; and,
b. every registrant who is the ultimate source of the active
ingredient(s) in your product subject to this DCI must be in compliance
, with the requirements of this Notice and must remain in compliance; and
c. you must have provided to EPA an accurate and current
"Confidential Statement of Formula" for each of your products to which
this Notice applies.
To apply for the Generic Data Exemption you must submit a completed
Data Call-in Response Form. Attachment 2 and all supporting documentation.
The Generic Data Exemption is item, number 6a on the Data Call-in Response
Form. If you claim a generic data exemption you are not required to complete
the Requirements Status and Registrant's Response Form. Generic Data
Exemption cannot be selected as an option for product specific data.
If you are granted a Generic Data Exemption, you rely on the efforts of
other persons to provide the Agency with the required data. If the registrant(s)
who have committed to generate and submit the required data fail to take
175
-------
appropriate steps to meet the requirements or are no longer in compliance with
this Data Call-In Notice, the Agency will consider that both they and you are
not in compliance and will normally initiate proceedings to suspend the
registrations of both your and their product(s), unless you commit to submit and
do submit the required data within the specified time. In such cases the Agency
generally will not grant a time extension for submitting the data.
4. Satisfying the Data Requirements of this Notice - There are various
options available to satisfy the data requirements of this Notice. These options
are discussed in Section ni-C of this Notice and comprise options 1 through 6
on the Requirements Status and Registrant's Response Form and option 6b and
7 on the Data Call-In Response Form. If you choose option 6b or 7, you must
submit both forms as well as any other information/data pertaining to the option
chosen to address the data requirement.
5. Request for Data Waivers. Data waivers are discussed in Section ffl-D
of this Notice and are covered by options 8 and 9 on the Requirements Status
and Registrant's Response Form. If you choose one of these options, you must
submit both forms as well as any other information/data pertaining to the option
chosen to address the data requirement.
C. SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call-in Response Form that you agree to satisfy
the data requirements (i.e. you select option 6b and/or 7), then you must select one of
the six options on the Requirements Status and Registrant's Response Form related to
data production for each data requirement. Your option selection should be entered
under item number 9, "Registrant Response." The six options related to data
production are the first six options discussed under item 9 in the instructions for
completing the Requirements Status and Registrant's Response Form. These six
options are listed immediately below with information in parentheses to guide
registrants to additional instructions provided in this Section. The options are:
1: I will generate and submit data within the specified time frame
(Developing Data),
2. I have entered into an agreement with one or more registrants to develop
data jointly (Cost Sharing),
3. I have made offers to cost-share (Offers to Cost Share),
4. I am submitting an existing study that has not been submitted previously
to the Agency by anyone (Submitting an Existing Study),
5. I am submitting or citing data to upgrade a study classified by EPA as
partially acceptable and upgradeable (Upgrading a Study),
176
-------
6. I am citing an existing study that EPA has classified as acceptable or an
existing study that has been submitted but not reviewed by. the Agency
(Citing an Existing Study).
Option 1. Developing Data , ;
If you choose to develop the required data it must be in conformance
with Agency deadlines and with other Agency requirements as referenced
herein and in the attachments. All data generated and submitted must comply.
.with the Good Laboratory Practice (GLP) rule (40 CFR Part 160), be
conducted according to the Pesticide Assessment Guidelines (PAG), and be in
conformance with the requirements of PR Notice 86-5. In addition, certain
studies require Agency approval of test protocols in advance of study initiation.
Those studies for which a protocol must be submitted have been identified in
the Requirements Status and Registrant's Response Form and/or footnotes to the
form. If you wish to use a protocol which differs from the options discussed in
Section H-C of this Notice, you must submit a detailed description of the
proposed protocol and your reason for wishing to use it. The Agency may
choose to reject a protocol not specified in Section n-C. If the Agency rejects
your protocol you will be notified in writing, however, you should be aware
that rejection of a proposed protocol will not be a basis for extending the
deadline for submission of data.
A progress report must be submitted for each study within 90 days from
the date you are required to commit to generate or undertake some other means
to address that study requirement, such as making an offer to cost-share or
agreeing to share in the cost of developing that study. A 90-day progress report.
must be submitted for all studies. This 90-day progress report must include the
date the. study was or will be initiated and, for studies to be started within 12
months of commitment, the name and address of the laboratories) or
individuals who are or will be conducting the study.
In addition, if the time frame for submission of a final report is more
than 1 year, interim reports must be submitted at 12 month intervals from the
date you are required to commit to generate or otherwise address the
requirement for the study. In addition to the other information specified in the
preceding paragraph, at a minimum, a brief description of current activity on
and the status of the study must be included as well as a full description of any
problems encountered since the last progress report.
The time frames in the Requirements Status and Registrant's Response
Form" are the time frames that the Agency is allowing for the submission of
completed study reports or protocols. The noted deadlines run from the date of
the receipt of this Notice by the registrant. If the data are not submitted by the
deadline, each registrant is subject to receipt of a Notice of Intent to Suspend
the affected registration(s). . . '
177 .
-------
If you cannot submit the data/reports to the Agency in the time required
by this Notice and intend to seek additional time to meet the requirement(s),
you must submit a request to the Agency which includes: (1) a detailed
description of the expected difficulty and (2) a proposed schedule including
alternative dates for meeting such requirements on a step-by-step basis. You
must explain any technical or laboratory difficulties and provide documentation
from the laboratory performing the testing. While EPA is considering your
request, the original deadline remains. The Agency will respond to your
request in writing. If EPA does not grant your request, the original deadline
remains. Normally, extensions can be requested only in cases of extraordinary
testing problems beyond the expectation or control of the registrant. Extensions
"will not be given in submitting the 90-day responses. Extensions will not be
considered if the request for extension is not made in a timely fashion; in no
event shall an extension request be considered if it is submitted at or after the
lapse of the subject deadline.
Option 2. Agreement to Share in Cost to Develop Data ~
If you choose to enter into an agreement to share in the cost of
producing the required data but will not be submitting the data yourself, you
must provide the name of the registrant who will be submitting the data. You
must also provide EPA with documentary evidence that an agreement has been
formed. Such evidence may be your letter offering to join in an agreement and
the other registrant's acceptance of your offer, or a written statement by the
parties that an agreement exists. The agreement to produce the data need not
specify all of the terms of the final arrangement between the parties or the
mechanism to resolve the terms. Section 3(c)(2)(B) provides that if the parties
cannot resolve the terms of the agreement they may resolve their differences
through binding arbitration.
Option 3. Offer to Share in the Cost of Data Development
If you have made an offer to pay in an attempt to enter into an
agreement or amend an existing agreement to meet the requirements of this
Notice and have been unsuccessful, you may request EPA (by selecting this
option) to exercise its discretion not to suspend your registration(s), although
you do not comply with the data submission requirements of this Notice. EPA
has determined that as a general policy, absent other relevant considerations, it
will not suspend the registration of a product of a registrant who has in good
faith sought and continues to seek to enter into a joint data development/cost
sharing program, but the other registrant(s) developing the data has refused to
accept your offer. To qualify for this option, you must submit documentation
to the Agency proving that you have made an offer to another registrant (who
has an obligation to submit data) to share in the burden of developing that data.
178
-------
You must also submit to the Agency a completed EPA Form 8570-32,
Certification of Offer to Cpst Share in the Development of Data. In addition,
you must demonstrate that the other registrant to whom the offer was made has
not accepted your offer to enter into a cost sharing agreement by including a
copy of your offer and proof of the other registrant's receipt of that offer (such
as a certified mail receipt). Your offer must, in addition to anything else, offer
to share in the burden of producing the data upon terms to be agreed or failing .
agreement to be bound by binding arbitration as provided by FIFRA section
3(c)(2)(B)(iii) and must not qualify this offer. The other registrant must also
inform EPA of its election of an option to develop and submit the data required
by this Notice by submitting a Data Call-in Response Form and a Requirements
Status and Registrant's Response Form committing to develop and submit the
data'required by this Notice.
In order for you to avoid suspension under this option, you may not
withdraw your offer to share in the burdens of developing the data. In addition,
the other registrant must fulfill its commitment to develop and submit the data
as required by this Notice. If the other registrant fails to develop the data or for
some other reason is subject to suspension, your registration as well as that of
the other registrant will normally be subject to initiation of suspension
proceedings, unless you commit to submit, and do submit the required data in
the specified time frame. In such cases, the Agency generally will not grant a
time extension for submitting the data. ,
Option 4. Submitting an Existing Study
If you choose to submit an existing study in response to this Notice, you
must determine that the study satisfies the requirements imposed by this Notice.
You may only submit a study that has not been previously submitted to the
Agency or previously cited by anyone. Existing studies are studies which
predate issuance of this Notice. Do not use this option if you are submitting
data to upgrade a study. (See Option 5).
You should be aware that if the Agency determines mat the study is not
acceptable, the Agency will require you to comply with this Notice, normally
without an extension of the required date of submission. The Agency may
determine at any time that a study is not valid and needs to be repeated.
To meet the requirements of the DCI Notice for submitting an existing
study, all of the following three criteria must be clearly met:
a. You must certify at the time that the existing study is submitted
that the raw data and specimens from the study are available for audit
and review and you must identify where they are available. This must
179
-------
be done in accordance with the requirements of the Good Laboratory
Practice (GLP) regulation, 40 CFR Part 160. As stated in 40 CFR
160.3(7) " raw data means any laboratory worksheets, records,
memoranda, notes, or exact copies thereof, that are the result of original
observations and activities of a study and are necessary for the
reconstruction and evaluation of the report of that study. In the event
that exact transcripts of raw data have been prepared (e.g., tapes which
have been transcribed verbatim, dated, and verified accurate by
signature), the exact copy or exact transcript may be substituted for the
original source as raw data. Raw data may include photographs,
microfilm or microfiche copies, computer printouts, magnetic media,
including dictated observations, and recorded data from automated
instruments." The term "specimens", according to 40 CFR 160.3(7),
means "any material derived from a test system for examination or
analysis."
b. Health and safety studies completed after May 1984 must also
contain all GLP-required quality assurance and quality control
information, pursuant to the requirements of 40 CFR Part 160.
Registrants must also certify at the time of submitting the existing study
that such GLP information is available for post-May 1984 studies by
including an appropriate statement on or attached to the study signed by
an authorized official or representative of the registrant.
c. You must certify that each study fulfills the acceptance criteria
for the Guideline relevant to the study provided in the FIFRA
Accelerated Reregistration Phase 3 Technical Guidance and that the
study has been conducted accordingjo the Pesticide Assessment
Guidelines (PAG) or meets the purpose of the PAG (both available from
NTIS). A study not. conducted according to the PAG may be submitted
to the Agency for consideration if the registrant believes that the study
clearly meets the purpose of the PAG. The registrant is referred to 40
CFR 158.70 which states the Agency's policy regarding acceptable
protocols. If you wish to submit the study, you must, in addition to
certifying, that the purposes of the PAG are met by the study, clearly
articulate the rationale why you believe the study meets the purpose of
the PAG, including copies of any supporting information or data. It has
been the Agency's experience that studies completed prior to January
1970 rarely satisfied the purpose of the PAG and that necessary raw data
are usually not available for such studies.
If you submit an existing study, you must certify that the study
meets all requirements of the criteria outlined above.
180
-------
If EPA has previously reviewed a protocol for a study you are
submitting, you must identify any action taken by the Agency on the
protocol and must indicate, as part of your certification, the manner in
which all Agency comments, concerns, or issues were addressed in the
final protocol and study. '
If you know of a study pertaining to any requirement in this
Notice which does not meet the criteria outlined above but does contain
factual information regarding unreasonable adverse effects, you must
notify the Agency of such a study. If such a study is in the Agency's
files, you need only cite it along with the notification. If not in the
Agency's files, you must submit a summary and copies as required by
PR Notice 86-5,
Option 5. Upgrading a Study
If a study has been classified as partially acceptable and upgradeable,
you may submit data to upgrade that study. The Agency will review the data
submitted and determine if the requirement is satisfied. If the Agency decides
the requirement is not satisfied, you may still be required to submit new data
normally without any time extension. Deficient, but upgradeable studies will
normally be classified as supplemental. However, it is important to note that
not all studies classified as supplemental are upgradeable. If you have questions
regarding the classification of a study or whether a study may be upgraded, call
or write the contact person listed in Attachment 1. If you submit data to
upgrade an existing study you must satisfy or supply information to correct all
deficiencies in the study identified by EPA. You must provide a clearly
articulated rationale of how the deficiencies have been remedied or corrected
and why the study should be rated as acceptable to EPA. Your submission must
also specify the MRID number(s) of the study which you are attempting to
upgrade and must be in conformance with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a. study
classified as unacceptable and determined by the Agency as not capable of being
upgraded. - - .
This option should also be used to cite data that has been previously
submitted to upgrade a study, but has not yet been reviewed by the Agency.
You must provide the MRID number of the data submission as well as the
MRID number of the study being upgraded.
The criteria for submitting an existing study, as specified in Option 4
above, apply to all data submissions intended to upgrade studies. Additionally
your submission of data intended to upgrade studies must be accompanied by a
181
-------
certification that you comply with each of those criteria as well as a certification
regarding protocol compliance with Agency requirements.
Option 6. Citing Existing Studies
If you choose to cite a study that has been previously submitted to EPA,
that study must have been previously classified by EPA as acceptable or it must
be a study which has not yet been reviewed by the Agency. Acceptable
toxicology studies generally will have been classified as "core-guideline" or
"core minimum." For ecological effects studies, the classification generally
would be a rating of "core." For all other disciplines the classification would
be "acceptable." With respect to any studies for which you wish to select this
option you must provide the MRID number of the study you are citing and, if
the study has been reviewed by the Agency, you must provide the Agency's
classification of the study.
If you are citing a study of which you are not the original data
submitter, you must submit a completed copy of EPA Forms 8570-34 and 8570-
35, Certification with Respect to Citation of Data, and Data Matrix.
D- REQUESTS FOR DATA WAIVERS
* , ป '
There are two types of data waiver responses to this Notice. The first is a
request for a low volume/minor use waiver and the second is a waiver request based on
your belief that the data requirement(s) are inapplicable and do not apply to your
product.
1. . Low Volume/Minor Use Waiver Option 8 on the Requirements Status
and Registrant's Response Form. Section 3(c)(2)(A) of FIFRA requires EPA to
consider the appropriateness of requiring data for low volume, minor use
pesticides. In implementing this provision EPA considers as low volume
pesticides only those active ingredient(s) whose total production volume for all
pesticide registrants is small. In determining whether to grant a low volume,
minor use waiver the Agency will consider the extent, pattern and volume of
use, the economic incentive to conduct the testing, the importance of the
pesticide, and the exposure and risk from use of the pesticide. If an active
ingredient(s) is used for both high volume and low volume uses, a low volume
exemption will not be approved. If alTuses of an active ingredient(s) are low
volume and the combined volumes for all uses are also low, then an exemption
may be granted, depending on review of other information outlined below. An
exemption wiU not be granted if any registrant of the active ingredient(s) elects
to conduct the testing. Any registrant receiving a low volume minor use waiver
must remain within the sales figures in their forecast supporting title waiver -
request in order to remain qualified for such waiver. If granted a waiver, a
registrant will.be required, as a condition of the waiver, to submit annual sales
reports. The Agency will respond to requests for waivers in writing.
.182
-------
, To apply for a low volume, minor use waiver, you must submit the
following information, as applicable to your product(s), as part of your 90-day
response to this Notice: ' ,.
a. Total company sales (pounds and dollars) of all registered
product(s) containing the active ingredient(s). If applicable to the active
irigredient(s), include foreign sales for those products that are not
registered in this country but are applied to sugar (cane or beet), coffee,
bananas, cocoa, and other such crops. Present the above information by
year for each of the past five years.
b. Provide an estimate of the sales, (pounds and dollars) of the active
ingredient(s) for each major use site. Present the above information by
year for each of the past five years. '
c. Total direct production cost of product(s) containing the active
ingredient(s) by year for the past five years. Include information on raw
material cost, direct labor cost, advertising, sales and marketing^ and
any other significant costs listed separately.
d. Total indirect production cost (e.g. plant overhead, amortized
plant and equipment) charged to product(s) containing the active
ingredient(s) by year for the past five years. Exclude all non-recurring
costs that were directly related to the active ingredient(s), such as costs
of initial registration and any data development.
e. A list of each data requirement for which you seek a waiver.
Indicate the type of waiver sought and the estimated cost to you (listed
separately for each data requirement and associated test) of conducting
the testing needed to fulfill each of these data requirements. -.
f. A list of each data requirement for which you are not seeking any
waiver and the estimated cost to.you (listed separately for.each data
requirement and associated test) of conducting the testing needed to
fulfill each of these data requirements.
g. For each of the next ten years, a year-by-year forecast of
company sales (pounds and dollars) of the active ingredient(s), direct
production costs of product(s) containing the active ingredient(s)
(following the parameters in item c above), indirect production costs of
product(s) containing the active ingredient(s) (following the parameters
in item d above), and costs of data development pertaining,to the active -,
ingredient(s).
183
-------
h. A description of the importance and unique benefits of the active
ingredient(s) to users. Discuss the use patterns and the effectiveness of
the active ingredient(s) relative to registered alternative chemicals and
non-chemical control strategies. Focus on benefits unique to the active
ingredient(s), providing information that is as quantitative as possible.
If you do not have quantitative data upon which to base your estimates,
then present the reasoning used to derive your estimates. To assist the
Agency in determining the degree of importance of the active
ingredient(s) in terms of its benefits, you should provide information on
any of the following factors, as applicable to your product(s):
(1) documentation of the usefulness of the active ingredient(s)
in Integrated Pest Management, (b) description of the beneficial impacts
on the environment of use of the active ingredient(s), as opposed to its
registered alternatives, (c) information on the breakdown of the active
ingredient(s) after use and on its persistence in the environment, and (d)
description of its usefulness against a pest(s) of public health
significance.
Failure to submit sufficient information for the Agency to make a determination
regarding a request for a low volume minor use waiver will result in denial of the
request for a waiver.
2. Request for Waiver of Data Option 9 on the Requirements Status and
Registrant's Response Form. This option may be used if you believe that.a
particular data requirement should not apply because the corresponding use is
no longer registered or the requirement is inappropriate. You must submit a
rationale explaining why you believe the data requirements should not apply.
You must also submit the current label(s) of your product(s) and, if a current
copy of your Confidential Statement of Formula is not already on file you must
submit a current copy.
You will be informed of the Agency's decision in writing. If the
Agency determines that the data requirements of this Notice do not apply to
your product(s), you will not be required to supply the data pursuant to section
3(c)(2)(B). If EPA determines that the data are required for your product^.
you must choose a method of meeting the requirements of this Notice within the
time frame provided by this Notice. Within 30 days of your receipt of the
Agency's written decision, you must submit a revised Requirements Status and
Registrant's Response Form indicating the option chosen.
IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE
A. NOTICE OF INTENT TO SUSPEND
184
-------
The Agency may issue a Notice of Intent to Suspend products subject to this
Notice due to failure by a registrant to comply with the requirements of this Data Call-
in Notice, pursuant to FIFRA section 3(c)(2)(B). Events which may be the basis for
issuance of a Notice of Intent to Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your
receipt of this Notice.
2. Failure to submit on the required schedule an acceptable proposed or
final protocol when such is required to be submitted to the Agency for
review.
3. Failure to submit on the required schedule an adequate progress report
on a study as required'by this Notice.
4. Failure to submit on the required schedule acceptable data as required by
this Notice. '
5. Failure to take a required action or submit adequate information
pertaining to .any option chosen to address the data requirements (e.g.,
any required action or information pertaining to submission or citation
of existing studies of offers, arrangements, or arbitration on the sharing
.of costs or the formation of Task Forces, failure to comply with the
. terms of an agreement or arbitration concerning joint data development
or failure to.comply with any terms of a data waiver).
6. Failure to submit supportable certifications as to the conditions of ,
submitted studies, as required by Section m-C of this .Notice.
.7. Withdrawal of an offer to share in the cost of developing ^required data.
8. Failure of the registrant to whom you have tendered an offer to share in
the cost of developing data and provided proof of the registrant's receipt
of such offer, or failure of a registrant on whom you rely for a generic
data exemption either to:
a. inform EPA of intent to develop and submit the data required by
this Notice on a Data Call-in Response Form and a Requirements Status
and Registrant's Response Form; or,
b. fulfill the commitment to develop and submit the data as required
by this Notice; or, ,- -
c. otherwise take appropriate steps to meet the requirements stated
in this Notice, unless you commit to submit and -do submit the required
data in the specified time frame.
185
-------
9. Failure to take any required or appropriate steps, not mentioned above,
at any time following the issuance of this Notice.
B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS
UNACCEPTABLE
The Agency may determine that a study (even if submitted within the required
time) is unacceptable and constitutes a basis for issuance of a Notice of Intent to
Suspend. The grounds for suspension include, but are not limited to, failure to meet
any of the following:
1. EPA requirements specified in the Data Call-in Notice or other
documents incorporated by reference (including, as applicable, EPA Pesticide
Assessment Guidelines, Data Reporting Guidelines, and GeneTox Health
Effects Test Guidelines) regarding the design, conduct, and reporting of
required studies. Such requirements include, but are not limited to, those
. relating to test material, test procedures, selection of species, number of
animals, sex and distribution of animals, dose and effect levels to be tested or
attained, duration of test, and, as applicable, Good Laboratory Practices.
2. EPA requirements regarding the submission of protocols, including the
incorporation of any changes required by the Agency following review.
3. EPA requirements regarding the reporting of data, including the manner
of reporting, the completeness of results, and the adequacy of any required
supporting (or raw) data, including, but not limited to, requirements referenced
or included in this Notice or contained in PR 86-5. All studies must be
submitted in the form of a final report; a preliminary report will not be
considered to fulfill the submission requirement.
C. EXISTING STOCKS OF SUSPENDED OR CANCELLED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of
existing stocks of a pesticide product which has been suspended or cancelled if doing so
would be consistent with the purposes of the Federal Insecticide, Fungicide, and
Rodenticide Act.
The Agency has determined that such disposition by registrants of existing
stocks for a suspended registration when a section 3(c)(2)(B) data request is outstanding
would generally not be consistent with the Act's purposes. Accordingly, the Agency
anticipates granting registrants permission to sell, distribute, or use existing stocks of
suspended product(s) only in exceptional circumstances. If you believe such
disposition of existing stocks of your product(s) which may be suspended for failure to
comply with this Notice should be permitted, you have the burden of clearly
186
-------
demonstrating to EPA that granting such permission would be consistent with the Act.
You must also explain why an "existing stocks" pro vision is necessary, including a
statement of the quantity of existing stocks and your estimate of the time required for
their sale, distribution, and use. Unless you meet this burden the Agency will not
consider any request pertaining to the continued sale, distribution, or use of your
existing stocks after suspension.
If you request a voluntary cancellation of your product(s) as a response to this
Notice and your product is in full compliance with all Agency requirements, you will
have, under most circumstances, one year from the date your 90 day response to this
Notice is due, to sell, distribute, or use existing stocks. Normally, the Agency will
allow persons other than the registrant such as independent distributors, retailers and
.end users to sell, distribute or use such existing stocks until the stocks are exhausted.
Any sale, distribution or use of stocks of voluntarily cancelled products containing an
active ingredient(s) for which the Agency has particular risk concerns will be
determined on case-by-case basis.
Requests fpr voluntary cancellation received after the 90 day response period
required by this Notice will not result in the Agency granting any additional time to
sell, distribute, or use existing stocks beyond a year from the date the 90 day response
was due unless you demonstrate to the Agency that you are in full compliance with all
Agency requirements, including the requirements of this Notice. For example, if you
decide to voluntarily cancel your registration six months before a 3 year study is
scheduled to be submitted, all progress reports and other information necessary to
establish that you have been conducting the study in an acceptable and good faith
manner must have been submitted to the Agency, before EPA will consider granting an
existing stocks provision. .
SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLE UNREASONABLE
ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6(a)(2) states that if at any time after a
pesticide is registered a registrant has additional factual information regarding unreasonable
. adverse effects on the environment by the pesticide, the registrant shall submit the information
to the Agency. Registrants must notify the Agency of any factual information they have, from
whatever source, including but not limited to interim or preliminary results of studies,
regarding unreasonable adverse effects on man or the environment. This requirement
continues as long as the products are registered by the Agency.'
SECTION VI. INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by
this Notice, call the contact person listed in Attachment 1, the Data Call-In Chemical Status
Sheet.
: ' . 187
-------
All responses to this Notice (other than voluntary cancellation requests and generic data
exemption claims) must include a completed Data Call-In Response Form (Attachment 2) and
a completed Requirements Status and Registrant's Response Form (Attachment 3) and any
other documents required by this Notice, and should be submitted to the contact person
identified in Attachment 1. If the voluntary cancellation or generic data exemption option is
chosen, only the Data Call-in Response Form need be submitted.
The Office of Compliance (OC) of the Office of Enforcement and Compliance
Assurance (OECA), EPA, will be monitoring the data being generated in response to this
Notice.
Sincerely yours,
Lois A. Rossi, Director
Special Review and
Reregistration Division
188
-------
RODENTICIDE CLUSTER DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Generic Data Call-In Notice because you have product(s)
containing one or more rodenticides.
This Generic Data Call-in Chemical Status Sheet, contains an overview of data
required by this notice, and point of contact for inquiries pertaining to the reregistration of the
rodenticides. This attachment is to be used in conjunction with (1) the Generic Data Call-in
Notice, (2) the Generic Data Call-In Response Form (Attachment 2), (3) the Requirements
Status and Registrant's Form (Attachment 2), (4) a list of registrants receiving this DCI
(Attachment 4), (5) the EPA Acceptance Criteria (Attachment $), and (6) the Cost Share and
Data Compensation Forms in replying to this rodenticide Generic Data Call In (Attachment
F). Instructions and guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the generic database for each of
the rodenticide cluster active ingredients are contained in the Requirements Status and
Registrant's Response. Attachment C. The Agency has concluded that additional product
chemistry data on the rodenticides are needed. These data are needed to fully complete the
reregistration of all eligible rodenticide cluster products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic data requirements and procedures
established by this Notice, please contact Dennis Deziel at (703) 308-8180.
All responsades to this Notice for the generic data requirements should be submitted to:
Dennis Deziel, Chemical Review Manager
Reregistration Branch I
Special Review and Registration Division (H7508W)
Office of Pesticiafde Programs
U.S. Environmental Protection Agency ,
Washington, D.C. 20460
RE: Rodenticide
189
-------
190
-------
SPECIFIC INSTRUCTIONS FOR THE GENERIC DATA CALL-IN RESPONSE FORM
This Form is designed to be used to respond to call-ins for generic and product specific
data for the purpose of reregistering pesticides under the Federal Insecticide Fungicide and
Rodenticide Act. Fill out this form each time you are responding to a data call-in for which
EPA has sent you the form entitled "Requirements Status and Registrant1 s Response."
Items 1-4 will have been preprinted on the form Items 5 through 7 must be completed
by the registrant as appropriate Items 8 through 11 must be completed by the registrant 7
before submitting a response to the Agency. ,
, Public reporting burden for this collection of information is estimated to average 15
minutes per response, including time for reviewing instructions, searching existing data
. sources, gathering and maintaining the data needed, and completing and reviewing the
collection of information. Send comments regarding the burden estimate or any other aspect
of this collection of information, including suggesting for reducing this burden, to Chief,
Information Policy Branch, PM-223, U S Environmental Protection Agency, 401 M St, S W,
Washington, D C 20460; and to the Office of Management and Budget, Paperwork Reduction
Project 2070-0107, Washington, DC 20503. '
INSTRUCTIONS
Item 1. This item identifies your company name, number and address.
Item 2. This item identifies the ease number, ease name, EPA chemical number
and chemical name.
Item 3. This item identifies the date and type of data call-in.
i
Item 4. This item identifies the EPA product registrations relevant to the data
' call-in. Please note that you are also responsible for informing the
Agency of your response regarding any product that you believe may be
covered by this data call-in but that is not listed by the Agency in Item
'/ 4. You must bring any such apparent omission to the Agency's attention
within the period required for submission of this response form.
. Item5. Cheek this item for each product registration you wish to cancel
voluntarily. If a registration number is listed for a product for which
you previously requested voluntary cancellation, indicate inTtem 5 the
date of that request. You do not need to complete any item on the
Requirements Status and Registrant's Response Form for any product
that is voluntarily cancelled.
Item 6a. Check this item if this data call-in is for generic data as indicated in Item
3 and if you are eligible for a Generic Data Exemption for the chemical
191 ' ;
-------
listed in Item 2 and used in the subject product. By electing this
exemption, you agree to the terms and conditions of a Generic Data
Exemption as explained in the Data Call-in Notice.
If you are eligible for or claim a Generic Data Exemption, enter the
EPA registration Number of each registered source of that active
ingredient that you use in your product.
Typically, if you purchase an EPA-registered product from one or more
other producers (who, with respect to the incorporated product, are in
compliance with this and-any other outstanding Data Call-In Notice),
and incorporate that product into all your products, you may complete
this item for all products listed on this form If, however, you produce
the active ingredient yourself, or use any unregistered product
(regardless of the fact that some of your sources are registered), you
may not claim a Generic Data Exemption and you may not select this
item. ,
f i
Item 6b. Check this Item if the data call-in is a generic data call-in as indicated in
Item 3 and if you are agreeing to satisfy the generic data requirements of
this data call-in. Attach the Requirements Status and Registrant's
Response Form that indicates how you will satisfy those requirements.
Item 7a. Check this item if this call-in if a data call-in as indicated in Item 3 for a
manufacturing use product (MUP), and if your product is a
manufacturing use product for which you agree to supply
product-specific data. Attach the Requirements Status and Registrants'
Response Form that indicates how you will satisfy those requirements.
Item 7b. Check this item if this call-in is a data call-in for an end use product
(EUP) as indicated in Item 3 and if your product is an end use product
for which you agree to supply product-specific data. Attach the
Requirements Status and Registrant's Response Form that indicates how
you will satisfy those requirements.
Item 8. This certification statement must be signed by an authorized
representative of your company and the person signing must include
his/her title. Additional pages used in your response must be initialled
and dated in the space provided for the certification.
Item 9. Enter the date of signature.
Item 10. Enter the name of the person EPA should contact with questions
regarding your response.
Item 11. Enter the phone number of your company contact.
192
-------
IH
0
H
0)
tr
nS
*
>H
ฃLj
0
o
EH
fe
K>
I"-N- ฐ
C3 1/> W
T-O 01
OO L.
C i , -
s> op 9-
> r*-rป- X
O OO LU
C. CVCM
a.
O m
< 0 >
s z <-
!_ m a.
o z a.
u. O ^
_
^i
O
ฃj
0)
al Protection Ag
,C. 20460
RESPONSE
3 ฐ *
1 rt '
C* ซ% H
0 -S !^
^ _!
jH "2 *^
rt r>
Q)
rtS
4J
CQ
TJ
(D
4J
-H
ฃ3
e:
O
**"
CO
.e
c
o
TJ
01
4V
CO
13
?
C
o
4V
1
O
M-
-
01
-C
^
t
CO
1
1
4V
CO
C
a
01
.C
0
CO
4V
CD
01
J=
|
"S
CD
O
T>
(0 .
c.
01
CO
CD
01
a.
J
^
.5 >.
c.
4_ป m
c ซ
F- CD
t- 01
^ g
4V CO
ID
a
O
0
CQ 0
CQ 0
1 1 9 S
?OEH
w O W *
02 p^J ^4
i^gg
^CU CQ O
ง^ O O
cj CQ S S
V*
CD
CD
O
O
V
u>
4v
"g
t-
0.
f^
CD
<0
a
u
i
o
"ฐ
a ~o \
co a. x: 4v
33 u C
a. uj a o
3 4V 6 CO
UJ 01 4V C9 -.
j= a t- 4v
C 4V *r- C
CD 01 3 CO
>*-C u C.
CO *f- 4V 01 4V
- CO Qฃ CO
4V 4V O = '5ป
fa TJ ai
co eo oi ee.
6 c 4v -a =
a. E~4^ co 01
ai S c co
>. 01 I- 01 01 C
X ra'5 6 S 8.
CO CT c- CO CO
S ซ c- >4- to o:
TJ
o 01 co
C Q. JZ 4V
CD => U C
Z CD 01
a. 4v s co
Z3 01 4V S ~
3E X: CD I. 4V
CO ซ* 4v 01 4v
eo ce co
4V ซ ง = B
o en T3 0)
f 'CO CO ^ Of
o c ฃ -o s
Q. E 4V CO 01
01 01 C CO
>. 01 i. 01 CO C
SE t- 3 Q
CO O" I. CO CO
N. <-> t. H- en ae
u "O
'Z S S
01 CO v
C 0 4V
6b. I agree to satisfy Gel
Data requirements as indii
on the attached form enti
"Requirements Status and
Registrant's Response."
0 C 3
- 01 . 1 O
fe - T3 -2 "S
Of (U C. 01
C3 tfl O> L. T3
3 C S
0) CO - ซC **
U Q. W
ฃ JB > *" *<"*
E C 4-ซ 0 t.
v O O ^ CU
10 .F- CD 3 42
u Q. 01 co 3
e rt ^*' ni
CD X J= C
U C 4V O
CO CO E 4V
. iv 4V S CO
CO CD J3 C- &.
^ O O **- 4V
ซ *
O - 3
I5 i c
x u o x
03
MM O "D 4V
SO CO C.
I. C.
4V
ll
< 4V
a. co
*" '5
. 01
-* ac
' - -
"'
'
.
S
5 '
^5
f
g
g
5
2i
'
CO
0
o
^
*^ s
II
-ฐ.t
CO -
|i
U 01
"3
ป CD
01 -C
3 CO
4V C
01 S.
CD 01
"ฃ
4V X
c 2
i!
u c
CD O!
4V w 41
CO 4V >
CD "-
1^ CO CO
CD 4V
-o c S
C CO
E oi a.
O CO Oฃ
71 "8
C- N
vZ O - "~
** o> . o
งcn -c
. 4V
CO 3
0] *4> ^C
1 -2"- *
S 3 CD
C Z .CD O.
CO >* J3 H.
4-> C CD O
W ".JJ 01
-C CO O. 4V
C 4v jr K .^
O 4V CO 1
5 5 ft fe "P
CO _*^ O) O C
^ X 3 01
"** O JC D
t_ 4-ซ C 4-> 4-ป
o> c_ ^ o co
CJ 0ป O -Q C
U CO OJ
CO ปซ- O
-------
H
f rป- x
O OO LJ
& "
a
0
al Protect:
.C. 20460
RESPONSE
W Q ,_
$3 ซ
Q) .. H
S 53 L
(~J ^-* 1*^1
ฐ s s
*"j CD fj
T fl
sl s
tn S w
nJ
CO
TJ
4J
H
g
t
*
B
E
L.
0
*f-
co
^
"O
M
Cfl
?
i
o
H-
c
cu
v=
4V
^"
g-
3
CO
J2
CO
rfl
ached instruction:
4-*
CO
JC
r?
H-
CU
d>
to
u
"S
CD
0)
CO
CU
Q.
^
""
4-* CO
C CO
- CO
C_ CU
p o
CU
o
4V CO
CU 4V
CO CU
to cu
* CO
CL
in c
if .2
- 4J
CJ Tj
fs* Cfl
t
CO 31
3 ซ
_ 3
U
a
o
ii" H
Tt O^
1? H
co rh
O ^"^
r*i
<-
ง.
j=
i
i
o
L.
Q.
^ 1
CU
g.
1
^ป
1
X
o
L*
Q) 13
fl Jc
O rH (o
HO.
O 0 C
H tN >
O H -f
(T$ i"H
S si
|ซ -o -2-
ง c xi
Z CO J
^0 S ?
8 1 ฃ
tj vN CJ CO
01
O
0
CO O
CO O
wo
S >j DJ
ฃ S Q
5 < Q X
3 Oj<3x
iSs -
g ta>*
1 W ซ EH
= J EH H
I'Dj CO U
|ง D Q
^
e
a
o
o
^
&
CO
"i
a.
^ป
2
a
a
o
i
cu
C9
*
2 -"8
D Q- j: 4J
^ U CO CI
=9 4J g CO
U J 4J V ซ*
5 0 U *
B fll *5 0
a ^^ g- 1.
*- ca ec co
4J ^W O " "S
u cs -p cu
5 co co ^S at
5 O C 4J "D =
L. 4J S C
Q. g 4V CS tl
cu cu c cn
>fc CU ^ CU CO C
CO p* C fll Cfl
Q CU O 4V ft!
i. at
a 8 eo
n. S H ca
E J= CO L. **
4J ป C
eg cu 3. co
- to ae co
w ซ S ~ '01
o a -p ซ
3 ca ca cu ซ
6 4V
5 o c -M-O =
Q. ^ | ซ S CU
O>'5 g 4-> Q.
co Zr i- a eo
o ฃ o 4- cu
fw ซ- t- *^ CO K
^ V "O
f_ ^J ^
งCB
.2 i
CJ ^ 4J ^ _
>ซ*^ v co
*- cu
CO CO g CO CO
a E 3 c
4V O 4V O
a co x- a a.
6b. I agree to s
Data requirement
on the attached
"Requirements St
Registrant's Res
ocx
. V 1 O
C_ CO
01 0) L. CU
CO CO *- < 4v
U CL CO
>IK *^ CU
g C 4V u C.
ป O O C- CU
O CO 3 .g
7ป g. cu S g
fS 4V ซ)
X J= C
IU C 4V o
"" CD'S g 4v
. 4V 4V 5 CO
CO CO J3 t. ซ-
vO 0 0 *- 4V
2 "S ^
If tl g X
"^ i e o 71
Q C. L. CO
in u a. 4-> 4->
4^
Is
O ฃ
a. ซ
a. CA
III **>
a
J- CB
e
i
i
S? '
1 '
Is
g
0)
o
o
0
4->
0) CU
cu Z
7? o
Q. co
C T"
O c.
E"
ue, accurate, and
ishable by fine, i
"1
flj Qj
L.
*ฃ
W
*^ ^^
i^
JZ *^
U C
0 CU
M W flJ
CD 4-* >
03 *^"
rf Cfl <8
CD -M
O) C
o c v
O Cfl Oฃ
I! 1
* ) 0
ง2 ซ
CO ?
E ' -
M C ฃ
4^ I a
c x a a.
g g- if
& ^ t, u
o xS ซj-
4V C CD O
* ฐ ^ CU
CD 4V ' '
f CO Q. 4V
C 4V .C E
O 4V 0) 1
4V CO CU t- "D
g S-ff-S i
H^ >h^ ง CU
*-ป*- 3 t-
o t, ^ o co
u cu o .a c
^ 0 CO ^ 0ป
oo ซ <ปi o c/>
i
3
?
5
ฐ"
*"
1
"
4v
U
CD'
4V
C
o
u
>.
c
CO
U
g
z
o
-------
!
to
o
oin co
- O CU
00 I-
cu oo 'a.
2 ss 5
1 0 1
z o
E t-
t- ca a.
ox; a.
u. S <
SN
O
0)
CD
<
o
-H
:al Protect
i.C. 20460
RESPONSE
"5 <3
Q) . , H
1 0 ^
il.i
m. g 0
*-
c
"~
CU
JC
*
Q.
3
CO
CO
CO
c
o
1
4-*
1
JC
u
CO
CO
CU
JC
4.
ead carefully
t-
co
CO
CD
O.
C
c
4-1 CO
C CO
CO
I. d>
Q. u
H-
01
CL ^
CU u
CO CU
S JC
tn
a.
tn c
o
HO *-
33
Cฃ CO
in cu
u
o
1 o
ฃ H
1 W . '
S W
eo rri
Q v->
i
o
ฃ.
_2
3
4-
o
1
t
I
fl ฃ
-H CN ^
*"* ฐ 3
I O EH
u w -
1 w ^
C ^ p '. t^j
0-H rt r^
g-Oj CQ O
|< 0 0
gcn&&
a
'4-1
to
0
o
JJ
4rf
o
Q.
rC
CO
0
o
c.
tu
g
(9
= 3B I ซ
*** J= O t_ *ป
C 4-> * C
o ^ป 3.S
CA <*- 4J At 4-ป
"" .2 c * .2
4J *- O ~ D)
u a -p cu
3 to ซ tu ee
i_ 4-> g ซ- e ~.
Q. E 4J a 01
^llgll
p v o -f a>
*~ (. ซ*- u> ec
"O So)
0. * g ซ
5 * i c
0) * 4J S 4->
- .2 g ? "
00 Tl 0?
3 co o> ซ a:
6 o e 4J-D s
c. 4J o e .
5^ CU S- Ol 'to C
to o* u to co
to ai
s. -> i. x. to ae
o -p
~ w 13
01 CO
g ป .t^
C9 "O 4-ป "O
x S a ~.
EO to E to to
a i. 3 c
4-> 0 4-> 5
to w ซ*- to a.
6b. I agree to s
Data requirement
on the attached
"Requirements St
Registrant's Res
4-*
Z J i I
5 "O Q)
g o,ฃ I?"0
o jogu-g
tD tO ซt 4-1
u a. co
53^01 a ai ~
i c ซ S c.
o u L. tu
<0 "- to 3 Jg
j ^. tu tn 3
1 X ** JC C
Ul C 4-> O
"" SI'S E ซ
4-> 4-< O tO
m eo ja t- t_
vO 0 0 M- 4-.
ซ E
j=S S ^
5~- c c
.1 ' U O >-
c o ซ *-^
s <- t. a
ซ tn o o. 4^ 4-*
4--> 4-1
^ CO tO
O -W
Ol C
g c g
E 41 o
O CO fiฃ
I_ M
-C O i-
g-2 1
|3 I
i|r ?
4-> X tO
c x to Q-
82- -g
tu ^ o -cj
to X JO H-
4-> C CO O
0) ID U .
01 4->
p *"' ~5 to il-
-* CO tU C. "B
to jc e> tu c
ซ "8
H ^> C A*' ^~
CU 1- Jtt O to
cj eu o ja c
U CO D)
. i- -
co o to
L.
-g
Z
JC
Q.
^~
4-*
U
CO
4-*
C
o
i
ง
0
S
o
-------
OJ
O
H
Q)
cr
rri
lv
CM
O
rj
EH
fe
ri
P
O
S
1
tn
i
to
C31O *A
O-O C.
a i i
5 oo a.
O OO Ul
<- CM(M
* 5 i
s <-
u co a.
o s S
u. S ซr
O
a
- *>
4-* 03
w a
3(1
j=
-J M
a.
"e
II
t-f 4-1
ซ 0ป
3C JO
_
O
o
i w
0) M
4-> H
CD rh
o ^^
M
S
3 H
O o
O C-
nJ cvj
4-1 H
-H H
Case # and Name
2755 Brod
chemical # and Name
Brodifacoun
M
o
0
CO 0
co o
"> >s_i S
co ?ซ K
< CU rfj Pi
*n ป*"<
1 OE-1
a O W -
ง| ฃฃ] >!
1 m a& EH
^ M-l CO \J
|9 o o
IMS; iz;
ซ-
CO
CO
o
o
JJH
1^
u
CO
4-ป
u
c-
Q.
**"
CO
4-1
CD
O
U
1
01
a
o
? "So.
O Q. J= -M
Q. UJ CO 42
U fll 4-* w ^
C 5 "* ฃ C
0 01 3 CD
CO H- 4-ป CU 4J
^ CO Ctf CO
4-ป *-ป O "" D9
o co T? eu
3 co o) oj eet
E S ง i "E =.
Q. ฃ 4^ CO 01
oi 5 c to
>. 01 t. 01 01 C
en 3 g 4^ S.
CD tT t- CO CO.
- ~ L. H- CO CX
n B co
ฃ Q. JC 4->
CD 3 O C
1 J= 2 1 i
CO *^*5 414^
ซ OS CO
. c =
4-* 4J O O>
U CD TJ 0)
S o) Mjoe
5 o c 4---0 =
01 w C CO
>. CU t. 0) CO C
ac u 30
O> 3 S 4J D.
CD tT I- CO CO
CD 01 O 4J 01
f- c- M- co cr
o-p
tl ง ^
CU CO -^ '
C U 4->
OI M- ซ
>..- 01 CO ~.
^- fll
co co E co co
^ CD C- 3 C
+* O 4^ O
CO CO M- CO Q.
6b. I agree to s
Data requirement
on the attached
"Requirements St
Registrant's Res
. I am claimimg a Generic
ta Exemption because I
tain the active ingredieni
om the source EPA regis-
ation number listed below,
CO CD J3 t- <-
O O O H- 4->
o is
*ป 09 O) ป
a o
.rue t- >
2 ** 4J c
01 3 ป^ ^
ป O "El 4-> -
, g 5 CD c-
CD C- ฃ- CD
in u Q- 4J v
4J
|g
C_ 4J
ฐ- ฃ
sa
""S
* ae
f
"
<
t^
S .
fZ
i
^5
ง .
13
4>
H
a
}s
4--
01 ฃ
01 c
^ o
.ป JT
fr.SS
e
re true, accurate, ano
punishable by fine, i
:orm and all attachments a
sleading statement may be
Representative
*- C. N
4-* t.
01 O
C CO JC
O 4->
S > co
OT Jฃ 01 CJ
ซ xS ซ-
4J C CO O
CO CD CJ
4) 4-> -^
^ CO Q. 4^
C ^ JC S
O 4-ป CD H-
4-ป CD 01 (- "O
co j: en 01 ฃ
o 4^ TJ n co
**- ^ * 3 .
s
B-
u
M-
o
fll
i
CD
2
o
-------
CD "O
-------
-------
SPECIFIC INSTRUCTIONS FOR COMPLETING THE REQUIREMENTS STATUS AND
REGISTRANTS RESPONSE FORM
r
Generic Data
This form is designed to bevused for registrants to respond to call-in- for generic and
product-specific data as part of EPA1 s reregistration program under the Federal Insecticide
Fungicide and Rodenticide Act. Although the form is the same for both product specific and
generic data, instructions for completing the forms differ slightly. Specifically, options for
satisfying product specific data requirements do not include (1) deletion of uses or (2) request for
a low volume/minor use waiver. These instructions are for completion of generic data
requirements.
EPA has developed this form individually for each data call-in addressed to each registrant, and
has preprinted this form with a number of items. DO NOT use this form for any other active
ingredient. .
Items 1 through 8 (inclusive) will have been preprinted on the form. You must complete all other
items on this form by typing or printing legibly. ..
Public reporting burden for this collection of information is estimated to average 30 minutes per
response, including time for reviewing instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing the collection of information. Send
comments regarding the burden estimate or any other aspect of this collection of information,
including suggesting for reducing this burden, to Chief, Information Policy Branch, PM-223,
U.S. Environmental Protection Agency, 401 M St., S.W., Washington, D.C. 20460; and to the
Office of Management and Budget, Paperwork Reduction Project 2070-0107, Washington, D.C.
20503. '-...-
INSTRUCTIONS
Item 1. This item identifies your company name, number, and address.
Item 2. This item identifies the case number, case name, EPA chemical number and
chemical name.
Item 3. This item identifies the date and type of data call-in.
Item 4. This item identifies the guideline reference numbers of studies required to support
the product(s) being reregistered. These guidelines, in addition to requirements
specified in the Data Call-In Notice, govern the conduct of the required studies.
Item 5. This item identifies the study title associated with the guideline reference number
and whether protocols and 1, 2, or 3-year progress reports are required to be
submitted in connection with the study. As noted in Section HI of the Data Call-in
Notice, 90-day progress reports are required for all studies.
199
-------
Item 6.
If an asterisk appears in Item 5, EPA has attached information relevant to
this guideline reference number to the Requirements Status and Registrant's
Response Form.
This item identifies the code associated with the use pattern of the pesticide. A
brief description of each code follows: .
A.
B.
C.
D.
E.
F.
G.
H.
I.
J.
K.
L.
M.
N.
O.
Terrestrial food
Terrestrial feed
Terrestrial non-food
Aquatic food
Aquatic non-food outdoor
Aquatic non-food industrial
Aquatic non-food residential
Greenhouse food
Greenhouse non-food crop
Forestry
Residential
Indoor food
Indoor non-food
Indoor medical
Indoor residential
Item 7.
This item identifies the code assigned to the substance that must be used for
testing. A brief description of each code follows.
EP
MP
MP/TGAI
PAI
PAI/M
PAI/PAIRA
PAIRA
PAIRA/M
PAIRA/PM
TEP
TEP_*
TEP/MET
TEP/PAI/M
TGAI/PAIRA
End-Use Product
Manufacturing-Use Product
Manufacturing-Use Product and Technical Grade
Active Ingredient
Pure Active Ingredient
Pure Active Ingredient and Metabolites
Pure Active Ingredient or Pure Active Ingredient
Radiolabelled ;
Pure Active Ingredient Radiolabelled '
Pure Active Ingredient Radiolabelled and Metabolites
Pure Active Ingredient Radiolabelled and Plant
Metabolites
Typical End-Use Product
Typical End-Use Product, Percent Active Ingredient
Specified
Typical End-Use Product and Metabolites
Typical End-Use Product or Pure Active Ingredient
and Metabolites
Technical Grade Active Ingredient or Pure Active
Ingredient Radiolabelled
200
-------
TGAI Technical Grade Active Ingredient
TGAI/TEP . Technical Grade Active Ingredient or Typical
End-Use Product ,
TGAI/PAI Technical Grade Active Ingredient or Pure Active
Ingredient
MET Metabolites
IMP Impurities
DEGR Degradates
*See: guideline comment
Item 8. This item identifies the time frame allowed for submission of the study or protocol
. identified in item 2. The time frame runs from the date of your receipt of the Data
Call-in Notice.
Item 9. Enter the appropriate Response Code or Codes to show how you intend to comply
with each data requirement. Brief descriptions of each code follow. The Data Call-
in Notice contains a fuller description of each of these options.
1. (Developing Data) I will conduct a new study and submit it within the time
frames specified in item 8 above. By^ indicating that I have chosen this
option, I certify that I will comply with all the requirements pertaining to
.the conditions for submittal of this study as outlined in the Data Call-in
Notice and that I will provide the protocol and progress reports required in
item 5 above.
2, (Agreement to Cost Share) I have entered into an agreement with one or
more registrants to develop data jointly. By indicating that I have chosen
this option, I certify that I will comply with all the requirements pertaining
to sharing in the cost of developing data as outlined in the Data Call-in
Notice.
3. (Offer to Cost Share) I have made an offer to enter into an agreement with
one or more registrants to develop data jointly. I am submitting a copy of
the form "Certification of Offer to Cost Share in the Development of Data"
that describes this offer/agreement. By indicating that I have chosen this
option, I certify that I will comply with all the requirements pertaining to
making an offer to share in the cost of developing data as outlined in the
Data Call-In Notice.
; 4. (Submitting Existing Data) I am submitting an existing study that has never
before been submitted to EPA. By indicating that I have chosen this option,
I certify that this study meets all the requirements pertaining to the
conditions for submittal of existing data outlined in the Data Call-in Notice
and I have attached the needed supporting information along with this
response. , '
201
-------
5. (Upgrading a Study) I am submitting or citing data to upgrade a study that
EPA has classified as partially acceptable and potentially upgradeable. By
indicating that I have chosen this option, I certify that I have met all the
requirements pertaining to the conditions for submitting or citing existing
data to upgrade a study described in the Data. Call-In Notice. I am
indicating on attached correspondence the Master Record Identification
Number (MRID) that EPA has assigned to the data that I am citing as well
as the MRID of the study I am attempting to upgrade.
6. (Citing a Study) I am citing an existing study that has been previously
classified by EPA as acceptable, core, core minimum, or a'study that has
not yet been reviewed by the Agency. I am providing the Agency's
classification of the study.
7. (Deleting Uses) I am attaching an application for amendment to my
registration deleting the uses for which the data are required.
8. (Low Volume/Minor Use Waiver Request) I have read the statements
concerning low volume-minor use data waivers in the Data Call-In Notice
and I request a low-volume minor use waiver of the data requirement. I
am attaching a detailed justification to support this waiver request
including, among other things, all information required to support the
request. I understand that, unless modified by the Agency in writing, the
data requirement as stated in the Notice governs.
9. (Request for Waiver of Data) I have read the statements concerning data
waivers other than low volume minor-use data waivers in the Data Call-in
Notice and I request a waiver of the data requirement. I am attaching an
identification of the basis for this waiver and a detailed justification to
support this waiver request. The justification includes, among other things,
all information required, to support the request. I understand that, unless
modified by the Agency in writing, the data requirement as stated in the
Nqtice governs.
Item 10. This item must be signed by an authorized representative of your company. The
person signing must include his/her title, and must initial and date all other pages
of this form.
Item 11. Enter the date of signature.
Item 12. Enter the name of the person EPA should contact with questions regarding your
response.
Item 13. Enter the phone number of your company contact.
202
-------
H
E z 2
t- CO Q.
o JE SI
u. o <
. '
u ta
ง o
CD Pi
<: ca
s S
o
H 01
VJD 55
S i ง
a. QN ta
H
H r i O
a* . H
fl ฐ
u) ซ. Q ,
1 ง ง
S ฃ ca
g en y*
"n C3 g
^ ~rH "J
$ ^ 01
s
(U H
4J tj
-
e
o
at
.c
4J
C
o
s
4-*
CO
u
ง
4->
O
C -
M
^
&
3
CO
g
CO
CA
ง
4J
U
t_
+J
ซ
W
1
U
ซ
4->
4J
03
CU
~
-^
2
*ฃ
c.
CD
~o
ca
0)
L.
CU
CO
it
s s
r: s
a. u
CU
& c
k~
^2
0) *-
CO O
o -c
ซ* CA
a.
.. CO
en c
2 'ฃ
I
a: a
i_
C/> 0
a: co
u
o
**-
o
.^* 1 1
i H
lw
01 ^
0
OJ
O l>
a <=>
-H C-
(4 VO
X! 0
a
O
ง ta tt! EH
I-QJ CQU
%< oo
s CQ & a
--
"1
.28
s?s
01 O
ae a.
CO
<>0ฃ
lซ
h- g
. ฃ-
CO u.
CU
(0 ID
h- CO
"ง
N. CO
si
*> 4^
CO .
K>
ca
01 *-> '
la ~
ซ-
n^^^-Q^O .
t
+ป
to
in
' -
s~
- S
2 5 1.
J,
_.
-'<
- ~ -,
||ง||||ง|g|g
OJOtHHHHCN OJ CS '
' '
"
' ' .
< ซC ซC << < ซฃ ซC <ฃ tf
>-^J 1 +- 1 1 1 t t
.
-,.,
O O 0 '
I^J kjป l^/
W W o o C5
uowwo'ou o_a
'
'
tซ J>t >. |x >*
&H ^< ^T
O: O
s 3 ra c ^
.V O' ^*
01 01
4J C^ 4J t.
CO 3 CD 3
CO CO
' 01 O 0) O
c- a. t- a. >. >.
3 X 3 ปซ
^ g JU g M '5'3 .
'( x~ a S" S ฃ" 'x ' 'x
m .ป, uj < . o p
co -*ป ca x x x
E <0 E ea o *- t.
o" ""u" t- - - o _* o n- - ,
CU CLOOOOOoC,QCQ.
X^coco-cocn> co co-
* * * * * ,
'^ ' '
, v-
x^A CQ CQ CQ
* ซ** OT ^ W
*s;** , pq
ca '
ซ CO
01 J=
2.
til
CO CU
4-* >ป
01 E
E
U C
S s
4J 0) 0)
CO 4> >
CO
CO ,CD
|? 1
OT^ S
CD L.
EH) CL
c 0)
*"1 -a
"- i, N
.CO *-
4J C_
01 O
C CO J=
O -M
CO 3
0>--Q *-
4J C CO O
CO CD O
01 *j" ^!
ง 55 & i
. 4J CD I
CO CO 01 C. T3
O J= 0) 01 C
"- X D 0>
4J S- 2 C.
C- - 0 JC 3
0) 4J C 4J 4J
ej o "o 5 c
O CO O>
ฐ ~~ฐ "
c.
9
2
O)
c
o
o
JO
u
ca
1
o
c
u
o
ง
z
ซ
CM
-------
T~
c
Q)
tn
nJ
P4
o
a
(U
tp
a H
o la
"o 1
(D ง H
,|_,lJ , II ฃ(^
8 ฐ S
Jnvironmental
hington, D.C
OR GUIDELINE
w tn fa
01 & 01
f> &
tf M
CO li
33
TJ ง
j
ป 4f
s-
(1)
0) O
fl fl
O -H
lame
hlorophacin
md Name
Chlorophac
g * t-
ra O
=8: O o C-
ซ>0 'e^
en H o> AD
S 05 g 0
COMMENT
UJ
J
L1J
3
1
*
1
n ro n oo
O5 O5 OQ O5 .
o o o o
o o o o
* o^ en cr\ ^
n
OJ CO CQ CO CO
O fl] F3} Stl rf
o O O U O
4J 4J 4J 4J .
CQ O O O O
J) rO 'CJ 'O T3
O 0 O O
y . Oj ft ft ft
3
3 4J 4-) 4-) 4J
j f^ f_j P-] - S-)
^ o o o o
O4 ft ft ft ft
ft ft ft ft
q CQ to tn CQ
o
ft O O O O
^ 4-) 4J 4J 4-)
3
-Q KN K^l ฃ*1 K^l
H H rH rH -
0 C S fl fl
4-> O O O O
3 "CJ T3 T3 T3
d> (U (U (U '0) ' '
$-1 S-i J-i 5-1 M
H -H -H -H -H
U1 O1 D1 O1 O1
Q)
-------
Ch
0
1
o
oin co
T-O Ol
OO C_
01 oo a.
> t^t^- x
o oo m
t- CMCM ,
OL CO
< 0 >
E Z 2
i- m a.
O ฃ Q.
u- 5 ซc
Si H
U Ol
Cn Oi
rtl CQ
a S
o
H CQ
j_j ^
u o H
i-i S S
r\] IT"
CM CQ
H
1 ซ' S
!ง.- i
O i_)
tj T!l rซ
, cn S
T1 d P
ง3 S
w m tซ
ro 5ป
(I)' 1=" CQ
Q)t>%
o vo -t:
fl 0 g
2 Is
x; z i
g a TJ ~
S -H c ^
z /"^ (B
? % 1.
CD ' C
% in g '5
8 S 1 i
CO ro ^ "IT
Cj -CN 0. Q-
~
0
o
CQ 0
CQ 0
H/-*k
C5
93 >bj rv/
co gj P5
is la
is &
U H ป
| fO OH EH
^J E" M
fc s .
0 CQ S 55
-i
4-f
CO
c.
CO CU
' ?
u) C
cu o
ce. ฃL
CO
ฐ>ซ
01
ฃ.
OOU.
0)
u
4-> C
CO CD
01 4J ,
s!cf
CO CU
13 4->
4^
CO
-O 0.
ro
CO
"2t: M
ง8. ~
ซ.. m
ซ~r>f-o"r>
5'
f
CO
in
I*
f || ซ.
( . . -
>
*
K
nซnr?nrtnt^nrtn??n
p5 jปy C j^. ps ^5 pS ^S pS ^S p5 ^3. pS
^lC*tNOaCNCSc>3ซ*VDซ*U)
cNt-tHHHHHO] Cซ (N
-.
^
(3งC3C9C3cac3c3 3 C3
h->-l t h-h-t-t- t- 1
.
%
O O 0 O
b^ j^l jy^ tyi/ tj ^J
uoowwooo o o
^ X SM *
^M ^4 ^(
W 4J ง 4J
a CD C- CD -
*
(U Q)
< *J: t.' *u L.
ffl 3" ซ 3
CA CO
QJ O 01 O
C Q, ฃ C3U >^ >.
3 X 3 X *J *ป
Wป UJ CO LU ป ซ^-
O Q U U
CL C S. C >^ l "- <
งX 0 X 0 *ป X X
Tij > ur **~ ^*^< o O
._UI4J'U4J0 l2 <2
4_t ซ* CD -~* CD *"
E L_ E- "ซ E "o O ฃ~ L.
00 O t- .C t- .C + OF 03
^- COOCCttC. TJ "O
-*oo ซ >-gc
Q^^^ t- _* O _, O _*
ซซ.oc.cc.c&iiii +3
oi S "5 J -- *5 -^^ S ง i
ca ar i uj uj tu LU < i:" z:
f f f f " " jj -" " .
oj co ca
OJ CQ Ol
'rt rH ' f t *
H * 1 H H H:
LO ' ^O" ^O PO1 CO CO" CO C3~ C5" 3-
oo it ^^ ^3 c^ P^T ^^ f** ^^* i^^
cu
CO
o
^ .
y
0) Ot
0) C
- o
a. co
o Q.
T3-
01ฐ
4-* H-
CD
U 0)'
CD -^
- CO
'E
at a.
"^
o E
-C 4-*
0 C
(O CU
ฐ4J g
4^ CU CU
CO 4J >
fD *^
4-ป 4J
'CO CD
CO , 4J
t3) C
tj C 0)
C CO
CD "O 0)
E S Q.
I . 01
O CO Oi
"""'i T3
CO CU
C- N
.CO
4^ C_
CU O
C CO J=
0 > 4J
CD 3
!|- I
4J - 2 CO
C 2 CO <"ป
0) -S^ 0) O
CD >*^ H-
4J C CO O
CO CD U
CU
0) 4J
c j: co a. 4^
o 4Jj: a.
. 4J CO h-
CO CO O c- 73
O Si Ol CU C
4J 73 "D ca
H- CU ฃ
X 3 0)
t! ฃ O.C 3
01 *ซป C 4"* 4-1"
cj t_ .ad o ca
CU OJ2 C
u CD ro
ฐ. -. .-. o 'co
0)
z
0)
c
o -
rt
jo
-
o
to
c
o
u
CD
ง
o
u
o
0)
ci
CN1 '
-------
H
O
rt
tr
itj
P4
o
o
t-t
[V,
^*
(i,
Q
S
i
t
N-b. 8
215 S
oo <-
TjJ i I ป.
^ f^l^ SC
k fk"y _
ซF o ง
ซ z 2
t- CQ O.
o =e ZC
u. o <
o ca
CJ g
Q) O
Cn fit
flj 00
a S
o
H CO
4J .
I ฐ 1
0 0 g
P4 03
. H
nJ . H
Q) ซ, Pi
E c2 j^i
Bn "^
5-1 t7) CO
^ *^ Pj
(o ***
CQ *3*
a) ca
CO SB
d) H
j i Cl
H O
B a
**
*
o
td
c
*-<
g
L.
ง
M
|
1
5
.
1
03
0
C9
ง
|
*J
*ซ
I
U
*B
01
x:
**
i"
3
M
ฃ
5
1
o
to
B
a 5 m
CM
o
o
CQ 0
CO O
to W ฐ
ฃ & Q
3 S Q ^
^B is ^
* O H *
^ J E-< H
|-CU 03 U
111 OO
grass::
4->
01
4->
03 Ctt
^ CO
OI C
ฐ!|
I
.,. g
(OU.
01
o
1 . ^
CO CO
ttt 4J
h- CO
^t?
c
O L.
ca 01
a
NO a.
Kl
CO
ss
f r
DJ o CM
o a.
^
a^o-ocjoj
ฃ
^
t
4-1
m
in
4. Guideline
Requirement
Number
,
%
ro <& ro to CQ
iliii
OJ H H H rH
^
C3 ^3" CD C3 U
^- *-. |_ + |
1
o
ซ wwoo
'
%>i
S -M -g- 4-ป
3 ซ c ai
fl Jr*t
a cu
CO CO
<&- o ซ g
ti ฃX t* Q.
4-. S. C S. C
to x o sc o
i> '5 _, '5
4-ป * CO ** tO
. m _. g. _.
4 S to E to
2 u- .e L .e
ctj U C eซ c
*<#-. M- H- H-
a> o o o o
44- 4^ *> 4J
T *? 7 v !M
c\j w iS itt i2
CN
1 t-f IN ซ:*
00 fif CJ Cป tN
ซ
ra'
z
^
c.
si
^ o
Q. S
O Q.
n
CO -
4-> H-
ca
3^"
o tu, "
oTJ?
3 CO
L. >f-
a> a.
CD 01
CO
M >>
|1
is c
to v
4^ w fl
CO 4J >
4J 4-'
to a
CO 4->
?.ฃ 1
COT} 01
to u
E tu a.
ฃ_. a>
o ca ae
"U"5 "s
^- ฃ_ N
-CO *-
*-ป t-
01 O
ง.2 is
CD 3
ป
4J-5 3 S
c'g jo a.
S5 o o
*J ^^ M-
4-1 C CO O
CO CO U
*- CD
01 4->
c j; to g. 4J
10. Certificat
1 certify that
I acknowledge
or both under
Signature and
8
B
1
o
j:
a.
o
u
CO
1
u
>ป
ฃ
CO
CJ
M-
o
-------
H
H
Oj
O
O
EH
ELI
rt
p{
Q
t>
fo
ro
oin co
00 C.
"73 ii'.-
cu oo Q-
O O O UJ
c_ ruc\j
Q. CD
< o >
z o
E <-
!_ co a.
0 SE 0.
u. O <
,
u to
(U ง
(7) Oi
)< CO
u
fl OB
0
-H CQ
J-) ซ
0 VO Z
Cj ^^ ' ^^
"CM "
CU CO
H
i i r } CJ
ai Ed
V fv
d ;
CU ^ Q
i g ง
O jj
w h^ ' m
i -i i
rvi *"^ E.J
03 m
to g
CD1 "* CQ
TO g
0) H
r) (3
,-rl &
a a
ฃ3 (6
- -
^
0
CO
M
c
o
I
CO
Q)
1
C
o
4J
t_
O
ฃ
^j
1
1
1
CO
c
o
*>
o
3
"S
c
I
u
CO
4-*
4-*
CO
0
5
^
^3
1
s*
TJ
CO
cu
c.
CO
CO
01
a.
c
.c
j or print
if necessar
Q"
>^ **
en a
CJ ^
' CO
fl
II
i!
en Oi
Z JJ
u
a
H-
O '
|a
t- H
"8-w
ซ &
I o
.
fO
c-
1
'***
1
o
ฃ_
g
' Q.
I
I
H j|
cu o j.
fl O '
O H
| ca cj EH
c J H H
g'Oj TO U
111 0 0
5 TO S S5
1 ' '
4-ป
CO CU
52 .
CO
cs at
i
S 01
t e
OT
ฃ_
CO li-
CU
o
4-ป C
CO CO
O 4J
'"^
N- OS
c
cu c_
CO O
D !-
4-*
CO
O Q.
M
CO
I*. t
t- J O3 CXI CM
tH H H H H -
o S ca ca a . . - - .
'
-
' ,
*s<{ [vj |v*j ^^ ^^
>*,
E '
TJ 0
4-ป 4-* T3 4J .
3 CO C CO
ฐ 2: 2 ฃ
CD 3 CO 3
CO CO
cu o cu o
i- a. i- Q. '
3 X IT X
CO. UJ ^tO UJ
S. c S. c .
c x o x o
O UJ UJ
4-* ซ CD ป CO
Q. ca ca '
C- E CO E CD
O t- J= <~ JC
CO O C CU C
3 o -*ป-..
^V <ซ-**- H- M-
0,0000
o c. c tz c '
CO O O O O
"g "5 ฃ w '43
S4J *J 4J 4-ป
en .co co co
-J .C": lil.;,'.UJ- LU _
.
rH ..-''
fl H CM r<> ^l1
vo {*} rn -TO- rn
H
CO
o
,ฃ
,
CO "
ป CO CO
CO 4-*
0) C
a c o
C - CO
el fe.
t. . cu
O CO Oฃ
ฃ_ N
J= 0 '
4-> C-
flj O
g^ 5
"ra >. co
CO? . ฅ
4J -^ 3 CO
c 3 ra a.
CU O ' , g
' CU *^ 01 CJ
4-ป '
4-> C CO, O
CO CD U
CU 4->^
c j= co a. 4->
o 4-ซ j: a.
r- 4^ CO *
o o oป t- -a
U _C O) <0 " C
5: --gl -0
X^ 3 4J C 4-1 4^
CJ t- Ji O CO
0) OJ3 C
o co ra
? ^ ~ c5 ซ
'
t_
o
1
g
JC
a.
5
o
CO
4J
c
o
CJ
1
CJ
o
ซJ
* '
-------
r-
c
T"!
kZ
0
rt
D4
PM
O
U
*
fe
rf
ftf
Q
i
i
M
O
OMI co
oo t-
o i i M
c-|v. X
O OO UJ
8u 'a
< 0 >
2E O
E t-
1_ ฃ0 fj.
O 3E O.
u. S <
U CQ
r* ggp*
Q) O
en cu
fl! TO
H
rt ff.
0
H CQ
4J ป
S g g
^ M E*
04 TO
. H
ttf . H
JJ Q flj
rt
d} ^ c^
i g ง
p jj
H tn SJ
H ฃซ n
^ "fj ^ซ
w m g
ra -1 ra
a)-12 ca
s i
CO ฃ
d S
0) 1-1
4-3 ^
H O
>H B^
-
O
to
4-*
g
tJ
111
4"ป
1
C.
g
S
0
H-*
C
f
j^
to
?
ง
tn
g
M
t_
W
w
g
j=
5
a
u
j=
4-1
-;
"s
M-
cu
T>
ca
cu
c.
o
CO
8
a.
c
c
L.
4-> CD
C CO
- CO
t- u
ฐ* cu
lซ
o ir
CD a
_eu j=
UCTIONS: P
dditional
at eg
H-
u
o
M-
o ,
"O PH
1 w
I o
to
i
o
H-
*^
1
O
1
"5^
c
cu
i
u
OJ 5
o t
G co
rH H *
nJ H ซM
^C"* , ^J*
4_J z
(Deo
S z ฃ
i| ll
u % **
01 LO a j
VD '5 *
1 OJ 5 I
a
CM
O
O
CO 0
CQ 0
|ggฐ
S ^ R b!
< Pป ^ซ ^s
s U H *
i H >*
1 H DJ E-ซ
c i4 E^ M
g-Oi CO U
งง O O
S ซ> S! S
w-
C
CO
CO 4)
*- 01
wg
Cw O
oc CL.
ปi
J ง
ฃ_
03 U-
81
4-S
SCO
**
K- 0)
NlS
O c.
CO CD
CO
oo.
M
ca
..t
O> O ซM
ฃง-
-
^1 iVOl Of >O f
M
^~
1
w "
in
II,
3li
< >. >H }H
>^ 9*4 ^H
TJ: O
3 03 C ซJ
O "-
cu di
M 21 *J L.
CO TT CO 3
O) CO
ฃ a 2 S.
3 x 3 x;
to UJ- to uj 2
^, S. e 8, c i "H r"E
e* X O X O CD *^ *^
O^ UJ >>H- til < 3E m OQ^
sSrง'ซง"cdc c
2 ซ- ซ "S ซ> ง 'E 'E 'E ,
jป- o ปซ o *-ซ o o o
41 Q C C! C C ^^ 2 2 2
e= tfl OOOQ^Q>>O>ซQ
cu ซ-<. -^ >ป o o o
CI04-*ซi>4-*4^-U U O
a>4!co<0to cu cu
C3 _ฃ 111 m UJ lu CO O ซ
* * *
^ - '
CQ CQ CO
CQ , CO' CO
-rt iii
HK- rtj m m
1 -C*V rH CSf CO ^J* I I l
in vฃ>- n f} n n> o o o
eoH-cNCNjcscMr- c- i>
cu
a
j;
4-J
, j^
CU C
o
Q. W
U Q.
o .
c""
"c"
Q> ซ
CO
ฃ_ X
o
u
CO
..* 3! 0
C 3 CO g.
S -^ t-
4-> C CO O
CO CD O
_ CU
-'
c ^: o Q. 4-1
O 4J JC 'Q.
4-> O 1
CO CO O C_ -D
O .C O) CU C
>. ' 3 O
4-* M- 3 t_
ซ- O -C 3
CU 4-ป C 4-ป 4^
cj i--v: o co
Oป O ^2 C
O CO D)
O [_
ซ^ o en
cu
cu
c
o
rป
Kl
f
u
CD
c
o
CJ
>.
c
CO
H-
0
CO
C\J
-------
H
4-1
o
H
CD
- tr
(d
CU
*
*
o
a
CD,
f^
CQ
j-j EH
o 5
i ly
4J S
CD ฐ S '
4-> i# p
ฐ CM M
K
I *
fd . B
4-> Q 3
d -
fc3
es Environnu
Washington,
fS FOR GUIDE
jj E
Id 5
4J ง
CQ S
0 1
4J
. 4f, . -
"3
!D
*~-^
XI
jj
ฃ
5
o
i-H
4-1
-H
fj
,
i
i
i
ibromopheny;
(i
.j
i
kD
k
"*
CM
^
i
O
5-1
jH
j-i
-H
/d
,,
d -
-H CM
i i '
rd iH
4-> a, X!
CD E 4J
a s CD
1 0 TJ S
(D H C
z CQ ra
a qt cxj
m ^ O
ซ: in S oo
ซ, <-D 1 CM
co E"^- S r~ I
S CM 5 rH
' . \
I
UJ
s:
u
'
-z
_j
UJ
t-1
C3
(D
CD M - ' .
rl Cd ' . .
(d
4-) .--'-.
4-1 4-5 d
0 d ฃ!
-.X} .-. '" - . '-.
CQ '
i-H = =
-H " CQ CQ
rd CD tn
& . fl ' fl
-H -H
CD -d .'d
"d rH i-H
-H -H -H
co d d
O 4-1 t[ |
o o
CD ,
X! CO CQ
4->t-Hi-H -
4J id rd
co . 9 S
SH
-H CD CD "-..''
(d T^ *d
CD -H . -H
rdrora
4J ,4J
r^ 3 ' 3
rH O O
QJ >
4J CD CD '
fd xl xl
-H 4J 4-)
d - .
CD CQ CD CD - .
e CD a a
S co o o
-H d rH rH . '
d JH
cj CD "d "d ,
(d x! d fl.
4J td (d -
CQ O
JH tn m .-.'..
O ^s S-i V[
o d o o
d fd o o
fl -d -d .
-H r) fl S , ' '
= O -H ,-H
4-1 = =
in
O T3 JH SH
4HCDOCQOCQ
^1 4^ 0)- . 4-1 CD
TJ -H CQ CQ .
SH d1 (D CD
-H CD !H JH SH JH
d r< -H CD -H CD
d1 d xl d x!
CD cu d'jj d"4-)
M ^ 0 O CD O
fdrfrl
4-J p"i ^*i , '
O 4J 4-> fl - 4-> fl
d d o m o rd
^C^ SH d
(D t JH 5-i
5-l-CDOCDO ,
frt c 5 1 '1 i S-i ti^i
CQ nj fd
CQ in *d *d .
CD fl CQ CD / CQ CD
H -H CD 5H CD 5-1 '
d "d -H -H -H -H . '
d rH >d d "d d
4.) -H d d1 d d1
CQ' d 4-) CD 4-) CD
*XJCQ5HCQ$H
CQ . CQ 03 '
CQ ' CQ. CQ
i 11 _ .
<1 ffl CQ
iii *
O O ~O
i> o r-
-------
210
-------
0
o
-H
O
43
a
0
o 1
E *H ซ
ID 43 c
Z r\ <0
H *
o; .
tii ^ " , .
i .
i
. ' '
3 ' -
' v
o .' ' "
o ' .'..-'
CJ
Z r
3=
CJ
LU .
s?
0.
-1 , . '
;
P2 ' ' - ;
pi
o
o ...'.'
-------
(D
O
-H
*cj
(3
*H-
H
ra i
.u ro
r-l
nJ H
OQ t
O H
nl -u
Q)
U
(U rcS
fl H
a &
Sit
^^ s* "rH
1-H4! ฐ
*D "Ifc i
I* ^^ |~1
*mlS
o o -g r-
e> OJ 5 VD
S CNJ 5 0
CL
01
CO
oB
CJ
U)
- N. N.
ro ro KI
in in in
- . , , , ,
333
0 ง g
W C/3 C/? ,
O O O
i i g
ง
m
uj
| 5 .
to en
ง S 3 '
^- ^ ^
X S N-
o ^ ro
m ro in
,
o
CO
UJ
i
< .
^ o
=C CO -ซ
^ "^ d*
O -J CJ
O I O
^C UJ <
=c CD =n
,
o* in co
K>
-------
.
0)
a
o
o
-H
d
1
i o
CD SkJ
CO
* 0
ป-vo
ฃ0 C1*-
3 oj
o
JH
a
rH
cT
0)
i
rH
i
o
>i
,Cj
m
'rH
1
1
8.
L.
0)
E
!
o .''
ซM '-''' ,
; .: '... v '.'. '. ':
3
UJ - " '
UJ . . ...
i . '-'- . " '
I - . . , . .
UJ - .
i
en
u
00
UJ
3 . '
1 ' ' '
o .
^ ,
o- ' . ' -
" - .
UJ
3= .
a. ' '
t~* '
LL. - '
O
o - ' .
CO '
< ' " '
" , '.. '
1 .
UJ .
o
c ;
o
o . .
-------
1
m
H
o 03 g H
-------
t
CO
CO
o
S
"3
S-
o
o
O
nj
in
-H
8
g
ง
o
tti
-H
-a
=
PQ
g *^
co O
% m S r-
g m -g CM
I CM 5 rH
eo
C5
O
-------
216
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFB1CE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
DATA CALL-IN NOTICE
CERTIFIED MAIL
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the active
ingredient identified in Attachment 1 of this Notice, the Data Call-in Chemical Status Sheet, to
submit certain product specific data as noted herein to the U.S. Environmental Protection
Agency (EPA, the Agency). These data are necessary to maintain the continued registration
of your product(s) containing this active ingredient. Within 90 days after you receive this
Notice you must respond as set forth in Section El below. Your response must state:
_ ' 1. How you will comply with the requirements set forth in this Notice and its
Attachments A through G; or
2. Why you believe you are exempt from the requirements listed in this Notice and
in Attachment 3, Requirements Status and Registrant's Response Form, (see
section ]H-B); or
' ' , ~~~x
3. Why you believe EPA should not require your submission of product specific
data in the manner specified by this Notice (see section TTT-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply
with its requirements or should be exempt or excused from doing so, then the registration of
your product(s) subject to this Notice will be subject to suspension. We have provided a list
of all of your products subject to this Notice in Attachment 2, Data Call-in Response Form, as
well as a list of all registrants who were sent this Notice (Attachment 6).
The authority for this Notice is section 3(c)(2)(B) of the Federal Insecticide, Fungicide
and Rodenticide Act as amended (FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
information is authorized under the Paperwork Reduction Act by OMB Approval No. 2070-
0107 (expiration date 12-31-99).
217
-------
This Notice is divided into six sections and seven Attachments. The Notice itself contains
information and instructions applicable to all Data Call-in Notices. The Attachments contain
specific chemical information and instructions. The six sections of the Notice are:
Section I - Why You Are Receiving This Notice
Section IE - Data Required By This Notice
Section HI - Compliance With Requirements Of This Notice
Section IV - Consequences Of Failure To Comply With This Notice
Section V - Registrants' Obligation To Report Possible Unreasonable
Adverse Effects
Section VI - Inquiries And Responses To This Notice
The Attachments to this Notice are:
1 - Data Call-in Chemical Status Sheet
2 - Product-Specific Data Call-in Response Form
3 - Requirements Status and Registrant's Response Form
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5 - EPA Acceptance Criteria
6 - List of Registrants Receiving This Notice
7 - Cost Share and Data Compensation Forms, and Product Specific Data Report
Form
SECTION!. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient and reevaluated the
data needed to support continued registration of the subject active ingredient. The Agency has
concluded that the only additional data necessary are product specific data. No additional
generic data requirements are being imposed. You have been sent this Notice because you
have product(s) containing the subject active ingredient.
. SECTION E. DATA REQUIRED BY THIS NOTICE
H-A. DATA REQUIRED
The product specific data required by this Notice are specified in Attachment 3,
Requirements Status and Registrant's Response Form. Depending on the results of the studies
required in this Notice, additional testing may be required.
H-B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements specified in
Attachment 3, Requirements Status and Registrant's Response Form, within the time frames
provided.
218
-------
II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test standards
outlined in the Pesticide Assessment Guidelines for those studies for which guidelines have been
established. ,
These EPA Guidelines are available from the National Technical Information Service
(NTIS), Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (tel: 703-487-4650).
Protocols approved by the Organization for Economic Cooperation and Development '
(OECD) are also acceptable if the OECD-recommended test standards conform to those specified
in the Pesticide Data Requirements regulation (40 CFR ง 158.70). When using the OECD
protocols, they should be modified as appropriate so that the data generated by the study will
satisfy the requirements of 40 CFR ง 158. Normally, the Agency will not extend deadlines for
complying with data requirements when the studies were not conducted in accordance with
acceptable standards. The OECD protocols are available from OECD, 1750 Pennsylvania
Avenue N.W., Washington, D.C. 20006.
All new studies and proposed protocols submitted in response to this Data Call-In Notice
must be in accordance with Good Laboratory Practices [40 CFR Part 160.3(a)(6)].
n-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3fc>mrF> NOTICES
ISSUED BY THE AGENCY
Unless otherwise noted herein, this Data Call-in does not in anv wav supersede or change
the requirements of any previous Data Call-Infsl or any other agreements entered into with the
Agency pertaining to such prior Notice. Registrants must comply with the requirements of all
Notices to avoid issuance of .a Notice of Intent to Suspend their affected products. '
SECTION HI. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
m-A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice for product specific data must'
be submitted to the Agency within 90 days after your receipt of this Notice. Failure to
adequately respond to this Notice within 90 days of your receipt will be a basis for issuing a
Notice of Intent to Suspend (NOIS) affecting your products. This and other bases for issuance of
NOIS due to failure to comply with this Notice are presented in Section IV-A and IV-B.
HI-B. OPTIONS FOR RESPONDING TO THE AGENCY
The options for responding to this Notice for product specific data are: (a) voluntary
cancellation, (b) agree to satisfy the product specific data requirements imposed by this notice or
(c) request a data waiver(s).
A discussion of how to respond if you chose the Voluntary Cancellation option is
presented below. A-discussion of the various options available for satisfying the product specific
219
-------
data requirements of this Notice is contained in Section ffi-C. A discussion of options relating to
requests for data waivers is contained in Section tH-D.
There are two forms that accompany this Notice of which, depending upon your response,
one or both must be used in your response to the Agency. These forms are the Data-Call-in
Response Form, and the Requirements Status and Registrant's Response Form. Attachment 2 and
Attachment 3. The Data Call-in Response Form must be submitted as part of every response to
this Notice. In addition, one copy of the Requirements Status and Registrant's Response Form
must be submitted for each product listed on the Data Call-in Response Form unless the
voluntary cancellation option is selected or unless the product is identical to another (refer to the
instructions for completing the Data Call-In Response Form in Attachment 2). Please note that
the company's authorized representative is required to sign the first page of the Data Call-in
Response Form and Requirements Status and Registrant's Response Form (if this form is
required) and initial any subsequent pages. The forms contain separate detailed instructions on the
response options. Do not alter the printed material. If you have questions or need assistance in
preparing your response, call or write the contact person(s) identified in Attachment 1.
1. Voluntary Cancellation - You may avoid the requirements of this Notice by requesting
voluntary cancellation of your product(s) containing the active ingredient that is the subject of this
Notice. If you wish to voluntarily cancel your product, you must submit a completed Data Call-
in Response Form, indicating your election of this option. Voluntary cancellation is item number
5 on the Data Call-In Response Form. If you choose this option, this is the only form that you
are required to complete.
If you chose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice which are contained in Section IV-C.
2. Satisfying the Product Specific Data Requirements of this Notice There are various
options available to satisfy the product specific data requirements of this Notice. These options
are discussed in Section ni-C of this Notice and comprise options 1 through 6 on the
Requirements Status and Registrant's Response Form and item numbers 7a and 7b on the Data
Call-in Response Form. Deletion of a use(s) and the low volume/minor use option are not valid
, options for fulfilling product specific data requirements.
3. Request for Product Specific Data Waivers. Waivers for product specific data are
discussed in Section IH-D of this Notice and are covered by option 7 on the Requirements Status
and Registrant's Response Form. If you choose one of these options, you must submit both
forms as well as any other information/data pertaining to the option chosen to address the data
requirement.
ffi-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call-in Response Form that you agree to satisfy the
product specific data requirements (i.e. you select item number 7a or 7b), then you must select
one of the six options on the Requirements Status and Registrant's Response Form related to data
production for each data requirement. Your option selection should be entered under item
220
-------
number 9, "Registrant Response." The six options related to data production are the first six
options discussed under item 9 in the instructions for completing the Requirements Status and
Registrant's Response Form. These six options are listed immediately below with information in
parentheses to guide registrants to additional instructions provided in this Section. The options
are:
(1) I will generate and submit data within the specified time frame (Developing Data)
(2) I have entered into an agreement with one or more registrants to develop data
jointly {Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing
study that has been submitted but not reviewed by the Agency (Citing an Existing
Study) -
Option 1. Developing Data - If you choose to develop the required data it must be in
conformance with Agency deadlines and with other Agency requirements as referenced herein
and in the attachments. All data generated and submitted must comply with the Good Laboratory
Practice (GLP) rule (40 CFR Part 160), be conducted according to the Pesticide Assessment
Guidelines (PAG), and be in conformance with the requirements of PR Notice 86-5.
The time frames in the Requirements Status and Registrant's Response Form are the time
frames that the Agency is allowing for the submission of completed study reports. The noted
deadlines run from the date of the receipt of this Notice by the registrant. If the data are not
submitted by the deadline, each registrant is subject to receipt of a Notice of Intent to Suspend the
affected registration(s).
If you cannot submit the data/reports to the Agency in the time required by this Notice
and intend to seek additional time to meet the requirements(s), you must submit a request to the
Agency which includes: (1) a detailed description of the expected difficulty and (2) a proposed
. schedule including alternative dates for meeting such requirements on a step-by-step basis. You
must explain any technical or laboratory difficulties and provide documentation from the
laboratory performing the testing. While EPA is considering your request, the original deadline
remains. The Agency will respond to your request in writing. If EPA does not grant your
request, the original deadline remains. Normally, extensions can be requested only in cases of
extraordinary testing problems beyond the expectation or control of the registrant. Extensions
will not be given in submitting the 90-day responses. Extensions will not be considered if the
request for extension is not made in a timely fashion; in no event shall an extension request be
considered if it is submitted at or after the lapse of the subject deadline.
Option 2, Agreement to Share in Cost to Develop Data - Registrants may .
this option for acute toxiciry data and certain efficacy data and only if EPA has indicated in the
attached data tables that your product and at least one other product are similar for purposes of
depending on the same data. If this is the case, data may be generated for just one of the
221
-------
products in the group. .The registration number of the product for which data will be submitted
must be noted in the agreement to cost share by the registrant selecting this option. If you choose
to enter into an agreement to share in the cost of producing the required data but will not be
submitting the data yourself, you must provide the name of the registrant who will be submitting
the data. You must also provide EPA with documentary evidence that an agreement has been
formed. Such evidence may be your letter offering to join in an agreement and the other
registrant's acceptance of your offer, or a written statement by the parties that an agreement
exists. The agreement to produce the data need not specify all of the terms of the, final
arrangement between the parties or the mechanism to resolve the terms Section 3(c)(2)(B)
provides that if the parties cannot resolve the terms of the agreement they may resolve their
differences through binding arbitration.
Option 3. Offer to Share in the Cost of Data Development ~ This option only applies to
acute tOxicity and certain efficacy data as described in option 2 above. If you have made an offer
to pay in an attempt to enter into an agreement or amend an existing agreement to meet the
requirements of this Notice and have been unsuccessful, you may request EPA (by selecting this
option) to exercise its discretion not to suspend your registration(s), although you do not comply
with the data submission requirements of this Notice. EPA has determined that as a general
policy, absent other relevant considerations, it will not suspend the registration of a product of a
registrant who has in good faith sought and continues to seek to enter into a joint data
development/cost sharing program, but the other registrant(s) developing the data has refused to
accept your offer. To qualify for this option, you must submit documentation to the Agency
proving that you have made an offer to another registrant (who has an obligation to submit data)
to share in the burden of developing that data. You must also submit to the Agency a completed
EPA Form 8570-32, Certification of Offer to Cost Share in the Development of Data,
Attachment 7. In addition, you must demonstrate that the other registrant to whom the offer was
made has not accepted your offer to enter into a cost sharing agreement by including a copy of
your offer and proof of the other registrant's receipt of that offer (such as a certified mail
receipt). Your offer must, in addition to anything else, offer to share in the burden of producing
the data upon terms to be agreed or failing agreement to be bound by binding arbitration as
provided by FIFRA section 3(c)(2)(B)(iii) and must not qualify this offer. The other registrant
must also inform EPA of its election of an option to develop and submit the data required by this
Notice by submitting a Data Call-in Response Form and a Requirements Status and Registrants
Response Form committing to develop and submit the data required by this Notice.
In order for you to avoid suspension under this option, you may not withdraw your offer
to share in the burdens of developing the data. In addition, the other registrant must fulfill its
commitment to develop and submit the data as required by this Notice. If the other registrant
fails to develop the data or for some other reason is subject to suspension, your registration as
well as that of the other registrant will normally be subject to initiation of suspension
proceedings, unless you commit to submit, and do submit the required data in the specified time
frame. In such cases, the Agency generally will not grant a time extension for submitting the
data.
Option 4. Submitting an Existing Study If you choose to submit an existing study in
response to this Notice, you must determine that the study satisfies the requirements imposed by
this Notice. You may only submit a study that has not been previously submitted to the Agency
222
-------
or previously cited by anyone. Existing studies are studies which predate issuance of this Notice.
Do not use this option if you are submitting data to Upgrade a study. (See Option 5).
You should be aware that if the Agency determines that the study is not acceptable, the
Agency will require you to comply with this Notice, normally without an extension of the
required date of submission. The Agency may determine at any time that a study is not valid and
needs to be repeated. . , '
To meet the requirements, of the DCI Notice for submitting an existing study* all of the
following three criteria must be clearly met:
a. You must certify at the time that the existing study is submitted that the raw data
and specimens from the study are available for audit and review and you must
identify where they are available. This must be done in accordance with the
requirements of the Good Laboratory Practice (GLP) regulation, 40 CFR Part
160. As stated in 40 CFR 160.30 " 'raw data1 means any laboratory worksheets,
records, memoranda, notes, or exact copies thereof, that are the result of original
observations and activities of a study and are necessary for the reconstruction and
evaluation of the report of that study. In the event that exact transcripts of raw
data have been, prepared (e.g., tapes which have been transcribed verbatim, dated,
and verified accurate by signature), the exact copy or exact transcript may be
substituted for the original source as raw data. 'Raw data' may include
photographs, microfilm or microfiche copies, computer printouts, magnetic media,
including dictated observations, and recorded data from automated instruments."
The term "specimens", according to 40 CFR 160.3(k), means "any material
derived from a test system for examination or analysis."
b. Health and safety studies completed after May 1984 must also contain all GLP-
required quality assurance and quality control information, pursuant to the
.requirements of 40 CFR Part 160. Registrants must also certify at the time of
submitting the existing study that such GLP information is.available for post-May
1984 studies by including an appropriate statement on or attached to the study
: signed by an authorized official or representative of the registrant.
c. You must certify that each study fulfills the acceptance criteria for the Guideline
relevant to the study provided in the FIFRA Accelerated Reregistration Phase 3
Technical Guidance and that the study has been conducted according to the ป
Pesticide Assessment Guidelines (PAG) or meets the purpose of the PAG (both
available from NTIS). A study not conducted according to the PAG may be
submitted to the Agency for consideration if the registrant believes that the study
clearly meets the purpose of the PAG. The registrant is referred to 40 CFR
158.70 which states the Agency's policy regarding acceptable protocols. If you
wish to submit the study, you must, in addition to certifying that the purposes of
the PAG are met by the study, clearly articulate the rationale why you believe the
study meets the purpose of the PAG, including copies of any supporting
information or data. It has been the Agency's experience that studies completed
223 ,
-------
prior to January 1970 rarely, satisfied the purpose of the PAG and that necessary
raw data are usually not available for such studies.
If you submit an existing study, you must certify that the study meets all requirements of
the criteria outlined above.
If you know of a study pertaining to any requirement in this Notice which does not meet
the criteria outlined above but does contain factual information regarding unreasonable adverse
effects, you must notify the Agency of such a study. If such study is in the Agency's files, you
need only cite it along with the notification. If not in the Agency's files, you must submit a
summary and copies as required by PR Notice 86-5.
Option 5. Upgrading a Study If a study has been classified as partially acceptable and
upgradeable, you may submit data to upgrade that study. The Agency will review the data
submitted and determine if the requirement is satisfied. If the Agency decides the requirement is
not satisfied, you may still be required to submit new data normally without any time extension.
Deficient, but upgradeable studies will normally be classified as supplemental. However, it is
important to note that not all studies classified as supplemental are upgradeable. If you have
questions regarding the classification of a study or whether a study may be upgraded, call or
write the contact person listed in Attachment 1. If you submit data to upgrade an existing study
you must satisfy or supply information to correct all deficiencies in the study identified by EPA.
You must provide a clearly articulated rationale of how the deficiencies have been remedied or
corrected and why the study should be rated as acceptable to EPA. Your submission must also
specify the MRID number(s) of the study which you are attempting to upgrade and must be in
conformance with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a study classified as
unacceptable and determined by the Agency as not capable of being upgraded.
This option should also be used to cite data that has been previously submitted to upgrade
a study, but has not yet been reviewed by the Agency. You must provide the MRID number of
the data submission as well as the MRID number of the study being upgraded.
The criteria for submitting an existing study, as specified in Option 4 above, apply to all
data submissions intended to upgrade studies. Additionally your submission of data intended to
upgrade studies must be accompanied by a certification that you comply with each of those
criteria as well as a certification regarding protocol compliance with Agency requirements.
Option 6. Citing Existing Studies If you choose to cite a study that has been previously
submitted to EPA, that study must have been previously classified by EPA as acceptable or it
must be a study which has not yet been reviewed by the Agency. Acceptable toxicology studies
generally will have been classified as "core-guideline" or "core minimum." For all other
disciplines the classification would be "acceptable." With respect to any studies for which you
wish to select this option you must provide the MRID number of the study you are citing and, if
the study has been reviewed by the Agency, you must provide the Agency's classification of the
study.
224
-------
If you are citing a study of which you are not the original data submitter, you must submit
a completed copy of EPA Forms 8570-34 and 8570-35, Certification with Respect to Citation of
Data, and Data Matrix.
Registrants who select one of the above 6 options must meet all of the requirements
described in the instructions for completing the Data Call-in Response Form and the
Requirements Status and Registrant's Response Form, as appropriate.
HI-D REQUESTS FOR DATA WAIVERS
If you request a waiver for product specific data because you believe it is'
inappropriate, you must attach a complete justification for the request, including technical
reasons, data .and references to relevant EPA regulations, guidelines or policies. (Note: any
supplemental data must be submitted in the format required by PR Notice 86-5). This will be the
only opportunity to-state the reasons or provide information in support of your request. If the
Agency approves your waiver request, you will not be required to supply the data pursuant to '*
section 3(c)(2)(B) of FIFRA. If the Agency denies your waiver request, you must choose an
option for meeting the data requirements of this Notice within 30 days of the receipt of the
Agency's decision. You must indicate and submit the option chosen on the Requirements Status
and Registrant's Response Form. Product specific data requirements for product chemistry,
acute toxicity and efficacy (where appropriate) are required for all products and the Agency
would grant a waiver only under extraordinary circumstances. You should also be aware that
submitting a waiver request will not automatically extend the due date for the study in question.
Waiver requests submitted without adequate supporting rationale will be denied and the original
due date will remain in force.
IV. CONSEQUENCES OF FAILURE .TO COMPLY WITH THIS NOTICE
IV-A NOTICE OF INTENT TO SUSPEND
The Agency may issue, a Notice of Intent to Suspend products subject to this Notice due to
failure by a registrant to comply with the requirements of this Data Call-in Notice, pursuant to
FIFRA section 3(c)(2)(B). Events which may be the basis for issuance of a Notice of Intent to
Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your receipt oflhis
Notice.
2. Failure to submit on the required schedule an acceptable proposed or final protocol
when such is required to be submitted to the Agency for review.
3. Failure to submit on the required schedule an adequate progress report on a study
as required by this Notice.
4. Failure to submit on the required schedule acceptable data as required by this
Notice.
225
-------
5. Failure to take a required action or submit adequate information pertaining to any
option chosen to address the data requirements (e.g., any required action or
information pertaining to submission or citation of existing studies or offers,
arrangements, or arbitration on the sharing of costs or the formation of Task
Forces, failure to comply with the terms of an agreement or arbitration concerning
joint data development or failure to comply with any terms of a data waiver).
6. Failure to submit supportable certifications as to the conditions of submitted
studies, as required by Section UI-C of this Notice.
7. Withdrawal of an offer to share in the cost of developing required data.
8. Failure of the registrant to whom you have tendered an offer to share in the cost of
developing data and provided proof of the registrant's receipt of such offer or
failure of a registrant on whom you rely for a generic data exemption either to:
" '
a. inform EPA of intent to develop and submit the data required by this
Notice on a Data Call-In Response Form and a Requirements Status and
Registrant's Response Form:
b. fulfill the commitment to develop and submit the data as required by this
Notice; or
c. otherwise take appropriate steps to meet the requirements stated in this
Notice, unless you commit to submit and do submit the required data in the
specified time frame.
9. Failure to take any required or appropriate steps, not mentioned above, at any time
following the issuance of this Notice.
IV-B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS
UNACCEPTABLE
The Agency may determine that a study (even if submitted within the required time) is
unacceptable and constitutes a basis for issuance of a Notice of Intent to Suspend. The grounds
for suspension include, but are not limited to, failure to meet any of the following:
1. EPA requirements specified in the Data Call-in Notice or other documents
incorporated by reference (including, as applicable, EPA Pesticide Assessment
Guidelines, Data Reporting Guidelines, and GeneTox Health Effects Test Guidelines)
regarding the design, conduct, and reporting of required studies. Such requirements
include, but are not limited to, those relating to test material, test procedures, selection of
species, number of animals, sex and distribution of animals, dose and effect levels to be
tested or attained, duration of test, and, as applicable, Good Laboratory Practices.
2. EPA requirements regarding the submission of protocols, including the incorporation
of any changes required by the Agency following review.
226
-------
3. EPA requirements regarding the reporting of data, including the manner of reporting,
the completeness of results, and the adequacy of any required supporting (of raw) data,
including, but not limited to, requirements referenced or included in this Notice or
contained in PR 86-5. All studies must be submitted in the form of a final report; a
preliminary report will not be considered to fulfill the submission requirement.
IV-C EXISTING STOCKS OF SUSPENDED OR CANCELLED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing
stocks of a pesticide product which has been suspended or cancelled if doing so would be
consistent with the purposes of the Act.
The Agency has determined that such disposition by registrants of existing stocks for a
suspended registration when a section 3(c)(2)(B) data request is outstanding would generally not
be consistent with the Act1 s purposes. Accordingly, the Agency anticipates granting registrants
permission to sell, distribute, or use existing stocks of suspended produces) only in exceptional
circumstances. If you believe such disposition of existing stocks of your produces) which may
be suspended for failure to comply with this Notice should be permitted, you have the burden of
clearly demonstrating to EPA that granting such permission would be consistent with the Act.
You must also explain why an "existing stocks" provision is necessary, including a statement of
the quantity of existing stocks and your estimate of the time required for their sale, distribution,
and use. Unless you meet this burden the Agency will not consider any request pertaining to the
continued sale, distribution, or use of your existing stocks after suspension.
If you request a voluntary cancellation of your product(s) as a response to this Notice and
your product is in full compliance with all Agency requirements, you will have, under most
circumstances, one year from the date your 90 day response to this Notice is due, to sell,
distribute, or use existing stocks. Normally, the Agency will allow persons other than the
registrant such as independent distributors, retailers and end users to sell, distribute or use such
existing stocks until the stocks are exhausted. Any sale, distribution or use of stocks of
voluntarily cancelled products containing an active ingredient for which the Agency has particular
risk concerns will be determined on case-by-case basis.
Requests .for voluntary cancellation received after the 90 day response period required by
this ^Notice will not result in the Agency granting any additional time to sell, distribute, or use
existing stocks beyond a year from the date the 90 day response was due unless you demonstrate
to the Agency that you are in full compliance with all Agency requirements, including the
requirements of this Notice. For example, if you decide to voluntarily cancel your registration
six months before a 3 year study is scheduled to be submitted, all progress reports and other
information necessary to establish that you have been conducting the study in an acceptable and
good faith manner must .have been submitted to the Agency, before EPA will consider granting
an existing stocks provision.
SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLE
UNREASONABLE ADVERSE EFFECTS
227
-------
Registrants are reminded that FIFRA section 6(a)(2) states that if at any time after a
pesticide is registered a registrant has additional factual information regarding unreasonable
adverse effects on the environment by the pesticide, the registrant shall submit the information to
the Agency. Registrants must notify the Agency of any factual information they have, from
whatever source, including but not limited to interim or preliminary results of studies, regarding
unreasonable adverse effects on man or the environment. This requirement continues as long as
the products are registered by the Agency.
SECTION VI. INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by this
Notice, call the contact person(s) listed in Attachment 1, the Data Call-In Chemical Status Sheet.
All responses to this Notice (other than voluntary cancellation requests and generic data
exemption claims) must include a completed Data Call-in Response Form and a completed
Requirements Status and Registrant's Response Form (Attachment 2 and Attachment 3 for
product specific data) and any other documents required by this Notice, and should be submitted
to the contact person(s) identified in Attachment 1. If the voluntary cancellation or generic data
exemption option is chosen, only the Data Call-in Response Form need be submitted.
The Office of Compliance Monitoring (OCM) of the Office of Pesticides and Toxic
Substances (OPTS), EPA, will be monitoring the data being generated in response to this Notice.
Sincerely yours,
Lois A. Rossi, Director
Special Review and
Reregistration Division
Attachments
1 - Data Call-In Chemical Status Sheet
2 - Product-Specific Data Call-In Response Form
3 - Requirements Status and Registrant's Response Form
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5 - EPA Acceptance Criteria
6 - List of Registrants Receiving This Notice
7 - Cost Share and Data Compensation Forms, and Product Specific Data Report
Form
228
-------
2665 DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent one of the following Product Specific Data Call-In Notices because you
have product(s) containing a'rodenticide.
This Product Specific Data Call-in Chemical Status Sheet, contains an overview of data
required by this notice, and point of contact for inquiries pertaining to the reregistration of the
rodenticides. This attachment is to be used in conjunction with (1) the Product Specific Data Call-In
Notice, (2) the Product Specific Data Call-In Response Form (Attachment 2), (3) the Requirements
Status and Registrant's Form (Attachment 3), (4) EPA's Grouping of End-Use Products for Meeting
Acute Toxicology Data Requirement (Attachment 4), (5) the EPA Acceptance Criteria (Attachment
5), (6) a list of registrants receiving this DCI (Attachment 6) and (7) the Cost Share and Data
Compensation Forms in replying to your rodenticide Product Specific Data Call-in (Attachment 7).
Instructions and guidance accompany each form. ' .
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the database for the rodenticides are
contained in the Requirements Status and Registrant's Response. Attachment 3. The Agency has
concluded that additional data on the rodenticides are needed for specific products. These data are
required to be submitted to the Agency within the time frame listed. These data are needed to fully
complete the reregistration of all eligible rodenticide products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding this product specific data requirements and procedures
established by this Notice, please contact Frank Rubis at (703) 308-8184.
All responses to this Notice for the Product Specific data requirements should be submitted
to: .
Frank Rubis
Chemical Review Manager Team 81
Product Reregistration Branch
Special Review and Reregistration Branch 7508W
Office of Pesticide Programs .
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: Rodenticides
229
-------
INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORM FOR
PRODUCT SPECIFIC DATA
Item 1-4. Already completed by EPA.
Item 5. If you wish to voluntarily cancel your product, answer "yes." If you choose this
option, you will not have to provide the data required by the Data Call-In Notice and
you will not have to complete any other forms. Further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing
Stocks provision of the Data Call-in Notice (Section IV-C).
Item 6. Not applicable since this form calls in product specific data only. However, if your
product is identical to another product and you qualify for a data exemption, you
must respond with "yes" to Item 7a (MUP) or 7B (EUP) on this form, provide the
EPA registration numbers of your source(s); you would not complete the
"Requirements Status and Registrant's Response" form. Examples of such products
include repackaged products and Special Local Needs (Section 24c) products which
are identical to federally registered products.
Item 7a. For each manufacturing use product (MUP) for which you wish to maintain
registration, you must agree to satisfy the data requirements by responding "yes."
Item 7b. For each end use product (EUP) for which you wish to maintain registration, you
must agree to satisfy the data requirements by responding "yes." If you are
requesting a data waiver, answer "yes" here; in addition, on the "Requirements
Status and Registrant's Response" form under Item 9, you must respond with Option
7 (Waiver Request) for each study for which you are requesting a waiver. See Item
6 with regard to identical products and data exemptions.
Items 8-11. Self-explanatory.
' - ' "* :
NOTE: You may provide additional information that does not fit on this form in a signed
le.tter that accompanies this form. For example, you may wish to report that your
product has already been transferred to another company or that you have already
voluntarily canceled this product. For these cases, please supply all relevant details
so that EPA can ensure that its records are correct.
230 .
-------
H
/^
O
H
tn
ซJ
>-i
ft
O
O
fa
P^
P
o
o
t
1
O '
r^i^-
oin co
*-O CU
oo t-
~O IIM
CU 00 Q.
O 00 UJ
t- CMCM
Q. ' '
OL 10
< Z 0
fi- m Q.
0 ฃ Q.
u- 0 <
'
o
fl
(U
O
2
CO
c
T3
CU
JZ
u
4J
CO
0
lease read carefully
ex
jj
-
E >!.
4J 10
C CO
ซ- en
5. o
5
H-
C
2-
-ป CO
0) 4J
CO CU
10 CU
V _C
en
a.
to
c/) c
z o
D
J "5
ฃ CO
n cu
z en
- =>
a
H
fa
H
0 w
"*- QJ
o *~^_
Q.
"g ฃ>-
to p
ฃ O
M
0
fl
O
-H
(ti
X!
ฐ
0
' งฃ|
D
C
CO
^t O
ai 0
w rH
S OJ
CNJ
0
O '
03 0
CO 0
WO
% !ป Pi
ฃ a P ^
5 ^ P X .
3 ft ซi X
gO EH
01 O pq. -
Si PL] ^J
C t -^ T" . II
^ Cu co D
f ง 0 0
CJ ^ ^~^ ^*
to
to'
0
o
j:
u
s.
u
3
o
O
L.
CL
^
CO
CO
o
o
ฃ~
CD
C
CU
o
E-D
CD CO
co ex f 4-j
So c
CO
C 4J .- C'
CO CD 13 CO
(0 M -1_ป Q) 4.1
-co o; co
4-> -M O *5)
o co ~n GJ .
fco co ^CD a:
^ 0 C 4^ -0 =
Q. E +-ป CO > CD ฃ_ CU CO C
z 0,'S E 5 a.
co tr c. co co
.Q CD O 4-J tt)
1^ N-._ L. s- (0 0ฃ
T5 tti (0
C Q_ .C 4-ป
CO 3 O C
s: co cu
a. 4-j E co
ID CD 4-> tt) "*
E _F~ (C ^ 4-J
4-ป - C
co a> 3 co
CO M- 4-J CU 4-J
CO 0ฃ CO
C r
4-ป 4-ป O O)
O CO tJ . cu t- eu en c
D) 3 E 4-> Q.
to cr t- to en
co eu o 4-* co
t^- t t- H- to o;
0 T3
- o T3
t. 4J 0
CD CO '
C O 4J
S S '43 -0
>~'^ CU 10 "
S- O)
en co E en en
- CO I- 3 C
4J O 4-> O
co en H- CD a.
en 4-j 4-ป en
c ~o w eu
O O CU 0ฃ
4-> S J= en
cu o 4-ป en
01 fi- to c: -
01 - 4-< O) 4J
- 3 4J E C
D) cr to cu co
CO CU fi- t-
fi- 0) 4J
-ซ JZ 3 CO
CO 4J ?T'ซ-
4-' CU O5
-Q co c o; ID
vo a o = a:
4-1 '
O C 3
- CU i O
I am claimimg a Gene
a Exemption because I
ain the active ingred
m the source EPA regi
tion number listed be
4J 4J O tO
CO 10 J2 C- ฃ-
O Q O S- 4-ป
t 1
CO C
O 3
4-ป CO D) '
tt) O
JC JZ S- > .
CO +->
4J C
3 ' O O >.
CD D
0 T3 4-ป
C O CO C-
CO C- ฃ_ CO
in O Q. 4-ป 4-J
4-J
u
ซ S"
4-1 E
. en
~a> ~>.
en c c
4-* - 3: co
C. 3 to Q.
0) 0 ' S
EC 0
CU .i,; CU CJ
4-> *
~ Si H-
4-> C tO O
CO CO U
.1- o
CU 4-> '
JS to Q. 4->
5 4-ป CO 1^-
4J CO CU 1- T3
CO J= D) CU C
O ,4-> 13 T3 to
eu c
H- >^ ' 3 CU
- H- 3 t_
t 'Z 8 5 5
CD !- -M O CO
cj 01 o ja c
U CO O
CO >- O W
cu
-Q
z .
cu
c.
o
^
.
^
J
D
u
5
=
5
o
3
i
o
-------
H
0) <# W
4J 0 CO
O C3 f$
J-l O
O4 P4
O CQ
rrt * o^
IU HM
ซฐ B
0) - H
ง ^ '
0 ฐ ฃj
H (4 O
1> ,_j
t~i C* tf*
W CQ E"<
^ 5
ra ? Q
1 4J
CO
d
0)
-H
ฃ|
5:3
E
O
H-
CO
JC
4-ป
g
*D
CD
M
B-
u
g
t-
o
H-
1
_*V
CO
1
u
L.
4J
1
1
u
CO
CO
OJ
>.
H-
CD
L.
CO
O
CD
L.
CD
CO
CO
0}
a.
^
JC
c
L.
4-ป CO
.5 S
ฃ- Q>
Q_ 0
ii
5*> ^*
4-ป CO
CD 4-ป
CO CD
CO CD
CO
a.
as
3T O
O ซ-
I *^"
O "O
of co
ซ 0)
ZZ CO
u
H
to
- H
Q U
H- Q,
O *"*
a.
' r ^
"ฐ &
CO f~\
ฃ O
a C*!
Q Oj
ro
m
4->
H
m
"ง
(U
fl
o
-H
0
^
E Pi
a
ca
% in
CD CD
CO (^
S CM
cu
O
O
CQ 0
CQ O
WO
S >< Pd
| S Q
rf Of ^C bd
"S o FH
10 O W -
^ J EH H
ฃOj CQ U
CO 53
f 9 o o
g co S S
f
CO
CO
o
M-
i
Q.
-r- C
ra oj 3 ra
>..= tr L.
CA S- *J OJ 4-ป
ป- CO OS CA
4-> *j o ro
O CO 73 0)
3 co co ^ o;
O O C 4J TJ =
a. E +J ra o
OJ QJ C CO
>* OJ ฃ- GJ CA C
z: c- - 30
a> 3 E 4-> D.
CO O" t- CO CO
jQ OJ O 4-ป OJ
t- M- CO Oi
T3
T3 OJ 0)
C O. JC *J
CO 3 0 E
ฃ ra o
O. +J ฃ CO
1 (J) 4J {y *.
z -c ra t- *J
ra oj '5 ro
>-^ O- c-
CO H- 4-ป O) 4J ,
-CO Qi CO
4J 4J g " 'ro
o ra ~o oj
3 CA Ul J1J Oi
O O C *^ "D =
Q. E *J CO OJ
OJ QJ C CA
>. OJ t- O) CO C
Z c_ - 30
0) 3 E 4J Q.
CO CT c_ CO CA
CD 01 O *- 0)
t*- i C- H- CO Qฃ
0 13
OJ T3
C_ *J OJ
OJ CO '
C 0 *->
O ^ 4J T3
c c c =
>-'p- oj ro
S- OJ
CA CO E CO CA
ra t- 3 c
4-> O -M O
CO CO M- CO Q.
CO 4-> 4-> CO
c ~o in ' aj CE:
4J E x: co
CU 0 JJ M
OJ t- CO C ป
I 3 4-ป E C
tn t7 ro QJ ro
ca OJ c- t-
4-ป QJ D)
J3 CO C CX CU
>O C2 O = Oฃ
4-1
O C 3
0) 1 O
CD -5 M- "o
c oj roxi
CU OJ t. QJ
o CA en c- "n
3 C CU
CO CO - ซS 4-*
u a. co
W ^ OJ L1J "^
'E c 4J u i_
.ป- O O ฃ- CU
ro ro 3 J3
4J OS
U O. OJ CO 3
E QJ 4J OJ
ra x jc c
UJ C 4-< O
ra co E 4-<
4-ป 4-ป o ro
co ro J3 c_ c-
la c:
o 3
4-> M 0)
01 o
j= j: c- >
.2 ~ +, c .
3 --ซ O T3 !-ป-
C 0 CO t-
CO ฃ- I- CO
in o Q. <-ป *-ป
li
o
f- 4-*
a. co
a. CA
ttl ,f-
0)
01
* o;
.
. c
OJ 0)
4-* E
OJ C.
o
CX CO
II
ro -
-c
CO *r-
**-ป 4-*
' co ca
CO -M
D) C
"DC 0)
C - CO
CO "O 0)
_. co t_
ฃ 01 Q.
ฃ_ _ป . co
tn ^.
CO C C
+-ป >r- 3 ca
g i-2 t
15 0 S
4_> *
ro >ป ^3 **"
4-> c ca o
CO CO U
r- CU
fl) 4^ _ _,
j: co Q. ป-ป
C +J .C Q. *-
O 4-t CO I
r- +J
4J CO 0) t_ T3
CO XI D) CD C
O 4-" ~O ~O <0
ป-- CD C
H- >- ' D 0)
- M- 3B t.
+j - o .n D
t- 4-ป C +- 4->
0) t_ j^ o ca
o cu o .a c
O CO D)
C_ ซi
CO -ป*-' O C/>
L.
0)
ง
-------
H
O
H
(L>
tn
1
!><
DJ
0
O
EH
t^
ft,
P
o.
o
/
8
l"-f-
om co
ซ-o cu
oo c.
TJ i i 'p
CU OO Q.
O OO LU
t^ CMCNI __
EL "co
< o >
g . * g
u- 0 '<
o
ฃn
Pi
o
-H
4J 0'
O <ฃ> .
Q) <# M
4-) O CO
O CM S3
te O
Q_j p.[
0 CO
H H
nj ' Pi
4-> Q
S-H 53
0) - H
c fi i_n
ฐ'jj d
">-H .
w m E-<
H> ?!
(U
4J
nJ.
CO
d
4J
-H
g
P
o
CO
C
0
"S
4-*
tu
g-
CU
L.
g
'ฃ
o
H-
C
0)
.c
4-ป
D.
Q.
CO
o
C.
CO
CO
c
o
u
D
u
1.
-D
CU
.c
o
4->
CO
0
.G
-5-
M-
01
CO
u
TJ
CO
CD
CO
CD
OL
ฃ
-
5 >.
4-> CO
C CO
- CO
<- cu
0. 0
cu
c_ C
o
M-
cu
>* /"*
O +J
CO 03
CO Q]
CU .C
' CO
Q.
CO
V> C.
Z 0
3
..
D ง
^ CO
y> cu
Z CO
- D
U
H
pf[
- H
8S
s.03
>.. r .
^ ' ]- *
"c [D
ro_P
Oi '
M
3-
O
O
rt
-H
| O
"C
CD
% LO
co [<
cS CX!
C\J
O
O
CO 0
co o
w H 0
Is Q
?? Wj Q psj
< ft fa; x
0 H >T
| H Di E-"
c J H H
^a co.p
*ฐ IS
i-^ o o
S CO S3 S3
*~~
CO
4_)
CO
0
u
o
8.
C/5
4J
o
T?
ฃ_
D.
CD
CD
a
o
t ฃ_
CU
o
^
-u -o
C CU CO
co Q. .e j->
3 0 C
ZD 4-> S CO
LL1 tU -M CU *
JZ CO ฃ_ 4->
^ 4V .,_ ^
CO CU 3 CO
>>^ cr t-
to a: co
4-ป 4-ป O D)
o to ~a tu
13 CO CO CU Oฃ
T3 4-ป -J
O O C 4-* "D ฑ
I- 4-ป tU C
Q- E 4-i CD CU
tu tu c co
>- tU ฃ_ tU CO C
D) Z3 E 4-* Q
CD G~ ฃ- CO CO
-Q CU O '4-1 CU
h- t- M- w Q;
TJ tu to
fO Z3 O C
E CO QJ
Q. 4-ป E CO
^) CU 4-* ป CU I_ CU CO C
E t- -^ 30
135 3 E 4-> Q.
* CO D" ฃ_ fO CO
tO CU O 4-ป CU
N- -. ฃ_ M- CO.CS
O "D
- tu-o
ฃ- 4-> CU
tU CD '
C O 4J
S Tl +* tJ
X'^ tU to "
M- CU
CA CO E CO CO
- CO t. 3 C
4-1 O 4J O
CD CO H- CD Q.
CO 4-* 4-> CO
C Tf 05 tU
o tu cu Qi
4-ป' E -c eo
CU O 4-> CO
Q) C- tO C -^
QJ -^ 4-ป 0 4J
D) O~' CO CU CD
CO CU L. L.
ฃ_ CU - 4-ป
.C 3 CO
4-ป
r- .1 CU
E C 4-ป 0 ฃ-
r- o o t- eu
(D -r- CO 3 JD
^ 4-ป O E
U Q. CU CO 3
E-C C
E cu 4-ป cu
CO X J= C
LU C -M 0
tO CD E 4-*
. 4-ป 4-ป O CO
co co .n t- c-
sO cn o H- 4->
t t
CO C
O 3
4-ป CO D) '
>. CU O '
2 " ^ c .
i O ~O 4->
c o to t_
. co t- t- co
in o a. 4-ป 4-ป
4-1
3 C
"O O
C- 4-*
a. CD
< i>
O- CO
LU -
O)
^ a:
'
,
- - '
. ' .
55 ;
, .
^M -
S3
S
g
|
J2
S
i
^ . .
o
CO
o
'
cu cu
+J C
0 C
f 8 '
P
CO *ป
cu
4-ป M-
li"
(j
O CU
* CD
tU ..E
3 CO
4-ป C
CU ฃL
ฃ_
CO tU
CO
c ro
CU E
E
0 C
to tu
4-ป CU > *
CO "-
"-ป 4J 4-*
W CD
CO 4-*
D) C
1 .E : g
co "a cu
CD t-
ฃS CU Q.
f _j (u
O CO Oฃ
'E 13
CO CU
JZ O -
4-> ฃ_
CU O
C CO J=
O * 4-*
CO "3
CU <4- <ฃ
CO >K- CO
~a> V
CO C C
4J - 3 CD
C 3 JO D.
EC O
CJJ *"* CU CJ
M ~J
CO >* ^ S
U C CO O
CO CD U '
CU *J '^
JC CO CL 4-ป
c 4-> ^: a.
O *- CO 1
4-*
ป-" CO CU t- "O
CO .E D) CU C
O -ง-ป "D "n CD
- cu c
M >^ ' 3 CU
M- 3 t_
w -^ o j: 3
CU f- Jnฃ O CO .
o cu o .a c
0 CD CD
co 1-1 ~ o cn
f_
cu
z
cu
o
Q.
^J
CO
4-ซ
c
o
CJ
>%
c
g-
o
C_3
o
cu
o
-------
r-
M-l
O
H
a
a
JH
04
O
CJ
EH
to
fl!
Q
ฃ
1
fo
1
M
o
N.N.
oin co
T-O 01
oo t.
S jp^ ^*
o oo w
t, CMIM __
JS "co
E m H
ฃ S <
CJ
a
(U
rt
o
H
O VD
CD <# W
aJ o CQ
O CN 3
M 5
pLj * ftl|
U CO
ns S
s cT i
O 4-J 3
-H ^ U
a,s flj
CQ & Q
nJ
.u
CQ
T"J
/Hi
4J
-H
ง
.
L.
o
H-
Ui
ฃ
C
o
"S
CO
t.
ง
4-*
o
c
0)
h*
^
1
to
"g
CO
n
j
i
3
ซ
"O
u
J
J
ca
2
2r
2
0
u
a
CO
U
0
CO
u
a.
5
*-
5 >.
4-ป CO
z to
ป- CO
. CD
3 -
1.
> CO
CD 4-ซ
W CU
3 CU
CD x:
-* CO
CO
1 ง
3 ^
O 0*
C CO
" 3
CJ
H
to
ซ H
cj r_)
0 M
**"* n t
CO
cu
J^EH
g y
CO Q
?J O
m Ptj
Q CM
(U
o
rH
0
-H
al
01 |
a J_|
z CQ
CO
% O
and Address
COMPANY
!ET ADDRESS
', XX 000
S P4 pn
g W ซ EH
|P_l CQ CJ
& E W
m CD 4-ป cu
_C CO t- 4-ป
f- ฑ1 , ^
OT cu 3 ca
CO Qฃ CO .
4J 4-ป O "" D)
O CO 13 CD
3 0) CO CU Dฃ
*O 4->
0 0 C 4-* "D =
a. E 4-ป co cu
CD CU C CO
>>. CU L. CU CO C
E t, M- DO
OJ D E -M Q.
co cr t- co co
Q CU O 4-ป CU
"*- ซ- ฃ_ H- C/3 t^
"D
"O CU CO
CO Z3 O C
a. -M E co
Z> CU 4-ป <1J -
:E .c co L. 4->
ca CD 3 co
>..c cr t-
tO M- 4-ป CD 4-J
to a; co
O CO "D CU
is eo co cu a:
0 O C ^ -O S
a_ E +j CD . 0) t. CU CO C
co cr t_ co co
ca
>*.r- cu ca "
h- CU
CO CO E tO CA
CO t- D C
4-r O 4-ป O
co to *t- ca Q.
CO 4-ป 4J CO
CT3 W CU
o cu cu a:
-M E -C CO
(D O 4*1 CO
aj L_ to G -
U 4-ป CU 4-1
5j cr co cu co
CO CU ฃ_ C~
"ml S-"
4J 0) 0)
.Q CO C Qฃ 0)
>o a o = ai
CJ C 3
CU 1 O
% r: 0
eo eo B 4-*
4-ป 4J O CO
CO CO .Q t_ C_
>O Q O H- 4J
, ,
O 3
4-> CO O) '
^- CO O
=<= "- >
CO 4-ป
" . , ^ B
3 0 O >.
O 3
0 T3 4J
C 0 CO c-
CO t. L. CO
in o Q. 4-ป 4J
O
|g
a. co
c.
a. co
UJ "-
O)
.
ซ CO
CO 4->
n E" g
c to
CO T3 01
CO ฃ_
E 0) 0.
t_ __/ QJ
o to " a:
E "D
CO CU
.,- t_ N
x: o
4-1 , L.
CJ O
C CO _C
O ' 4-ป
ca D
CJ H- <
T1
n
the statements mai
hat any knowingly
ppltcable law.
itle of Company's
O 4-> CO 1
-< CD cu i- -a
co ~.c tn cu c
O 4-ป T3 tj CO
- cu c
M- >. . 3 O
M- 3 t-
J 0 J= 3
U t_ JKi O CO
O CU O J2 C
O CO 0>
CO 0 CO
O
-Q
s:
c
ง
n
*~
pany Contact
0
o
V
^
r
-------
H
M-l
O
rH
Q)
CD
(tJ
Cu
s^
l1^*
CM
O
O
E-i
4
&
P
O
O
i
Kl
O
oin co
^ O fl)
OO ฃ-
U 1 1 >
CD OO Q.
> I"-N. X
O 00 Ul
t- CMCM
Q. CO
< 0 >
1" 1 1
u_ o <
^"J
o
(D
fl
O
.*-!
n
JJ 0
O VO
CU-1^ H
U o CO
O C^ fj
cu a
a CQ
rH P3
4J P
Q) - H
S CH '
O 4J. J
ฃ_| ^) |rf
-H C! U
S ^H rtl
W ra E-j
CQ IS O
0)
. ctf
4J
CQ
O
(U
4J
-H
g
.
|
M-
CO
C
o
-jj
cu
CO
cu
i"
c
o
4-J
E
o
H-
c
.c
^
^
&
3
CO
c
ro
ructions
4J
CO
C
a
cu
JZ
o
to
ID
CU
c
X
r
3
1)
L>
f
ro
C CO
CO
t- cu
a. o
cu
3 c
J CO
0 CU
' CO
a.
CO
CO C
E O
-ซ 4-*
3 73
ฃ Q
: co
>-i Z>
j. .
H
H
CJ O
>*- Q.
O *~^
Q.
t ป
-o g
CO Q
CU (~*)
ro f^i
Q pi[
no
S
-H
cti
4-1
1
1 o
co LJ
CD
% LO
a, ^
co C**-
3 CM
CM
O
0
CQ 0
CQ O
8*'0'
^ ง Q X
3a,^x
"" C-i
'" O 'W -
g IX] >H
ro H Cd F-)
C3 P H
^ft CQ U
ro Jg:
g-2] o o
S CQ S !S
tJ *^ *^
.
ซ~-
03
to
O
4-
o
'&
CO
*-ป
o
a.
*
;^
ro
ro
a
u
cu
c
cu
a
T3 T3
C CU CO
CO Q. JZ 4J
DOC
QU uj ro T3 s
ฃ- 4-> tU - C
Q. E 4J CO CU
CU CU C CO
X CU t- CU CO C
^ TO '5 E 3 Q.
ro JT t- ro co
-D 0) O 4-> U
l>~ - i- >4- co a:
o
T3 CU CO
C D. JC,4->
ro z> o c
x: co cu
ฃ ^ ro t- 4^
4-ป - C
co cu 3 ro
X-c tr c-
CO S- 4-ป CU 4-ป
CO ฃK CO
C =
4J 4-> O TO
O ffl T3 0)
3 co co cu a:
O O C 4J T3 s
Q. E 4-> ro cu
CU CU C CO
X CU C_ O CO C
E I- 't- 3 O
TO 3 E 4-ป n.
- ro cr ฃ- ro co
ro tu o 4-> cu
r- t-t-tnm
0 T3
CU T!
t- 4-> 01
cu ro >
C O 4-ป
X cu ro "
H- CU
CO CO ฃ CO CO
ro L. 3 c
4-* O4^O
co 40 M- ro D.
CO 4J 4-> CO
c 73 eo eu
o cu cu a:
4-> E j: co
CU O 4J CO
cu t- co c -
3 4-* E C
n cu 1-1-
1_ QJ >r- 4J
" ro 5 B--2
4J CU TO
si ro c o; tu
>o Q o = en
O C 3
CU i O
- GJ O) J2
1} QJ C CU
C3 CO TO t- 73
3 C tU
ro ro
o a. co
3) CU CU LU
- cu
E C 4J O <-
o o t- tu
ro ro 3 .a
' 4J O E
u a. tu co 3
= CU 4J CU
ro x jc-c
UJ C 4J O
"" tO ffi E 4J
. 4-> 4-> o ro
ro ro J2 t- i-
<3 Q O -4- 4J
, ,
O 3
4J CO O>
n- CU O
-C J= I- >
CO 4J
5 U B .1 i"
i O T3 4->
c o ro t-
ro c. i. ro
mo Q. 4-ป" 4-ป
o
C- 4-*
a. ro
ฃ_
O- CO
ป cu
-* ce.
.
* '
'. "
s
*
1
%
1
*z
^y f
1
s
s ,
*
C (0
E E
^: 4->
u c
4-* QJ ' Q)
CO -M >
CO *i
* 4-* 4-*
co ra
CD 4->
0) C
"DC a.
O CO Of
'[ ,^
E 73
CO CU
t- N
-C O
cu o
C CO -C
ro 3
- CU M- <
ro X co .
co c c"
4J 3 to
c 3 ro a.
cu o > E
cu ^ eu o
ro x ja **-
4-> c ro o
co ro o
tu
CU 4J i .*
^= ro Q. 4J
C 4-* .C Q.
o 4-> ro i
4J
4J (0 CU C_ 73
o ^: ro cu c
- ** ~o ~c "
- ] "j 2
< O .E 3
t- 4-> C 4J 4J
CU - t- 3ฃ O CO
to tu o .a c
u ro ra
CO O CO
tu
XI
3
0
JZ
Ou
- .
4-J
U
CD
-ป
O
O
1
5
u
3
u
0
ซ-
-------
236
-------
INSTRUCTIONS FOR COMPLETING THE REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORM FOR PRODUCT SPECIFIC DATA
Item 1-3 Completed by EPA. Note the unique identifier number assigned by EPA in Item
3. This number must be used in the transmitted document for any data
submissions in response to this Data Call-In Notice.
Item 4. The guideline reference numbers of studies required to support the product's
continued registration are identified. These guidelines, in addition to the requirements
specified in the Notice, govern the conduct of the required studies. Note that series
61 and 62 in product chemistry are now listed under 40 CFR 158.155 through
158.180, SubpartC.
Item 5. The study title associated with the guideline reference number is identified.
Item 6. The use pattern(s) of the pesticide associated with the product specific requirements
is (are) identified. For most product specific data requirements, all use patterns are
covered by the data requirements. In the case of efficacy data, the required studies
only pertain to products which have the use sites and/or pests indicated.
Item 7. The substance to be tested is identified by EPA. For product specific data, the
product as formulated for sale and distribution is the test substance, except in rare
cases.
Item 8. The due date for submission of each study is identified. It is normally based on 8
months after issuance of the Reregistration Eligibility Document unless EPA
determines that a longer time period is necessary.
Item 9. Enter only one of the following response codes for each data requirement to show
how you intend to comply with the data requirements listed in this table. Fuller
descriptions of each option are contained in the Data Call-In Notice.
1. I: will generate and submit data by the specified due date (Developing Data). By
indicating that I have chosen this option, I certify that I will comply with all the
requirements pertaining to the conditions for subrnittal of this study as outlined in the
Data Call-in Notice. By the specified due date, I will also submit: (1) aj completed
"Certification With Respect To Data Compensation Requirements" form (EPA
Form 8570-29) and (2) two completed and signed copies of the Confidential
Statement of Formula (EPA Form 8570-4).
2. I have entered into an agreement with one or more registrants to develop data jointly
(Cost Sharing). I am submitting a copy of this agreement. I understand that this
option is available only for acute toxicity or certain efficacy data and only if EPA
indicates in an attachment to this Notice that my product is similar enough to another
237
-------
product to qualify for this option. I certify that another party in the agreement is
committing to submit or provide the required data; if the required study is not
submitted on time, my product may be subject to suspension. By the specified due
date, I will also submit: (1) a completed "Certification With Respect To Data
Compensation Requirements" form (EPA Form 8570-29) and (2) two completed
and signed copies of the Confidential Statement of Formula (EPA Form 8570-4).
3. I have made offers to share in the cost to develop data (Offers to Cost Share). I
understand that this option is available only for acute toxicity or certain efficacy data
and only if EPA indicates in an attachment to this Data Call-In Notice that my product
is similar enough to another product to qualify for this option. I am submitting
evidence that I have made an offer to another registrant (who has an obligation to
submit data) to share in the cost of that data. I am also submitting a completed
"Certification of Offer to Cost Share in the Development Data" form. I am
including a copy of my offer and proof of the other registrant's receipt of that offer.
I am identifying the party which is committing to submit or provide the required data;
if the required study is not submitted on time, my product may be subject to
suspension. I understand that other terms under Option 3 in the Data Call-In Notice
(Section IH-C.l.) apply as well. By the specified due date, I will also submit: (1) a
completed "Certification With Respect To Data Compensation Requirements"
form (EPA Form 8570-29) and (2) two completed and signed copies of the
Confidential Statement of Formula (EPA Form 8570-4).
4. By the specified due date, I will submit an existing study that has not been submitted
previously to the Agency by anyone (Submitting an Existing Study). I certify that
this study will meet all the requirements for submittal of existing data outlined in
Option 4 in the Data Call-in Notice (Section ffl-C.l.) and will meet the attached
acceptance criteria (for acute toxicity and product chemistry data). I will attach the
needed supporting information along with this response. I also certify that I have
determined that this study will fill the data requirement for which I have indicated this
choice. By the specified due date, I will also submit a completed "Certification With
Respect To Data Compensation Requirements" form (EPA Form 8570-29) to
show what data compensation option I have chosen. By the specified due date, I will
also submit: (1) a completed "Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-29) and (2) two completed and signed copies
of the Confidential Statement of Formula (EPA Form 8570-4).
5. By the specified due date, I will submit or cite data to upgrade a study classified by
the Agency as partially acceptable and upgradable (Upgrading a Study). I will
submit evidence of the Agency's review indicating that the study may be upgraded
and what information is required to do so. I will provide the MRID or Accession
number of the study at the due date. I understand mat the conditions for this option
outlined Option 5 in the Data Call-in Notice (Section IH-C.l.) apply. By the
specified due date, I will also submit: (1) a completed "Certification With Respect
238
-------
To Data Compensation Requirements" form (EPA Form 8570-29) and (2) two
completed and signed copies of the Confidential Statement of Formula (EPA Form
8570-4).
6. By the specified due date, I will cite an existing study that the Agency has classified
as acceptable or an existing study that has been submitted but not reviewed by the
Agency (Citing an Existing Study). If I am citing another registrant's study, I
understand that this option is available only for acute toxicity or certain efficacy data
and only if the cited study was conducted on my product, an identical product or a
product which EPA has "grouped" with one or more other products for purposes of
depending on the same data. I may also choose this option if I am citing my own
. data. In either case, I will provide the MR1D or Accession number(s) for the cited
data' on a "Product Specific Date Report" form or in a similar format. By the
specified due date, I will also submit: (1) a completed "Certification With Respect
To Data Compensation Requirements" form (EPA Form 8570-29) and (2) two
completed and signed copies of the Confidential Statement of Formula (EPA Form
8570-4).
7. I request a waiver for this study because it is inappropriate for my product (Waiver
Request). I am attaching a complete justification for this request, including technical
reasons, data and references to relevant EPA regulations, guidelines or policies.
[Note: any supplemental data must be submitted in the format required by P.R. Notice
86-5]. I understand that this is my only opportunity to state the reasons or provide
information in support of my request. If the Agency approves my waiver request, I
will not be required to supply the data pursuant to Section 3(c)(2)(B) of FIFRA. If
the Agency denies my waiver request, I must choose a method of meeting the data
requirements of this Notice by the due date stated by this Notice. In this case, I must,
within 30 days of my receipt of the Agency's written decision, submit a revised
"Requirements Status and Registrant1 s Response" Form indicating the option chosen.
I also understand that the deadline for submission of data as specified by the original
data call-in notice will not change. By the specified due date, I will also submit: (1)
a completed "Certification With Respect To Data Compensation Requirements"
form (EPA Form 8570-29) and (2) two completed and signed copies of the
Confidential Statement of Formula (EPA Form 8570-4).
Items 10-13. Self-explanatory.
NOTE: You may provide additional information that does not fit on this form in a signed
letter that accompanies this form. For example, you may wish to report that your
product has already been transferred to another company or that you have already
voluntarily canceled this product. For these cases, please supply all relevant details
so that EPA can ensure that its-records, are correct.
239
-------
240
-------
CM
t .
o
H
(!)
tn
ti
>->
CM
O
O
fe
P*
Q
0
'
t^\
i
N.N- ฐ
out co
* o cu
oo t-
~a ii
> N-h- x
o oo uj
I- CMtM
D.
Q. . .CO
C- GO Q.
o s: Q.
u- o <
O CQ
ฃn S3
(U O
Cn PJ
-H H
cd _^"*i i^c
H CQ El
OS CQ
CO &
(U CQ
'rt |
CO E
TJ P4
(U H
] \ |*j
-H O
ฃ
t-
Q
M-
(0
"~
ง
o
OJ
w
u
tr
o
ฃ_
c
o
L.
O
c
JC
,
>s
1
CO
ง
o
E
1
01
CO "
CO
Q)
4J
^.
^
M-
tu
t_
10
o
TJ
CO
0)
L-
(0
CO
cu
Q.
_jj
C
4-* CO
C CO
CO
I- t ^>
4-ป CO
o s
.S I
"a
o
r-l O
o s
fi* ., 1
z o tn
"g- 3 ^j
TJ ^ Q X
<|^X
g 0 W -
C H-l EH H
ฃ& CO O
co Jx
i"^ O O
2 co S 121
^
c
TO
C.
CO d>
-.1- (0
0) C
U 0
en Q.
co
Os Oฃ
cu
.1 CO
t~ ฃ
CO
CO u_
u
4-ป C
Q) 4->
1 CO
^1
c
0) 1-
0) U
CO
SO Q.
CO
CU 4->
O) O CVI
0 Q.
o. cx:
3-QiOl-OOO-I
D
* en z
-
,
',
, *
oo o ooooooooo
0000 00 OOCQCOCQCOCOCOCQCO
,
-
C^J P^ CU Oj D^ (j-j flj Qi f^ P[ pvj PI
W&iJ W WpdJHBgpLlpgCLl B3-W
SS S SSSSSSSSS
OO O OOOOOOOOO
WW ซ Wi^WWWWWMW
173 H, HD hj Hj lo (^ h3 HJ h3 hj h3
^
X
oo o- ooooooooo
,
,
f
'
'
1 ' J "
?"""
^
UNI ro *^ in -'^N >> ^x
^^ V^ ^^ \^ -\*S \^ Xa^ ^^ ^^ ^^
c
0 ^
t: 2 g-
' -^ ca *- , .-
ra co ซ>- o 4J
(J O L. o
5 n. cu c co co
6 E f c o 4J
u) o ro 4-* - 'ป- o)
JCOEJ04JCOE C
^ 4-. -M o ป- "CO*QJC , x*r- 4-* O
o c c <- i- w < co
1 C4-ปcflO4JCOCOCO D)
E 4-> ^Q. 3 o to '!! -^ >- "co X
cj noE2ol~l-3'ฃ_-o'cof-.''co ^
OUQ.QLCO"->vOC ซ^-
-g t.o i-iucojc-2a)---a:x
p a- o a a.uTฃ> ^D ^)^)Vฃ>\OVDXDVDTJ3^D
to
ซ
*~
4J
C
O CJ
' O
Q. co
^ fr
ง ^
-c
4-* S-
co
3^" ;
0 (U
(O '
- to
CD *"
' CO CO
CD- 4->
O) C
TJ C O
C *- CO
CO .TJ CD
CD t-
E v CO
ซ1 . ฅ
4-ป >^- 3 CD
c 3 ca a.
CO O * ฃ
I C 0
a> j^ ^ u
co >. ja H-
4J C CO O
CO CO U
C JC CO Q. 4-ป
4J CO ฃ
CO CO O C- *O
O JC 0) 0) C
- 4-> T3 -n co
M- CU C
ป- >s U GJ
4-> H- 3: c_
t- O JC 3
fl) 4J C 4-1 4-ป
U I- J>ฃ O CO
Q) O o C
O CO O)
o t- -
^ _, O CO
GJ
1
22
cu
c
o
a.
1^1
*^~
v
'
CO
4-1
c
o
CJ
i
CJ
s-
o
CJ
CO
CM
-------
l[ ]
o
OJ
ill
w
21
n$
CM
I
Jw
CU
O
O
EH
fri
p4
Q
o
Tซ
r^i
0
oui N-h- X
O OO LU
L. (MCM
f s f
U- O ซฃ
M
O CO
c a
0) O
en PH-
M
n
w
H CO
iJ 0 ซ.
01 rt Cu
vu C"i
-iJ O 5j
O 03 CM
5-1 t-ป
ft CO
Ut t
M
H O
rrf M
-U Q K
a
ฃ Cj pS
O J->
M tr> co
H Cj IP
> -H EH
r* c* ซ3*
M r^H f^H
H m EH
rt CO
ra 3:
Q) CO
4J P-C
(tJ g!
-U M
CO S
O 3
Q) H
4-J j^
H Of
fl M
t> 3
e
i_
o
H-
U>
4-1
C
o
g
4->
CO
1
U
g
M
t_
O
c
5
^
1
CO
1
(O
(0
g
u
c-
4^
1
*o
0)
o
M
M
(0
01
M
ฃ
**-
(U
E_
U
"i
0)
L.
(U
CO
CD
CU
Q.
C
*~
c
4-> CO
C CO
- CO
t- cu
Q. 0
CO (!)
CD 0)
cu jc:
CO
Q.
' ?
n C.
n
i?
j: CD
/) O
"t r>
S
O a
i t tpp
[X, |
HO
I I
" o PCS
ฐ H >
|"|
g 1=3 g
CD Q
ซJ O =8=
ro CcJ Q
0 CU H
Kl
g
I
0 S
fl '
o s
SH ^5
O Z
nj p
D<
o
M O
i >H
= O tf)
g Q)
* 0 ^
cu O rt!
ซ H CU
S oq H
c\!
*
o
o
CO 0
co o
pa o
w Sj fV
co ?H PH
0 H Q
5 3 Q >H
ฃ-04 CQ 0
co 2
|ง 0 0
I co S 52;
*-
4-*
C
m
4->
CO 0)
o c
cu o
fป* Q,
CO
CD
o a;
o
H~ ฃ
L.
CO U.
(U
u
4J C
CO CD
CU 4->
N. CO
c
CU c-
co
(U
ro
CO
CU 4J
ฐ ง
f\ cฃ
2_QฃOf-OCJO I
CU
+-*
1
t
CO
in
M ^r
ID
U
co IE
.^ i
4J j:
CO U
t_ !
- r- 2 1
>. -M" S J-: "*
^ ffl >. ii C U
_Q 4-ป ^-* O "
ง^7 O CO ^" CO O
_ 1 | | 1 | 0
IJ LLJ tf) ^> JET CJ 3
<
10 vo t^ oo a\ o
i-{ H r-t H T-f CN
) I '( I I I
CO ro rO ro CO ro
10 ซXI ซ> VS
CQCQ tnmrom ram
OO OOOO OO
eg eggs gs
0000 OQOOC000 CDCO-
J
'"
'
CU CU CU. CU CU CU
M pฃf ipฃJ H JiJ pq
Pi pf ฃjj Pi pi PI p. p .
S ^t iฃ( S (\iv-N3- *J min
1 "
-*-> 4-* ซC
cO
t ^ o 'S
>s CO C 1- TO
ซ-* t- O 4J CO
4-ป -*- I -^ C CD (0 X " 4' C O TO
>. t,04J'>-0 (U .-.H-
4-ป *^-4-rC04--r- 4J 4-ป
4J 4J U 4J 10 CC
0 .^C.^4^[0 1. 00
-Q O L. N ' XI T>
x .a..- Ti oซco
O CD4-'"-r-CO
S >. <8 X *> c > ca_crcu'T7cu cov-cu
E-iU-r-C CO 1 C4-*O)
oTjo4:>,>, cucc
- t-t- > g O t- 1_ 0) 'r-
x.
S.
CO
ฃ
c
o
c
o
i
c_
o
"" o
o
D>
M CO
Is
4J W
(0 ซ^-
M- O
4-> +-
L. (0
cu u
.0 -
M-
CU
* +J
CO
'*- Z3
ฃ^
-------
tn
U-t
o
,_
CU
t
n
>.
f^ j
o
o
Co
al
|V
Q
>*<
o
fl
CU
a
0
States Environmental Protect!
Washington, D. C. 20460
d
0)
4-J
-H
g
PH
H '
cj
S
Oi 0)
W M
rtf O
*^ jjj
M -H
S n
ID KEY DEFINITIONS FOR GUIDELIl
:e # and Name: 2100 Chlorophac
9
03
|
S^
f*i
QJ 4J
*"* m
"77 cr
0 -
'3 1
4J cr
CD
CO 4J 4J
CU O
4-ป TJ CO
E >.-
c 1b
TJ to t_
CU 3
CU O Q.
C 4-> B
>ป 4J II
O O
J= CU ซZ
ฃ
CU CO Q.
U
ฃ_ 4-* *
0 C C
^ ? ^
^j * ^3
QJ CO QJ
E- ฃ.
CU CO 0)
co c *-
^ CO
D) ฃ_ QJ
t- CO ซ^-
- 4J
CO D) U
E S. "
o =
M- 4-ป ฃ.
O 3
TJ CO
4J O
O -U CU O
co j: -
H- ro 4-ป "o
3 E CO
E E C-
CO TJ 4^ป
II 4j 5 E
O- CD M ป^-
CO E L_
X 4-* CD OJ
S -S3. 5
t_
o
o
TJ
O CO
0 E
O CD
O CO
C = CD
X i-
U t-
4-ป .CO O
CO E O
CD CU O
3 CJ C
'^ CO - CD
t. CD 4J TJ
O C_ CD -r-
0) <- 3 CO
Cy C) CT CD
csTTT
|.
E
ฃ_
O
>*-
UJ
C/}
g
a.
tn
Ui
Cฃ
tn
yz
S
\-~
tn
3
UJ
Q
V>
3
1
tn
31
UJ
UJ
Cฃ
ง
UJ
CD
.c
o
CD
1
in
o
E
3
"o
O
:erenced in
CD
C_
CD
t_
CO
CO
0
o
E
g
1
o
*f-
o
JZ .
w
(U
d
o
s-
8
1
S
t_
eg
^
3
I
t
U
O.
4->
0. CU
in c. u
in o r_
ป- s- o
co S. "c
in ปo cu
* t-
co p
CO *" 0
c co
o ซ-
o CM in
CD i ซ
CO * *
TO ^S
"- CO E
3 CO CO
O CD
_. 0 .
t o ^^
O t- OJ
H- CL 1
CM
0) ro so
C- CO
E 3 4J
ซ 4J it
fel5
r- 2J
4-* C "4
f- CO O
r T! ง
QJ CO 4^
' CO
CO O
CO -J >^-
4-ป CO '4-
QJ
"O t_ 4-ป
CL) L.
1 Q) 4-> CL>
,L- CO O
= m C
tion, analysis, and certification of ingredients <
158.162, and 158.165 for description of starting n
70 for preliminary analysis (62-1); *158.175 for
CO ซ
O O CO
Q.ซo in
0 "^ *~
U 03
in >ป
>~*~ ro
4^ 1
CU *- ^
.TJ i to
* v CD
^-t ^S 'P*
O -
III
CO
o o >t-
4-> CL 0 ~
O) O C T
C U O CM
'c TJ 4J 5
E CO
CO CO E CO
4J t. TJ
c- X o o
O 4-> H- Jd
Q."- '4-*
4-> S- CD
CO C O E
E-8 E^
QJ -i- O CO
QJ 4-J CO
L. O CO 4->
O* O CO CO
.
CO
CU
c_
eo
4-*
o
c
CO
production. process will suffice if the pesticide i
CD
JC
4->
O
c
0
4->
Q.
O
~
CD
-a
O -E
c o
CD CO
S TO
ro 'S
u
4-1
1 1
.C Q.
u
CO CD
CM
o -^*
H (D
O T3
-n .^- QJ
a> c *-*
4J .C 4-ป
4"* (j ซ^
jง ** "ง
3 O CO
CO _C
4~* CD
1-1 4-* ' --
CO Q> 4-* ป
CO >s QJ
' C CO T3
QJ CO)
CO t-
~O D)
CU <3J C
L. - f* i i
C 4J CD
CD O
E 4-* H-
4-> ..- O
C T3
QJ QJ Q)
"Ji "S
C D) CO
T c h.
C - D)
"S ฃ S
E 0 E
0 ซฃ JC
CO M- CD
CO O 4-1
U CD CU
_eo TJ ^
'5 2 t*
ro H-
co o
duction and an experimental use permit is sought,
uced by an integrated system or not, the technical
tement of composition of the practical equivalent
e basis.
nts in products proposed for experimental use.
er.
g .agent. - .
O TJ CD CO CD 4J E
t- O 4-ป CO - CO -
Q. S- CO 0 TJ 3 O
CL i .CU 3
JU CO >. t- .C TJ CO
CO CD ** i C '- t- ซr-
0 .E TJ CB -^ 3 3
CO 4-* CU CO t_ D" CD
CU 4J CO 4J CD O- - >
-CZCOUI ' -r^
3 4-> t_ TJ TJ O J3 '
X ฃ:E3t_CDEOCOTJ
TJ CO C C- CD c- 1. t_ t_
CD E t! & TJ "~ "~ "~ "~ "~
4->CLOC'. CDCDCUCUCD
4-> CO TJ CO 4J 3 '5 '5 3 '5
CD C04-'t-CTO"CTCTCT
- - -00,-CMp
w
ป *_>
"o S
CO "D
O O
JCZ C
4-* f_
(0 0
^ "S
CU
3 4J
O 0
.C CU
CO Q.
03
CO 3
4J CO
TJ CO
4J X
!5
4-> CD
CO t '
ai
CO
O 0
4-ป 3
cox.
CD 1.
*" r*.
2 -3
X^
"S ฐ
4J TJ
4-< CD
VI' CD
to be diluted with petroleum solvents.
or EP unless (a) efficacy data are required to be
ts or toxicologically significant degradates are d
5 for more information.
CO M- 1
- *=!!
E 4-i CU
10 -D - "g .2
TJ CD S 4->
3 -^- 3 ซ^ Z
D* 3 CO 4-ป
.CT t_ Cฃ.
' CU CU O Q.
t- J2 0
CD O
CD 4J CD 4-<
CD CD E 4-* E~
*t- CO TJ C H-
co to 3 j= o;
' TJ O 4->
i >. ซ '3 .
CO 4-" 4J CD
E O 3 O 4->
CO H- D_ ^* D,
TJ CO CO
c- 3 E "~ >.
TJ t- CO
V- C- M- 4J
p- f~ O
"O 3 TJ CD CO
CD CT CD 4->
ซ t .^ "S E
^^CO
,_
'ซ
CU
^3
.
(D
E
, O
11
C-
o
ro
CD
CO
u
. ^
4J
O
O
t
CO
fo
"S
.^
CO
CO
CO
"o
CD
, -0
3
o
3
O
h.
CO
JZ
u
3
co-
in
C
CO
.c:
' t_
0
CO
CD
t.
D>
t-
O
OJ
c
CO
-G
4-ป
CO
'
3=
CL
QJ ซ '
' CO
4->
CO E -
'-So
O
> E
ป CO
't gฃ.
O -^ OJ
eo
CO O C
CD L- O
O) t-
O 4J
CO O CO
4-i
(0 CO
ฃ_
CO CO
' t_ L. CO
g oj a; g
1 4? 4?^
U CO CO C
QJ Q) CO
I_ 4-ป 4J
tO . QJ
3 .,- ^ o
G(! QJ QJ CO
1 ii IP 4_)
o cr cr QJ
8" il"% J! J! o
CL
o SS'-S
S
O ป- CM
-------
to
tl_l
o
C^
0)
en
PM
O
a
1
f~*
0
Protect!
. 20460
rH O ;
S ฐ !
c: . !
Environn
hington,
m ;
m ns '
0) & i
4J
CQ j
ni '
u/
4-J .
"H
C
P
1
j
PL, ]
O
o
EH
S
p.;
Q
CQ
3
9
-M
c)
S
a
T
y
j
i
^
3
a
rj
rH
>
1
*
J
O
o
(Q
0)
JJ
JJ
8
fc
^
o
4-ป
to
3
CJ
4-*
L,
CO
CL
O
CO
O
L.
0)
CO
CJ
t- "D
O "
to" co
QJ o
0 J=
c a.
CD
4-ป U
1 n
ซ _
0 1
ป fO
CO C
> CO
". 4->
CO CU
CD O
t_
- ca
ro .
cu
c
(U o
^ .ฃ
table material
It, Chlorophac
to to
E ป
3
c -
CO TJ
ป CU CO
C CO
30)
4J ซ4- -p-
3 ฐ-0
CO CO C
01 C CO
t- 0
sSS
5E.S
0 U
CU O CO
CO .C
3 c- a.
CD ซ-
ซ- TJ 0
o c
CO CD
C t- C
O 3 O
ซr- O '
4-i U CO
._ 0 -
TJ TJ
8 8 ง
c_
C. CO CQ
0) CU
g-8 i
cu o,
c- c- o
o 3 co
CO H-
. o -
* CLTJ
O X 0
CU t-
a> ca
to co t-
CO L. S-
ง0)
TJ o
o in
TJ
4-1 CU CU
3 CO O
a cu c
O O. 4-1
C- 01 O
a. c- o
LL.
O CO
J= U) >.
4-1 CU 4-1
M- C O
TJ TJ 0
CU CU t
._ ._ CU
ง"ง"3
ee. Cฃ "O in
o .-cv;
D. O O
- a. o
CU JZ
U - 4J
c_ cu
3 4-1 L.
0 CO O
CO t- S-
TJ C CO
C O 4-1
> ฐ -
.*- CU
4-1
*~ m
CU CO
E E [j
CO CU LU
U
OJ I
"o "5 >. o x
4-1 ฃ- CO C_
CO CD O O
XI C 0) D)
4J - 0) CO C)
O CU > 4-1 CJ 4-1
3 4J S CO CO - CO
TJ O CO -C O C O
O 3 CO -C
C- TJ 4-1 X U X
a. o c o 4J cu 4-1
t_ *- 3 - 4-1 -
' D. TJ O i O
CO 4-1 O C
3 0 I- X 0 X
4J CO 3 O. O C O
0 3 TJ 4-1 4J
CO 4^ O X CD
0 I- C CU .C CU
c co a. co .c 4-1 j=
O 4-1 +<
C C C C
CO O O O CU O 01
4-i CD Dl
co co co co c co c:
TJ 4-1 4-ป 4-1 CO 4-1 CO
co ca co .c co XT
l-i TJ TJ TJ 0 TJ 0
j= O CU 0) O CU O
'" '" '" "S '" U
T- CM ro -* u in o
8. S.
X X
cu cu
a>
f*
"o
1
u
{
8
4-1
1
1
jj
u
LU
cu
s
CO
o
-CZ
OL
u
c
TJ
- c
CO
c
CO
-c
4-1
C-
co
cu
c
o
c
t, Chlorophaci
CO
CO
3
TJ
o
CO
CO
4^
TJ
CD
c
o
c
8
1L
0
cu
ง
.i
i
t_
CO
ง
o
CJ
CO
M-
o
c_
m
t-
o
s-
0
in
cu
o
c
o
o
LL.
CO
4-1
CO
o
CD
0
H-
LU I
o
in
c
o
cu cu
CO
x: o
CO
4-* CO
C 4-> .
CO CD
ฃ_ ~O
CO **-
t o
O)
CU CO
CL
CO
CU X
J= O
c o
cu
JZ
tO 4-*
c
ง8
5 c
O CO
4-1 +-*
c
CO CO
CU i-
CO 4->
CD tO
CU "-
CO D)
ir Q)
TJ t-
4-1 ป
CO CU
C J2
CO CD
[ 1
4-1
>- c
^ cu
4-1 L-
o <-
0 3
c- u
T! c
c o
x!
' U
0 ^=
CU 4-ป
ฃ_ '
r- CD
-o o
JC
X
CO O
4-ป 2
CO 3
j: Q.
S S
ฃ- ..- "o "cU "flJ
C- C * LU LL. LL.
O O
S- O < oS oa oB
f
co.o < >>. >ป >->.
Eh- o t_f_ ฃ- t t
*- O O O O O
CO* LL. 4-'4-> 4-ป 4^4-J
' U) O O CO tO tO ID tO
O E LUC.L. t- L. L.
L- ' >-LUCOCO CD COCO
g.
3 '"
CO '
CO 4-ป
O CO
M Q OS
T3 C H- CO
CU O '
4-^4^ O CU Q.
-3 fiฃ L- Q.
o ja c- co
* CO ป-
t- - 4-* CU Dl 3 CO
O4-ป COtOO- O CT3
CO C-O-MQi" O CV3O
^3 O LU CO ?s* co
CUE CV3CU>. *
-^ .3a.tocu t_ ci=
"-O Z t_3 CD Oฃ-
1= H- 1 OO ฃ- ฃ_CU
to t 2C "*" O_ O CL
3 > <
CO U LU
to a=
_Q - >ป O
M- 0
4-ป S- C 1
CO CU CU CQ
3 O) ID
_C
CO 4-* CU CO
4-1 .C CU 1 1 J 1
COT34-> 4->_J ^ _1ซJ
"D QJ **" ^ * CO 4J
CJ t^ .
CD 3
u .a
r- CD CU
H- 4-ป
S- CO *-
i LU CU M- . t i i
-------
in
'o
m
0)
ti
1
^*
ft
o
0
rfj
rt
p
u
fl
0)
Jr"'
ซ<
aental Protection
. D. C. 20460
s Enyironn
ashington,
cu !s
[ \
4J
CQ
-o
cu
4J
-H
g
"~^
.
CO
jH
H
53
M
rt
H
D
M
psj
NS FOR GUIDELINE
DEFINITIO
^H
r^
i~i
Q
ง
CO
ij
o
|5
^^
o
to
CO
S
0
100 Chlorophacin
ex
ป*
cu
TJ
5
**
^^"
cu
ra
u
-7
o
**
CQ
CD
O
H
O
O
to
.
T3
upporte
CO
tn
c
I
o
D.
U
4J
C
CO
CD
C
bait formulatio
o
M-
O
Q.
4-1
j:
4-* ,
" 3
C
JU
tfi
g
o
5
u
CO
o
CD
U
*4
H-
- ^ ฃ
-"OMON- ,Oป*OCO OJCJ OhOO^ O-^-O O O 05 O 3 O O CO 3 O O rrt
; a H s . . a ง a 5-ฐ 1 i t- 1 I
^'z uj^ S= S^-2^ E-O.SJ| *
* f a. a cocu cocc.ro cu ci_co cu
g 1 *- S - ii 1 1 la I 3
.j;1- z crccon-ia. ac CSQ.Z =
Of z co co co co co 4?
cu o 4J . .- .^ 4j ji ^. .7;
-ซ f~* *r- U CO OT
x 5 S ro .t: ฃ 5 o | . S
O -I3CO CO m T3
tu ^ - c "** 2x"cu '5
<- o"Sc~ ~ "03ฐ- tf
a u-cn^-. ^ co^os ^
1 i , , ,
i i , , '
^
o in
c- O
i rvj
1 O ซ
Jorway/Roof Ral
D)
vy CU
O 73
CO 3
ฃ ฃ.
-------
0
OJ
tn
nS
CM
t.
^*
CM
O
O
fo
rij
P4
O
.
0
1
nental Protection
, D. C. 20460
s Environr
ashing ton,
0) 12
jj
ri
4J
CO
d
0)
4J
-H
g
CO
1
Qfl
3
r"j
1
NS FOR GUIDELINE
DEFINITIO
><
S
p
H
^M
CO
g
S3
C**
o
o
fc
1
100 Chlorophacin
1
OJ
*
(I)
CO
ri
**
t
4J
d
0
0
^1^
m
(U
AJ
o
d
.u
o
o
^
CO
~o
co
T3
. O
c.
s.
CD
3
CO
O
a. ' .
X
o
CD
_C
4^
T3
0)
ฃ_
CO
Cl)
D
CO
E
u
.1
'5
cu
0
H-
O fO ซ "O OOvO ^ O O CMCM O^ ON- OfM
v ซ v- CM ซ CM ^ r r CM CO r ^ i^- r r CM ^ r ซ ^ t CM ซ CM
iCM iCM iCMiiCMCM "D ฃZ iCMCM iCMCM 11 iCM iCM iCM
Os t~" O^ ^"~ O* r~*' Os Ov ^~~ * E 1 CO O* ^ ^ O** ^~ r Ox O\ Ox T- Ox ^~~ Ox T
z o
fl) *~m ^ 3 ^
*-ป o rs ~o TI co
&.CGJ ^ ,o oi
O CO <1J ฃ C- O "DO"-COCOO'COCI-CO CD (0
CO 3: COOO4-> fl)Z ป2 *tO ซ 3 *r- 3: CO 3:
3 t- nt-CJO O tOt-OLDCLOCOL- D t-
O O O O CO (0 CO CD
4-> C t- 4-ป -r- 4->
CO ป ซป- CO ซ^- CO ป
t. CO CO vx CO -M -M D) L. CO
-MO = flQ .P- ._ C 4->0
C '^- CO CO - C- E -
OC O T3J2 .Q Ji^CD CDC
CO ^ H- M- COUC C"5
OCU H- O * i-ซ I- O OO
CJl - 1-1 o>"-ป ซ-< , J fl. CJI
ii ill i
'i ii
-
O NO
ซ CM
CM
Ox ซ~~
CD
CO
I
o
CO
3 '
O
-------
in
0
LO
(D
O$
iv
ft
>1
o
a
0)
to
i CM CM .JZ
\O ^O 4-*
o o T- -ซT-
i xx oT
QJ TJ
4-* O CO
Q.JZ QJ
CL 2 CO
co - .-
- Q)
CO QJ CJ E
3 0 -^
o E co
co E '
>- TJ O
E *- QJ
o QJ 4-ป a
C- QJ O CD
QJ TJ O C
'"8
JB
I
CO
=
o
c
s-
' CU
.Q
5-
c
CO
CO
TJ -
o"
.CD
U
H-
QJ
z-
c
o
ฃ
\ ^
CO
TJ
O
ป-
S-
OJ
t- ,
CO
8. .
i X TO
O C.
CO _D
-D CO
K> ""
E.
.C O
M <-
*- M-
co cu
1 4J.
CD QJ
i?
M- QJ
O ฃ-,
CO
CO
4-> CO
"3
CO CO
QJ
t- u
C D)
!4J
CO i
O)
LU CO
CO CD
JZ *-*
TJ
H- E
O CO
U D}
C C
CO CD
3 -C
CO U
CO
o c
CO
c- QJ
.2-8
ซ^ o
JJ" %
S-3
O E
> o
QJ H-
ฃ_
Q- 4J
CO TJ CD
** "' <">
CO 4->
QJ Q. QJ
1 QJ J=
X ' O
CD CO 4->
O CD
ro cu 4-**
M- J3 O
O LU
CU 0
ฃ co >
S ^'i
CO ' -
0 CO TJ
.^ -0)
a. M- cu .
>B
CO
u
8.
0)
u
CO
o.
3
CO
CO
c
CJ
CD
ฃ_
I C3
jCf
CM
^~
-
cn
OJ
CO
QJ
4-1
c
o
03) plus a placepack-penetrat
CM
01
QJ
CO
QJ
4->
D)
C
TJ
CU
cu
M-
QJ
U
. o
o ,
CD
QJ
C
. CO
u
Q.
CU
u
CD
1_
0
's-
co
E
L.
g.
t-
>*
O
CD
O
4-
1 LU I
v
Stations
-M
CD
m
QJ
CO
o
X.
CO,
QJ
O
CD
CO
c
u
CO
t-
QJ
. I
' "'
CO
QJ 3
4J CO , -
4-" >-
(0 O
TJ <
O UJ
E Qฃ
O
O 1J^
o
CD
O
O UJ
4-f rtf
*""
4-* UJ
Q.S
CO
TJ Hi
co a:
ซ<
CO
4-* '
CO -
ป UJ
CO u.
CM CO
CO 4->
CM "-
placepacks, but protocols 1.
ed by EPA before tests are in
5- *?
ฃ 8-
U
0) O
CO CO
CO
ST,
QJ
c_ 2
CO QJ
"^ '>
J ฃ
CO
c_
CO TJ
'Si
O f"
^ CO
CD CO
CO O ="
O 1
V O ^
4-" <
CO O 1
XI t- O3
O_ i
CU CO
3-dS
I QJ I
O 4-> Cฃ
4-i CO UJ
1 QJ O.
>. 4J E
. TJ <
CO D) (
QJ c a
f_ -
CU UJ
I- -Q CQ
O
ซ*- C O
-o> i
CO -i-
M CO Q
C OJ UJ
rj TJ
cr o iu
QJ t- Cฃ
t- CL<
>* CJ CO
U *p- Z
CO H- O
o *- -
.^- O 1
s- cu o
o
1
s
Nl
g
CO
o
o
CD
E
CD
r
- '5
ฃ_
. O
S .
CO
CO
QJ
4-J
0)
c/>
cu
JZ
4J
4-*
0
^3
CO
W CO*
4-* C
CO O
t 4->
CO
4-i QJ
.0 ฐ"
CD Q)
CO CO
ง *'
4-> O
CO >ป
cu
U M-
'1 GF i -ง i
CD
4-*
S
si -:
CO O
3 Z
0 C
3 O
CO
C CO
- 8
CO 0
4-> ^ 4J.
E O TJ
CU O
t- 1-1 O.
CO CU QJ
4-i L. CU I-
C TJ Q)
Q) CO -4-'
E 4J > CO
CU CO O "-
t- TJ t- D)
Q. Q)
3 CU ^s Cฃ
CT .E
CU . 4-> d) ฃ-
Qi 4J QJ
>* H- CJ 4^
1-0) O
CO ' - t- C
4J O <
4J CO
CD CO 4-* ^
O CO ^ Q.
CO Cฃ :
i ง . . '
i =C i >- i <- CM
-C
.
o
w
.=
CO
o
QJ
O
4^
TJ
5
QJ
J3
TJ
QJ
^
QJ
Q
CO
E
o
1
(_
r>
3
O
L.
O
S-
TJ
CO
"o
CO
CO
8.
TJ
c
CO
CO
01
CO
Q>
H-
CD
CD
TJ
Q
CU
O
1
TJ
QJ
CJ
CD
Q_
Ct>
CO
CG
4-*
4-*
O
TJ
O
ฃ_
Q.
QJ 4->
JC O
QJ O
J? C_
4-ป Q.
QJ TJ
4-> QJ
CO U
CD
Q.
CU
-------
00
^t-
01
-------
CM
t. .
o
H
(I)
en
&
5>H
ft
o
o
ฃ_,
PL,
05
p
0-
, 1
to
fo
h-N. ฐ
om co
t-O CD
oo i-
"D ii-^-
> N^N. X '
O OO LL)
S- CMCM
t o " 1
,E 2 2
fe 1 &
LL, O ^
,
>i H
0 CO
ฃ-! |2J
OJ O
en ft
O 3
O/VI '^^
CN MH
ft GO
UL 1
r-l
J-J P O<
a
CD P
O J-)
j-i en co
-H a p
>-rH h
S-H rM W(
H CQ H
nS CO
m Is
CU CO
(ti S
CO ' ซEJ
d PC!
0 H
-H CX
E
o
CO
ฃ
c
o
TฃJ
01
CO
CD
3
ET
CU
ฃ_
C.
O
4-ป
CO
E '
O
C
o
.c
It
D
CO
T3
C
CO
CO
c
o
o
c_
CO
c
1
o
CD
4-ป
CO
.E
4J
^
~J
u
H-
co
u
"D
CO
CD
O
CO
CO
01
a.
jj
c
4-> CO
C CO
- CO
ฃ_ o
t_ C
H-
CD "
>T ^
4-> CO
CO CU
CO CD
CD f
a.
ซ CO
w c
SE O
a -
- *w
3 ?
a= CO
Z CO
tg.
g
o s
1 | K^
fc) 1
H Q
o o 05
ฐ w '
ฐ CQ 2
i^" E-< g
g ฃ3 g
CO p
f 05
ฃ !5j P
T3 p| *J (^J
"H L$ r i
ro O w -
g W >H
| W 05 EH
>-ft CQ 0
CO |j>|
& ^ o o
Q CQ ^ S
^
c
CO
t.
(A O
*- CO
0) C
0) O
Oฃ Q.
CO
CU
0 OS.
i E
CO
. t.
CO u.
o
(J
4-ป C
-8"S
^ง
h- c/j
o ฃ
3 4-ป
CO
\O CL
m
CO
dj jj
D) O ^
O Q.
D_ Qฃ
XQiOI OCJO I
(
4-"
H-
t
in
CD
rg
0) E
2 21 ฃ.
3 CD
"B-l
Q) 3
ปป at: z
s
^
.
J
J
CQ09 CQ tQIQ.CQQ[10^^/lCQtQU}
OO O OOOOOOOOO
se g essssessg
OOCD 00 OOOOOOCXICDCX)OOCOCD
^
*
J 'jf f : -
"
,
'f
Piipi ฃLj p^ P^ P^ pU P^ P^ Oj jpt)> p^
pf] frj PL] [V] |xj po] [i3'[xj PEJ pฃJ fxj EjO
oT^T oT oT'ft'ar"ft1or'ft'or^'ar
SS " S SSSSSSSSS
oo o ooooooooo
s s s sss s ss s s s
-1
t^I ^ fce4 MN^MMi^lMi^MM
1 j r^J I"^j r|U F^ r^ ^J r^J r||j| r^ t""J r^
'
-
|"T*] Frj prT Ppl fjl pr"[ Ffl PtH f^l fyi FT! fjn|
OU CJ OCJOtJOCJOUU
%
, r
'
,,
^
s
'
*
-5 5 55-s ฃ ฃง'
c ' "
0 .,
*< -2 g
-^ -^- CO M- .^
8 8 T ฐ S
g & S c ง 5
S3 o ra 4-> - -r- D)
fOECD4-*COE C
oฃJ O5 n E CO ' o
i- c E ฃ x -a rj
_i n 4^ 4^ O S- CDO.C 0)
3 ป t- +- C4-ปCU t-
V C -M o^J Ot4 OE TO C_
OS ' (D Ui ^COO ' --C
OWQ.Q.CO'^'tiJt^'cO *>-OC
TI t-CU - t-
CO
CO CD
CD 4-ป
-o? g
ง5 S
CO ฃ~
E _CU g.
o co cei
"*~ 'E -o
CO CU
- L. M
.E O
4-> ฃ.
01 O
C CO J=
O ' 4->
CO 3
CU M- '
CO >~ ^J H-
4-ป C CO O
CO CO U
>*- CD
c 5 1o "o. Tl
0 4J S2 Q.
j3 4j ** " "-
CO CO 0) C- "O
O J= O) O) C
- 4-ป "O "D CO
M- CU C
- > t 3 CD
4-ป M- 3: C.
ฃ- O J= .3
CD 4-* C 4-* 4-<
CJ ฃ- -i^ O CO
cu o ja c
U CO D)
S _ _ fe ซ
'
0)
i
22
!
o
o
H-
o
CD
E
CD
CM
-------
OJ
U_l
O
OJ
ni
gป
rtJ
CM
*
CM
o
u
EH
to
d*
p4
O
i
ro
s
h-N.
om w
T~^D Q)
_ OO t.
"O | | M-
w CZ)^3 Q.
O OO HI
t- OJCM
S" "m
SS
t. m Q.
o 3: a.
u. S ซc
W
0 CO
<~J p>|
(!) O
tn CU
rij CO
DP
g rt
O
H CQ
4J O ป
-H |H
ซr* t&
AH "<
W CD EH
Cti CQ
CQ 3:
0) CO
4J M
CQ S
O 3
Q) H
H O
d C|3
t> ซ
O
*^.
.c
4-*
C
o
"8
4-*
W
g.
C.
g
to
g
o
M-
_C
.
_J
3
M-
t.
0
TJ
f.
a
CO
L
i_
c to
- CO
t- cu
o
CD ซ^-
i^"w
a) 4tT
W CO
CO 01
CU J=
' CO
a.
"ca
||
ii
a: co
oo oj
S 5
&
O ง
| i frjป
Etl I
HO
) 1
g o 3
s.03 s
^ EH p
CO Q
ra OH P
0 CU H
ro
CQ
rH
01 1
fl S
as i
" S
Q) ง
JH ^?
o s
-H
0
dS O
i &
co vrH *
2 P tn
^ (U
* in ^
o o rt!
CO O5 P[
CO _ _ r *
u OJ H
.
CM
O
O
CQ 0
CQ 0
CO H ฐ
cl i^i f 1
^ B ! ^*
01 O P3 ป
cu ry| K^
S M ptj EH
js-oj co u
ง^00
g CO S S
^
4-*
C
CO
ฃ_
CO <1>
^ CO
D) C
0) O
0= Q-
Oป Dฃ
I.
CO
t
CO U.
1 CO
.-ง
r- w
c
CU I-
CO QJ
-j 4j
CD
NO a.
^o
t. i_ _,
o o ^
o a.
a. G;
XOฃOI OCJO-J
4J
i-
&
w
in
c *-*
"O O
*-ฃ_ฃ_
CD 5 .Q
D^ E
0) 3
sd- a: 3:
^
V
m ra ra m coco racococQ cora
iiii ii liii งa
cocooooo coco oocooooo coco
u
AtOiAtOi PjAc flt&P^ft
JxfHStJW Wti} IX|CI:]{:LJ|JL|
oT&i Aป oT PJ& oT&r&r&r &&ป
S S S S S S S S S S W H
OOOO OO OOOO O
SSJsJS SS JSJSSS S
MMM^i W W M fclH M W fc*H
hJbbb b^ bbbb b^
li-t Ix] JxJ M W &3 H PL] Jxi W
OOOU OUOOOO UO
1
" ^
^ j '''''' ^ -
y
J
^ ^
*^N ^^ /-H- *-^ ^^ J^^
0 *. O^ 0 *. O
*/** ^%<*v inra mincMin ^X^N
x^ฃ*~ ^ T- Kkc\Tv^ซ*' *J inR
1
S t' S "3 "S
to -s IK co ir t_ ซi
u g +* t- o *J co
MX: ca ocX^ O"DS
CO U U 4-> '*- O -ฃ.
i CO X *- -4-*- C O . C_ O 4-ป ซ O ^sl'4VCDi-'ซ-+J4-J
>* 4J ' 4J 4-ป t, 4-ป C8 CC
4^ O 3 O -f- C ซ- sU I flj i * O tซ CO O (D
*^ *-* ' E >. C& >. C > CO t> '
ซ>>.*r-c O eoi-4->.c: > ซ>H t, i( o TTJ- Q -^~ ^, *>v ฃ- O 334-'3'ป-JT-I- U CJA^
4-r t>- t> o 4-1 UO t> ฃ < CU ป!
0>>EO 3 <<
VO VO Vi> *^D CO CO CO CO CO CO OS OS
D)
CO CO
. CD Q.
gg
M CO
CO
r- 'f-
<- CO
O U
o
M-
o >^
CO t-
U CU
- o
c ซ*-
"- O
O 4->
-------
in
>w
O
H
d)
tn
rti
!>M
O
a
tn
fl
O
-H
4->
o o
0) U3
4-J <#
O o
^ CN
dl
rH 6
4J
S Q
(U
s Environri
ashington,
0) !S
4-)
CQ
0)
-H
5
^
ft
u
EH
fฃ
&
Q
CQ
i
H
H
B
ซ
S
(^1
3
Q
H
U
g
i
DEFINITIO
>*
*
CQ
EH
g
4-J
H
tti
m
-a
OS
inone,
o
3
a
-H
Q
in.
o
(N
S3
8-
rt
(D
CQ
M
04.
4. C 0 ^
7-0 <,..+> a - co .;:;
- Si ; fe S -5 "g '-E 5 i7 ฃ ' ฃ
0 3 - ' - ' i g C -g ฃ 83 ^ ~
.t^S" o in c- o E ฃ CD E ' CD cu
E= i_ cp ~cj ^- s- o t- _ง 3 ' ' .c' c " ' 5 In
J2 > 4J M- CD 3 CD CO 4-ป ซi- Jj
3 CD S-' CO N- C OL. tt J= C^
co 4^ 4J oca in "O CD . x 4-ป 4J TJ - u
c"^tb o CD , in H- co * co CD >* co
"U CO t. C - CO * O "U CO1 * B OO 0 -5" '
CD 3 OCO C CO C .= -0 . .C CD S ^
CD o o_ CQ) o <- co co CD 4J wo. 'oo
C 4-> ~ >ป fป ป.. N C "* tfi j_i m
O C s 4-J ^C ffi t" rn 5L oj " m ~t
>> 4-* 11 ' "^ 4-> * I .0 CM lf\ O 4-* ^J * J-ป CO O I
4-* ?1 > Qฃ 3 t. "U >O O . ซ CO Lm . . 'oo-
CUWQ. O -r-COCOt_^2i-i .,-17 .;IU
O ill**- 3WCOH.O) ..r- X^
C_ 4-> ' *. OCU Q.C4-ปOJ' '^- OM
304-* UJ-30LU 0-ป.^CO> .a ฃm
o c c , . . t/> ' * o ^N cy 3 Q. a: 4. .^- 4. t^ o co """ .^ *ง
4J4JC O t- CO ' C T3 I_4-> ilm
COC-^- t- CO CD4J3O.OO) OO ป-
CO O 4. ซ- M- 4. <- TJ 4J 3 -co O
ro'-o i- OE ctnra co-n ซ-
O4.> T3=:z t_cO"-t_'r-cf- o ra.^-
C-COf- Q.O. ซฃ OH 'OCซ-*C3) Of- -.14.
Q) CO ' O C -1 t/) ' f CO O 3 - v^ ^ CO >% o O
E t_ - O CO ซ 3 E O ซ^- O ^^ o n >
f-.*O O UJ T3OT3COC *-*' .
V<-4JI- OOT30S TJ C CO O - ซt JZ I- _,cn
__^03 M-COO 0> CO 4. 0 0 .0 ^ . S -'
"ซTJ= o'o^"ง CO 0 -b CO "o 2 ^~ 30)
*^ O ' jrf-*X C0^'^-C03 4.T5 4J*
l-si ill 1 !!! s 1 |f II | 'i
*U t- ' H . ^CDOCOCO O - COO) P- ^x
t. Q) . ii i . . (/) to E '*~ f ^3 '
CCOC O t 3C C/) CO D) O (JJ-4J OC o Qj "J^
D) .' 2E C "- ซ O) C ' O CO O 'tl
<1)0)T3 uj O4-'IAO3_C(0t-CO CO oi+j^
t- _UJ DCOT-4-ปcO "oo a: ""ฐ*^.t^'|J"foฃ 45-S"oi '""c?
5s-t) M-ฐ.C ฐ.ฃj!CH-o'o'43'[I > 'CO
3COO L.3C ' ปf- "O "- 3 CO 4J 4J, S- ' 'E t_cTcO
OOJ CO XT t- " 4Jฃ_>. ^>^M-.~D Eo-2* O) '^- 3
U ฃ ^3 , (U C O : H- ฃ O ' ' O W O Q) 4-1 tO CO ฃ_ 4-> M
*-CO t_ Q> O CDS-CO 'ฃ CO (DOC O O
S|fe o21-| ^tngz-Zlll 1 ฃ^^ ~3co
' O ' 4-ป C^->sCOQ_C04Jt. ^4JCD*COCO*- C t- O
3 *- CO iiiW COซฃ-COXt-'.-Q_ .^ OE CO *F-
E 0) 3*-^' ฃ JZ 4J
L_a.'ฃ: oars:. '*mco oow cocno ^_*.t-
^"ง"0 ** 1eo^'io.(a.5o8 2^-^^* co'3~c
1 ซ " 2" 'ฃ c c * Q. -2 ro ""o-li .=5 ^ 1 ง ป ' ^ fe
*- '< O 3' *ซ- O 3 - CCO*r-CD_Qa.t-ฃ- G)CO 3
Q. 4-> O T3^ - . CปH- "D 4-* "DCUCO CD UJ O O "CO CO
oj Q) "~ o oco oocuE-Qco-coo s- ซr-jrct-
* 3 ป^ OCO O '<~inO ฃ- 3 OQJ 4Jฃ_ 4-* I-CO +- O3
4JT34J ^-O 4-ปtr-N.CLTJ34JCDCOtn O4Jin CO L. - U
3^3 -D1" .C 'eo!4-ปc co M-.^I Jio 4JO
DQ.T3 OT3 *" 0 O* CO x: D- i-WO^Ds'o "" TJซ O >C 73 'ฐ
OO OO T3 CL\Oin4J Q. i o 3 "D CD - -^C4J
C.COC- 4-O O E*~.ฃ-J=-OC4JCU >.JซiOO
งW ป C O t- T s^i C CO ,4^ QJ CO C ปป ฃ O s O ซ^- 4-* O G) CU
ป 3 C *^ C1J , >ซ. -)e p^i O CD 4-J CO +J Q) O 3 * 3 2 _C O "O O
C O d ' 0) 4-* O C )-* sO O. 3 CD O CO C C ' OJ QJ fl) Q_ O C1J Q)
O . O TI I- ^3 *O +- CO -^- COCOC4-*ฃ- , O4JH-OL
1 UU 3 - . iii CO +J ^ +s ~o CCOO O) - X -' CD COOCOOX
BTID. CD 0-^ 3>4-*ฃ-T3T3OH-CO'OCS- 4->S
O O. C O *- Q. - ~O CO C D" "- L. CO - ' "O O 4-* , ft. CO (0
O Q) d. CO C ,Cfl t_ C CD CO C ซ CD O "D "- 'CCD
I_ CO L1J ;*~ '^- O O M L- 4-* ' O M -M CD fc- CD "~ ' CO 4-* 4-* CD "^ ฃ_ L_ CO O *O
Q. to (_ t_ 3 4-* Q, O -^^ O ,.*~ CO '^~ O C -P O CO C O 3 'O 4^ (D CD CD E O
CD O Q, CO ' tO OOC>"n34JCOC*^- ' O CU C M- O '* CD CO CD 4-> OJ
COt-r-.^ O3 ' ^CJ COOCMCOOEOT3 >C+JOซ"cOM-Q_*^a. E EE*DO4J
D) CDCD ซ-ปO S - C. CO EDltOM-COO) 1- 3 .4-* 4^ 4-> CO *O CO CJ CO tO C O Q.
3 -M CO ซ H- O O ป- t- tU4-*M-JCfOjQTF CO *-.CDCO
*^ O *' >* v^. {Q O ii +-> *r (-> tf- o) 2> 1- ซ^- CD ฃ C L. 3 JE >ซ. 3 ป CD CT CO
Iral^^Sl^ ^J' l2gฐg^"-i3'5"'-sฐr^-4!'^"^'2[3Sr I "S"Sm^-c
m^C ^'^-CO' O jj . E OgEQ-CDOM- CD'D'D'n"D3TJCDCO 33C~DT3
x. ._ a o 4> tr a fl S 3-00 ' o 4-ป co.-Dtoj--3333 31--^ S 0,33
a_G>M-'.-4Jj ,OOCKttceiKZtt" O (U 22=Oa:f^
ซ CO C *- rt X '- *"*
-------
in
H-4
o
CM
tJl
ft
!>4
U
rt
0)
*3
ง
-H
o o
(U VD
4J ttfป
O 0
JH 01
ft
r-J U
4J
S
tes Environn
Washing ton ,
nJ
4J
CQ
d
fl)
M/
.p
-H
g
N
ft
O
o
to
ฃjl
P4
Q
CQ
g
rv* CQ
W i
H^ r~i
/NJ tO
fui CQ
ง
H g
^5
ซ S
rj t!
R 0
rft "f"*
el
CO l""1
g
!Y DEFINITIO
Name: 2205
j~J rg
W fl
0 m
1 *
<*> m
13
o
g
t
" *
S
ฃ}
'^i*
ro
0)
4J
o
o
o
fe
o
*p
Q.
CO
o
J=
Q.
0
C
IM
T-,
CO
C
CO
JC
M
E
m
c"
g
'o
CO
f
o
5
4J"
CO
5
o
CO
Diphacinone and its
^
C
O
CO
ง
CO
1
u
CO
M-
"5
O
t.
CD
ฃ_
O
M-
O
in
CD
ootnot
u.
^
4-J
O
JX
o
1
o
-g
o
c,
0.
CD
CO
3
i
CD
"g
CO
cn
c
I
u
CD
M-
JC
U
CD
CU
4J
ฃ_
O
CO
o
CO
4->
-ง
CO
(U
ฃ_
' ;
CT
L.
y
g
<
CD
J=
I 1
..
ง.
CD
0)
0)
t-
JC
c
4->
1
t_
t-
co
JC
4-ป
^
s-
co
4->
CO
4-ป
C
CD
ฃ_
CO
D)
CU
t.
CD
U
~0
L.
Q.
O
CO
3
i
cn
c
t-
4-1
U
CO
H-
^
I
CO
c.
o
U. 1
c
o
CD
^CD ja JD ^
4-J CO
4-> O J= O
O C 4->
C CO CO
T3 C 4-> CO
T3 ' O C 4-ป
* 3 .^ CO CO
3 O 4-ป t- T3
O 3 CO 4->
3 CO H-
CO 3 O
CO 4J E O)
U CD O ฃ- CD
CD C t- Q.
D) CO CO
cn c 3 co cn
C l Q. C
r- C T3
C C CD 3
- CO CD CD JZ O
g E "D 4J ^
CD t- 3 J= C "o
L. O Q. *- S-
CD U CO
CD J= CO O O
" T3 TJ CX W 4-.
"O C O O CO TJ
' C .CO L. C E CD
CO CO "- 3 CD
w -.ซ N -= c
Co 5<
co in T3 o co
CO O - CD ฃ-
4J CO C CO 4->
CO E 4J CO CO
E CO ' CD
CD O CO CO D)
CD TJ E . J= ."8
T3 CO V -Of.
CO C- 4-ป CD
ฃ_ O) ฃ_ E ' 4-> ซ
a o a. co to eu
o o 3 c .a
O H- CO * CO CO
S si 1 ^
o o -~ - cu
co 3: o 4-> t_
C C CD O S-
CO CO 4-1 , D. t_ O
4-ป 4-> CD O "-
C C ฃ- I- TI C
O O 4J O C O
o a c ' .
Cll r~ y)
CO 4-J O CO ฃ_ E
4^ O C. O *ป~
O 3 O - CD
3 -a o 4-> >._^
T3 O ' ^ O
t. Q. 3 W O JC
Q. O CU 4->
CU U E ฃ_
JC CO CD 3 - CO
4-ป 3 H- M- TJ O
0 1 ซr- *D J=
J3 -D -0 OX
CO CO CO CO O
>* -o cu ฃ_ , E ป-
CO CU CD CO *
3 ~O *O 4^ +J rQ
- cu frS -^- ca 3
cu > -D in , j= Q.
> O "- C\t *O 4-ป
iป > . c X
M- a. o o, co co c
ฃ- 4-* CD
c a. cu oj c
- CU JC COO
O*4-* O"U3 "O"O "O
4-* 1-0) COC __-_ป_,
C 34JL. -^ ฃ_-^ CD CU CU
CD O CD O CJ 4-> . *- it
E coc-^- cac_c u.u_u_
CU 4-* JC O O
ฃ_ T3 c (D Q *^- o ^ - oฃ( oi( o&
< C CJ 4-1 *r-* I
3 caoco Q coo <>.>.>ป >.!>.
o C"D El o l_ ฃ_ t_ i_ L.
cu cuo ..._ ooooo
"- O C ' ซ OQCOCOCOCOCO
CO +j _* _/ o OE UJ C, t- ^ I_ t_
- UCDQ- ' -- LLJOOQOOO
JC CO *" E O 4-* tO O ^11 _Q J2 jQ jQ jQ
4-* oC_CD - ฃ_ >-UJCOCDCDCOCO
>. 4-> 0) CO Q.
*ซ E 1 *- o ง"-T
-- co o t- co ป -
4-ป ซ OJ U- CQ CD 4-i
CD O O CD
CO d) L. ป , *J 4-* Qฃ
*5>* *55>Lo>. ง-oc M- ซ
4-J fll 4J (- ซ E_ OCU O '
03 E CO D) O O U 4-*4-> O OJQ.
JQ jDCO'-'cn co 3 oฃ t-G.
4-ป 4-*4-)ซ-4-*O4-* ป- . * (/)
34-ปE CD 34-'ECDCO'^"CO "U t- - 4-ป0) D>3CO
"D O CD t- .13 OCOjCUCO O O4-* CO CO O O D~3
O3C04-* O3CO JC 0) U. CO ป o >ป 4Jco TJO LUCOS: co
CLOC DLOC04JCU4J C -CUE WCUX 0) TI>-
L.-^- cn c_ M- 3 M- 4-ป M- 35 t 4-ป r)o.cocu t- CE
' Q. cu ' Q. "n o i o cn o 4-*ฃ_ 3: M n o
CO 4-* ฃ_ CD4-ปO"-C'r- C03 CD 4JC03Q.OCO ' O JtS 1 ZZC Q_ CJCL
03-0 CJ3-a4-ป4J Otn 3 X . < u-ซ-ปu-
CD +-> O - OJ 4-> O X <1> t- COO UJ
Of-4^ 0 ฃ- .C GJ O
O 3O 4J4-ป OO JO XO
CCTJ CCCC UC s-o^,
CO O O O CD O O O CU O CD 4-> 4->M-C I
4-i f_4-> cn cn O o cocucuca
cacoro Q. CDCOCOCOCCDC 4J o 3 cn 3
CO CD O CD CO CO JC CO JC ^ f~.
4-ปTJ"O CO 4->"DTJ"DO'DO JQ CO CD4J ซ W4-ป 4-> JC l ECUCUOOCUO ** CO COp4-< 4J_I _J _I_I
COOU O COOGU~OO"O > >- XC04J
'
O XXtDM-S-CO**-
IU.I (DO U UJ t i UJ
-------
in
O
m
d)
CD
P4
ft
0,
O
EH
PLI
fSj
Q
>-t
O
d
(U
tn
d
o
-H
4-3
rotec
p|
H
rd
d
Q)
. 0
-H
>
H
tn
4J
4J
CO
d
0
H
g
20460
6
Q
d
o
tn
d
ฃ|
m
S
CO
[H
ฃZJ
Pj3
5jjj
H
p*j
g
t^.
M
rH
g
H
1
w
1
Xj
0
H
EH
C
H
to
Q
s^
W
|
CO
0
S
&H
1
to
4->
H
nj
CQ
rrt
S
*
inone
o
I
i
H
Q
in
o
CM
CM
OJ
i
53
tซ
CO
ri
CJ
*
i \
a
o
0
CO
-f
^
"8
ฃ-
g.
ง-
CO
01
c.
'5
_a
o
3
|
Q.
CU
, -C
c
CO
CD
' 4J
C
o
CD
E_
O
*.
J
o
t+-
'o
S.
CO
* ' ' -
o =00 o
4-ป Ul O
O _I O < i CO. CM CM i CM CM CM i i i CO CM
"m ^"^ 'งfP"""'f?""" r?r? r?"*
g 1 '- 3 " S ^ ' ^ g ป . ...
2 I . (0 03 CO O CO
O 3 OC i_ i rv-
' CD ป ซ * t- CO
ป c; *t- -M.
'4->< O-COtO OJ CO Ct. CO
CO3 _... ซฃCQCOป- "- CQ 'O
O 3E C *^ X CU ฐ
0) --g -^ 0 S- - H- _ (5 Q.
< OOCปซ ^-. 03
U. (/) xx " i *-J CO xx e^S
.c '
1 i -
t
t i i
' '
..'/"'
in * in in in
L_
O
i CM CO I I i CO i CM I CM
\o-ป ^o^o ^oซ ^o NO
CO
0) CO CO
L. Q^ ry>
t- CO . . - ซ.
CJ * n) M CU H-
Cfl D O O CO O
13 cro. o a o
O CO ฃ11 O Oฃ
Z O "^x 3ฃ '-x.
-o - >i " >.
fl) ' C ฃ_ CU 0) CO
CO 3 ป- 3 CO 3
D" O CO t- 3 t.
O ฃ_ t. O O O
rc CD a. z m z:
CO
*-*
to
ca . a>
U -^ t.
f ฃฃ flj
3 o -a
tr co 3
ฃ- O
J 1 Q_
i it
'
-------
in
"w
O
(U
tn
nj
CM
ฃ*
cu
o
o
*
^
P
^*t
o
a
0
*$
S-J
o
-H
Protect
20460
rH U
nS
S P*
Q)
0 0
5-1 4J
H O)
> a
W 4n
to
m nj
d) 3:
nS
4J
CO
d
0)
4-1
-H
a
&
P
25
H
K m
H H
S nJ
9 ra
W rj-j
(VI ^1
S ro
GUIDEL]
cinone.
Dd !S
?^ JB
fa .yf
CO 0
^5
8 m
U ฐ
r3 C^
M
g 5
*23 K
" to
fel
S "O
g i
S ^tt
^
(1)
w ra
o u
s?
g
..
^
0
o
m
0
a
o
o
fa
X.
CM
z o *~ ^~ *"" ^~
i ^x CO < J=
CD .r- ซJ Q_ .. ..
4-> 0 ^ TJ "O CO
.-^-4J ฃ004^13 -QJ:i 4J
D. j= cu - <; c co to co cu co
Q.3: ca o a: t-Dฃ
CO.- _ปCJ|SJ - -*t.CO
CU CO -CD O*-i<4-^CO.^"-D]H- O CO
CO 4-* COCOCOO t DOOCOO3OO CO -M CO
u co 33o szcocorjtaiTQO 3 ca 3
O _ Oฃ O O E O)*itOQฃQ.OCLC/3 Oฃ O tt O
> >>TJ 'r-zC>.O OT3 >- >. E
CO CO 4^ o i- CD
MO, = m >->ซ- c 4->o
C fO CO ฃ_ C
W C O ^~ J3 JU ' ^^ CO <0 C
OJ= C O"D OJC
CO _,ซ4-H_ C03 CO
OCO **- Oซซ >-t t_O O<0
cot- >-> ty)i-j 1-4 ^.^ Ul_
II 1 1 1 1
1 1 II
-------
in
in
O
in
(L>
en
en
>i
o
(U
Q~J
ri!
r~i
0
Protecti
20460
rH O
nJ
-i-i
d p
Q)
tes Environr
Washington,
nS
CO
t5
CU-
4-1
-H
g
>t
0)
o
o
fa
<
cฃ
Q ,
CO
25
S
S CQ
1.3
fvi CQ
S
CH rp4
y
M - W
C (Q
GUIDELI]
cinone.
ง 1
fa ฃ
CO Q
S?
5Y DEFINITIO
Name: 2205
S "2
w c
^j
S *
CO ฎ
a ra
S (ti
o u
S
o
o
ptl
,
' -
,
1
1 i
o
^u
CQ
0)
4J
ง
JJ
O
o
b
i
Q
r~
CO
^
'^
CU
Q.
CU
ฃ_
to
o
D.
X
CU
CU
J=
1
1
cn
_E
CO
c
,1
o
i
.CU
OJ
c
's-
^
-g
CM
CO
CU
c_
3
, CO
o
t- DL
0 X
CU
CM ซ IA >d-
^- ป- ซ- CM CU
> ' CM CM .C
O O ^ ^ *"
CU ^ TJ
4J O CD
n *-* (y
Q. 3 CO
to
> CU
to cu o E
3 0 !-
0 E CO
cn E >
tTJ o
ฃ- CU
O CU 4-> =
t- cu o cn
CU TJ O C
a. *^ M-
cu
cu
H-
cu
cn
c
CO
o
s-
cn
4J
' CO
cu
I
X
CD
O
M
>.
|5
CO
U
Q.
Q-
^
>.
CO
CO
4J
TJ
O
CD
O
t
g
c
o
f"
_
cป
CU
Q,
CU
ฃ_ ,
. 3
O
Q.
x cn
CU C
4-ป
ซt- CU
CO o
XI CO
>-'^
"U -^
i to
ps
_C O
'3 **"
o
Cfl CU
* -M
CO O
'ฃ "GJ
M-
*:i
O CO
O CU
O O>
C C
CO CO
3 JZ
cn o
CO
4-ป
i. S
.2-8
Q. C
' CO
CU S-
Q. 4->
"Si
g-|
0
CO 4->
CO
CU 4-ป
> 2
51
*
J2"g
o -o
S- S
M
acepacd
CO
4J
3
O
XI
CO
g
1
.
CO
ฃ.
CU
i S
^^
1^
f\i
^j
O)
CU
4-f
in
CD
4-*
c
o
"~
CO
4J
flป
placepack-peni
S
o
.
vx -
GJ
0)
. C
i '
CU
**-
CU
0
1
CO
CU
5
o
~
-V
CO
Q.
CU
o
c_
o
H-
co
4^
1
'5
- C_
^>
(D
S .
Stations:
+-
cd
i
M
t
0)
a:
4-1
3
O
XI
CO
g
j
*
L.
o
c
QJ
UJ
.2? -
S 0
CU *7*
4-" >-
ง ง
1 Cฃ
O LL.
O -<
O
0 LU
lu ii
4J UJ
a. a:
CO
T> UJ
co az
<
.So
ซ S
P tfi
1
Tuj
ฐ *~
CU >-
CO U-
CM CO
TJ TJ
C CU
CO 4->
1*^ i.
v- 4^
CM
* tS
jป 2
O CO
o
O CO
4-* 4-*
2|
II
P
"Q.TJ
Is-
U
GJ O
J4,
CO
o
+j "D
C. 3
If
U
CU
a) .a
ฃ_
05 "O
C 0
to
4^
CO CO
CO O =
O t
? 4J o
o
in
0
4-t
CO
1
OT
""
(0 -
i_. ^
, 5 -ง
J ?. -7
a to o
^ ' 1 g
U -M *-
* C CO
CO -^ CU
M 0
CO WO
GJ 4-> ^ 4J
g C. ง
S ง ฐ"ง
CU C_ Q t_
4-1 CO CU CU
.3 4J ฃ_ ^ CU c_
O C TJ CU
O CU CO ' ' 4-*
CO E 4J > to
CU CD O *-
CO CO c. TJ t. O)
4-ป C Q. O
1 *J CU 4-> O l-
3 3_ ^. <*- CJ 4J
XI CO ฃ- C
a > 'J3 ra ฐ "*
co co co cn 4-ป ^^
g j: co .g o
'5 I 2 S ' 1 f
GJ 33'
(U
5
0
"D
_!
3
GJ
"OT
O
"D
C
o ,
1
_^
-^
CU
x
CU
c
CD"
5
T3
ฃ
Q^
U
t- ' ,
H-
oL
1 .
t
M
0
-------
8
o\
-------
CM
H-t
O
Q)
t
&
>H
ft
O
u
EH
pLj
<
ptj
Q
o
o
* ,
ro
oin co
* O O
OO I-
CU OO Q.
> gg X
L- CMCM
O _j
Q- ' CO
< 0 >
Z 0
E c_
t_ tฃ) Q.
0 E CL
u. O <
>i H
U CO
(U O
tn ft
-H EH
ฃH f* ri|
H CQ EH
cC CO
m &
0) CO
4J EH
CO S
Ti ง
(!) H
4_) ' [""S
-HO
Cn W
o
CO
f
i
1
to
ง
i
t_
o
W
ฃ
^-
ง:
CO
1
to
CO
g
M
O
E
1
u
c
5
n
c
-j
2*
n^
3
u
5
u
TJ
^
U
k ^^
4-> CO
ft
S CM H
OJ
-
O
O
CO 0
CO 0
j
f ง O 0
tS co S z
CD
CO (U
'o> c
(U O
Cฃ. Q.
to
fl)
OtS
.r- CU
CD
C_
CO u.
C1J
u
CO CO
0 V
\ CA
_ Si
t^ ta
,
en o
Z) -M
4->
CO
VD a.
ro
ฃ. ฃ_ -,
0) 0 ^
o D-
0.0- ^
3_QฃOl OOO I
O
4V
|
CO
2-s
T3 S
CD 3 ^
.|-ง
-* 0- Z
_.
. "
CQCQ CQ CQQlCQtQCQCQCQTOCQ
OO O OOOOOOOOO
C -S S S fi & $* 5"* -C^ C*!- CI fr!
OOCD. oo cooacxitxicooocooQoo
- "
ซ AV*
^
,
ftft ftftftftftftftft
'E? -^ WWHHHWHpt]
ftft a<" ftftOiftftftftftcn
OO O OOOOOOOOO
SS S S^SSSSSSS
WW W ซMWMWWWMW
.
,
'
,
,
; . -
"
f -,
s i
^% ^N ^v ^^ _,
x^ฐL '"'L ^^L^xjC1 p x^,ฃ
^^ ^ ^^^^ "^ S^3
g
, o -^
** co
' - (Q H-
ffl CO ซr- O
0 0 L.
'*~ Q. OJ C CO ""
E E -H C , O 4*
g 0 E CO 'ฃ CO 'E
o3 D5 !3 ฃ co v
_ro >,>SEJo,^"^-"o ' 4^
3 i_ H- **~ c0^ tu 1!3
S C4Jo3 OCO ^E CB !5
0ฃ- -r- 4-> CU
"D C C <- C. 4J ' CO '4J
i "-C4-*wo4->taroco co
4-t O CO ->- COO '
g "o ^D" -n S W % *S m^~ "~ *ฐ ^" ^
g Q-O * QQ-OU>X0^0
4-*
CO
*J
*~
4J
Q) E
ฃ_
o a.
c_
CO
CO -f-
' CO CO
O) C
TJC 0)
C - CO
CO T3 CU
CO *
E CD O.
o co az
E T3
CO CD
J~ O t^-
cu o
C co j:
O ' *J
- CO 3
a> H-
S > CO
"ro 3>-
co c . c
c '3 ro Q.
is- i
CU .iฃ O LJ
CO >. S >t-
<- C CO O
CO CO O
0) 4J _
I JC CO Q. 4J
- -M CO I
M -M
CO CO CD ฃ- ~O
U J= D)
-------
C
OJ
m
&
(ti
CM
{H
CM
O
O
EH
Pi
Q
ro
ro
otn &
ซ-0 0)
> N-hซ X
L> CMCV
|||:
>-i M
Q) O
tn CM
rtj co
-H CO
jj O
O vo E^
4J o a
P4 CO
ULJ
ro M
4J P S
d
O 4J
j-ป tn CQ
-H d p
a -d rf
W CD EH
(ti CO
CQ |S
(D CO
OJ 1
CO S
United
REQTJIR]
o
s-
VI
4-ป
ง
requested
ง
-M
O
_c
4->
!
w
CO
g
1
E
1
a
a
0)
3
O
1
n
CO
1)
o.
X
L.
4J ca
C CO
- CO
i- a>
a. o
cu
0
H-
D n
INSTRUCTIONS: Please tyf
Use additional sheet(s)
rj ง
i i J-^
fo i
1 1 O
"0ง
ฐ H i
cB 1
CO Q
CM
S (N W
<\I
o
o
CO 0
CO 0
Hf )
S X Pi
<" IS Q
1. Company name and Addt
SAMPLE COMPA
NO STREET AD
NO CITY, XX
9. Registrant
Response
c_
00 U.
u
in co
eu u
:ง
N- W
O t_
CO 0)
CO
0) 4V
O Q.
Q. Qฃ .
XOiOH-OCJO I
4-*
1
f "
en
tn
4. Guideline
Requirement
Number
to ED m CQ co m ro
i ii งง!ง
CO CO CO 00 CO CO CO
.
CM CM CM CM CM CM CM
St 5xJ W H PP H fxJ
CM CM CM CM CM CM Qt
S SS SSSS
O Q O O O O O
s s s s s s s
-
> ' -
J
,: ,
O 0
o "^ S S "^ S
u\ cvj in in CM irv
x v- ro tvt ป- -a- **
o
^ 4-> 4-* tf
^^ CO "
<0 t. Jl ^
si i- f ง 1
-^- , , .r- e
4-* ,C <5 o ฃT 4-* w
ป} U t- 4-> -r- O CO U
"* vj: g t> s c "~ "" S ^
ฃ S "x x( -2 fc - "8
OT Dฃ O -(IX 4-* T^* (D 4-*1 +^
j^ :: -iJ^^ro E4 ฃ.
o- i co < ป xi> t_ o> ttt
C t> OJฃ-4->.CJ r-f CNJ m -^p in *iD
i i i i i i i
<*1 r4 rH H r-t (1)
D)
C/) CO
co a.
งง
4-J CO
CO '
^ C
>*- o
Initial to indicate cert
.(full text of certificat
-------
LO
>w
r
w
_
Q)
fC
>.
M-l
O
U
EH
[X,
Q
t
u^
?*!
a
(D
tn
Cental Protection A
D. C. 20460
States Environn
Washington,
United
03
fS(
M
M
'H
f>*
H
S
NS FOR GUIDELINE Rl
D KEY DEFINITIO:
s-
CO
o
o
to
'"
2755 Brodifacoum
0)
1-
rd
0
ra
0 43.
M C
*o if.
t_ t_
O ซ
4-> cr
E L. CU
3 CO
CO 4-> 4->
CO O
4-* TJ CD
8->.=
C G)
TJ CO c_
CU 3
CU O Q.
C 4-" =
^ -
CU O
4J . a-
jQ t
0)" CO Q.
o
L, 4J ป
304->
0 C C
CO CU
CU
TJ t- TJ
H) CO CD
t. C_
cu co o>
4J 4-J C
CO C
*ni 2 m
o i; > -
C- CO -
CO 5) O
g o co
o =
i_ -a)
M- 4J t-
O 3
urchase their active ingredient
ackage of another registered pr
of the active ingredient; PAI =
t; provided formulators p
duct is a 100 percent rep
t;TGAI = technical grade
o o o
ft_ 3
O.TJ
O
C- CO 1~
CU O
CO CO
3 3
i UJ I
TJ I- TI
C O C
CU Z CU
II >
4-* CO
Q. 0 O
^ 11 *O
*r2-2r
3 II
TJ TJ
o cu ci-
Key: HP = manufacturing-use pr
data pertaining to the purchas
identified in the tables.]; TE
ingredient, radiolabeled.
c_
0
o
TJ
o "co
TJ "-M
. o c
ECO
CU
>- t-
O t
M CO 0
CD CU O
3 t- TJ
D" O C
LU -3 O
-ง
O
TJ
S- 2
O O
C- M-
0 C '
O ID
TIC 0
O CU TJ
M- CO ID
'Sit
8-21
< ca
a.
o
1 ง
H-
C TJ
O 0 TJ
C O O
ป*- o
M-
co cU'c
- CO O
C_ 3 C
feed crop C - Terrest
esidential H - Greenhoi
M - Indoor i
g-o
O 0
t- o
M-
C TJ
CO O O
- C 0
C- M-
4J O
CO ป- L.
CU 4-> O
C- CO O
C- 3 TJ
o tr c
!-<ฃ--
1 1 1
CO O I
"co
Use Categories Key:
A - Terrestrial food crop
F.* Aquatic nonfood Industri
K - Residential outdoor
^
E
ฃ_
O
4-
UJ
CO
Q_
CO
UJ
2
' <
t
CO
o
UJ
o CD x 4-< cu
r^ t. ฐ ^ H--ฐ
u, CO O C -ซ 4-*
in H- co ' co
co" *" o TJ "co . E
C CO C JZ TJ
O ซ- CO CO O 4-*
* - M C
4-* **x CO C CO >- CU
CU i T- - C CO TJ
co ซ- * 4-j cu c: cu
O) vx 3 1-5 OJ
C TJ TJ CU 0) C
CO C O f_ J2 ซ-
3 CO CO S~ O)
O CU Q. C 4J CD
-* 0 ^ -^ ซ >
s- D. i- "co ^ t)
(V O C 4J <
CD TOO CO O C
4-ซ ซr- _/ 4-ป ' O
ฃ- CO . C TJ
C D -M U CU O CD
, O E *C . 0) CO
, ฃ_ |0 ii f ,,_ ^ f
QJ M- ' O C ซ-i O)
x: D TJ D
4-ซ C **- C CU -^
^ ro o u H- > CD
.^ f- >. ^ JJ .^
TJ 0 TJ C 0 'E
TJ C CO o -
CU 1- C TJ t-
CU 4-> CU O) S-
ฃ- CO 4-ป
CO O) O CU ,4-ป CJ C
C * CTJ E
.CD4JLTV O D JCCO CU
.^- C- N- -^ O O > CO
TJCOv- 4J C* CU'^ D
t- co co eu co cr j
135 LO Q, CD CU (0
ซr- O -JC CD ' 4-ซ 4-ป ^ - C
-c . - co eu
*ป- C -ME - o E
O O ป. I- 4-ป *ป- ly.
*-*. S- CU 'O 4J ฃ_
C 4.* T- .^ Q. CO CU
O Q. i CO ฃX
CM CU CU t- t. X
*- L. <| 0 CO 0 Q. CU
O3 O ' *r- 3
O CO 4- ฃ O ฃ_
ฃ_O ' ' O> COO CU
eu M- CD ฃ= co
in CD 3 E cu o Q.
TJ ^O CU 4-> ซซ o
C^->^ CO Q. C04-> ฃ_
CO t_ CO X E- Q.
CO CO CD CU D) CO
w"^ .5 .g c ฃ 8. 5
ซ -D J ' fe. ซ .5 1 ฐ
>ซ C * TJ O TJ
-* CO CU C C C 0
CO C_ O CO CO S- I_
cBcM ^ '43 c ;xฐ co' ฐ-
.1^0 3 .2 "ฐ C 'ซ -S
C H- TJ 4J.TJCOCO
o co o o CUEE.QC/)*
Q. ^O in 4-ป Q. i CD
O CO O CD CU * i C " TJ
. in <- o jz TJ eu - 3: cu
J^ v^- *** C CO 4-ป CU CO t-
O CD CO ฃ1 ฃ_ * CU ป CO CU
C TJ 4^ ^^ - O 4-* ^ 3 CU JQ
^ฃ5 E o> co M co O) i_ ^ co
4-* ฃ TJ L. "^ ซ^' 4^ t t /> ซ. O O OJ Q) CU C/) 3:* 03 4_> ^j
CO C O E - ซ- 4-ป ฃ- -M .^ -Q
4JCU O 4J ,UCO 'M-CU
CTJC ^4-ซC04-*4-ป'^-euCE- niTJ ซ
E OCOEQ-CUOH- CUTJ3
eU 4-> co - E f- *-> Q_ o c cu D"
zt TJ o ' o 4-> coTJco'ij'S1"
iOฃ CLTJ C0< U^-t4-ปI CTQCJe^Z
cu
"~ 4J
o cu
CO TJ
cu eo
4-J ฃ_
CO O
"g
gs
-C CD
CO CL
CO
CO 3
1 ซ
ฃl
jD ซ^-
4-ป CD
CO 4->
CO
cu. c
03
CO
C- *J
O 0
CO TJ
cu ฃ
f Q.
^^
^? o
ฃ.
"S ฐ
J_l Tt
data are required to be submiti
lificant degradates are detectee
>r EP unless (a) efficacy
:s or toxicologically sigr
i.for more information.
2 ~" a>
^ ฐ 0
4-ป CU 4-ป
O .C
QJ
~5 IE &
CO 3
18 Required for MP and EP but
ingredient(s) is (are) not
. of instability are reporte
en
tn
-Q
CD ID
.C 4->
4-> CO
c "3
o o
>. CO
1 ฃ
CU O
4-ป tn
CO 0
CJ L.
ID
> CO
.r- t- TJ
O O -
'x 'o.
O W CO
1 CU O
O JC
CO C Q.
ID CO
. -o | 8
'ซป- CO
CO O ' C
CO CO
CO "P-,
O CO C~
CU O
JQ > CO
- co" cu
^'5 0) 0
l_
eater than 11.5; such a produci
i, an inhalable material (e. g.,
;e.
Sodium Salt, Chlorophacinone, E
i_ L. en
O) -30)
, 4-"
ฃ_ 4J M- -
o o
3 TJ
0
co '5 -g ฃ
CO O O
/ o) cu o eo
- 3 ซ-ง.
3= CU ปr-
Q. S- TJ Q
O C
0 W 3 *
CO CO CU
-C C I- C
4-ป O 3 O
eo t- *^ o -*
* O 4J O CD
o o
> C TJ TJ
- C 4J CD
>*^ซ; o o E
' ซ O C O
J= CO t-
o) o 4-> c- co m
ป- 4-ป O CU CU
^: cu TJ o
eu H- c TJ E
f ^ H~ 3 3
O "^ O O O
CO !_ t_ O
CO O C O 3 CD
CO I- O CO S-
t5J JL- '^- ป O ซr-
O 4-ป H- Q.TJ
CO U CD O X O
4-J CU C *
to co co m
ป-- t. 4J >
C- CO CD L.
co co eo t- s-
._ ._ , (- (11
Acute Toxic - Regular Chemical
1 Not required if test mater
2 Not required if test mater
of potential eye and derma
3 Required if the. product coi
4 Required unless repeated di
50 Acute Toxicity Footnote 50
-
o
3
TJ
O
O.
CU
1
T3
C
CO
manufacturir
o
ID
CU
L.
O
Q.
Q.
CO
r\
The Agency requires data t<
-------
in
o
fl>
&
S
^
04
O
o
ฃ-<
fa
|Cj]
P4
P
O
ซ
a)
S
o
-H
Protect
20460
r-i O
nJ
JJ
s Environmen
ashing ton, D
M-
c
c
OJ
ฃ-
D"
CJ
CO
M-
CO
to
CO
>
B
c
CO
L.
CO
D)
CJ
C-
to
4J-
u
3
TJ
O
t_
Q.
CJ
CO
3
i
1
0>
CO
c_
0
u.
01
01 J2
o c
C CO '
73 C
73 0
3
3 0 4->
O 3 CO
CO "Ej
co 4J e
4J ฃ_ C_
1- 01 O
01 C M-
C
CO CO
01 C 3
'c c
ง01 E
i_ 5
t- O
01 O
01 J= CO
J= 4J M-
73 CO
C CO i-
co m
CO
CO ' &S
co in
CO O
L. 0
C- 01
01 4-> CO
4-* CO
CO E 4-ป
E CO
"D CO
CO t- 4-ป
c- cn c-
05 73 S.
73 00.
0 O 3
O M- CO
H-
CO 3
C C
CO CO 4-ป
4>* 4^ CO
C C t-
O O 4J
ฐ ฐ g
CO 4J CJ
4J O C
CJ 3 O
3 73 CJ
73 0
O t- E
5. ฐ-i
CJ O
j= co CD
4J 3 H-
5 i?
~a a L.
8 73m
5 -SS
0 -OJ
a. oo
- a, o
0 JC
U - 4J
I- 01
3 4J ฃ-
O CO O
CO t- H-
73 C CO
C 01 4->.
CO U CO
CD 0 ~ฐ
r CJ
4J * .
o to a.
ro m
t- CO
4-> CJ
to o
CO GJ U-
O
JTjl . S
s * t s t
ro cn o o
_a n a> m
4^ - 01 CO 01
U 01 > 4J O 4J
3 4J S CO CO CO
73 O CO J= O C O
0 3 CO _C
&_ 77 4J >^ U >.
Q. O C O 4J 01 4->
t_ 3 4J
Q. 73 O i O
CO 4-> O - C -
D O C- X O X
4J CO 3 D. O C O
o 3 -a w t.
co 4^ o >. 01
0 t- C 0 jc 01
c co a. co jr 4-ป jz
O 4J 4-ป
c c c c
CO O O O 01 O O
4-1 Cl CO
CO CO CO CO C CO C
TJ 4J 4J 4J CO 4-> CO
CO CO CO r' CO r~
4J 73 73 73 0 73 O
'g 01 01 0) O 0) O
CO 'o 'o O 73 O 73
01 01
ซ- CM M -3- O in O
S. 8.
g g
u
4-1
1
_,
o
4->
ง
tu
CO
4J
1
1?
8
M-
LLI
Ol
73
i.
CO
o
J=
Q_
O
C
M
73
C
CO
c
CO
Brometh
01
|
'o
, Chloropha
to
CO
o
CO
CO
g
CO
o
c
o
CO
ซ
1
o
1
c_
CD
o
o
CO
**-
o
ฃ_
m
o
**-
o
01
o
c
o
o
Lt_
4^
CO
^
u
o
M-
UJ 1
o
in
, c
o
tu oi
CO
J= O
CO
4J CO
C 4J
CD CO
I- 73
4J
CO ป-
o
CO
01 CO
* >-
CO
CO 0)
0. C
a) '5
j: o
co
o
CO 4^
c
3 Ql'
JZ C
O CO
c
SCO
t-
CO 4-*
CO CO
CO CO
=5 ฃ
4-* ป
CO OJ
CD CO
t_
4-<
4J t_
o c.
c- u
1 ง
o
CO
"o
CJ JZ
01 4J
- CO
73 01
JC
4j ja
CO 3
J= 0.
4_i m
c
II
t- C
o o
M- O <ฃ.
l_
.^- "~ ฐ o o
' CO ' O Q fO tO
U E UJ C_ L.
t- > > LU tD (O
I-
CO ' *
O CO
4j 4^
t3 C **-
CJ O
4-> 4-> O
3 fV
O -D
ฃ- - 4-i CJ
O 4-ป CO CD U
CO C/> 4-* tt -
TJ O UJ CO E
QJ ฃ CO CJ >s
ฃ & = "" I ง
%*- 5 ss
3 >. <
CO O UJ
CD =C
O O
^ ฃ g s
CO CJ CJ CO
3 D) D
,CO 4-ป CJ CO
-M JZ 0) 1
(D TI 4-> 4J _I
^: x: co
>^ CO 4-ซ
o - -
O -D
-(00
H- 4-ป
M- CO -
I UJ CJ 4- I i
ป
QJ CJ 0)
li. U- LU
oฃ 03 o3
ฃ_ f_ t_
O O O
CD CO CO
L. ฃ_ t_
E -55
CO CD CO
CO
"o> a.
t- CO
CO
CD 3 CO
'O tT 3
o (no
01 73 >.
CO O S-
L. L. 01
a. o a.
H ' -1
<ฃ <
-------
m
o
n
G)
tn
ttf
pH
ft
0
o
E-i
fe
rf*
&
Q
-
O
a
0)
tn
<
Protection
20460
s Environmental
ashington, D. C.
Q) IS
c
'S
0
Q.
01
_e
C
CO
to
JC
4J
g
CO
o
H-
1
o
H-
O
O
Q.
CO
CD
-C
4-ป
ฃ
2
ฃ_
O
i
w
1
J_J C0
"5 ฐ
o ฃ
r) .
ฃ- ^^ I_ t_ . ฃ_ t.
o z o o ; o o
4-ป UJ O
co z:a.ป-ซoroc>r^ o-Oซป >O.ซ* "O^O
__^ tff4 ^ l_t ^ O*OC^r Oปv ซ OซO*
ey> Z3 3: oo
ro i o UJ
C3CQ"D "DCOCO tO
^ , 4-ป*"D "D -4J : .
3 J COCO (OCUCO (D
O ^ Qฃ L. CC ฃ_
' O * *ฃ_CO - t_W
-j n> +- o en
OO COO OCO O3OO CO 3O
H-O ,UJO COD COCT"QO D O"O
*~* i-.Oฃ Q.O Q.C/> CC O V)
0) 1 O """s, ' O 3E - CO O *"x. ^ CO
JC3E UI>- 0 OT3 >. . D
"^ < ง33 5 - S -2ง-^ง tO ง.^
CO t. Q.D Q.OCO-I- 3 OCO
fl)^ซ O O C_ ฃ_ O O ฃ_ฃ_
'5 "~ - "~
CT" =: to to co co co
CD O *-* **~ 4-* '^ ^\
L. _ .^ ^ ._ 0 M
h-COX4-ป 4-ป CO O 4->
>ป ^ CO fO ซ ' . CO 'O
o 3 -a ? ^ ro M ~*
W 0ฃ 'OS- S- ^COQ.
< O- O C *-* . . ~ OIB
- - v* (ft v^ oa =
H- i .
, i i
1 ซ it
,
-
in in in
o v- o oj o in
i OJ i CM . i (M
oซ * o* * o ซ
4-ป 4-i
CO (0
M-
-------
IT)
O
Q)
tn
CM
p<
o
o
Cc,
flj
O
O
d
0)
rf
Protection
20460
vironmentai
ngton, D. C.
d-H
P3 JH
to
CQ fCS
0) !S
4J
(ti
4-)
CQ
I^J
0
4J
-H
d
CQ
1
3
t!
a
E3 ci
P3 B
GUIDELINE
Brodifacou
CNITIONS FOR
Name: 2755
I 1 ^
w d
P to
.j _..
M ^^
5 L
CD
'
TJ
O
ฃ_
Q.
CU
t_
0
Q.
X
CU
I
ซ
CU
TJ
CO
E
CD
U
In
c
5
CU
01
c .
_ซ
CD
M-
1
in
CO
^j
ฃ_
0)
Q.
t_
CO
8. ' ^ '
SC_ ฃ_ t_ t-
o o o o
in i
T 4-* CM T- CM CM T- CM
5.
i- ^
O 4J x-.
OCM Oป OinCMซ >OM - T3 OOO CDOO CN1CM
T r- v PO ^- CM *e- * r CM CU - ซ-Oซ ซ-^-CM *ซ
ICM ICM iC\Jttc\JC\JTJ JT iCMOJ tcMCM 11
Z O
' *ป M < J=
0 _J 0. .. ..
4-* O Z3 tJ T3 CO
4^ E C3 O 4-* TJ TJ i r
Q. a: COCOCDU H-TJOOCOO3O
CO 3 30 = ZZC O CO 3 (0 O"Q
Qฃ O O---E D) . < (D 0ฃ Q.O O.W
> ^-^CJ ป- Z C >.' O O TJ -
fl> co d) E t- <-<*
CO -F- CO "
L. CO CO >-^ CO 4-* 4-ป
4-ป O r CQ *~
C CO (O
CU C O TJ .Q ' JQ
O CU S- "o H-. ซ
CJ 1 - <ซ-'-',
II III
1 1
o o
CM *- CM ซ-
Ox ON- OCM OsO
^- ซ * CM ซ-CM r-CM
i CM - CM i CM CM
^
CO
O CO 4-ป CO
O 3 (O ZJ
0ฃ O OS O
**iis BE ' 3ฃ
CO t
.
1
1
-------
in
*w
o
LO
(U
tn
cd
A
>1
o
a
Q)
~l
Protection
20460
rrf CJ
*o
s Environment
ashington, D.
0) IS
ns
4-J
CQ
d
(U
**~|
g
PJ.
o
u
E-"
f*!
P
CO
ง
w
H
1
05 E
GUIDELINE
Brodifacou
rt
O in
Cu in
DEFINITIONS !
and Name: 27
>H #
K (1)
CQ
Q nS
9
*^H
CO
e
53
S
ป--,
[cont.
otnotes (
o
to
-S
v TJ
*~
CO
ฃ_
s.
ฃ
CO
' . 0
a.
X
cu
I
to
cu
D
CO
_E
CO
u
_
c
5
s
s-
c
J)
CO
H-
i
CO
T3
CM
CO
eu
L_
3
CO
o
ฐ 1
>CM *- in XT
^- T ซ CM CD
i I CM CM JC
-\O sQ . 4->
O* C^ "T~ ^ i
1 ซ*x , CO
0) TJ
-MO CD
CLJC cu
a. 3 co
to *
D 0 " -S
co *i E -2
>ป "O O
O CD 4-> =
I- CU O , O
CO "D O C
D. -ฃM- .g
CO
o
M-
t
o
I
to
0
H-
CO
4-J
CO
CU
l_
ro
ro
M-
O
!5
ro
= o
J^
CD"
CD
CO
~a
o
CO -
u
s-
" CU
ro -D
ja ro
1=
. i ro
JC O
to co
ro co
'tl "ol
4-ป -D
H- CU
O L.
ro
CO
4-* CO
"D
co ro
o _ป
ฃ- U
" T3 CU
CU H-
CO 1
ro o
ja -^
^ c
Q
LU CO
co ro
jz
H- C
- o ro
CO CO
U D)
C C
ro ro
U JC
CO U
CO
4-* .
o
. o c
i!
t^
CO
CO '
3 3
O E
> o
cu s-
ฃ_
Q. 4->
TJ CO
CU -Q
4J
Q. CU
eu jc .
O 4-"
o
CD 4-(
^2
CU 4-> *
CU
Q Q
LU
Qฃ .
ro "o"
_< cu
, ซ ง ,
i
CO
u
s.
cu
0
CO
Q-
CO
3
O
_a
CO
CO
General Commen
-
iC
CM
^
ro
eu
-C
o
ij
placepack-penetrai
CO
to
?_
"o.
" CM
ro-
o!
1
ฃ?
13
r
cu
o
o
JC CO
o c
o
o ro
TJ 4-*
3 CO
O 4-*
.^- to
CO ' ป
.id o
O CO
s. ?
eu . o
U 4->
CO i
o cu
M-
4-1
CO 3
4-ป O
c ja
CU CO
C_ 4-)
Efficacy requi
General Commen
LU
O3
eu D
JC 1
t; o
"o ฃ
CD O
TJ <
O UJ
E Cฃ.
O u-
0 .
CD
O UJ
"Si
4_ป LU
Q.S
"D LU
ro t^
fi
CO <
3
E t/>
- w
Ul
O 1
o >-
^
fc III
CO u.
CM CA
CD 4J
CM -
CO CU
ฃ_
O CD
O CO
4-* 4-J
O CO
ja o
H-
- CU
CO JO
o <
f.Q.
UJ
0 X
CD ja
"Q.-D
0)
C. 4-ซ
o a.
H- CU
eu u
ง ซ
JC T3
CU
ฃ- 3 '
ro cu
i!
CO
as
ot ja
ro TD .
CO 3
c o
O JC
^ to
ro co
to o =
O f
4-J O SE
ro o t
ja t- co
a. ป-i
O CO
CO LU
* i cu a_
ca co H-
o c =
ฃ_ ซ^-
CU LU
(- -D CO
O
H- C O
D) I
CO -
4-> CO Q
C CO LU
g T3 IE
Q) 4J -
ro o
3 . Z
ง i
4V "r-
co
C CO
.^- cu
o
CO U
4->
E 4J > CO
o ro o
I- T3 t- 0)
r- Q. CU
3 CU ^ Qฃ
O" JC
CU 4-ป CU ฃ-
o: 4-ป co
>* ซ^- f*
>* H- CJ 4->
H- CO O
to -^ t- c
*- 4->. O ^
4J ro
ro co 4-ซ j^
'CO "- O
S i 11
=t 3 Mtt: ,
0 0
1 S 1 >- 1
X
CU
c
CO
s
4-)
o
8
o
' a.
c.
1
L.
0
M-
*o
1
CO
u
CO
4-*
to
cu
a.
TJ
c
CO
4-(
'co
eu ,
JC
1
CO
1
o
o
4J
0
t
o
t^_
_Q
00
cu
o
CO
a.
ฃ
CO
4.1
ro
4->
o
T3
o
Q.
CO 4->
cu o
ฃ &.
eu T!
4J CU
U 0
CO
a.
CU
ฃ_
-------
.3
cs
-------
CM
C
0
a
,
>H
ft
O
u
EH
fe
PH
Q
O
,_
to
N.N. ฐ
oui a>
* O CU
oo t-
T3 i i -
CU OO CL
> N-N- X
Q. ^^ _
Q_ CO
Em Q.
O E D.
u_ O ซt
1
>i H
0 CO
ฃ-* (25
Q) O
tn ft
pa! co
' W
ฃl rt
o
-H CO
4J O ป
4-> O ง
O CM " DH
ft -CO
rj H
rH 5
4-> P rt
a
Q) *ป Q
1 0 ง '
O 4-)
^ tn CO
H S3 & -
> -H EH
ฃ4 r*"l 1^1
H CQ EH
ซ CO
CQ JS
CD CO
4-) EH
ttf 2!
CO ij
T) &
(U H
4J JD
-H &
fl - W
,
E
t_
o.
CO
12
4-*
c
o
TJ
u
4-*.
CO
CU
tr
cu
ฃ_
C
o
CO
E
o
"c
cu
.e
^
1 '
CO
T3
C >
CO
CO
c
o
4-f
3
2
"' '
u
o
J
0
2^
zi
jj
D"
0
o
3
u'
cu
CO
D .
cx
_^
I
>.
c_
4J CO
C CO
*- CO
I- CU
a. u
o
t- C.
o
H-
u ซ
4J CO
! CU
CO CU
) .C
CO
dl
o
M 4-)
J ^
3 TJ
ฃ CO
n cu
Z CO
s
g
1 1 ^^
H Q
* W g
^EH 1
"i D H
CO Q
<" O =H=
n P4 Q
Q ft H
to
g
g
g
x s
1
t;j
0 e
o S
O E3
-H
frt O
iu w
Ip S
co S-J *
4S ^* )
PQ &)
"2 0
03 fV1
I-M
CO f- P|
S CM pq
~
0
o
co o
CO 0
CO M ฐ
9* j.**^ |_|-
S 3 Q X!
< ft ^ X
c O EH
O W -
| W Di EH
c J EH H
|ft CO U
lip o
Cj CO ^H S
T~
[D
L.
CO
O) C
o o
Oฃ O.
Cfl
QJ
O Oi
ttl
E
CD-
" t-
eo u_
at
o
4J C
CO CD
0 4->
h- CO
.3 >
t^ en
c
cu t-
CO CU
CO
*O n
- rn
CO
S "
oi o ~
o a.
n fff
OiOJ-OCJO-I
^* ^N S*.
^ ^L **I ~^ "I ^.p tC ^5
^ ^^ ^ T ^^ ซ T V Qv r
r"
O s .
'w
i - CB M-
CO CO >r- O
_0 0 t.
Si" S c o "
O fO 4-> >- 'r-
" *3 0> "i i 'S 5
ffl ' ^> >" I "' O -^ 4 O 4-ป
ง*^ ^ H" C *-* O r-*
C 4J o$S O W) O E CO o
flฃ 0) WJ GJ >. ป- 4-ป (O
"O d C <- ฃ- 4-1 ^ CA 4-*
4J O CO .- >t- COO -^ W
S o D)
U "DOi-1 OE ^4^ 'OtOi-'cO ฃ_
OWQ.O.CO'^a>K.CO ->xQC O
g 0.0 Q cuc3 C
o
a. co
o c.
o a.
CO ^
o
- c
(B
4-* M-
03
o
u cu
CO '^
ซ CO
CU J=
3 CO
4-1 S
ฃ_
a o
Ol
I ro
eg E '
-C 4-ป ,
0 C
CO
CD -
ป CO CD
CO 1 -'
0 g g
ง=5 S
CD I-
g_r-
" I- N
^; O
4-* ฃ_
CU O
C CO J=
O ' 4-"
CO 3
-ง *" "*
CO >* CO
Ero >-
CO C C
4-ป -^ 3 CD
C 3 co CL
QJ O ' E
4-ป '
CO >- .Q S
4J c nj o
CO CO O
.- (U
CL) 4-* > _.'
c x: CD a. 4-*
O 4-ป .C Q. -
^ 4J CO 1
0 03 fl) U t3
j x: CD tu c
5 til I
UL.Ji.iO CD
CU O _Q C
0 CO O)
O L. ,-
;
ฃ_
CD
E
2
O
C
o
-*-
ฐ~
M
-J
D
1
>.
i
L
1
1
-------
M
CปJ
o
tN
rti
tn
nJ
CM
X
O
O
ft*
rij
P4
Q
0.
?*
M
i
N.N. ฐ
otn w
OO ฃ-
O II
CU OO Q.
O OO UJ
<- CMCM
t- CM
1 CO
J3
N- CO
C
(U c_
CO CU
CO
>O CL
CO
0,0 ~
O Q.
Q. CU
xoioi ouoi
0)
1
CO
in
0)
c *-
*ป c
dj ฃ
T3 eu
O *3 _Q
D" E
*- C - <& t-
{0: B 'ซ- ^ O i* M iฃl
t- S x S t- ซ
i> ) CO < ^
O 4*" i- CU *rr C W < '
'ป- X 0 T3 0 - >' >- ^
<& O *-t j_, ซ_ - r J>!
fc ซ> 33^3 -ง -~ 1_ S
O ^J OO Ol-ฃ-3> i*-
o 3 <<: ซstxa.o ^H
ซ UJ
o
CSt T~t O3 OO '*?? LO ^O
J ft lilt
fTJ 1^1 T^ I~n T~l T"H T"t
vo co oo oo co oo oo
CQ
o
g
03
aป
o
s
.
^
s
OS
at
; TJ
"o
C.
CO
I
1
o
o
T-t
1
Vฃfc
0V
tt)
O)
co m
CG a_
Is
4-> CO
ฃc
H- O
1 <^
4-1 4-"
CU U
<1> ฃ'
4-> 4-ป
CO C-
o o
.P> O
"E M-
0 -M
4J X
0)
' *- J
CO
4_t _j
C H-
-------
m
IVA
o
CD
tn
rt
o
ti
(U
S1
73 CO
' C ^" Tiป
c cu
73 CD i-
11) O Q.
C 4J =
>. 4-> II
CU U
ฃ .ซ <
-Q
cu" co o.
U
3 O 4^"
O C C
CO
73 t- 73
CU CO ,0)
t_ . C_
CU CO D)
to c ฃ
CO
D) Cซ CU
CU 4-" >
t- CO
CD C) O
CU CO
ฃ_ * "cu
*" y 2
'co 73 ^"
*~r O
C D.
CU t
2 0 ..
D) +* 4-*
cue
CU CU 73
> i. CU
4J C- 0)
O O C
CO JC "-
i I S
end-use product; provided formulators purchase the
:NOTE: If a product is a 100 percent repackage of a
end-use product;TGAI = technical grade of the acti
n
4-> CO
/t o O
UJ 3
-72 ฃ
tJ a.*"*
O 01
c- *- co ja
3 -M CO
-MO '
o 4-* 4-> CU O)
fl-83ฃ
O *
f *-* CO * ~CJJ ' ซ)
-M . 0 TJ > 03 ..--
.. fe S S "8 ''5 ซ . r ฃ * g - -
. H-EC-MJS+J OflJ .Q
ฃr *ro
| ซ ' ^ง 1 1 73'1 1 8 . - | ง
c^JJ Or-coeocu4-' coo. cuo
"ฃ ซ- ' JfSS g 2 ^.S si to 8
SKฐ ' .' o^S .2 ฃ 073 ID" "cu
SP^" CO^-*4JCUCCU 73CO >~CO
3 i- 73 ซ , ".-ซ_-ง
< "- c- C7373CUCUC 4V>. OoS
o co c o t- ,J2 .^ 4-T .i: - ?
ill*- 3COCOI-D) _.. 5ป0
ฐ ซ =1^ "- g> 1= I s |
1 ;-; g g :ง ซ| . . .ป 1 t
*" CU a) ^O O3 O C QJ C T5 Ol (T
g. S -|^- -^ ? --o 9".- 5 1 K
fe . CO C'&S- 3 g^O fetJ ฃ " -0,
ฐ "* -*-> -+- 4-ป t. TJ -M3 COCDC'
-D S c- 8 J ซ_ .5 . g 2 -ซ "g 1 ^ i
Q-O ซฃ OM 'CDC.-.O) CUt- >47.
ฐ>ฃ " ซ E *. "H 3 ' 'o - 5 a ococ
ฐg-ฑ" S- g '0 3 *- ? 0 x^ CD'S
. -g c o 3 >2 c >v, ฐ 4^ ." S3 -ฐ .'> . JS
I'll s- 15 1ฃ 1 1 <| ซ ~.c5 = .g |
,,3EO co t- co H- cu 73 3roo
oo z coo w o 4-1 5. * *" . r
-<='-< CO CO 3 4J73 4->.m
to g ง s .2 1 4, -8 -8 Jg -t: ฃ 3 i . .
fl 1 | "&ฃ g 73 2W .J8 Ig
-^^ (D +-ป CJ O3*f- 34-> t_CUO'
J t_ซOtOCO O 03CU 'Q.v-'C
b-z co ซgo ; ฃ-. || ^: ซ. .5 |
2 gSe-oSJocJ-S" 3 fc &
1 iS-S8'8^8' ^2 ".tocS
U. OS CD -U CO 4->3 CD*-1 --. i=
0 ^j . I-COCOCD03 tr " 2. ซ I/C JC
n-= o) in- n. - O O . 03 O Q CD ' CO O CD C
locu'c^ Stov'*^::'EeUฃ- to'-T to.*- 73 ฃ.? CT - = 2
CD C O i -I- O ' * Q) CO O CD COCO> t-4-><4-*T-
IP f T^S i" ! **. i ^^.2 ^ 1^ 1
TT7- I l*t a S- ?5 !' -si : i -ง: 1
o rn = . -S e 8 ฐ S1 8 co -co-'S, c5 5 U Z g ' ฐ-
in - tO ซ ซ- O C 4-ป Q. 4J j^x O ซ*- .^-TJCCD
v -Et.cacEo c oisc-^w
O3 TJ "- Q. . -i- O 3 (0 O CO O O 3
0 ^'S'Ti^13 OTJ COO (UOOCOi
0.15 3 mra2งงci*.ฃ.^x2f -J.3t--ง.^,
ง1 g s'sF^ ซ ' c frฐ ^ sss i. H--SS "
OC.E >OE-OOJ3-M-^C OC TJ
"S2 -S ง5*" 'H 'i ;S ll'ป . fe ฐl ^1 gZg s
0)03 O inpI_3OCD-Mฃ_t_cO +J O3OO)
^~ CD 4-ป T~ r*ป o ~Q 3 4-* in co t o ฃ
^* C 'f- ^ . O TJ CO W CD 4-1 *fr- I " ' O 4-* O CO ซ^
^ _. >f~ eo ป o t_ O4-*co*r-co ECM o .1- o i-
|1 -g &SS 5 ฐ- k"?-S3 "Sr^ >.5^-g4J-g 5
*-O CU E * ^ CU COXL..fZ4^CU >*.^ฃ O O S O
_, "t _ a R^* "S "^ !r Jao)4J.4J73o co o c o co
"^SxS oeo ฐ <" o ป i c 73 o - j: co (_*-
coo.o o in-. o JITJCU 3 o g *- 4J 0)04Ji_eocn 3
J- CO I- ..^-x^ Cซ 4JCUCO C-i-4-0 4J O CU CU C
i **- QJ ^ซ, ^c ro O CD 4-* ro 4-ป CU ซ^- .3 '*~ Z f~ flj -T3 o . m
s.^^'s .tj.^=i.-sjsoc3S-i-t/'t:Q: tsitl"8!11
.CD 4-ป O ฃ- 4J .^^o D. 3CD OCOC't-OOJCDO. O"-CD CDO -E
J- CO 0 C-^% v^.^ H '-03 -^031.^20 03L.L.O O
J O QJ ' QJ ^~ u. .Q ^ ซr C t O &3OCO3COCO
H^5"ฃ CO TJi03 O L. CD UJ OC-CDCD4-*CD4^ COt-O COM- CD
111 W 4Jvx4JTJ CCDO OJ.t- CD COOCOOXO f-
M a ~* . o TJOง *ฃ ^COQ"S'5,Si^'co^*^^ -cocfl.tlco^m o.
C O JQ. ซ TJ 03 C O""" t_TJO4-ป ' L-COCOt- 3
t_4-ปE t- CO-^CCOCD3(0 .C-r- _^_,.^.^. = O CO
ซ g. ฐ-S- -ฐ . E e ra ฐ *- cJco j?w 373 5'S-afe"- o
'*- "" OO'*--ซt_4-> *OS-4J(Dฃ_aJC04-ป4-ป<0 - * ฃ-ฃ-COOTJO 4-ป
t- 3 4->Q_o>-so.c:co"-ocj2 OO3O4-* eo CDCDEO in
Q.M- ^ n o,ict175ง'4Jt5c-2--Sci*:-acc5. .S -S S fc *, "8 ซ 2
P = . U COOC>JCOOE073-'C4J*-Q.'>Q.. E ES73O4;!" to
t-T^J- 0 >g . -p - ซ0 CO CO C I. - 0 - COCUUJCUCU S 3COO 73
ฐ c 8 " *" fi C734-"v^ O4-"t_3CUJ2 t-I_ JS 4J4J7373CUC
^.-^ ,. 2 CCO EO>CO*(-COtn I-3C073CO U COCOCOQ.4J (0
oT3*J-.ฃ 5 S~OOD)CUCU COS:C04-' COCO *(B O iฃ
s^ t^- co o -^ j ป lr- ,_ __ Q. ^ ^ ,_ s ^ ^ *~ ^ 2 ,^ /" ^^ 2- S2 ^^ 5-
sS'S'i'S "3 cocil3"D3 H-4-ป4-* CTCT3 CD
,*? IT ** CDI_'ป-C tOH-jnot-coojciJOQJCM- oo H- CD CD o _<
ซ' ' ' O _ DSQ-TJCO^S 4JI D)QCJQ:ZQฃ.^-O
-------
to
0
(U
CD
to"
04
O
a
*?
rt
0
H
4J
O 0
CD VO
| \ .
*f-
r-
4-J
03
CO
CO
E
4-J
C
CO
4-f
CO
ra
CU
ฃ.
CO
4-J
3
^
C.
CL
CU
3
1
O)
C
L.
O
to
<*-
1
CO
r_
o
1 U. 1
C
o
CU
4-J CO
4-J O f n
0 C *i
C co to
TJ C 4-J CO
TJ O C 4-J
' 3 - 03 CD
3 0 4J 1- -O
O 3 CO 4->
3 tO M-
CO 3 . , o
tO 4-ป E ra
4-J C- t- CU CO
L. CD O t- CU
CU C H- Q.
ra to co
ra c 3 to ra
C i Q. C
C T3
C ฃ 0) 3
to tu cu .c o
CD E "U 4-J
tu t- 3 IS c "o
t- O CL M-
CU 0 CO
tU -E OS O CU
-E 4-j s- j= .E
4-J - O- CO 4-J
T3 T3 C
T3 C O O CO TJ
C CD c- C E tU
CO CO 3 tU
co M _e C
CO J SS
' to in "o o to
CO O C 4J 4-J
t- O CO C
t- tu to co
CU 4-J O ป tU C_
4J 03 C tO 4-J
tO E *-J - CD CO
E CO CU
CD o CD co ra
CU "D E r* it- CU
CO t- 4-J CU
c- ra t- E 4-J -
T3 O Q. QQ CO CU
O O 3 C JQ
O H- CO - CD CO
**" S^ "D C 4J ~"
fr? in ป o 4^
tn o 3 , c X c
o o tu
CO 3 O 4-J ฃ-
C C (001-
- eu jr o 3 i
03 CO 4-1 CL t_ O
4-J 4-J CO O ป-
n c L. t- T> c
0 O 4-J O CO
0 O C
CO 4-J U CJ 1- ฃ
4-J O C O -
O 3 O ป CO
3 T3 O 4J >*
no _.. _, o
O t_ E CD 4-J
t- O. 3 ป 0 .E
Q. 0 * "D CU ฃ_ E -
CD CU CO (fi
3 "O TJ 4-J 4-J J2
CU SS '^- CD 3
tu > -a in j= a.
Z 2 > ~ ^ ^ SK
*f- D_ O O tO CO C
C- 4-J CO
c - a. tu ' tu c
g^.C g^ง __-_-
4-> t_CU C O C _/_*_*
C D4-JL- .^I_.^ CUCUCU
งO CD O U 4-J -^- - .t-
COC-H- (0 f-C Q_ U_ LL.
4-> J= O O
t- TICCO CLM-O < 000000
. C tU 4-ป (
3 CO O CO Q CO O 4 X X X> X X
O" CTJ El Q ฃ_ฃ_ฃ_ L_ฃ_
CU GO ซป- OOOOO
"> CU C 'CO OOCOCD CD tOtO
CO 4-ป t ' O ^UtO ' I- >- UJ CO CO CO CD CO
X 4^ CU tO Q.
- CO O ฃ- W ' ->
4-* CO CU U- CQ CO 4-ซ
CD O O CO
CO CU L- * . 4J 4-> Qฃ
jr x: .c I? S o ,
OX 04->XOX ^ TJC **- CO
4->tO 4->C.COฃ- O CU O * .
03 E tODlOO O 4->4-> O CUQ.
& ^2 C D) D> to "-3 a: t-Q.
4-J 4-> 4-> CU ra (LI ^-O^ t-CO
CJtUCOCU>4-'O4-ป -- * ซ-
3 4-ป E CD D *-> E CO CO M- CO TJ ฃ- -. 4-*CU D) 3 CO
.TJOtO t-TIOtOJZOCO O O4-J COflJO O CT3(
o3co4^O3co jz co L_ co co4-'a:->-oc/>o
L.TJ COฃ-TJ4-ปXOX 4JCQ "DO LU CO ฃ CO
a. o c -^- a.oco4^ .c CUE ootux tu TJX
ฃ_ O) L. 3 ป 4J tl) L- 4-> ^ Q_ CO '4J O in 3X <
CO 4-ป O -CD4-*OXCU t- COO UJ
Ot-4-> Oฃ-CCU^:tU 4-*tU tO 3Z
c co a. u c ra Q. ro jz -M jz c 4-* a; o
O 3O 4-ป4-ป OO _Q'r-XO
CCTJ CCCC OC "ป*. 4J (0 4-> C0 CO LL. ECU^ CL
CO CO CU CO CO CO JZ CD JZ ^ JC
4-ปTJTJCO4JTJTJTJOTJO XI CO C04-JCU CO
*- rjซr- CU 4-J 4-1 .C CU 1 _J _J 1
eOJO i E <1J OJ O O (D O 4J tO fOTJ4-ป 4J_J _J -J-J
MO'O CU COOOOTJCJ-n > X XC04-*
CU CU O o
*-e\jrotOT-tMM-
-------
in
"o
ro
(D
cn
,04
>X
O)
0
O
E-"
p.
Q
Agency
d
o
-H
Protect
20460
rH U
nS
| \ *
tip
0)
s Environn
ashington,
o &
4-)
4J
CO
cu
4-)
-H
rt
S
CO
i
I
s
REQUIRE
i
B
' GUIDEL]
ps
y
f~n
ter~
DEFINITIO:
.
S
I
***(
CQ
PL)
^
bj
Fj
o
S
o
H
o
Bromadi
o
^3
t>
CN
*
OJ
125
a
*.
ra
cti
U
'
,
T3
0)
ฃ_
to
O^O
_. ,-. 0
O) 1 C3 UJ
C z O ' T3 "D CO
^ .< 4J -D -a _.
31 CO CO CO CD
O =3 ' <ฃ t-
^ CS ป ซ ฃ- B)
oo coo oco o5o
H- cj in o co 3 co era
o; a. o Q. co
-C^ UJ>* O OTJ"-
4^<: a.co COCD cocc-
CO 3 CO 3
to i-Q.rJQ.oro
CD O O ฃ- ฃ_
t--- Z C3T CC3CL
5 "~
U" :z to co co
H^ CO X 4-> 4->
>- < m co '^>
U 1 3 CO CO
ง - iSt -0- -0
O) ^ O S- "4-
< O 0 ^ ~ ~
x: -
' 1
in v- m t- ' in in in
. t- c-
o o
oroc> o-^o CMCM oซ- OCM oin
i OJ OJ I OJ OJ ii i OJ i OJ i OJ
^O"ซ ^O^ซ *O^O *Oซ \O" *>Oซ
^^- ^T- Os 0*- OV^-ONT-
co to .
to to to 'ro
^ t- ce o;
i- to
M- m c
-D m Ii ' 1ฐ S ai
- x
-------
in
C
Q)
bi
cti
04
JH
o
O
fa
*3<
Q
.
O
ซ
0)
Cn
j^J
a
o
H
1 1
O 0
0) U3
AJ *4<
O 0
M CJ
CM
ctf
a Q
r*1
Q O
3 -H
M ^
W g
R o
s M
0 PQ
ซ
S g
B a
DEFINITIO
and Name:
H *
^ Q)
Q m
S ffl
2 u
"S
CO
1
o
s
t*
,^
4-3
o
u
CO
(U
u
o
rt
4J
o
o
fe
x^
S
CO
CD
Q.
O) <
2
t-
* E
t QJ "o o 'ป~ *~* g ป- >-
ft) D) O CO CO CO ft)
M C ฃ_ 4-> ป- ป- 4J
to -^ m - co
., t_CO COvxC04J +-> O) L.BJ
+JO S ^ ป .1 'C -MO
Ii g 2 5' ^ ฃง ง1
gg ^ oi:^ ฃg งS5
Oh- ซ (/,_ L-J ^.Q, Ul_
ii lit i
' i i i
-------
in
O
in
Cn
tti
CD
><
ft
O
u
*
^
pi
Q
^i
u
(D
a
ซ
o
-H
JJ
O to
Q) vo
JJ <3<
O 0
M IN
CM
rH U
fti
JJ
fl Q
0)
1 d"
o o
H JJ
H tn
> rt
fl-H
H 43
m
GO ftf
4-)
JJ
co
a
Q)
JJ
H
s-
"
CO
I
w
H
a
1
Mll
H
1=
Cfl
1
i
DEFINITIO
>H
w
_
hJ
ง
~J
CO
EH
>2
O
g
(U
ง
H
O
H
^j
(ti
o
PQ
o
U)
!>
Oj
0
S3
1
#
(D
ra
M
0
t
jJ
ง
U
s>
CQ
(U
otnot
o
1
ra"
D
*""
CO
ง
f_
(D
Q.
to
ฃ_
CO
O
Q)
4-ป
TJ*
0)
^
CO .
-s
CO
E .
'ra ,
u
"en
c
o
o
In
c
ro '
M-
ฃ.
. ra
~ฐ
CVJ
CO
""
o
CO
o
ฐ t
CM T- m vf
* ซr- T CM CO
i i CM CM .ฃ:
t> C> *- ^ ^
4J O (O
- 4-ป ฃ
Ci _C CO
a. 3: co
CO - 'c
- co
CO 0) O ฃ
>* "D O
O CO 4-> ฃ
t- O O D)
o
I
o
c
1 1 * I
OJ
>.
ro
(0
4-*
"D
X
O
(0
"-
M
s
OJ
c
o
c
co"
"o
"-
8.
o
c_
CO
1 O
a.
x ra
o c
.- "o
ซJ JQ
1=
4-J ฃ_
CO 0)
^fO CO
"^ *OJ
~*o-ฃ
CO
' "3 -^
CO (D
to *
c- o
C 0)
Q_ C
= 1
O)
ง1
4-ป
"o ra
CD O
0 D9
c c
ra ^
CO O
4J
0 C
4^
CO
t- 0)
O 0
.,- -o
*^ o
>N. 4J
CO >
11
> 0
. 0
to ra 4->
o ra .
i C -C
M O 4->
"o "ฐ S
x > 2
= ' gl
-O E
S 'ra ~
i "1
Q. v- O
.
ra
a.
o
o
'ฃ
ra
4-*
o
ra
a>
0
CJ
General
.
iC
cv
.
\*s
4J
-c
O
4->
CO
t_
1
CO
a.
'
o
o
CO
"o.
CO
4-*
m"
0
.g-
ra
QZ
4-1
O
& '
ra
CO
0
o
CJ
General i
LU
V)
o rs
+J O
z*L
ra o
0 LU
งK
O 11-
Q
O LU
4-> a:
o a
4-> LU
a. a:
ra
"D LU
ra aฃ
-a O
CO
4-* _l
E CO
." LU
0 1-
0 >
1 '
* LU
CO "
ru co
ซ-
/c "o
ra 4-1
'c
1 ฃ_
O CD
U
O CO
4J 4-ป
O CO
' a. 4->
' 4J ffl
3 C.
."o
J^
0 *C.
ra CL
Q-LU
0
u >-
ra -Q
~ฐ~~m
Is-
o
o o
co ra
o
4J C
o
ra o
il
CO _Q
CO "O
CO 3
c o
O jc
- CO
flJ CO
4_i i .
CO O =
O H-
4-ป O 3C
'ซ 0 5
^t *- C/3
a. ซ-ซ
CO LJU
ry T3 o:
i CO i
>,ฃ E
S g?
O LU
o B>
S- C O
05 1-
CO
4J CO Q
C O LU
o -a E
CD 4J <
'5 -a "
2 Q-<
J5-.HS
05 M- O
(U
"^
_^
*
o
E '
CO
0
o
- - -D
c
^
ฃ
73
O ,
X
81
>~
i
o
o
c_
Q.
" ,. I
fe
(O
~0
CO
4-ป
S
Q.
D
S '**
1 , o
2 -^
4^ .
o
0 0
ra . 2;
CO .
r ra ฐ '
* . to
3 ง ฐ
co ^v .ti
ฃ- >- . 'g
1 I 1
CO t3
ป C ' CO G)
co - > CO O
tO CO 0 3
CO CO , C- "O L. D> "D
+-* C ' - CL CO O
CO O 3 0) ^* OS t
tu cr j= Q.
H 4J ' CO jj* tO L. ^^
CO Oฃ 4-> tO ' -CO *J
o ง ? : '^" ฐ ^ ^ ง
OT O '*- 4-ป Q *f r- f
> 4J ro 4-< Q.
o >- 'i ro ฃ'~o
lp~ .3 O CD o p ซ ^y;
4-ป O 4^ ฃ DOCJO
,1 .^.,1.1 M-ฐ- ' 1
-------
-------
H
Vi
O
r-
0)
fC
cu
>>
CU
O
O
EH
.,
ft!
Q
t>
/
i
N.N. S
otn co
*~O 0)
oo t-
N.N- x
o oo iu
t- OJCM
CL CD
< O >
z o
o 1 |
-O1
0)
a
o
-H
aJ o
U VD
tt) <* W
j-> o CO
2" ง
CM CM
a co
rH H
nS ft!
CO H (ij E-l
c J E-" H
ji-Cu CQ O
|^ 0 0
o CQ S S
CD
4-ป
CO
Q
O
^
O
'S.
to
*J
o
"g
o
.
CO
CO
a
u
01
c
cu
C3
>O
c 5 co
CO Q- J= 4->
=> o e
CL UJ CD CD-
3-*-ป E CO
CD 4-* CD <^-
jr co c- 4J
C *J. C
CD CD 3 CO
X-j: IT s-
a> H- *j cu +J
to a: to
c = .-
^ 4J O D)
O CO 13 O'
3 co to cu a:
"O 4^ '
O O C -U "O =
U V <> - C
CL ' E 4-> CO CU
CU CD C tO
X CU <- CU CO C
Z t- DO
O5 3 E +^ Q.
CO ET t_ CO CO
-Q CU O 4-* CU
N. t- M- in Q-
o
D CD CO
c a. ^i v .
ID O O C
Ct- 4-ป- E CO
0 0 4J CU -
ฃ .C CO ฃ- 4J
4-ป "- C
CO CD 3 CO
X-E-cr i-
CO Dฃ CO
*-ป 4-> O "* D)
O CO T3 CU
3 co co cu a:
O O C 4-* "D =
CL E 4-> CD CU
CD CU C CO
X a c. cu to c
D)'5 E 4-> Q.
co cr s- co to
CO CU O *-> CU
0 TJ
O) -a
i- 4-> CU
o co >
"~ o t '
cu
C3 73 V T3
C C C =
X-r O 4J O
co co 4- CD a.
(0 4-* 4-> CO
S"^ (X5 CJ
cu a:
4-ป E -C CO
CU O 4-* CO
CD t- CD C -
CD 4-ป CD 4-*
(L. D 4J ฃ C
D) O" CO CD CO
10 t o o o = a:
.
J C 3 ,
5 ^, ^5 "CD
C 0) 01 -Q
U CD t- CU
C3 CO D) t- "O
n c cu
CD CO -r- CJ CJ
CD 4-* >
CO -
__, 4^ 4_,
' CO CO
CD 4J
O) C
a c CD
C Cfl
CD -O O
E^ S-
t_ * QJ
ซฃ.2 "*
E T3
CO CU
t- N
^: O
CD O
C CO .E
CO 3
CU H- <
CO X CO .
"in , "x
CO C C
4-* 'w- 3 CO
c 3 co a.
CD O S
CO X J2 M-
+J C CO O
CO CO U
CD 4-> , _.
JZ CD Q. *-
4J ^* O ir
3 4J CO 1
J CO CU t- T3
CO JZ D) CD C
O 4-> T3 TJ CO
^ (U C
f- X 3 CU
ป H- 3 c_
*> " O JC 3
t- 4^ C 4J 4J
CU C- ^^ O CO
CJ CD O X! C.
U CD O)
CO i ~i O t/5
ฃ_
CU
S!
c
o
-E
.
J^
4-1
U
a
5
o
i
5
CJ
>
j
:
T
-------
N.N. x
O OO HI
t- OJCM
t ฃ 1
lit
(
>i M
O CO
(0 O
&1 ft
flj CO
H CO
4J O ซ
Ot rt fปl
\JJ ft
U o g
8 ฐ* EH
ft CO
UKJ
M
JJ P 8
fl
Q) - P
S d rj
O 4-J
H tn co
-H d p
He1 icT
M CO EH
ttf CO
CQ &
0) CO
4J EH
4J H
co E
CH
IT-J S3
0) H
4-3 P
pj M
JD pi{
E
L.
o
\t.
n
c
0
4-1
a>
c_
g
4-*
O
CD
JC
*-ป
1
CO
1
CD
o
4->
O
t_
1
I
CO
4-*
CO
CD
JC
^.
t
3
CD
L.
CO
O
CO
CD
CO
CO
2
a-
f p
c_
4-1 CO
C U
r- 01
(- CD
Q. 0
O
H-
CD *-
M CO
CO CD
CO CD
01 JC
n.
"a
& o
!ง
/) CD
S3
g
o s
| t i^F
rT -
HQ
J 4
o rj ctj
0 H i
"S ft g
||
"8 B s
" Q
ra PH P
0 ft H
fO
|
n
ง
1
s 1
H a
1-1 P
ฃ3
4J
/ll /^
vU U
s s
1 0
z m Cn
g Q)
% in
co F* ft
o CN H
<
CM
0
O
co o
co o
PL| o
2 S P
lftง><
"O ซ -
f~ ^j E~^
0 o w -
ft) p^J K^
| W PS EH
c J EH H
^ft CO U
|^ 0 0
S co a S
^
c
CO
L.
CO CD
'tป C
CU O
f* r>
CO
CD
t> 0-
1,
CD
L.
CO u_
C
CO CO
N- CO
E
CO CD
4-1
CO
\o a.
CO
CD 4->
*- *- rvl
0> O ^
0 Q.
i_o;oi-oc_3O-i
4-1
t
4-*
in
Is
o E
T3 CJ
C- t-
S'5|
sf^z
1
w t
,
OO O OOOOOOOOO
ss g, esesesess
OOQQ oo OOCOOO'GOCOOOCXJCOOO
w
^
~ ' ..'
!
ftft ft ftftftftftftftftft
-ss g -ssslissss
OO O OOOOOOOOO
ss g ss'sssssss
M K M WWWWW^WKW
^ J ^
"
i'^
'
t
*
f.
J
r>J ro ^? in x^ /^. ^x
ซ--e- * r ^- *- -e T- X>T
C
O
VI j C
4-> O
CO M- ..-
CO CO ป O 4-*
O 0 I_ U
"~ o QJ C CO CO
g g -H C 0 W
ฐ o3 D) 3 ง 'ซ ^ *0
f"
ง4-ป (D H- CO p. CU 4-ป
C4-^oฃ( O U) O E CO L.
Otf OJ W OJ >^ -r- 4-> O
T3 C C <^ L. 4J ' CO
i "-C4-ปtflO4->coroca ro
_ +-ปuco ->- coo c
g 4-ป p. 3 flj CO L. -^- ซr- ป- CD >. *-
.C 13 T O O 3 O. -^ ^ ^L t. -H ฃ .^1
CJ -DOi-t-OE-'-M-'OcOt-eO T3
OU3Q_Q.C/)'^-CUt.(D 'XQC -
U
a
% - i
11 j i-"-*
*
7j S
HCN CM HtS|rr)
' co CD
CO 4-*
at c
"DC O
C ' CO
CO "O 0)
CO t-
E o a.
t_ - * 0)
O CO Oฃ
M
E -T3
CO CU
JC O
CD O
C CO JC
O ' 4-*
CO 3
CU 4- <
CO >. CO
we- c
4-ป ป- , 3 CO
c a co a.
CD O ' E
cf c ฐ
4-* -^
CO >ซ JQ (-
4-> C CO O
01 CO O
it- Ql
CD 4-. -^
c jc co a. 4J
O 4-" JC Q. :i-
"- 4-ป CO 1
*J 4J
CO CO (U C- T}
O JC O> CD C
- 4J -O T3 CO
4-* M- 3 C_
4->
CJ C_ Jiฃ O CO
CD o ja c
O CO D)
O i,
r- ป >-< O CO
OJ
I
CU
c
o
JC
a_
ro
(
u
ro
4->
c
o
o
^-
CO
a.
u
H-
0
CD
CM
-------
c^
H-A
o
03
d)
tn
PJ
-
!*
Ai
O
O
EH
fe
rt!
rt-
P
o>
o-
o
om co
^ f t . <]J
OO t-
~O it.
> N-F^- X
i- CMCM
Q.
a. to
< 0 >
m = 2
|||:
O CO
(U O
tn ft
O ซ
4-) O ง
PJ CO
-U Q Pi
Ci
O 4-)
^ tn, co
-H a p
c _c! S
H CQ EH
rt co
CQ |S
CU CO
1 4J H
rd S
CQ 2
Q) H
4-1 S3
-H a
o
H-
4->
c.
o
T3
01
CT
0)
t_
C
o
o
-C
4J
1
CO
g
CO
c
o
I_
01
c
.2
to
4-J
CO
cu
4-J
"Ej
H-
r_
O
To
Ol
ฃ_
01
CO
to
cu
a.
4
ฃ s
- CO
t- 0)
CL O
CU
f_. C
o
cu ฃ
INSTRUCTIONS: Please tyf
Use additional sheet(s)
rVi i -
w o
5'uS
ฐ'M '
10 Q
ฃ O *
o Pi Q
a P4 H
.-. 1
1
^
ll ^
z CQ tn
"i 3)
* in
co r-. PJ
S 03 W
CM
\
ess
NY
DRESS
00000
1. Company name and Addr
SAMPLE COMPA
NO STREET AD
NO CITY, XX
4-*
c -
4-ป
W 03
- CO
D) C
C) O
t* a.
oCl
01
E
CO
CO u-
u
4-> n
CO CO
CU 4-J
t CO
.ง
N- CO
c
CU t-
co o
ID 4J
4-J
CO
tvi
u
CU 4-> .
0 Q.
fX Qฃ
XCKOI OCJO-J
CD
1 ,
TJ
cn
in
4. Guideline
Requirement
Number
>
;
CQtQ CQtQ CQCDD3CQ
OO OO OOOO
es ss ssss
COCO COCO COCOCOCO
' J-
j^^ CM p4 At ("W"- pt4 A* Qi ^
63W Wfn} JilpElJitpL]
OO OO OOOO,
-
' ,
^0 O
o - o o ซ. o
>> in CM m in CM in
^ ซ- ^- }OCMป-~*1*iJ
' V *. ฐ
j ซ -^
CO t- J3
U i JJ O
81 +> ฃ ง fc
4-ป JS C0 O- C +-* O
CO U L- J-> O . ฃ-0434-0 ซJ
+*0 3 0 ^C'^^-CO L.
*ซ CO PI "- ^2 O t- N J3
^ fO tt O CO 4J -^ 'S 4J 4->
J^JC 4-ป>-J-C_ ^ >x X& C >
WC (U tOf-4->JTQJ
CD CO O > t ฃ- ' ^ป
Xff O ^ O d)' X O CO -CO CO O
oit la - -w- E u
J-* O 4V O "O" O- ^ ^ Q) *
*- o
<- CO
03 O
0 i
>t-
to c-
o cu
o
T3
ฃ*B
O 4-J
' 4-J
CO
IS
-------
in
a
P4
o
o
l
C
e
-a
m
m a
flj U
o-ฐra
nraฃ=
o JL
igs
CMC
r-.r-Q)
--ซ
2 u "S
:
..T.
s..s
"
? a -
T. s
OC
-
* 8 -
s-
o
ง ฐ
o c .
""
S
c- 3 C '
O C O ฃ
c- CU O
^1= %
4->
til CO
cj z s:
in
-0
c- co o
t- u "o
i
ซ
4J C
8-8
oo
-g a
.a
co JD
O)
CO
C_ 4-1
O O
> CO
o E
.
2"
a>
-
(0 ' - O
ซ '5 1.5
.
- ฐ ซ
"D i ซ U C.(OUJ O ฃ- <1> (D 4-ป QJ
.^*-aj w o ' 0 OQ.-DL.OJC
-ฃ_4JปOS-*-ปQJL.O' (04^4^0)
.M-^-OJ *-ป OJ 4-ปC4-ปซป-^CI-
O '^~ (U O O
CO C. t_ O
W O C O 3 (0
aj t_ o ซ M-
O) C- ป- - O -r-
ซJ C. C. (D O '
U 4-> 4J ฃ_
i 3
54-* -M TJ T3
U) W C O
3CT3T3O
-------
'in
H-l
O
(U
tn
rt
P-<
a
o
a
fc
rtj
ctj
Q
-
O
(U
Cn
* i
Protectior
20460
rH O
rt
d Q
0) ,
1 d~
0 0
Ni 4-J
, *" y '
d-H
H .3
m
CQ Oj
Q) |2
4J
(tj
4-1
co
d
(U
:-H
!=>
"-
CO
2^
1
ง
GUIDELINE
&
g
o
H
ii
21
H
h
M
O
H
Q
S
^H
CO
H
g-
g
o
s.
'
-S
Bromethal
, tf>
w
c-
CM
or
fn
jg>[
1
#
0)
rn
UJ,
td
O
'
13
Q
Q.
CO
ง
TJ
C.
CD
"" - "g'
CD
O
C
ฃ_
2
o
M-
co
.E
-C-
u
CO
CO
4-1
t-
O
CL
ง-
CO
o
+*
* ซ CD
4J "ง
o |
^^ 0-
CO
03 ^
0) ฃ
JJ S
o 5
d
jj j
o .>-
o ,
.
-
CD
3
CD
CD
(_
JI
c
4-ป
CD
CD
ฃ_
t
CO
'JZ
H-'
tfi
CO
CO
^
CO
E
4->
C
4^ JZ
CO O
.- 4_ป
O] CO
O XI
O CU
CO 3 4J E
ป O 3 CO
4J C_ 73
U Q. O C
3 I_
TJ Q.
O CO 4-ป
ฃ_ 3 O
Q. 4-> CO 3
0 3 13
CD CO 4-> O
ง c S k-
i O
tn c c
C ' CO O O
4-*
C- CO CO CO
3 -O 4_ป 4J
4-> CO CO .
O 4-ป TJ TJ
CO
H- j= CU CD
g CO O '5
CO T CM M
O
1 U_ 1
..
1
CU
>
M-
c
c
CD
'5
cr
CU
CO
**
^^
H-
(0
CO
CO
CO
E
4-*
gistran
CU
ฃ_
CD
1
0
0.
CD
i
S
CO
L.
O
u. i
E-
1. CD O
.CU C *+-
c
i CD
CT M
0) C 3
1 li
co E
I- O
CD U
- cu j: co
4_l lr_
T> -a
? S P
. C CO t_
co m
co * 5*2
co in
t. o
1_ (U
(U 4J O
0) O
-S "S E
CO i. 4-"
C. O) ฃ-
D) 0
TJ a.
o o a.
O O 3
O M- CO
M-
&5 ฃn '
in o 3
0 0
- i :
CO CO 4-ป
4-* 4-> CD
C C t-
O O 4-*
o o c
CU
CO 4-ป O
3 TJ CJ
T3 O
O t- E
t_ Q. 13
Q.1 C3
O O
.C CO CO
O i
^ -O TI
C O
"D OJ I_
cu .m
O -FT (M
Q. 00
t_
- a. co
CO JZ
O ป 4->
L. Q>
n 4-> ฃ_
O CD O
CO t-,S-
4-ป
C CO +^
CD O CD
'ฃ _, fT
o CD "o.
CO E ..
> S- CO
55 QJ X
4_i Q}
i E o
CO 0) u-
o
o t-
JI -E 3
0 4J X O >*
4J <_ CO t-
CO D) O O
.Q C O5 ' C3)
4J . CU CO CU
U CD > 4J O 4-ป
3 4-* E CO CO "- CO
TJ 0 CO JI 0 C O
0 3 CO JI
C- TJ 4-ป >x O >ป
D. O C O 4-" CD 4J
1_ "^ 3 4J - .
D. TJ O i O
CO 4-> O C
3 ' O ฃ- X O X
4J CO 3 Q. 0 C 0
U 3 Tf 4J 4J
CO 4-* O >. CD'
O i- C. (U JI CD
C CO CL CO .E 4-> JC
O .4-' 4->
C C C C
CO O O O OJ O CU
4-> U) U)
CD CO CO CO C CO E
"O 4-ป 4-ป 4-ป CO 4-> CO
co co co jz co j:
_4J TJ TJ TJ 0 T( 0
j= CD O CD O 0) O
CO O O O Tf O T(
* CM M sd- o in o
8. 8.
X X
CU (U
CO
g
s.
1
I
L.
1
1
'
0
o
ฃ
LU
,
CU
TJ
a.
CO
o
a.
2
ivj
CO
c
CO
J=
E
o
L.
co
CD"
, Chtorophacinon
CD
j
CO
4-*
TJ
c
CD
acinone
.E
CL
C
o
o
;j~
CO
o
ฃ_
m
o
o
CO
4-
5
O
t_
m
ฃ_ "
O
M-
O
in
CU
4J
O
c
o
o
u_
CO
CO
u
CO
o
H-
s-
. UJ 1
o
in
c
o
_Q
J= O
4-*
CO
4-* CD
C 4-* h
CD CO
t_ T3
4-*
CO *-
r- O
O>
-CO CO
t- CU
a.
CO
D.*.
o
O JC
0) 4->
L_ r
CO
-C
4-* <">
CO 3
^: Q.
CO C
4-> CO
c
CU (U
a n
25
0 0
M- O
CO O
ฃ t
O . E
4-* CO
ฃ_ '
O O
CO -^
CO
o
4-* 4J
o
IS c
4-* 4-*
o 5
ฃ_ ^
O 4->
-o S
CO E
4-*
CO O
CO
CO O
' S O
4-* M- E
CO CO CO
rf~
CO 4J CU
41 "S ^
t? (U
.c _c
CO * 3C
O J3
^ CO CU
H- 4-* '
^- CO "-
i UJ CD M
""'
.
T3 T3 T3
CO CO CU
jQ O
>- LU CO CO CO CD CO
CO
t-yf _
M CO
O "o Q.
rv* f_ Q_
I- CO
' * - CO * '
4J CO CO 3 CO
CO CO 0 O D- 3
CO 4-* Oฃ O CO O /
IJLJ CO E CO
CO CO >. CO T3 >-
Z) CL (D CU ฃ_ C E
3! CO DO
3= t- D CO O t_
H- O O ฃ- L. CU
I 3C =C Q. CD O.
CJ
""I
CO
d) I - _J LJ 1
'ซ r
1 I 1 I 1 1 1 I
-------
in
O
ro
0)
en
nJ
PU
K-j
Al
O
o
_
yv i
ปaj
Q
^
O
d
0)
5>
ft
Protection
20460
3ฐ'
XJ
d Q
0)
S d"
0 0
Vl 4J
H tr>
> d
w !d
m
0} (t!
Q) IS
4J
ti
4-1
CO
Tl
0)
_!
n
PJ
CO
Ib
J3
03
is
s
05
B
g
GUIDELINE
1
1
LJ
ฃ1
t;
2
Cci
p
KJ
M
e
s
^
CO
Q
g
(H
pt(
d
Bromethali
10
VD
OJ
s
m
ง
"
o
i
rf4"
^P
(1)
m
rti
CJ
*
'-*
jj
Q
0
u
01
0)
4J
o
d
o
o
,
TJ
Q>
L.
CO
g
I
4-ป
T3
O
t.
O.
jz
C
CO
4-1
CO
g
CO
=;
e
o
4-*
1
O
H-
O
0.
CO
CD
4-ป
x:
.^
c
=i
CU
-Q
4-*
CO
g
CO
CU
"g
4J
CO
CO
U
JJ;
01
c.
o
CO
< 1
CO
m
Q.
o
CO
CD
O
8,
CO
CO
o>
o '
CO
a.
CU
c.
o
en
c
1
CU
"O
co"
CO
tu
2
CU
M-
TI
CO
CO
g
CO
D) " "
CO UJ C- C_
CU Qฃ Q O O
c/s - in ซ in in ซ tn inซ
D. o o: ซ- T- T- ซ- T-
&Q- 111
X Q.
VX III
>_
t- ^^ ' C- I_ C_
O ZOO 0
co :zn_ป-ioroe>h- o^foco CMCNJ oiซoc>
O _JO<:tc\ICMCO ICNJCMCM 11 ICMCM
CO Q (3 O^ *~ ^~ ^ O^ ^~ ^~ ^~ O^ O^ O1* ^~ ^~
cn i ca uj
C 2 Q T3 Tl CO CO
0 ID o: C- 0ฃ
C3 ซ .ฃ- CO
> M-
oo coo oco 0=100
H- ej LU o Oฃ Q.O Q.C/3 Oฃ
CU ^ O "^ CO ฃ OJ CU "**,
-EZ UJ>ซ O 0 TI X
4-ป COO4-I
>* ซcmco-ป- - CQ 'CU
u -i x
-------
in
o
a)
Cn
ft
r*^
6
u
fc
.
- CO
73
CO
ฐ
Q.
0)
1
X
o
0) ซ
Lป
'i
TJ ,
' E '
CO '
"o '
- 1
1 . -
4_
i
o>
c
CO
. H-
co '
CO '
TJ
in
CO
ฐ
Q.
* >*T3 3! C >- O O
4-ป cu ^ / 3: -_. co
3 t- ZJ C- OJ O CO COฃ_Q.3Q.
O O OCUT30 M- jc O O
3= Z =C . Ou xx H- i ^-4-* Z C = C
Q) 1 t O tr iw
s "g i 2 .2 .^
2 "ra 'w S '5 4J jl
g"^ ' CO . CO
C . O "O .O o
O JT C ^^
CO * s- **-
O 0) S- O .
01- -. M u i_i
,' ' 1 1 ' 1
1 1
J
-
I
.
t_ I_
o o
tM ซr- CM T-
CM CM O ซ O r>- O CM O O
II I CM I CM 1 CM I CM
CO
O CO
s- cz.
t- CO
^ u> ซซ- o o
-J O O CO 4-> CO
D" a o 3 ca 3
C/3 - Oฃ O , ฃSฃ O
C ฃ- CO 0) CO .
CO
O) c_ CO '
!S en o E
O TJ O JZ
CO 3 CO
I- O O 0)
1 Q- O I
1
1
-------
m
3
g N
INITIO]
Name:
to >O
M Cl
Q (5
pj3
tn
CO
o
8
re
T3
(A
73
0
ฃ_
OJ
Q.
CU
ฃ_
1
Q.
X
CU
o
JC
i
ฃ_
o
-a
U)
E
CD
O
"cn
c
T3
CU
O
H-
I
CO
H-
03
CO
OJ
CO
CO
t_
3
CO
o
t- Q-
ฐ CO
OJ *- tn *
*r- r- *- OJ CO
i i OJ OJ _G
ซO >O 4-*
O "D
4-* O CO
*rป 4J ฃ
CLjr <0
CL. 3 CO
CO CU O E
" w 'i E -2
*~* >. ~D O
o co 4-> r
i_\ ฃ_ co o ro
d ฃ5ฃ .5
o -g
O ,ฃ
^*^ H
CD
CQ "f
2 1
2
CH c
4J _
8 ' '~'
to
CO LU
.Q
& 11
E t tu
O I -C
i CO 4-ป >- 4-*
"ro 13 ง t_
*D O LU O
E DZ H-
X 0
O O u_ TJ
CO 0 CU
O to . ^E
H- O LLJ CO
H- 4-ป Oi '
CU ป- O
3: to o eu
CO -M LLJ CO
c Q-a: o
CO JZ
O T3 LLJ 4->
C to oi
CO JO O O
-D C/J >s
O 4-ป _J CO
. . 3 ** "ฐ
CU ^ E CO , "D
a. N. i c
r- - CO CO
0) CM LU 4-ซ
ฃ- 0 (- ' X
3^-4-* CO
CO 01 >-
R*. t , 4-ป
. . * UJ O
X D) O) CO U- C
CO C *r- <
^ eu OJ ป
CO J2 4J *~
ja ro co ~o ~o 4->
' eu c cu o
>. 4-> CO 4J 3
to ' co ~a
TJ ' C N- O
i CO O *~ 4J t-
ro - CM - CL
E 4-ป C
4^ e. L- 3
^ M- 4-ป CO CO O
3 *o c "o co
CO CO CO O ฃ-
' 4-* CL O CO O
to eu i 4-ป 4-ป *4-
ป ' J^ O CO
ฃ_ CO O t. CO TJ
4J *D CO CL 4-J CO
M- O CO 4J CO
O L. O 3 t- CO
tD CO J3 O
CO M- 0
4-ป CO CL "CO
' E co ja co
3 CD -iฃ 4-ป
CO CO O < . CO
o ' co ro a. to
t. O 3 CL LU Q.
' CO
C D) CL O X T3
o c co ja c
o, if- ^\ t \Q CO
cu o tu >* co
~n eu CM t_ 4-> NO to
CO H- O CL i 4-*
co i * H- cu in -
to cu o o ซ 'co
ja - o o KI
D) CO CO i CU
'N c . o> o m -E
Q -i- ' .C TJ , O 1
tU CO CU 4-ป C N.
CO CO 4-ป 4-> TJ CO CO
IE "5 tO ฃ-3 CO CO
4-ป 4-ป CO CU _Q ^
n * -F- o
M- C D) > 0 O
O CO C E CU CO Z
eu eu "O co to
O O) tO 0) E 4-ป
c c o cu ja co "-
CO CO M * '"" O
3 x: ' co *u ' to
(0 0 0 ' ' 4-ป t.
CO O CO 3 - <0 O
4-ป CO 3 TJ
O O O _C ซ 4J
oc .ceo-r-co M *-* '~
4-* OC4-* t_ >NซE
co ococo o cooja
t_tO (0 .^-4J , 3=a: 3
,00 4-j co o = ' cn
. TJ eocooj- ' oc
ฃ_ T3 4-J4-ปOZ CO 30
CLC 3CO4->< 0 4J
N^O ra o i co TJ
f O 4-* -Q i t/S * C CO CO
>.4J C *-. fi. *- CO 'r-CUJMi
' ro tt'ir- co CD co 4-* o o
co ป co m to tu co coo co
33 JปiCO 3TJQ: CO 4J<4JCL
OE O -^ CU t CU i 4-< C O CU
ซ*-ฃป COO COO4-*^ C0t-3t-
>O.CLCO I34-*COU1 tO EOTJ
CD H- CD CL i i CU Q. CO CO OCO
L. ""OCU O>*4-'Z' tO ฃ_.Oฃ-""
CL4-ป COO 4-*TJ< -C "-ซ-fCL
.. - _/
4-iOja CL TJ*-" ~ 4-* COCO Q) _C
C04-> ' CO 0 LU 3 4-'L.tUฃ.4->
CD Q. CU ' f- ' CD ฃ- ja CO O C TJCO
h-tojc coo o;o _D o co - 4-* 4-ป
O4-ป H- H-CO CO E4J>COO
>ปO 4-ป 4J D)I " COCOO 3
CO C04-* 3 CO 3 CO . CO CO t,TJt-O)TJ
Q CO O4-> O4-ปCOQ 4-ปC "- CL CD O
i C.C _QC J3 C CD LU COO 3 CU ^^ OS C-
rotO4-ป coto COCUTJE co-ป- D~JZ CL
CO E ฃ . J 4J CD 4-ป CD ฃ_
ป4-jaCS CO~CO COCU4-'< CO Oฃ 4J * S- 04-* 4J3
>ซ > ^^ CU 3 CO 3 T3 O O~ ** CO O "O
4->co> Eo~ EO~OLU ja ซ t-ctoo
^ jr; O t CU fc CO t- Qฃ CO CO *" 4-* O ^C j^ ฃ_,
__r . Qฃ O C O t Q_ ^ ^ 4J , CO 4-* Q_
* CO Q_ O C_3 CO CO CO CO 4-* ->^'
OfOTJ CD CO COCOH-O "-D OCOJaCL"-^
!3~OTJ C0*ป- . COOS CO
CL CU C"4- C**-tO< CO 3D iQ.
Q_ **. <0 CO M- OH- Q. I 3 H- O O O
i - i ซ- CM t-
-------
H
O
H
0
tn
ft
><
ft
o
0
EH
CM
<
ซ
P
o-
o
1
?T.
M
is-h- ฐ
otn co
T o CU
00 ฃ-
TJ 1 1
CU OO Q.
O OO LU
C- CNJCM
a. - co
* ฃ g ,
E t_
i- ma.
o rฃ o
u. O <
d
a)
ซ?
d
o
-H
4-> 0
O VO
4-) 0 CQ
u co
nS * PH
u P
SH ' (3
i"
CL
ง-
CO
g
CD
CO
C
o
4-*
nstruc
"8
JZ
u
4_i
4-*
CO
O
JC
arefully t
u
T3
CO
ฃ_
4-ป CO '
c in
*- tfi
t- CU
CL 0
CU
ฃ- C
O
CU -
CL
CU 4^
CO CU
SO)
JZ
CO
o.
ll
K co
ป CU
Z CA
"*.=
O
H
_. H
o O -
Q H
a.
1 Jr '
_ O
? D
CO p
ฃ O '
CO Pn
Q pj
M
ra
rH
(ti
CQ
I7~i
s
_H-
i -H
CD
ซ: O
CU H
co CO
3 CN
CM
O
o
CQ 0
CQ O
W o
1 ง Q XI
"E O EH
"OH
| H >H
C J EH H '
c> ft CO CJ
ง" Jง3 o o
*~"
CO
u
fO
o
o
M-
o
Q)
fi-
o
3
O
t_
Q.
CD
CO
O
o
Generi
.
0
TJ TJ
C CU CO
-j= cr i~
"-CO Qi CO
^ c =
+-1 4-* O ' O)
O CO TJ CU'-
3 CO CO O Qi"
0 O C *J TJ =
Q. E 4J CD CU
CU CU C CO
X CU t- CU CO C
E t- 30
O) 3 E 4J Q.
CO .O~ ฃ- CO CO
.Ci CU O 4-ป 0)
^ ป-ซ c_ M- c/> o:
TJ
13 CU CO
c a. j: 4->
co rj o c
E CO CU
a- 4J E co
^J CU 4-> CD CD
CU CU C CO
>ป CU t. CU CO C
D) 3 E t ' CL
CO D" E- CO CO
CD CU O 4J CU
r^ >- L. M- tn cฃ
t- 4-1 CU
C O 4-ป
O ^ 4J TJ
c c c =
i1"" * o
co co E co co
- CO E 3 C
*-> O 4-> 0
CO CO H- CO CL
CO 4^ 4-ป CO
C "O C/> CU
O CU CU ys*
4J E s: co
CU O 4-ป CO
CJ C- CO C o
CU -> 4J CU 4-ป
[7} O~ CO CU CD
CO CD c- (-
-ซ .C 3 CO
CO 4-ป O"'
- 4-ป CU D)
-Q CO C Q; CO
O C 3
CD i O
t. "-CO
1) ป TJ -i- CD
5 co t- o
3 CO O) Cป ^3
CO CO
o a. co
3) CU CU UJ "-
- .t- CU
= C 4J O C_
O 0 t- CU
co co 3 ja
4J O E
O CL CD CO D
D X .C C
UJ C 4-> O
CO CO E 4^
4-ป 4-ป O CO
CO CO .Q t_ ฃ_
O O O M- 4J
, - ,
O " 3
4-1 cu "o
^ ^ L. >
CO V
- 4-ป C.
*!!ฃฃ
""" C O CO 'tl
, in O Q. 4J 4J
li
o
n. CD
ฃ_
Q. CO
UJ !-
D)
Q)
-* OS
?
' -
a
< - ,
"
1
i
I
1
a . -
-
o
CO
.
ป-*
O CU
M p
V C.
__. o
Q. CO .
c ""
CO ป /
CU
CO
o
to *
JQ
ซ CO
CU .C
7 CO
ฃ "c
CU D.
L.
CO CU
to,
_C 4^ ,
u c
CD O
CO 4-ป >
' CO CO
CO - 4-*
D) C
TI C 0
C M- .CO
(0 TJ CU
CO L.
E 2 'Q"
o to or
E TJ
CO (U
r- t_ N
^: o "-
o o
g CO -C
O ' 4-ป
CO 3
CU M^- ^
CD >- CO
CO C C
u 3 CO
C 3 CO CL
CU -^ CO U
4-J
CO >N -Q M-
4-ป C CO O
CO CD O
. CU
< >
.c co Q. 4->
C 4-> JZ CL
O 4J CO 1
4J
4-" CO CD t- TJ
CO -C' 0) CU C
O. 4-ป T3 "D CD
i (ii f
H- X 3 O
- 4-* C 4-> 4J
^
eo .- o w
L.
CU
_Q
s:
o
/%
*~
^j
CO
c
o
CJ
CO
D.
5
CJ
o
CU
CD
^
-------
CN
oo
cs
-------
EPA'S BATCHING OF PRODUCTS CONTAINING A RODENTICIDE CLUSTER
ACTIVE INGREDIENT FOR MEETING REREGISTRATION ACUTE TOXICITY DATA
REQUIREMENTS
In an effort to reduce the time, resources and number of animals needed to fulfill the acute
toxicity data requirements for reregistration of products containing the active ingredient
diphacinone, the Agency has batched products which can be considered similar in terms of acute
toxicity. Factors considered in the sorting process include each product's active and inert
ingredients (identity, percent composition and biological activity), product form (liquid, paste,
solid, etc.), and labeling (e.g., signal word, precautionary labeling, etc.).
Using available information, batching has been accomplished by the process described in the
preceding paragraph. Notwithstanding the batching process, the Agency reserves the right to
require, at any time, acute toxicity data for an individual product should the need arise.
Registrants of products within a batch may choose to cooperatively generate, submit or cite
a single battery of six acute toxicological studies to represent all the products within that batch.
The registrant has several options to participate with all or some other registrants, or to deal only
their own products within a batch, or to generate all the required acute toxicological studies for
each of their own products. If a registrant chooses to generate the data for a batch, he/she must
use one of the products within the batch as the test material. If a registrant chooses to rely upon
previously submitted acute toxicity data, he/she may do so provided that the data base is complete
and valid by today's standards (see acceptance criteria attached), the formulation tested is
considered by EPA to be similar for acute toxicity, and the formulation has not been significantly
altered since submission and acceptance of the acute toxicity data. TRB must approve any new
formulations (that were presented to the Agency after the publication of the RED) before data
derived from them can be used to cover other products in a batch. Regardless of whether new
data is generated of existing data is referenced, registrants must clearly identify the test material
by EPA Registration Number. If more than one confidential statement of formula (CSF) exists
for a product, the registrant must indicate the formulation actually tested by identifying the
corresponding CSF.
In deciding how to meet the product specific data requirements, registrants must follow the
directions given in the Data Call-In Notice and its attachments appended to the RED. The DCI
Notice contains two response forms which are to be completed and submitted to the Agency within
90' days of receipt. The first form, "Data Call-in Response," asks whether the registrant will meet
the data requirements for each product. The second form, "Requirements Status and Registrant's
Response," lists the product specific data required for each product, including the standard six
acute toxicity tests. A registrant who wishes to participate in a batch must decide whether he/she
will provide the data or depend on someone else to do so. If a registrant supplies the data to
support a batch of products, he/she must select one of the following options: Developing Data
(Option 1), Submitting an Existing Study (Option 4), Upgrading an Existing Study (Option 5) or
Citing an Existing Study (Option 6). If a registrant depends on another's data, he/she must
choose among: Cost Sharing (Option 2), Offers to Cost Share (Option 3) or Citing an Existing
Study (Option 6). If a registrant does not want to participate in a batch, the choices are Options
1, 4, 5 or 6. However, a registrant should know that choosing not to participate in a batch does
'283
-------
not preclude other registrants in the batch from citing his/her studies and offering to cost share
(Option 3) those studies.
Table 1; Batches for the active ingredient diphacinone
JBatch
1
2
Registration Numfeer
12455-25
61282-1
61282-5
56-23
56-41
56-42
56-44
56-57
70-133
70-170
769-653
769-655
769-660
769-669
769-670
769-671
769-787
2393-476
2393-497
2393-498
2393-501
2393-508
3487-26
5887-178
5887-180
5887-181
5887-182
6409-1
7122-32
7122-66
7122-69
11885-12
11885-15
12455-5
12455-14
12455-19
12455-29
12455-67
12455-78
Percent Active Ingredient
diphacinone ... 98%
diphacinone ... 98%
diphacinone ... 99%
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ...0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone .... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
Form
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solids
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
284
-------
2-
_
12455-80
12455-81
12455-83
12455-84
56637-1
56637-3
56637-4
61282-6
61282-7
61282-9
61282-12
61282-19
61282-23
. . . 61282-24
61282-26
AZ88001900
CA78014600
CA79002500
CA89002000
CA89002100
CA89002200
. CT881000100
CT96000200
FL78006200
FL86000300
FL88001800
GA95000700
, HI91000400
HI96000800
ID82002500
ro86ooi80o
ID87002200
ro96000500 .
MA77000100
MI84001200
MO97000200
MT86000300
NC92001000
NH76000100
NV88000800
OH84000300
OR76003600
OR85003800
PA82001600
diphacinone ... 0.005
diphacinone ^-. ...0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ' , ... 0.005
diphacinone ...0.005
diphacinone . ... 0.005
diphacinone ... 0.005
diphacinone ...0.005
diphacinone ... 0.005
diphacinone - ... 0.005
diphacinone , ... 0.005
diphacinone ... 0.005
diphacinone ,.. 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ...0.01
diphacinone , ...0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.01
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ...0.005
diphacinone " ... 0.005
diphacinone ... 0.005
diphacinone ' ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone -ซ ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone / ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ...0.005
diphacinone ... 0.005
diphacinone ... 0.005
- solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
Solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
. solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
. 285
-------
2
3
4
SC96000200
UT87000300
VA82001500
VA85000300
VT86000300
WA86003300
WA86003400
WA92003100
WV82000500
WV84000400
WY88000600
769-651
769-758
2393-488
2393-517
3240-17
12455-9
12455-61
HI91000400
12455-56
61282-8
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ... 0. 005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ...0.005
diphacinone ... 0.005
diphacinone ... 0.005
diphacinone ...0.005
diphacinone ... 0.005
diphacinone ... 0.1
diphacinone ... 0.1
diphacinone ... 0.1
diphacinone ... 0.1
diphacinone ... 0.1
diphacinone ... 0.1
diphacinone ... 0.1
diphacinone ... 0.1
diphacinone ... 0.2
diphacinone ... 0.2
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
powder
powder
Table 2 lists the diphacinone product the Agency was unable to batch. This product was not
batched because it was not considered to be similar to other products in terms of acute toxicity.
The registrant of this product is responsible for meeting the acute toxicity data requirements for
it individually. This product may not cite acute toxicity/ irritation data derived from any other
products in this RED. The registrant may cite pre-existing data conducted on their individual
product if it exists and meets current Agency standards.
Table 2: Unbatched Diphacinone Products
; Registration Number
2393-493
Percent Active Ingredient
diphacinone
... 2.0
Table 3: Batches for the Active Ingredient Chlorophacinone
Batch
1
2
Registration Number
OR78001800
UT78000600
WA78006000
WV77000300
7173-113
7173-172
UT77000200
Percent Active Ingredient
chlorophacinone ... 5.34%
chlorophacinone ...5.34%
chlorophacinone ... 5.34%
chlorophacinone ... 5.34%
chlorophacinone ... 0.20%
chlorophacinone ... 0.20%
chlorophacinone ... 0.28%
Form
spray
spray
spray
spray
solid
solid
solid
286
-------
3
56-56
56-58
56-69
56-70
5042-31
7173-80
7173-128
7173-151
, 7173-161
7173-184
7173-185
. *7173-190
AZ77000600
CA77001500
CA77049600
CA77049700
CA80015900
CA89002300
CA89002400
CA9002500
CA93002200
CT94000300
ID92000300
._ ED96001200
MD78000700
MI77001400
MO78000100
MT91000100
NC77002000
NV92000100
NV93000300
NY94000700'
OH79001300
OR78001800
OR8400480
OR85000300
OR92000100
OR95002000
OR95002600
PA80004500
SC78000200
UT77000100
VA77001500
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ...0.01%
chlorophacinone .... 0 . 005 %
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.005 %
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.01%
chlorophacinone ...0.005%
chlorophacinone ... 0.01 %
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone . ... 0.005%
chlorophacinone ...0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone . . . 0.01 %
chlorophacirione ...0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0. 005 %
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0 . 005 %
chlorophacinone ... 0. 005 %
chlorophacinone ... 0.005%
chlorophacinone ...0.005%
chlorophacinone - ... 0.01%
chlorophacinone . . . 0 . 005 %
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.005 %
chlorophacinone ...0.005%
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
. solid
solid
solid
solid
solid
solid
solid
solid
solid
287
-------
3
VT76000300
WA78006100
WA83002600
WA84002900
WA92002200
WA95004200
WA95004400
WV7700050
cMorophacinone ... 0.005%
chlorophacinone ...0.005%
chlorophacinone . ...0.01%
chlorophacinone ... 0.005%
chlorophacinone ... 0 . 005 %
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
chlorophacinone ... 0.005%
solid
solid
solid
solid
solid
solid
solid
solid
*Due to the formulation of registration number 7173-190, it is likely that the registrant would be granted a waiver of
the acute inhalation toxicity study for this product if one was requested. Registrants of other products that contain
substantial amounts of oil or paraffin wax should also request a waiver of the acute inhalation toxicity study for these
produces).
Table 4 lists the products the Agency was unable to batch. These products can not be
batched because it was not considered to be similar to other the products in terms of acute
toxicity. The registrant of these products is responsible for meeting the acute toxicity data
requirements for it individually. This product may not cite acute toxicity/ irritation data derived
from any other products in this RED. The registrant may cite pre-existing data conducted on their
individual product (or data cited in this RED for the technical product) if it exists and it meets
current Agency standards.
Table 4: Unbatched Chlorphacinone Products
Registration Number
7173-72
7173-75
Percent Active Ingredient
chlorophacinone ... 0.28%
chlorophacinone ... 96.03%
Product Type l
mineral oil concentrate
technical grade
Due to the probable toxicity of registration number 7173-75, TRB will not allow other less
concentrated products (beside other technical products) to bridge acute toxicity data from this
technical product.
All of the following 23 products in tables 5,6 and 7 contain only one active, bromadiolone,
3-(3-(4' -bromo-(l, 1' -biphenyl)-4-yl)-3-hydroxy- l-phenylpropyl)-4-hydroxy-2H-1 -benzopyran-2-
,one. .
'" ''",''
Table 5 batches the two technicals. The RED includes data on the acute toxicity of either
a pure or a very concentrated version (for acute oral toxicity), already clearly a I at the
concentration tested. No further testing of the technicals is required.
Table 5: Batch 1 for the Active Ingredient Bromodialone
EPA Reg. No."
7173-174
12455-70
% of Bromadioloixe
93.5
96.5
Formulation Type
Solid
Solid
288
-------
Table 6 batches the two Bromadiolone manufacturing use-products, each with
approximately the same concentration. It.should be possible to bridge, these with the technicals.
Table 6; Batch 2 for the Active Ingredient Bromodialone
EPAReg>No<
7173-173
12455-31
% of BronaadioloHe "
1.07
1.0
Fcsntnulation Type
Solid
Solid
The remaining compounds have the same concentration of bromadiolone (0.005 %) and are
batched together for acute oral and dermal toxicity purposes. The acute inhalation toxicity is
waived as all of these are baits. Product 12455-69 was tested acceptably and may be used to cite
data. . .
Table 7; Batch 3 for the Active Ingredient Bromodialone
EPA Reg. No.
602-306
602-308
602-313
7173-171
7173-186
7173-187
7173-188
7173-189
7173-202
7173-208
12455-34
12455-36
12455-68
12455-69
12455-75
12455-76
12455-79
12455-82. '
12455-86
% of Broimadiolone
0.005
0.005
0.005 ,
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.005 .
0.005
0.005
0.005
0.005
0.005
0.005
FcamulatioB Type
Solid
Solid
Solid
Solid
Solid '
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
However, the following sub-Batches are together for primary irritation testing purposes.
Primary eye and dermal irritation testing needs performing.
Table 8: Batch 4 for the Active Ingredient Bromodialone
EPA Reg. No.
602-306
602-308
602-313,
7173-171
7173-186
% of Bromadiolone
0.005
0.005
0.005
0.005
0.005
Formulation Type
Solid
Solid
Solid
Solid
Solid
289
-------
Table 9: Batch 5 for the Active Ingredient Bromodialone
EPA REG. NO.
7173-187
7173-188
7173-208
% of Bromadiolone
0.005
0.005
0.005
Formulation Type
Solid
Solid
Solid
The batch below contains 12455-69 which was adequately-tested, including primary eye
and dermal irritation, acceptable for citing. ,
Table 10: Batch 6 for the Active Ingredient Bromodialone
EPA REG. NO.
12455-34
12455-36
12455-68
12455-69
12455-75
12455-76
12455-79
12455-82
12455-86
% of Bromadiolone
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.005
0.005
Formulation Type
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
All of the following 19 products contain the active ingredient bromethalin (N-methyl-2,4-
dinitio-N-(2,4,6-Mbromophenyl)-6-(trifluoromethyl)benzeneaniine). The HED chapter for the
RED indicates the acute toxicity of this active is complete and valid. There are two (2)
Manufacturing Use (MU) Products, a 2% solid concentrate and a 1.5% liquid concentrate, which
are batched together. The highest concentration Manufacturing Use Product - 67517-64, is the
only product to have been tested, and it has nearly complete toxicity information. Only the
dermal sensitization was not performed. The active is not a dermal sensitizer, but the products
all have various inerts which may or may not be sensitizers.
/
These products are all baits and the inerts are primarily food-stuffs. Except for the MU
' products, all are batched together, and the toxicity ratings for the batch could be bridged from data
on the 2% concentrate, along with the conductance of an acceptable dermal sensitization study on
67517-66 or 67517-76. If the dermal sensitization study is positive, more studies may be
required.
Table 11: Batching for the Active Ingredient Bromethalin
Batch
1
2
BPA Reg. No.
67517-64
' 67517-65
432-746
432-747
432-748
~ %'ofBrcanethalin
2.0
1.5
0.01
0.01
0.01
JE^omiuJatibji Type
Solid
Liquid
Solid !
. Solid
Solid
290
-------
2
8845-125
67517-63
67517-66 -
67517-67
67517-68
67517-69
67517-70
67517-71
67517-72
67517-73
- ' 67517-74
67517-75
67517-76
67517-77
0.01
6.005
O'.Ol
, , 0.01
0.01 ;
0.01
0.01
0.01*
0.01
0.01
0.01
0.01-
0.01
0.01
Solid
Solid .
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Solid
Table 12: The Batches for the Active Ingredient Brodifacoum
,JBatcli
1
2
EPA Reg. Mb. ,
10182-28 .
10182-384
3282-65
3282-66
3282-74
3282-79
3282-81
10182-20
10182-21
10182-24
10182-25
10182-26
10182-38
10182-39
10182-40
. 10182-41
10182-48
10182-60
10182-61
10182-75
10182-76
. 10182-93
10182-334
Percent Active Ingredient
brodifacoum ... 0.25%
brodifacoum ... 0.25%
brodifacoum ... 0.005%
brodifacoum ... 0.005%
brodifacoum ... 0.005%
brodifacoum ... 0.005%
brodifacoum ... 0.005%
brodifacoum ...0.005%
brodifacoum ... 0.005%
brodifacoum ...0.005%
brodifacoum ...0.005%
brodifacoum ... 0.005%
brodifacoum > ...0.005%
brodifacoum ... 0.005%
brodifacoum ... 0.005%
brodifacoum ...0.005%
brodifacetum ...0.005%
brodifacoum ...,0.005%
brodifacoum ...0.005%
brodifacoum ... 0.005%
brodifacoum ... 0.005%
brodifacoum ... 0.005%
brodifacoum ... 0.005%
Form
liquid
liquid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
solid
291
-------
2
10182-335
10182-336
10182-337
10182-338
10182-339
10182-339
10182-340
10182-341
11715-218
brodifacoum ... 0.005%
brodifacoum ... 0.005%
brodifacoum ... 0.005%
brodifacoum ... 0.005%
brodifacoum ... 0.005%
brodifacoum - ... 0.005%
brodifacoum ... 0.005 %
brodifacoum ... 0.005%
brodifacoum ... 0.005%
solid
solid
solid
solid
solid
solid
solid
solid
solid
Table 13 lists the product the Agency was unable to batch. This product can not be batched
because it was npj considered to be similar to other the products in terms of acute toxicity. The
registrant of this product is responsible for meeting the acute toxicity data requirements for it
individually. This product may not cite acute toxicity/ irritation data derived from any other
products in this RED. The registrant may cite pre-existing data conducted on their individual
product if it exists and it meets current Agency standards.
Table 13: Unbatched Brodifacoum Products
Registration Number
10182-29
Percent Active Ingredient
brodifacoum
...90%
Due to the toxicity profile of registration number 10182-29, TRB will not allow other less
concentrated products to bridge acute toxicity data from this technical product.
There was only one technical product for pival and the sodium salt,of piVal each, and no
end-use products. As such, the two products covered in this RED could not be placed into
batches. These products are placed into the "No Batch" group. The registrant of these two
products must cite a separate set of acute toxicity data to support each of these products. Table
1 displays the two products covered by this RED.
Table 14: No Batch Group for the Active Ingredient Pival and Sodium Salt
; Registration Number
3240-9
3240-10
Active Ingredient
pival
pival, sodium salt
...99.99%
... 99.99%
292
-------
Cost Share, Data Compensation Forms, Confidential Statement of Formula
Form and Instructions
The Confidential Statement of Formula (CSF) Form 8570-4 must be used. Two legible, signed
copies of the form are required. Following are,basic instructions:
a. All the blocks on the form must be filled in and answered completely.
b. If any block is not applicable, mark it N/A.
c. The CSF must be signed, dated and the telephone number of the responsible party
mustbe provided.
d. All applicable information which is on the product specific data submission must
also be reported on the CSF.
e. All weights reported under item 7 must be in pounds per gallon for liquids and
pounds per cubic feet for solids.
f- Flashpoint must be in degrees Fahrenheit and flame extension in inches.
g. For all active ingredients, the EPA Registration Numbers for the currently
registered source products must be reported under column 12.
h. The Chemical Abstracts Service (CAS) Numbers for all actives and inerts and all
common names for the trade names must be reported.
I. For the active ingredients, the percent purity of the source products must be.
reported under column 10 and must be exactly the same as on the source product's
label.
j. All the weights in columns 13.a. and 13.b. must be in pounds, kilograms, or
grams. In no case wiH volumes be accepted. Do not mix English and metric system
units (i.e., pounds and kilograms).
k. All the items under column 13.b, must total 100 percent.
1. All items under columns 14.a. and 14.b. for the active ingredients must represent
pure active form. .
m. The upper and lower certified limits for ail active and inert ingredients must follow
the 40 CFR 158.175 instructions. An explanation must be provided if the proposed
limits are different than standard certified limits.
n. When new CSFs are submitted and approved, all previously submitted CSFs
become obsolete for that specific formulation.
293 :,
-------
294
-------
3
ฃซ
ป-
S
1-
Ul
5.
Q-
c
c
o
a
6
z.
* i
O
1
o.
ฃ
^^
Cft
^^
C2
0
i
ซ
i
c
' "c
u
93
0)
5
c
1
2^
^*
Does Not Contain
c
o
a
ฃ
,g
1
1
Q
* 5
ป
onfidential
O
s
m
0
{A
C
s
J
ฃ
c
o
V)
ซ !
c
o
g S
.2 3
ซ E
LJ Basic Formul
LJ Alternate For
*
0
3
& ง
i O
5ST IJ_
Environmental Protection >
Pesticide Progrims(TS-76
'shington, DC 20460
1 Statement of 1
1ฐ .2
2 ^rf
ซฃ C
go o>
1 T3
*G
O
0
S
LU
*fฑ
'
1
CL
N
ง
j
cluda ZIP Code)
*
^
5
I
c
j
*
_
w
5
ฃ
\
4
c
.2
m
^
(A
|
^ ;
c
o
5
c
i
UJ
(D
ป
U.
c ,
"5
a.
(D
u-
<ฃ
"
a 1
'i I
^"f-3
.s 5-*'
Ul
^*I
-
3=
I
** i"
S ye
C Cj,
a-s
3. Each Con-
in Formula
Amount
*~ d
d
Z,
m
tc
^
5
oi
8t Address
9
E
z
i
CO
'
,/i( ป actually inlroducad
nonty accepted chamical
w.l
~c^*-
2ฐ c
E^^
il-
N
s
g-C *t
j to
2.||
JSEONLY
<
a.
UJ
1
-
-
- ,
se
2
^
tal Weight
,2
ฃ
5
5
5
a
s '
3
1
ped Name of /
^
CO
S
(D
Q
^
M
"S-
2
re
s
I
ฃJ
^.
o
c
o .
ฃ
O
3
D
^
9
5
5
9
>
3
1
5
D
3
0
5
CO
>,
a.
S
H
s
<"
,
ฃ
"or
"D)
*c
o
^
J"
s
ir
UJ
i
g.
O
u
I
o
please submit an addit
ic
ง"
i
Q.
S
1
*ป
editions are obsolete.
3
o
1
ฃ
o>
,
?
cc_
o
g
0
a.
295
-------
296
-------
Ul
(a
United States Environmental Protection Agency
Washington, D.C. 20460
Certification of Offer to Cost
Share in the Development of Data
Form Approved
OMB No. 2070-0106,
2070-0057
Approval Expires
3-31-99
Public reporting burden for this collection of information is estimated to average 15 minutes per response, including
time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and
completing and reviewing the collection of information. Send comments regarding the burden estimate or any other
aspect of this collection of information, including suggestions for reducing this burden to. Chief Information Policy
Branch, PM-233, U.S. Environmental Protection Agency, 401 M St., S.W., Washington, DC 20460; and to the Office of
Management and Budget, Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Please fill in blanks below: ,
Company Name
Product Name
Company Number
EPA Reg. No.
I Certify that:
My company is willing to develop and submit the data required by EPA under the authority of the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA), if necessary. However my company would prefer to
enter into an agreement with one or more registrants to develop jointly or share in the cost of developing
data.
My firm has offered in writing to enter into such an agreement. That offer was irrevocable and included an
an offer to be bound by arbitration decision under section 3(c)(2)(B)(iii) of FIFRA if final agreement on all
terms could not be reached otherwise. This offer was made to the following firms on the following
date(s):
Name of Firm(s)
Date of Offer
Certification:
I certify that I am duly authorized to represent the company named above, and that the statements that I have made on
this form and all attachments therein are true, accurate, and complete. I acknowledge that any knowingly false or
misleading statement may be punishable by fine or imprisonment or both under applicable law.
Signature of Company's Authorized Representative
Date
Name and Title (Please Type or Print]
EPA Form 8570-32 (5/91) Replaces EPA form 8580 which is obsolete ,
297
-------
298
-------
Form Approved OMB No. 2070-0060
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
401 M Street, S.W.
WASHINGTON, D.C. 20460
Paperwork Reduction Act Notice: The public reporting burden for this collection of information is estimated to average 1.25 hours per response for registration
and 0.25 hours per response for reregistration and special review activities, including time for reading the instructions and completing the necessary forms Send
comments regarding burden estimate or any other aspect of this collection of information, including suggestions for reducing the burden to- Director OPPE
Information Management Division (2137), U.S. Environmental Protection Agency, 401 M Street, S.W., Washington DC 20460
Do not send the completed form to this address. -
Certification with Respect to Citation of Data
Applicant's/Registrant's Name, Address, and Telephone Number
EPA Registration Number/File Symbol
Active Ingredients) and/or representative test compound(s)
Date
General Use Pattern(s) (list all those claimed for this product using 40 CFR Part 158)
Product Name
NOTE: If your product is a 100% repackaging of another purchased EPA-registered product labeled for all the same uses on your label you do not need to
submit this form.. You must submit the Formulator's Exemption Statement (EPA Form 8570-27).
Dl am responding to a Data-Call-in Notice, and have included with this form a list of companies sent offers of compensation (the' Data Matrix form should
be used for this purpose).
SECTION I: METHOD OF DATA SUPPORT (Check one method only)
I am using the cite-all method of support, and have included with this form
a list of companies sent offers of compensation (the Data Matrix form
should be used for this purpose).
D
I am using the selective method of support (or cite-all option
under the selective method), and have included with this form a
completed list of data requirements (the Data Matrix form must be
used).
SECTION II: GENERAL OFFER TO PAY
[Required if using the cite-all method or when using the cite-all option under the selective method to satisfy one or more data requirements]
I hereby offer and agree to pay compensation, to other persons, with regard to the approval of this application, to the extent required by FIFRA.
SECTION III: CERTIFICATION
I certify that this application for registration, this form for reregistration, or this Data-Call-in response is supported by all data submitted or cited in the
application for registration, the form for reregistration, or the Data-Call-in response. In addition, if the cite-all option or cite-all option under the selective method is
indicated in Section I, this application is supported by all data in the Agency's files that (1) concern the properties or effects of this product or an identical or
substantially similar product, or one or more of the ingredients in this product; and (2) is a type of data that would be required to be submitted under the data
requirements in effect on the date of approval of this application if the application sought the initial registration of a product of identical or similar composition and
I certify that for each exclusive use study cited in support of this registration or reregistration, that I am the original data submitter or that I have obtained
the written permission of the on'ginal data submitter to cite that study.
I certify that for each study cited in support of this registration or reregistration that is not an exclusive use study, either (a) I am the original data
submitter; (b) I have obtained the permission of the original data submitter to use the study in support of this application; (c) all periods of eligibility for
compensation have expired for the study; (d) the study is in the public literature; or (e) 1 have notified in writing the company that submitted the study and have
offered (I) to pay compensation to the extent required by sections 3(c)(1)(F) and/or 3(c)(2)(B) of FIFRA; and (ii) to commence negotiations to determine the
amount and terms of compensation, if any, to be paid for the use of the study.
I certify that in all instances where an offer of compensation is required, copies of all offers to pay compensation and evidence of their delivery in
accordance with sections 3(c)(1)(F) and/or 3(c)(2)(B) of FIFRA are available and will be submitted to the Agency upon request. Should I fail to produce such
svidence to the Agency upon rfequest, I understand that the Agency may initiate action to deny, cancel or suspend the registration of my product in conformity with
"li r\/\. -
I certify that the statements I have made on this form and all attachments to it are true, accurate, and complete. I acknowledge that any
knowingly false or misleading statement may be punishable by fine or imprisonment or both under applicable law.
Signature
Date
Typed or Printed Name and Title
EPA Form 8570-34 (9-97) Electronic and Pap'er versions available. Submit only Paper-version.
-------
-------
-------
'O:
-------
1
d
2
CO
o
D
Q)
1
Q.
0..
E
o
U.
o
UJ
PROTECTION i
.W.
. 20460
TES ENVIRONMENTAL
401 M Street, S
WASHINGTON, D.C
ฃ
V)
Q
UJ
t
ID
ซป**,.
/g{s\
<>ป**f
*
JIQ-
ซS
*O) CD O
ฃฃ'ง
III
m i= n
25 hours per respom
Send comments regs
S. Environmental 1
nated to average 0.
necessary forms, i
Division (21 37), U.
j _
sis
(0 o) E
~* C 0)
III
(O C tO
j3 ฃ3 ซK
E o 2
j5 o c
.ฃ 1 =
"S E
*- C Q
If-
'S ~ of '
'o ฐ
^ ฃ o"
2 g "g
^ "O .
73 S? O
3 ?~ O
ie public reporting b
s, including time for
ducing the burden t
s address.
.. -S 0 0
St5 "- -S
._ ซ w p
^ 5 o ป
-S S = o
2 ~ To *:
jj S: o) y
^^ Tn 5^ *^
= '0 ป TJ
O qj . ,c
S3 CL ฃ' CB
0 U) ~ CO
|1| I
^ c3 ~-
s
Name and Title
2 .
1
CO
EL
O
o
0)
M
3
To
c
'S
s-
c
CU
5
n
0
*
5
>
0
a.
?
5
ฑ
5
CO
0)
5
D
Paper versions aval
3
3
o
5
5
J
E
"^i
)
}
m
)
>
3
) ,
-
)
J
-------
ซ^.
-
fro
pl
ai
3 CO .
55 E CD
m S -Q
.
UJ
available,
received
of Inform
is
or
ro
ect
'
R
re
e,
gi
S
ber
S %
he
rid
Sy
ich data
ata are
tration N
"C
r
lin
ien
fte
G
t:
CO gj Q)
-" c ซ2
ฃ -CD
"O CO 3
o u -a
ill
a5
t-ฃ
111
11.1
ซง-ฃ-
JC jjj 'ง
** o3 to
>or'ฃ
S|ซ
1-8 o
co =; t.
; ป -CJ
fe ฃ
ence
on tt
en &
enter "CITE-ALL" in the Guideline Ref
CITE-ALL" in the MRID Number column o
ethod of support is used and wri
pleted.] Othise:
ingredien
ber enter
te: if the selective m
ns must still be comple
pa
en
t lin
be
rti
e
on separat
En
is
for
ay
Q)
A
E
a
2
S
c
ฃ
1
ฃ
0)
"oJ
S
0
"c
CD
T3
CD
0)
CO
^
f
CD ฃ
CO
o ^
CD >ซ >,
^ CO "O
r E a
ill
CD" 3 CD
EZS
or each individual study cited in support of a Guideline Reference Number and Guideline Study Na
sment System (PDMS). Enter only one MRID Number on each line. Note that more than one MRID
maintain a registration/reregistration is not associated with a Guideline Reference Number and Gu
^"^
|||
Jlฃ
olf
& S^
S Q co
ฃ
C
CO
ฃ
o
"^
CD
CD
'S
CO
Q_
_c J2
^""~ CO
isi
*o
^ ^
"O CO
for each stu
) in footnote
the most recent Data Submitters List, identify the Original Data Submitter with their current address
lariy explain any variations (alternate addresses, data owners not on the Data Submitters List, etc.
|c3
^ -D
(D
si ง
32 CD
E-0
a S>
a
This Guideline data requirement is a data gap as defined in 40 CFR sections 152.83(a) and 152
Q_!
$
^
u_
CD
to
%i
>- to
Q) HI
.Q CD
o ^
*-* o
.ฃ2^
1 o
o Q-
o ฐ-
Q. CO
.52 ฐ
. (J)
sjjS
5^
> "o
T" O
irked "NA".
ie submitted
1 am taking the formulator's exemption for this ingredient only. Other columns of this line should be ma
uses for which the purchased EPA registered ingredient is not supported, additional data must b
iz.
0
U-
ฃZ
O
ys
to
c
CO
OL
ฃ
CO
'&
c
o
Q.
If additional explanation is needed, enter a footnote number in this column and attach the corres
I
-------
The following is a list of available documents for the Rodenticide Cluster that my further
assist you in responding to this Reregistraiion Eligibility Decision document. These documents
may be obtained by the following methods: ' - '
Electronic
File format: Portable Document Format (.PDFJ Requires Adobeฎ Acrobat or compatible
reader. Electronic copies can be downloaded from the Pesticide Special Review
and Reregistration Information System at 703-308-7224. they are available on the
Internet using ftp on FTP.EPA.GOV, or using WWW (World Wide Web) on
WWW.EPA.GOV., or contact CPMoran at (703)-308-8590.
1. PR Notice 86-5.
2. , PR Notice 91-2 (pertains to the Label Ingredient Statement).
3. , A full copy of this RED document.
4. A copy of the fact sheet for Cases 2100, 2205, 2755, 2760, 2765, and 2810. .
The following documents are part of the Administrative Record for the Rodenticide Cluster
RED and may included in the EPA's Office of Pesticide Programs Public Docket. Copies of
these documents are not available electronically, but may be obtained by contacting the person
listed on the Chemical Status Sheet.
1. Health and Environmental Effects Science Chapters.
2. Detailed Label Usage Information System (LUIS) Report.
The following Agency reference documents'are not available electronically, but may be
obtained by contacting the person listed on the Chemical Status Sheet of this RED document.
1. The Label Review Manual.
2. EPA Acceptance Criteria
307
-------
------- |